Sample records for methadone heroin cocaine

  1. Promoting Abstinence from Cocaine and Heroin with a Methadone Dose Increase and a Novel Contingency

    PubMed Central

    Schmittner, John; Umbricht, Annie; Schroeder, Jennifer R.; Moolchan, Eric T.; Preston, Kenzie L.

    2010-01-01

    To test whether a combination of contingency management and methadone dose increase would promote abstinence from heroin and cocaine, we conducted a randomized controlled trial using a 2 X 3 (Dose X Contingency) factorial design in which dose assignment was double-blind. Participants were 252 heroin- and cocaine-abusing outpatients on methadone maintenance. They were randomly assigned to methadone dose (70 or 100 mg/day, double blind) and voucher condition (noncontingent, contingent on cocaine-negative urines, or “split”). The “split” contingency was a novel contingency that reinforced abstinence from either drug while doubly reinforcing simultaneous abstinence from both: the total value of incentives was “split” between drugs to contain costs. The main outcome measures were percentages of urine specimens negative for heroin, cocaine, and both simultaneously; these were monitored during a 5-week baseline of standard treatment (to determine study eligibility), a 12-week intervention, and a 10-week maintenance phase (to examine intervention effects in return-to-baseline conditions). DSM-IV criteria for ongoing drug dependence were assessed at study exit. Urine-screen results showed that the methadone dose increase reduced heroin use but not cocaine use. The Split 100mg group was the only group to achieve a longer duration of simultaneous negatives than its same-dose Noncontingent control group. The frequency of DSM-IV opiate and cocaine dependence diagnoses decreased in the active intervention groups. For a split contingency to promote simultaneous abstinence from cocaine and heroin, a relatively high dose of methadone appears necessary but not sufficient; an increase in overall incentive amount may also be required. PMID:19101098

  2. Is Slow-Onset Long-Acting Monoamine Transport Blockade to Cocaine as Methadone is to Heroin? Implication for Anti-Addiction Medications

    PubMed Central

    Peng, Xiao-Qing; Xi, Zheng-Xiong; Li, Xia; Spiller, Krista; Li, Jie; Chun, Lauren; Wu, Kuo-Ming; Froimowitz, Mark; Gardner, Eliot L

    2010-01-01

    The success of methadone in treating opiate addiction has suggested that long-acting agonist therapies may be similarly useful for treating cocaine addiction. Here, we examined this hypothesis, using the slow-onset long-acting monoamine reuptake inhibitor 31,345, a trans-aminotetralin analog, in a variety of addiction-related animal models, and compared it with methadone's effects on heroin's actions in the same animal models. Systemic administration of 31,345 produced long-lasting enhancement of electrical brain-stimulation reward (BSR) and extracellular nucleus accumbens (NAc) dopamine (DA). Pretreatment with 31,345 augmented cocaine-enhanced BSR, prolonged cocaine-enhanced NAc DA, and produced a long-term (24-48 h) reduction in cocaine self-administration rate without obvious extinction pattern, suggesting an additive effect of 31,345 with cocaine. In contrast, methadone pretreatment not only dose-dependently inhibited heroin self-administration with an extinction pattern but also dose-dependently inhibited heroin-enhanced BSR and NAc DA, suggesting functional antagonism by methadone of heroin's actions. In addition, 31,345 appears to possess significant abuse liability, as it produces dose-dependent enhancement of BSR and NAc DA, maintains a low rate of self-administration behavior, and dose-dependently reinstates drug-seeking behavior. In contrast, methadone only partially maintains self-administration with an extinction pattern, and fails to induce reinstatement of drug-seeking behavior. These findings suggest that 31,345 is a cocaine-like slow-onset long-acting monoamine transporter inhibitor that may act as an agonist therapy for cocaine addiction. However, its pattern of action appears to be significantly different from that of methadone. Ideal agonist substitutes for cocaine should fully emulate methadone's actions, that is, functionally antagonizing cocaine's action while blocking monoamine transporters to augment synaptic DA. PMID:20827272

  3. Development and validation of a solid-phase extraction gas chromatography–mass spectrometry method for the simultaneous quantification of methadone, heroin, cocaine and metabolites in sweat

    PubMed Central

    Brunet, Bertrand R.; Barnes, Allan J.; Scheidweiler, Karl B.; Mura, Patrick

    2009-01-01

    A sensitive and specific method is presented to simultaneously quantify methadone, heroin, cocaine and metabolites in sweat. Drugs were eluted from sweat patches with sodium acetate buffer, followed by SPE and quantification by GC/MS with electron impact ionization and selected ion monitoring. Daily calibration for anhydroecgonine methyl ester, ecgonine methyl ester, cocaine, benzoylecgonine (BE), codeine, morphine, 6-acetylcodeine, 6-acetylmorphine (6AM), heroin (5–1000 ng/patch) and methadone (10–1000 ng/patch) achieved determination coefficients of >0.995, and calibrators quantified to within ±20% of the target concentrations. Extended calibration curves (1000–10,000 ng/patch) were constructed for methadone, cocaine, BE and 6AM by modifying injection techniques. Within (N=5) and between-run (N=20) imprecisions were calculated at six control levels across the dynamic ranges with coefficients of variation of <6.5%. Accuracies at these concentrations were ±11.9% of target. Heroin hydrolysis during specimen processing was <11%. This novel assay offers effective monitoring of drug exposure during drug treatment, workplace and criminal justice monitoring programs. PMID:18607576

  4. Former Heroin Addicts with or without a History of Cocaine Dependence are more Impulsive than Controls

    PubMed Central

    Nielsen, David A.; Ho, Ann; Bahl, Ajay; Varma, Priya; Kellogg, Scott; Borg, Lisa; Kreek, Mary Jeanne

    2012-01-01

    Background Personality traits such as impulsivity and sensation seeking may contribute to the initiation and maintenance of illicit drug use. Since studies have reported higher impulsivity and sensation seeking traits in cocaine dependent subjects, we were interested in determining whether former heroin addicts in methadone pharmacotherapy with comorbid cocaine addiction have greater impulsivity than those without. Methods Instruments to assess impulsivity (Barratt Impulsiveness Scale version 11) and sensation seeking (Sensation Seeking Scale version V) were administered to former severe heroin addicts meeting Federal criteria for methadone maintenance pharmacotherapy with (n = 71) or without cocaine dependence (n = 31) and to 145 normal healthy (non-methadone-maintained) volunteers. Results The methadone-maintained without cocaine dependence and the methadone-maintained with cocaine dependence groups, both scored higher than did the normal volunteer group on the Barratt Impulsiveness Scale total score (p < 0.001). On the Barratt Impulsiveness Scale Attentional, Nonplanning, and Motor subscales, the methadone-maintained and methadone-maintained with cocaine dependence groups scored higher than did normal volunteers with no history of drug abuse or dependence (p < 0.001). There was no difference among groups on total score or any subscale of the Sensation Seeking Scale. However, males in all groups overall scored higher than did females on Disinhibition and Thrill and Adventure seeking subscales of the Sensation Seeking Scale version V (p < 0.001). Conclusions This study demonstrates higher impulsivity in former severe heroin addicts meeting criteria for or currently in stable methadone maintenance pharmacotherapy, irrespective of a positive or negative history of cocaine dependence. PMID:22265192

  5. Desipramine in opioid-dependent cocaine abusers maintained on buprenorphine vs methadone.

    PubMed

    Oliveto, A H; Feingold, A; Schottenfeld, R; Jatlow, P; Kosten, T R

    1999-09-01

    Cocaine abuse occurs in 40% to 60% of patients entering opioid maintenance treatment, and effective pharmacotherapies are needed for this combined dependence. This 13-week, randomized, double-blind, placebo-controlled trial evaluated the efficacy of desipramine hydrochloride (0 or 150 mg/d) plus buprenorphine hydrochloride (12 mg/d) or methadone hydrochloride (65 mg/d) in 180 opioid-dependent cocaine abusers (124 men, 56 women). Supervised urine samples were obtained thrice weekly, and self-reported cocaine and heroin use was reported once weekly. Desipramine plasma levels were determined at weeks 4 and 10. In men, opioid abstinence was increased more rapidly over time when treated with methadone than with buprenorphine, whereas cocaine abstinence was increased more with buprenorphine than with methadone. In women, opioid abstinence was increased the least rapidly when treated with buprenorphine plus placebo, while cocaine abstinence was increased more rapidly over time when treated with methadone than with buprenorphine. Regardless of sex or opioid medication, desipramine increased opioid and cocaine abstinence more rapidly over time than placebo. Self-reported opioid use confirmed these findings. Desipramine plasma levels were higher in women than in men, particularly those on buprenorphine maintenance. Higher desipramine plasma levels were associated with greater opioid, but not cocaine, abstinence. Desipramine may be a useful adjunctive medication in facilitating opioid and cocaine abstinence in opioid-maintained patients. The efficacy of opioid medications to treat opioid or cocaine dependence may differ by sex. These findings highlight the importance of including sex as a factor when examining treatment outcome in these types of trials.

  6. A randomized controlled trial of interim methadone maintenance.

    PubMed

    Schwartz, Robert P; Highfield, David A; Jaffe, Jerome H; Brady, Joseph V; Butler, Carol B; Rouse, Charles O; Callaman, Jason M; O'Grady, Kevin E; Battjes, Robert J

    2006-01-01

    Effective alternatives to long waiting lists for entry into methadone hydrochloride maintenance treatment are needed to reduce the complications of continuing heroin dependence and to increase methadone treatment entry. To compare the effectiveness of interim methadone maintenance with that of the usual waiting list condition in facilitating methadone treatment entry and reducing heroin and cocaine use and criminal behavior. Randomized, controlled, clinical trial using 2 conditions, with treatment assignment on a 3:2 basis to interim maintenance-waiting list control. A methadone treatment program in Baltimore. A total of 319 individuals meeting the criteria for current heroin dependence and methadone maintenance treatment. Participants were randomly assigned to either interim methadone maintenance, consisting of an individually determined methadone dose and emergency counseling only for up to 120 days, or referral to community-based methadone treatment programs. Entry into comprehensive methadone maintenance therapy at 4 months from baseline; self-reported days of heroin use, cocaine use, and criminal behavior; and number of urine drug test results positive for heroin and cocaine at the follow-up interview conducted at time of entry into comprehensive methadone treatment (or at 4 months from baseline for participants who did not enter regular treatment). Significantly more participants assigned to the interim methadone maintenance condition entered comprehensive methadone maintenance treatment by the 120th day from baseline (75.9%) than those assigned to the waiting list control condition (20.8%) (P<.001). Overall, in the past 30 days at follow-up, interim participants reported significantly fewer days of heroin use (P<.001), had a significant reduction in heroin-positive drug test results (P<.001), reported spending less money on drugs (P<.001), and received less illegal income (P<.02) than the waiting list participants. Interim methadone maintenance results in a

  7. Randomized Trial of Prize-Based Reinforcement Density for Simultaneous Abstinence from Cocaine and Heroin

    ERIC Educational Resources Information Center

    Ghitza, Udi E.; Epstein, David H.; Schmittner, John; Vahabzadeh, Massoud; Lin, Jia-Ling; Preston, Kenzie L.

    2007-01-01

    To examine the effect of reinforcer density in prize-based abstinence reinforcement, heroin/cocaine users (N = 116) in methadone maintenance (100 mg/day) were randomly assigned to a noncontingent control group (NonC) or to 1 of 3 groups that earned prize draws for abstinence: manual drawing with standard prize density (MS) or computerized drawing…

  8. Methadone dose increase and abstinence reinforcement for treatment of continued heroin use during methadone maintenance.

    PubMed

    Preston, K L; Umbricht, A; Epstein, D H

    2000-04-01

    Although methadone maintenance is an effective therapy for heroin dependence, some patients continue to use heroin and may benefit from therapeutic modifications. This study evaluated a behavioral intervention, a pharmacological intervention, and a combination of both interventions. Throughout the study all patients received daily methadone hydrochloride maintenance (initially 50 mg/d orally) and weekly counseling. Following baseline treatment patients who continued to use heroin were randomly assigned to 1 of 4 interventions: (1) contingent vouchers for opiate-negative urine specimens (n = 29 patients); (2) methadone hydrochloride dose increase to 70 mg/d (n = 31 patients); (3) combined contingent vouchers and methadone dose increase (n = 32 patients); and (4) neither intervention (comparison standard; n = 28 patients). Methadone dose increases were double blind. Vouchers had monetary value and were exchangeable for goods and services. Groups not receiving contingent vouchers received matching vouchers independent of urine test results. Primary outcome measure was opiate-negative urine specimens (thrice weekly urinalysis). Contingent vouchers and a methadone dose increase each significantly increased the percentage of opiate-negative urine specimens during intervention. Contingent vouchers, with or without a methadone dose increase, increased the duration of sustained abstinence as assessed by urine screenings. Methadone dose increase, with or without contingent vouchers, reduced self-reported frequency of use and self-reported craving. In patients enrolled in a methadone-maintainence program who continued to use heroin, abstinence reinforcement and a methadone dose increase were each effective in reducing use. When combined, they did not dramatically enhance each other's effects on any 1 outcome measure, but they did seem to have complementary benefits.

  9. Efficacy of cocaine contingency management in heroin-assisted treatment: Results of a randomized controlled trial.

    PubMed

    Blanken, Peter; Hendriks, Vincent M; Huijsman, Ineke A; van Ree, Jan M; van den Brink, Wim

    2016-07-01

    To determine the efficacy of contingency management (CM), targeting cocaine use, as an add-on intervention for heroin dependent patients in supervised heroin-assisted treatment (HAT) with frequent cocaine use. Multi-center, open-label, parallel group, randomized controlled trial. Twelve specialized addiction treatment centers for HAT in The Netherlands; April 2006-January 2011. 214 chronic, treatment-refractory heroin dependent patients in HAT, with frequent cocaine use. Routine, daily supervised diacetylmorphine treatment, co-prescribed with oral methadone (HAT), with and without 6 months contingency management for cocaine use as an add-on intervention; HAT+CM and HAT-only, respectively. Primary outcome was the longest, uninterrupted duration of cocaine abstinence, based upon laboratory urinalysis. Secondary outcome measures included other cocaine-related measures, treatment retention in HAT, and multi-domain health-related treatment response. In an intention-to-treat analysis, HAT+CM was more effective than HAT-only in promoting longer, uninterrupted duration of cocaine abstinence (3.7 weeks versus 1.6 weeks; negative binomial regression: Exp(B)=2.34, 95%-CI: 1.70-3.23; p<0.001). This result remained significant in sensitivity analyses and was supported by all secondary, cocaine-related outcome measures. Treatment retention in HAT was high (91.6%) with no difference between the groups. The improvement in multi-domain health-related treatment response during the trial was numerically higher in HAT+CM (from 37.4% to 53.1%; +15.7%) than in HAT-only (from 44.5% to 46.5%; +2.0%), but this difference was statistically not significant. Contingency management is an effective add-on intervention to promote longer, uninterrupted periods of cocaine abstinence in chronic, treatment-refractory heroin dependent patients in heroin-assisted treatment with frequent cocaine use. The trial has been registered in The Netherlands National Trial Register under clinical trial

  10. Heroin Use Is Associated with Ruptured Saccular Aneurysms.

    PubMed

    Can, Anil; Castro, Victor M; Ozdemir, Yildirim H; Dagen, Sarajune; Dligach, Dmitriy; Finan, Sean; Yu, Sheng; Gainer, Vivian; Shadick, Nancy A; Savova, Guergana; Murphy, Shawn; Cai, Tianxi; Weiss, Scott T; Du, Rose

    2017-11-04

    While cocaine use is thought to be associated with aneurysmal rupture, it is not known whether heroin use increases the risk of rupture in patients with non-mycotic saccular aneurysms. Our goal was to investigate the association between heroin and cocaine use and the rupture of saccular non-mycotic aneurysms. The medical records of 4701 patients with 6411 intracranial aneurysms, including 1201 prospective patients, diagnosed at the Brigham and Women's Hospital and Massachusetts General Hospital between 1990 and 2016 were reviewed and analyzed. Patients were separated into ruptured and non-ruptured groups. Univariable and multivariable logistic regression analyses were performed to determine the association between heroin, cocaine, and methadone use and the presence of ruptured intracranial aneurysms. In multivariable analysis, current heroin use was significantly associated with rupture status (OR 3.23, 95% CI 1.33-7.83) whereas former heroin use (with and without methadone replacement therapy), and current and former cocaine use were not significantly associated with intracranial aneurysm rupture. In the present study, heroin rather than cocaine use is significantly associated with intracranial aneurysm rupture in patients with non-mycotic saccular cerebral aneurysms, emphasizing the possible role of heroin in the pathophysiology of aneurysm rupture and the importance of heroin cessation in patients harboring unruptured intracranial aneurysms.

  11. Pain of methadone-maintained heroin addicts: lonelier individuals feel more intense pain.

    PubMed

    Li, Fu; Xu, Yan-Min; Zhu, Jun-Hong; Lu, Jin; Zhong, Bao-Liang

    2017-10-03

    Managing pain in patients with heroin addiction is challenging, because most pain medications are addictive. A promising way to relieve pain of heroin addicts is to identify and address modifiable psychosocial factors associated with pain. This study examined the association between loneliness and pain intensity in Chinese heroin addicts receiving methadone maintenance treatment (MMT). A consecutive sample of 603 heroin addicts were recruited from three MMT clinics in Wuhan, China. Loneliness was assessed with a single question, and socio-demographic and clinical data were collected with a standardized questionnaire. Pain intensity was assessed with the five-point Verbal Rating Scale. Multiple ordinary logistic regression was used to control for potential confounders that may bias the loneliness-pain relationship. There was a significant and positive correlation between pain intensity and loneliness scores among methadone-maintained heroin addicts ( r = 0.453, P < 0.001). After controlling for potential socio-demographic and clinical confounders, an increase in the level of loneliness was significantly associated with an increase in pain intensity (OR = 1.22, P = 0.042). Loneliness is significantly associated with pain of methadone-maintained heroin addicts. Psychosocial interventions aimed at reducing loneliness might prevent or reduce pain of patients receiving MMT.

  12. Daily temporal patterns of heroin and cocaine use and craving: relationship with business hours regardless of actual employment status.

    PubMed

    Phillips, Karran A; Epstein, David H; Preston, Kenzie L

    2013-10-01

    Real-time monitoring of behavior using Ecological Momentary Assessment (EMA) has provided detailed data about daily temporal patterns of craving and use in cigarette smokers. We have collected similar data from a sample of cocaine and heroin users. Here we analyzed it in the context of its relationship with a societal construct of daily temporal organization: 9-to-5 business hours. In a 28-week prospective study, 112 methadone-maintained polydrug-abusing individuals initiated an electronic-diary entry and provided data each time they used cocaine, heroin, or both during weeks 4 to 28. EMA data were collected for 10,781 person-days and included: 663 cocaine-craving events, 710 cocaine-use events, 288 heroin-craving events, 66 heroin-use events, 630 craving-both-drugs events, and 282 use-of-both-drugs events. At baseline, 34% of the participants reported full-time employment in the preceding 3-year period. Most participants' current employment status fluctuated throughout the study. In a generalized linear mixed model (SAS Proc Glimmix), cocaine use varied by time of day relative to business hours (p<0.0001) and there was a significant interaction between Day of the Week and Time Relative to Business Hours (p<0.002) regardless of current work status. Cocaine craving also varied by time of day relative to business hours (p<0.0001), however, there was no significant interaction between Day of the Week and Time Relative to Business Hours (p=.57). Heroin craving and use were mostly reported during business hours, but data were sparse. Cocaine craving is most frequent during business hours while cocaine use is more frequent after business hours. Cocaine use during business hours, but not craving, seems suppressed on most weekdays, but not weekends, suggesting that societal conventions reflected in business hours influence drug-use patterns even in individuals whose daily schedules are not necessarily dictated by employment during conventional business hours. Published by

  13. Methodology for the Randomised Injecting Opioid Treatment Trial (RIOTT): evaluating injectable methadone and injectable heroin treatment versus optimised oral methadone treatment in the UK

    PubMed Central

    Lintzeris, Nicholas; Strang, John; Metrebian, Nicola; Byford, Sarah; Hallam, Christopher; Lee, Sally; Zador, Deborah

    2006-01-01

    Whilst unsupervised injectable methadone and diamorphine treatment has been part of the British treatment system for decades, the numbers receiving injectable opioid treatment (IOT) has been steadily diminishing in recent years. In contrast, there has been a recent expansion of supervised injectable diamorphine programs under trial conditions in a number of European and North American cities, although the evidence regarding the safety, efficacy and cost effectiveness of this treatment approach remains equivocal. Recent British clinical guidance indicates that IOT should be a second-line treatment for those patients in high-quality oral methadone treatment who continue to regularly inject heroin, and that treatment be initiated in newly-developed supervised injecting clinics. The Randomised Injectable Opioid Treatment Trial (RIOTT) is a multisite, prospective open-label randomised controlled trial (RCT) examining the role of treatment with injected opioids (methadone and heroin) for the management of heroin dependence in patients not responding to conventional substitution treatment. Specifically, the study examines whether efforts should be made to optimise methadone treatment for such patients (e.g. regular attendance, supervised dosing, high oral doses, access to psychosocial services), or whether such patients should be treated with injected methadone or heroin. Eligible patients (in oral substitution treatment and injecting illicit heroin on a regular basis) are randomised to one of three conditions: (1) optimized oral methadone treatment (Control group); (2) injected methadone treatment; or (3) injected heroin treatment (with access to oral methadone doses). Subjects are followed up for 6-months, with between-group comparisons on an intention-to-treat basis across a range of outcome measures. The primary outcome is the proportion of patients who discontinue regular illicit heroin use (operationalised as providing >50% urine drug screens negative for markers of

  14. Disciplining addictions: the bio-politics of methadone and heroin in the United States.

    PubMed

    Bourgois, P

    2000-06-01

    Biomedical understanding of methadone as a magic-bullet pharmacological block to the euphoric effects of heroin is inconsistent with epidemiological and clinical data. An ethnographic perspective on the ways street-based heroin addicts experience methadone reveals the quagmire of power relations that shape drug treatment in the United States. The phenomenon of the methadone clinic is an unhappy compromise between competing discourses: A criminalizing morality versus a medicalizing model of addiction-as-a-brain-disease. Treatment in this context becomes a hostile exercise in disciplining the unruly misuses of pleasure and in controlling economically unproductive bodies. Most of the biomedical and epidemiological research literature on methadone obscures these power dynamics by technocratically debating dosage titrations in a social vacuum. A foucaultian critique of the interplay between power and knowledge might dismiss debates over the Swiss experiments with heroin prescription as merely one more version of biopower disciplining unworthy bodies. Foucault's ill-defined concept of the specific intellectual as someone who confronts power relations on a practical technical level, however, suggests there can be a role for political as well as theoretical engagement with debates in the field of applied substance abuse treatment. Meanwhile, too many heroin addicts who are prescribed methadone in the United States suffer negative side effects that range from an accentuated craving for polydrug abuse to a paralyzing sense of impotence and physical and emotional discomfort.

  15. Transnational cocaine and heroin flow networks in western Europe: A comparison.

    PubMed

    Chandra, Siddharth; Joba, Johnathan

    2015-08-01

    A comparison of the properties of drug flow networks for cocaine and heroin in a group of 17 western European countries is provided with the aim of understanding the implications of their similarities and differences for drug policy. Drug flow data for the cocaine and heroin networks were analyzed using the UCINET software package. Country-level characteristics including hub and authority scores, core and periphery membership, and centrality, and network-level characteristics including network density, the results of a triad census, and the final fitness of the core-periphery structure of the network, were computed and compared between the two networks. The cocaine network contains fewer path redundancies and a smaller, more tightly knit core than the heroin network. Authorities, hubs and countries central to the cocaine network tend to have higher hub, authority, and centrality scores than those in the heroin network. The core-periphery and hub-authority structures of the cocaine and heroin networks reflect the west-to-east and east-to-west patterns of flow of cocaine and heroin respectively across Europe. The key nodes in the cocaine and heroin networks are generally distinct from one another. The analysis of drug flow networks can reveal important structural features of trafficking networks that can be useful for the allocation of scarce drug control resources. The identification of authorities, hubs, network cores, and network-central nodes can suggest foci for the allocation of these resources. In the case of Europe, while some countries are important to both cocaine and heroin networks, different sets of countries occupy positions of prominence in the two networks. The distinct nature of the cocaine and heroin networks also suggests that a one-size-fits-all supply- and interdiction-focused policy may not work as well as an approach that takes into account the particular characteristics of each network. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Chronic nephropathies of cocaine and heroin abuse: a critical review.

    PubMed

    Jaffe, Jared A; Kimmel, Paul L

    2006-07-01

    Renal disease in cocaine and heroin users is associated with the nephrotic syndrome, acute glomerulonephritis, amyloidosis, interstitial nephritis, and rhabdomyolysis. The pathophysiologic basis of cocaine-related renal injury involves renal hemodynamic changes, glomerular matrix synthesis and degradation, and oxidative stress and induction of renal atherogenesis. Heroin is the most commonly abused opiate in the United States. Previous studies identified a spectrum of renal diseases in heroin users. The predominant renal lesion in black heroin users is focal segmental glomerulosclerosis and in white heroin users is membranoproliferative glomerulonephritis. Although the prevalence of heroin use in the United States has increased, the incidence of "heroin nephropathy" has declined. Because reports of heroin nephropathy predated the surveillance of hepatitis C virus and HIV, the varied findings might be related to the spectrum of viral illnesses that are encountered in injection drug users. Socioeconomic conditions, cultural and behavioral practices, or differences in genetic susceptibilities may be more associated with the development of nephropathy in heroin users than the drug's pharmacologic properties. Administration of cocaine in animal models results in nonspecific glomerular, interstitial, and tubular cell lesions, but there is no animal model of heroin-associated renal disease. The heterogeneity of responses that are associated with heroin is not consistent with a single or simple notion of nephropathogenesis. There are no well-designed, prospective, epidemiologic studies to assess the incidence and the prevalence of renal disease in populations of opiate users and to establish the validity of a syndrome such as heroin nephropathy. It is concluded although there is a paucity of evidence to support a heroin-associated nephropathy, the evidence from in vitro cellular and animal studies to support the existence of cocaine-induced renal changes is more convincing.

  17. Trends in drug overdose deaths in England and Wales 1993-98: methadone does not kill more people than heroin.

    PubMed

    Hickman, Matthew; Madden, Peter; Henry, John; Baker, Allan; Wallace, Chris; Wakefield, Jon; Stimson, Gerry; Elliott, Paul

    2003-04-01

    To test the hypothesis that methadone is responsible for a greater increase in overdose deaths than heroin, and causes proportionally more overdose deaths than heroin at weekends. Multivariate analysis of 3961 death certificates mentioning heroin, morphine and/or methadone held on the Office for National Statistics drug-related poisoning mortality database from 1993 to 1998 in England and Wales. Percentage increase in deaths by year by drug, odds ratio (OR) of dying at the weekend from methadone-related overdose compared to dying from heroin/morphine overdose. From 1993 to 1998, annual opiate overdose deaths increased from 378 to 909. There was a 24.7% (95% confidence interval (CI) 22-28%) yearly increase in heroin deaths compared to 9.4% (95% CI 6-13%) for methadone only. This difference was significant (P < 0.001 by test of interaction) after adjustment for sex, age group, polydrug use, area of residence and underlying cause of death. The largest number of deaths occurred on Saturday (673). The OR of death from methadone overdose on Saturday and Sunday was 1.48 (95% CI 1.29-1.71) for methadone-only deaths compared to dying from heroin/morphine at the weekend after adjustment for other covariates, but the OR was not significant (1.09, 95% CI 0.95-1.25) if the weekend was defined as Friday and Saturday. There was no evidence that the threefold increase in deaths over time was due to methadone. There was equivocal support only for the hypothesis that there was an excess of deaths from methadone at weekends. Increased interventions to prevent overdose among injectors in England and Wales are long overdue.

  18. Six-month trial of bupropion with contingency management for cocaine dependence in a methadone-maintained population.

    PubMed

    Poling, James; Oliveto, Alison; Petry, Nancy; Sofuoglu, Mehmet; Gonsai, Kishorchandra; Gonzalez, Gerardo; Martell, Bridget; Kosten, Thomas R

    2006-02-01

    No effective pharmacotherapies exist for cocaine dependence, although contingency management (CM) has demonstrated efficacy. To compare the efficacy of bupropion hydrochloride and CM for reducing cocaine use in methadone hydrochloride-maintained individuals. This 25-week, placebo-controlled, double-blind trial randomly assigned participants to 1 of 4 treatment conditions: CM and placebo (CMP), CM and 300 mg/d of bupropion hydrochloride (CMB), voucher control and placebo (VCP), or voucher control and bupropion (VCB). Outpatient clinic at the Veterans Affairs Connecticut Healthcare System. A total of 106 opiate-dependent, cocaine-abusing individuals. All study participants received methadone hydrochloride (range, 60-120 mg). Participants receiving bupropion hydrochloride were given 300 mg/d beginning at week 3. In the CM conditions, each urine sample negative for both opioids and cocaine resulted in a monetary-based voucher that increased for consecutively drug-free urine samples during weeks 1 to 13. Completion of abstinence-related activities also resulted in a voucher. During weeks 14 to 25, only completion of activities was reinforced in the CM group, regardless of sample results. The voucher control groups received vouchers for submitting urine samples, regardless of results, throughout the study. Thrice-weekly urine toxicologic test results for cocaine and heroin. Groups did not differ in baseline characteristics or retention rates. Opiate use decreased significantly, with all treatment groups attaining equivalent amounts of opiate use at the end of the study. In the CMB group, the proportion of cocaine-positive samples significantly decreased during weeks 3 to 13 (P<.001) relative to week 3 and remained low during weeks 14 to 25. In the CMP group, cocaine use significantly increased during weeks 3 to 13 (P<.001) relative to week 3, but then cocaine use significantly decreased relative to the initial slope during weeks 14 to 25 (P<.001). In contrast, by

  19. Illicit Heroin and Methamphetamine Use among Methadone Maintenance Treatment Patients in Dehong Prefecture of Yunnan Province, China.

    PubMed

    Wang, Rongrong; Ding, Yingying; Bai, Hongling; Duan, Song; Ye, Runhua; Yang, Yuecheng; Wang, Jibao; Tang, Renhai; Gao, Meiyang; He, Na

    2015-01-01

    Methadone maintenance treatment (MMT) was introduced to China in 2004 to reduce the harm of injecting drug users (IDUs). However, little is known about continued drug use, especially methamphetamine (MAMP), among MMT patients. A survey was conducted among patients attending five major MMT clinics in Dehong Prefecture in 2014 to investigate the heroin and MAMP use and their associated risk factors. Participants were administered with face-to-face interviews, and urine tests for morphine and MAMP. A total of 2,121 were eligible and participated in the study. Among them, 220 (10.4%) were only positive for morphine, 12.9% were only positive for MAMP, and 196 (9.2%) were positive for both morphine and MAMP. Compared with neither use of heroin nor MAMP during MMT, heroin use (not using MAMP) was associated with ethnicity, shorter duration of MMT, lower dose of methadone, and having had no more than two sex partners in the past year; MAMP use (not using heroin) was associated with ethnicity, longer duration of MMT, higher dose of methadone and being aged <30 years (vs. ≥50 years); use of both heroin and MAMP was associated with being Dai minority (vs. Han), a marital status of divorced or widowed, having used drugs for ≥10 years and shorter duration of MMT. These findings indicate the complexity in the treatment of heroin users and underscore the importance in prescribing appropriate methadone dosages in order to reduce both heroin and MAMP use.

  20. Patterns of acquisitive crime during methadone maintenance treatment among patients eligible for heroin assisted treatment.

    PubMed

    van der Zanden, Bart P; Dijkgraaf, Marcel G W; Blanken, Peter; van Ree, Jan M; van den Brink, Wim

    2007-01-05

    To determine the patterns of acquisitive crime during methadone maintenance treatment among chronic, treatment-resistant heroin users eligible for heroin assisted treatment in the Netherlands. We retrospectively assessed the type and number of illegal activities during 1 month of standard methadone maintenance treatment in 51 patients prior to the start of heroin assisted treatment. Data were collected using a semi-structured interview focussed on crime with special emphasis on property crime. Volume analyses consisted of frequencies and descriptives of mean numbers of offences per day and per type. In a Dutch population of problematic drug users eligible for and prior to commencing heroin assisted treatment, 70% reported criminal activities and 50% reported acquisitive crimes. Offending took place on 20.5 days per month with on average 3.1 offences a day. Acquisitive crime consisted mainly of shoplifting (mean 12.8 days, 2.2 times/day) and theft of bicycles (mean 5.8 days, 2.4 times/day); theft from a vehicle and burglaries were committed less frequently. The majority of these patients (63%) reported to have started offending in order to acquire illicit drugs and alcohol. During methadone maintenance treatment, 50% of criminally active, problematic heroin users eligible for heroin assisted treatment reported acquisitive crime. Shoplifting, thefts and/or other property crimes were committed on average two to three times on a crime day. This study discusses that the detail provided by self-reported crime data can improve cost estimates in economic evaluations of heroin assisted treatment.

  1. Eye Movement Evidence of Attentional Bias for Substance-Related Cues in Heroin Dependents on Methadone Maintenance Therapy.

    PubMed

    Zhao, Hui; Yang, Bo; Zhu, Qian; Zhang, Guangqun; Xiao, Yuqin; Guo, Xiao; Huang, Xiu; Zhang, Zhuo

    2017-03-21

    Attentional biases toward substance-related stimuli might play a contributing role in addictive behaviors. This study investigated the selective attention to substance-related stimuli in heroin dependents receiving methadone maintenance therapy. Thirty outpatients receiving methadone maintenance treatment for heroin dependence and 38 healthy controls completed a visual probe task with concurrent eye movement monitoring. The results showed that the heroin group reacted faster to probes associated with substance-related pictures than neutral pictures, and they directed more initial fixations and maintained longer initial fixation durations toward substance-related pictures than neutral pictures. However, attentional bias was not correlated with addiction severity in the heroin group. These findings suggest that attentional bias towards substance-related cues occurs in heroin dependents, although this bias might not be associated with the severity of drug-using behavior.

  2. Asthma associated with the use of cocaine, heroin, and marijuana: A review of the evidence.

    PubMed

    Self, Timothy H; Shah, Samarth P; March, Katherine L; Sands, Christopher W

    2017-09-01

    A review of the evidence was conducted regarding asthma associated with the use of cocaine, heroin, and marijuana. A search of the English literature was performed via PubMed/Medline and EMBASE using the search terms asthma AND cocaine, heroin, and marijuana. When pertinent articles were found, salient references in those articles were assessed. Due to the relatively small number of studies, we included all studies and cases. For several decades, case reports, retrospective studies, and laboratory investigations have demonstrated that inhalation of cocaine or heroin is associated with increased asthma symptoms and reduced pulmonary function. Smoking crack cocaine, nasal insufflation of cocaine or heroin, and smoking heroin increases the risk of emergency department visits and hospitalizations for asthma. Although frequent smoking of marijuana may cause symptoms of cough, sputum production, and wheezing in the general population, more studies are needed specifically in patients with asthma. Smoking marijuana with concomitant tobacco use is common and further worsens the respiratory symptoms. Use of cocaine and heroin in patients with asthma should be avoided. Pending further studies, it would be prudent for patients with asthma to avoid smoking marijuana. Clinicians need to be vigilant regarding use of these drugs in their patients with hyperreactive airway disease.

  3. Contingency management treatment in cocaine using methadone maintained patients with and without legal problems.

    PubMed

    Ginley, Meredith K; Rash, Carla J; Olmstead, Todd A; Petry, Nancy M

    2017-11-01

    Legal difficulties and cocaine use are prevalent in methadone maintenance patients, and they are related to one another, as well as to poor response to methadone treatment. Contingency management (CM) is efficacious for decreasing cocaine use, but the relation of CM treatment to criminal activities has rarely been studied. This study evaluated whether baseline legal problems are related to subsequent substance use and illegal activities for cocaine using methadone maintained patients and whether CM differentially improves outcomes depending on baseline legal problems. Using data from four randomized CM trials (N=323), we compared methadone maintained patients with legal problems at the start of study participation to those without initial legal problems. Overall, the addition of CM to standard methadone care improved substance use outcomes regardless of initial legal problems. Endorsement of legal problems within 30days of study initiation was associated with reduced proportion of negative samples submitted during the 12-week treatment period. A significant interaction effect of baseline legal problems and treatment condition was present for subsequent self-reports of illegal activities. Those with baseline legal problems who were assigned to CM had reduced self-reports of reengagement in illegal activity throughout a six month follow-up compared to their counterparts randomized to standard care. Adding CM to methadone treatment improves substance use outcomes and reduces subsequent illegal activity in cocaine-using methadone patients with legal problems. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. High-throughput simultaneous analysis of buprenorphine, methadone, cocaine, opiates, nicotine, and metabolites in oral fluid by liquid chromatography tandem mass spectrometry

    PubMed Central

    Concheiro, Marta; Gray, Teresa R.; Shakleya, Diaa M.

    2011-01-01

    A method for simultaneous determination of buprenorphine (BUP), norbuprenorphine (NBUP), methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), cocaine, benzoylecgonine (BE), ecgonine methyl ester (EME), anhydroecgonine methyl ester (AEME), morphine, codeine, 6-acetylmorphine (6AM), heroin, 6-acetylcodeine (6AC), nicotine, cotinine, and trans-3′-hydroxycotinine (OH-cotinine) by liquid chromatography tandem mass spectrometry in oral fluid (OF) was developed and extensively validated. Acetonitrile (800 μL) and OF (250 μL) were added to a 96-well Isolute-PPT+protein precipitation plate. Reverse-phase separation was achieved in 16 min and quantification was performed by multiple reaction monitoring. The assay was linear from 0.5 or 1 to 500 μg/L. Intraday, interday, and total imprecision were less than 13% (n=20), analytical recovery was 92–114% (n= 20), extraction efficiencies were more than 77% (n=5), and process efficiencies were more than 45% (n=5). Although ion suppression was detected for EME, cocaine, morphine, 6AC, and heroin (less than 56%) and enhancement was detected for BE and nicotine (less than 316%), deuterated internal standards compensated for these effects. The method was sensitive (limit of detection 0.2–0.8 μg/L) and specific (no interferences) except that 3-hydroxy-4-methoxyamphetamine interfered with AEME. No carryover was detected, and all analytes were stable for 24 h at 22 °C, for 72 h at 4 °C, and after three freeze–thaw cycles, except cocaine, 6AC, and heroin (22–97% loss). The method was applied to 41 OF specimens collected throughout pregnancy with a Salivette® OF collection device from an opioid-dependent BUP-maintained pregnant woman. BUP ranged from 0 to 7,400 μg/L, NBUP from 0 to 71 μg/L, methadone from 0 to 3 μg/L, nicotine from 32 to 5,020 μg/L, cotinine from 125 to 508 μg/L, OH-cotinine from 11 to 51 μg/L, cocaine from 0 to 419 μg/L, BE from 0 to 351 μg/L, EME from 0 to 286 μg/L, AEME from 0 to

  5. [The Rorschach's test for heroin addicts treated by methadone: from reality to imaginary].

    PubMed

    Deslandes, C; Gourarier, L; Sanchez, M; Lowenstein, W

    2000-10-01

    The aim of this study was to analyze the role of the imaginary and its link with reality among 30 subjects treated by methadone. The Rorschach test was proposed to 30 heroin addicts treated by methadone, over an average 7 months. The formal answers (used preferentially in the 30 results, though often inappropriately) and socializing landmarks involving considerable individual investment, we were able to identify two ways of working within the same protocol. The first relies most on conformity and adaptation and tries to put the imaginary aside. The second is a more projective, unorganized approach evidencing the influence of the imaginary. This specific imaginary activity could not be assimilated with the traditional "lack of fantasy" observed in heroin addicts. It would be interesting to examine the course of this approach over a longer period.

  6. Impulsivity and opioid drugs: differential effects of heroin, methadone and prescribed analgesic medication.

    PubMed

    Baldacchino, A; Balfour, D J K; Matthews, K

    2015-04-01

    Previous studies have provided inconsistent evidence that chronic exposure to opioid drugs, including heroin and methadone, may be associated with impairments in executive neuropsychological functioning, specifically cognitive impulsivity. Further, it remains unclear how such impairments may relate of the nature, level and extent of opioid exposure, the presence and severity of opioid dependence, and hazardous behaviours such as injecting. Participants with histories of illicit heroin use (n = 24), former heroin users stabilized on prescribed methadone (methadone maintenance treatment; MMT) (n = 29), licit opioid prescriptions for chronic pain without history of abuse or dependence (n = 28) and healthy controls (n = 28) were recruited and tested on a task battery that included measures of cognitive impulsivity (Cambridge Gambling Task, CGT), motor impulsivity (Affective Go/NoGo, AGN) and non-planning impulsivity (Stockings of Cambridge, SOC). Illicit heroin users showed increased motor impulsivity and impaired strategic planning. Additionally, they placed higher bets earlier and risked more on the CGT. Stable MMT participants deliberated longer and placed higher bets earlier on the CGT, but did not risk more. Chronic opioid exposed pain participants did not differ from healthy controls on any measures on any tasks. The identified impairments did not appear to be associated specifically with histories of intravenous drug use, nor with estimates of total opioid exposure. These data support the hypothesis that different aspects of neuropsychological measures of impulsivity appear to be associated with exposure to different opioids. This could reflect either a neurobehavioural consequence of opioid exposure, or may represent an underlying trait vulnerability to opioid dependence.

  7. Hepatitis C Infection in Non-Treatment-Seeking Heroin Users: The Burden of Cocaine Injection

    PubMed Central

    Roux, P.; Fugon, L.; Jones, J.D.; Comer, S.D.

    2014-01-01

    Background and Objectives In heroin dependent individuals, the HIV epidemic has been controlled in countries where access to opioid maintenance treatment (OMT) and needle exchange programs (NEP) have been implemented. However, despite similar routes of contamination for both viruses, the prevalence of hepatitis C (HCV) infection remains high in drug users. The objective of this analysis was to identify the prevalence of HCV and the correlates of being HCV-positive in a sample of out-of-treatment heroin-dependent individuals. Methods Data were collected from five inpatient studies (n = 120 participants) conducted at the New York State Psychiatric Institute. A logistic regression was used to identify correlates of being HCV-positive at baseline. Results Among the 120 heroin-dependent volunteers, 42 were HCV-positive. Participants who had heavier alcohol use, a longer duration of heroin use, or who reported using heroin by injection were more likely to be HCV-positive. Interestingly, participants who had injected cocaine during the previous month had a ninefold greater risk of being HCV-positive compared to non-cocaine users and those who used cocaine by a non-injecting route. Conclusions and Scientific Significance These findings confirm the risk of being HCV-infected through intravenous drug use, especially with cocaine use. These results underscore the importance of rethinking interventions to prevent HCV infection with combined strategies using pharmacological approaches for cocaine dependence and tailored prevention for cocaine users. PMID:24131170

  8. Metabolic syndrome among individuals with heroin use disorders on methadone therapy: Prevalence, characteristics, and related factors.

    PubMed

    Vallecillo, Gabriel; Robles, María José; Torrens, Marta; Samos, Pilar; Roquer, Albert; Martires, Paula K; Sanvisens, Arantza; Muga, Roberto; Pedro-Botet, Juan

    2018-01-02

    Observational studies have reported a high prevalence of obesity and diabetes in subjects on methadone therapy; there are, however, limited data about metabolic syndrome. The aim of the study was to evaluate the prevalence of metabolic syndrome and related factors in individuals with heroin use disorder on methadone therapy. A cross-sectional study in individuals with heroin use disorder on methadone therapy at a drug abuse outpatient center. Medical examinations and laboratory analyses after a 12-hour overnight fast were recorded. Metabolic syndrome was diagnosed according to the National Cholesterol Education Program Adult Treatment Panel III (ATP III) criteria. One hundred and twenty-two subjects were included, with a mean age of 46.1 ± 9 years, a median body mass index (BMI) of 25.3 kg/m 2 (interquartile range [IQR]: 21.2-28), and 77.9% were men. Median exposure to methadone therapy was 13 years (IQR: 5-20). Overweight and obesity were present in 29.5% and 17.2% of the participants, respectively. Metabolic syndrome components were low high-density lipoprotein (HDL) cholesterol (51.6%), hypertriglyceridemia (36.8%), high blood pressure (36.8%), abdominal obesity (27.0%), and raised blood glucose levels (18.0%). Abdominal obesity was more prevalent in women (52% vs. 20%, P = >0.01) and high blood pressure more prevalent in men (41.1% vs. 22.2%, P = .07). Prevalence of metabolic syndrome was 29.5% (95% confidence interval [CI]: 16.6-31.8). In the multivariate logistic regression analysis, BMI (per 1 kg/m 2 increase odds ratio [OR]: 1.49, 95% CI: 1.27-1.76) and exposure time to methadone therapy (per 5 years of treatment increase OR: 1.38, 95% CI: 1.28-1.48) were associated with metabolic syndrome. Overweight and metabolic syndrome are prevalent findings in individuals with heroin use disorder on methadone therapy. Of specific concern is the association of methadone exposure with metabolic syndrome. Preventive measures and clinical routine screening should be

  9. A randomized clinical trial of methadone maintenance for prisoners: findings at 6 months post-release.

    PubMed

    Gordon, Michael S; Kinlock, Timothy W; Schwartz, Robert P; O'Grady, Kevin E

    2008-08-01

    This study examined the effectiveness of methadone maintenance initiated prior to or just after release from prison at 6 months post-release. A three-group randomized controlled trial was conducted between September 2003 and June 2005. A Baltimore pre-release prison. Two hundred and eleven adult pre-release inmates who were heroin-dependent during the year prior to incarceration. Participants were assigned randomly to the following: counseling only: counseling in prison, with passive referral to treatment upon release (n = 70); counseling + transfer: counseling in prison with transfer to methadone maintenance treatment upon release (n = 70); and counseling + methadone: methadone maintenance and counseling in prison, continued in a community-based methadone maintenance program upon release (n = 71). Addiction Severity Index at study entry and follow-up. Additional assessments at 6 months post-release were treatment record review; urine drug testing for opioids, cocaine and other illicit drugs. Counseling + methadone participants were significantly more likely than both counseling only and counseling + transfer participants to be retained in drug abuse treatment (P = 0.0001) and significantly less likely to have an opioid-positive urine specimen compared to counseling only (P = 0.002). Furthermore, counseling + methadone participants reported significantly fewer days of involvement in self-reported heroin use and criminal activity than counseling only participants. Methadone maintenance, initiated prior to or immediately after release from prison, increases treatment entry and reduces heroin use at 6 months post-release compared to counseling only. This intervention may be able to fill an urgent treatment need for prisoners with heroin addiction histories.

  10. Drug Prices and Emergency Department Mentions for Cocaine and Heroin

    PubMed Central

    Caulkins, Jonathan P.

    2001-01-01

    Objectives. In this report, the author illustrates the historic relation between retail drug prices and emergency department mentions for cocaine and heroin. Methods. Price series based on the Drug Enforcement Administration's System to Retrieve Information From Drug Evidence database were correlated with data on emergency department mentions from the Drug Abuse Warning Network for cocaine (1978–1996) and heroin (1981–1996). Results. A simple model in which emergency department mentions are driven by only prices explains more than 95% of the variation in emergency department mentions. Conclusions. Fluctuations in prices are an important determinant of adverse health outcomes associated with drugs. PMID:11527779

  11. Heroin and methadone prescriptions from a London drug clinic over the first 15 years of operation (1968-1983): old records examined.

    PubMed

    Strang, John; Sheridan, Janie

    2006-01-01

    We charted changes in the prescriptions issued to opiate addicts in treatment at a London clinic over the first 15 years of operation of one of the new National Health Service (NHS) drug clinics established in 1968. Having located the original handwritten ledger records of prescriptions issued by the drug addict treatment clinic, an SPSS data file was created of the prescriptions given to each of the clinic patients each month over the period 1968-1983 to permit examination of changes over this 15-year period in the drugs prescribed (e.g., heroin, methadone), the form (e.g., injectable or oral), the daily doses, and the extent of multiple items for single patients (e.g., both injectable ampule and oral forms). For each month, a list was available of all current patients detailing which drug(s) they had received during that month, in what form(s) and what dose(s). These items were the basic units of study. We report changes over the 15-year period for which the data were available. For the first 5 years, more than half of the prescriptions were for heroin (diamorphine hydrochloride), with the remainder of the prescriptions mostly comprising oral methadone. After 1973, methadone ampules for injection were increasingly commonly prescribed and thereafter remained at about a quarter of the prescriptions for the remaining 10 years for which data are available, whereas heroin prescriptions declined over the mid-1970s to only 20%. From 1973 onward, oral methadone was increasingly prescribed, rising from approximately one third of prescriptions in the early 1970s to more than two thirds by the early 1980s. Individual patients often received more than one drug or form of drug: From 1969 onward, oral methadone was commonly prescribed as a supplement to heroin prescriptions. This same practice was widespread with prescriptions for methadone ampules prescribed as a supplement to heroin prescriptions. Daily doses of heroin were at a mean of from 160 to 540 mg, in contrast with

  12. Field ion spectrometry: a new technology for cocaine and heroin detection

    NASA Astrophysics Data System (ADS)

    Carnahan, Byron L.; Day, Stephen; Kouznetsov, Viktor; Tarassov, Alexandre

    1997-02-01

    Field ion spectrometry, also known as transverse field compensation ion mobility spectrometry, is a new technique for trace gas analysis that can be applied to the detection of cocaine and heroin. Its principle is based on filtering ion species according to the functional dependence of their mobilities with electric field strength. Field ion spectrometry eliminates the gating electrodes needed in conventional IMS to pulse ions into the spectrometer; instead, ions are injected in to the spectrometer and reach the detector continuously, resulting in improved sensitivity. The technique enables analyses that are difficult with conventional constant field strength ion mobility spectrometers. We have shown that a filed ion spectrometer can selectively detect the vapors from cocaine and heroin emitted from both their base and hydrochloride forms. The estimated volumetric limits of detection are in the low pptv range, based on testing with standardized drug vapor generation systems. The spectrometer can detect cocaine base in the vapor phase, at concentrations well below its estimated 100 pptv vapor pressure equivalent at 20 degrees C. This paper describes the underlying principles of field ion spectrometry in relation to narcotic drug detection, and recent results obtained for cocaine and heroin. The work has been sponsored in part by the United States Advanced Research Projects Agency under contract DAAB10-95C-0004, for the DOD Counterdrug Technology Development Program.

  13. QTc Prolongation in Veterans With Heroin Dependence on Methadone Maintenance Treatment.

    PubMed

    Hassamal, Sameer; Fernandez, Antony; Moradi Rekabdarkolaee, Hossein; Pandurangi, Ananda

    2015-06-01

    QTc prolongation and Torsade de Ppointes have been reported in patients on methadone maintenance. In this study, QTc was compared before and after the veteran (n = 49) was on a stable dosage of methadone for 8.72 ± 4.50 years to treat heroin dependence. Risk factors were correlated with the QTc once the veteran was on a stable dose of methadone. Differences in the clinical risk factors in subgroups of veterans with below and above mean QTc change was compared. ECG data was obtained from a 12-lead electrocardiogram (pre-methadone and on methadone) on 49 veterans. Data and risk factors were retrospectively collected from the medical records. The mean QTc at baseline (pre-methadone) was 426 ± 34 msec and after being on methadone for an average of 8.72 ± 4.50 years was significantly higher at 450 ± 35 msec. No significant relationships were found between QTc prolongation and risk factors except for calcium. The methadone dosage was significantly higher in veterans with a QTc change above the mean change of ≥ 24 msec (88.48 ± 27.20 mg v.s 68.96 ± 19.84 mg). None of the veterans experienced cardiac arrhythmias. The low complexity of medical co-morbidities may explain the lack of a significant correlation between any risk factor with the QTc except calcium and methadone dosage. The absence of TdP may be explained by the low prevalence of QTc values > 500 msec as well as the retrospective design of the study. During long-term methadone treatment, there was a slight increase in the QTc interval but we did not find evidence of increased cardiac toxicity as a reason for treatment termination.

  14. White Matter Abnormalities Correlating with Memory and Depression in Heroin Users under Methadone Maintenance Treatment

    PubMed Central

    Lin, Wei-Che; Chou, Kun-Hsien; Chen, Chien-Chih; Huang, Chu-Chung; Chen, Hsiu-Ling; Lu, Cheng-Hsien; Li, Shau-Hsuan; Wang, Ya-Ling; Cheng, Yu-Fan; Lin, Ching-Po

    2012-01-01

    Methadone maintenance treatment (MMT) has elevated rates of co-morbid memory deficit and depression that are associated with higher relapse rates for substance abuse. White matter (WM) disruption in MMT patients have been reported but their impact on these co-morbidities is unknown. This study aimed to investigate changes in WM integrity of MMT subjects using diffusion tensor image (DTI), and their relationship with history of heroin and methadone use in treated opiate-dependent individuals. The association between WM integrity changes from direct group comparisons and the severity of memory deficit and depression was also investigated. Differences in WM integrity between 35 MMT patients and 23 healthy controls were evaluated using DTI with tract-based spatial statistical analysis. Differences in DTI indices correlated with diminished memory function, Beck Depression Inventory, duration of heroin use and MMT, and dose of heroin and methadone administration. Changes in WM integrity were found in several WM regions, including the temporal and frontal lobes, pons, cerebellum, and cingulum bundles. The duration of MMT was associated with declining DTI indices in the superior longitudinal fasciculus and para-hippocampus. MMT patients had more memory and emotional deficits than healthy subjects. Worse scores in both depression and memory functions were associated with altered WM integrity in the superior longitudinal fasciculus, para-hippocampus, and middle cerebellar peduncle in MMT. Patients on MMT also had significant WM differences in the reward circuit and in depression- and memory-associated regions. Correlations among decreased DTI indices, disease severity, and accumulation effects of methadone suggest that WM alterations may be involved in the psychopathology and pathophysiology of co-morbidities in MMT. PMID:22496768

  15. Anticipatory reward processing among cocaine-dependent individuals with and without concurrent methadone-maintenance treatment: Relationship to treatment response*

    PubMed Central

    Yip, Sarah W.; DeVito, Elise E.; Kober, Hedy; Worhunsky, Patrick D.; Carroll, Kathleen M.; Potenza, Marc N.

    2016-01-01

    Background Cocaine dependence among opioid-dependent methadone-maintained individuals is a significant public health problem and is particularly challenging to treat. The neurobiology of this clinically complex population has not been previously assessed using fMRI. Methods fMRI data from cocaine-dependent, methadone-maintained (CD-MM) patients (n=24), cocaine-dependent (CD) patients (n=20) and healthy comparison (HC; n=21) participants were acquired during monetary incentive delay task performance. All patients were scanned prior to treatment for cocaine dependence. Between-group differences in anticipatory reward and loss processing were assessed using whole-brain ANOVAs in SPM12 (pFWE<.05). Correlations between durations of abstinence during treatment and BOLD responses within the insula and caudate were also explored. Results Main effects of diagnostic group, primarily involving decreased BOLD responses among CD-MM patients in comparison to HCs, were observed during anticipatory reward and loss processing within regions of posterior cingulate cortex, precuneus, inferior frontal gyrus and dorsolateral prefrontal cortex. BOLD responses within the right caudate were negatively associated with percentage of cocaine-negative urines during treatment among CD-MM patients, but not among non-methadone-maintained CD patients. Conclusions These data suggest neurofunctional differences that may be related to treatment outcomes for behavioral therapies between cocaine-dependent individuals with and without methadone-maintenance treatment. These findings may relate to differences in treatment efficacies and to the elevated relapse rates observed in methadone-maintained populations. PMID:27430401

  16. The Effects of Sex, Estrous Cycle, and Social Contact on Cocaine and Heroin Self-Administration in Rats

    PubMed Central

    Lacy, Ryan T.; Strickland, Justin C.; Feinstein, Max A.; Robinson, Andrea M.; Smith, Mark A.

    2017-01-01

    Rationale Preclinical studies indicate that gonadal hormones are important determinants of drug self-administration. To date, little is known about the influence of sex and estrous cycle on drug self-administration in ecologically relevant social contexts. Objective Examine the role of sex and estrous cycle in a rat model during cocaine and heroin self-administration with male-female and female-female social dyads. Methods Male and female virgin rats were trained to self-administer cocaine and heroin in operant conditioning chambers that permitted two rats to self-administer concurrently but prevented physical contact. Experiment 1 examined cocaine self-administration on a progressive-ratio schedule in male-female dyads. Experiments 2 and 3 examined heroin self-administration on a fixed-ratio schedule in male-female dyads at constant and varying doses, respectively. Experiment 4 examined heroin self-administration in female-female dyads on a fixed-ratio schedule. Results Cocaine-maintained breakpoints increased by ~17% in females during estrus but remained consistent in males. Heroin self-administration decreased by ~70% during proestrus in females whether they were isolated, housed with males, or housed with females. Heroin self-administration was lower in males than females under some conditions and was not consistently associated with the responding of females. Conclusions Cocaine and heroin self-administration is influenced by the estrous cycle in females when in the presence of a male partner. As a novel finding, these data illustrate that heroin self-administration is reduced in females during proestrus regardless of the social context tested. Finally, these data suggest that drug self-administration in males is only minimally influenced by the hormonal status of a female partner. PMID:27370020

  17. The effects of sex, estrous cycle, and social contact on cocaine and heroin self-administration in rats.

    PubMed

    Lacy, Ryan T; Strickland, Justin C; Feinstein, Max A; Robinson, Andrea M; Smith, Mark A

    2016-09-01

    Preclinical studies indicate that gonadal hormones are important determinants of drug self-administration. To date, little is known about the influence of sex and estrous cycle on drug self-administration in ecologically relevant social contexts. The objective of this study was to examine the role of sex and estrous cycle in a rat model during cocaine and heroin self-administration with male-female and female-female social dyads. Male and female virgin rats were trained to self-administer cocaine and heroin in operant conditioning chambers that permitted two rats to self-administer concurrently, but prevented physical contact. Experiment 1 examined cocaine self-administration on a progressive ratio schedule in male-female dyads. Experiments 2 and 3 examined heroin self-administration on a fixed ratio schedule in male-female dyads at constant and varying doses, respectively. Experiment 4 examined heroin self-administration in female-female dyads on a fixed ratio schedule. Cocaine-maintained breakpoints increased by ∼17 % in females during estrus, but remained consistent in males. Heroin self-administration decreased by ∼70 % during proestrus in females whether they were isolated, housed with males, or housed with females. Heroin self-administration was lower in males than females under some conditions and was not consistently associated with the responding of females. Cocaine and heroin self-administration is influenced by the estrous cycle in females when in the presence of a male partner. As a novel finding, these data illustrate that heroin self-administration is reduced in females during proestrus regardless of the social context tested. Finally, these data suggest that drug self-administration in males is only minimally influenced by the hormonal status of a female partner.

  18. A series of forensic toxicology and drug seizure cases involving illicit fentanyl alone and in combination with heroin, cocaine or heroin and cocaine.

    PubMed

    Marinetti, Laureen J; Ehlers, Brooke J

    2014-10-01

    The Montgomery County Coroner's Office Toxicology Section and the Miami Valley Regional Crime Lab (MVRCL) Drug Chemistry Section have been receiving case work in drug seizures, death cases and human performance cases involving products marketed as heroin or as illicit fentanyl. Upon analysis by the Drug Chemistry Section, these products were found to contain various drug(s) including illicit fentanyl only, illicit fentanyl and heroin, illicit fentanyl and cocaine and illicit fentanyl, heroin and cocaine. Both the Chemistry and Toxicology Sections began seeing these combinations starting in late October 2013. The percentage of the combinations encountered by the MVRCL as well as the physical appearance of the product, and the results of presumptive screening tests will be discussed. The demographics of the users and the results of toxicology and autopsy findings on the decedents will also be discussed. According to regional drug task force undercover agents, there is evidence that some of the products are being sold as illicit fentanyl and not just as a heroin product. Also, there is no evidence to support that the fentanyl source is being diverted from pharmaceutical grade fentanyl. The chemistry section currently has over 109 confirmed cases, and the toxicology section currently has 81 confirmed drug deaths, 8 driving under the influence of drugs and 1 suicidal hanging. Both sections are continuing to see these cases at the present time. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  19. Do methadone and buprenorphine have the same impact on psychopathological symptoms of heroin addicts?

    PubMed Central

    2011-01-01

    Background The idea that the impact of opioid agonist treatment is influenced by the psychopathological profile of heroin addicts has not yet been investigated, and is based on the concept of a specific therapeutic action displayed by opioid agents on psychopathological symptoms. In the present report we compared the effects of buprenorphine and methadone on the psychopathological symptoms of 213 patients (106 on buprenorphine and 107 on methadone) in a follow-up study lasting 12 months. Methods Drug addiction history was collected by means of the Drug Addiction History Rating Scale (DAH-RS) and psychopathological features were collected by means of the Symptom Checklist-90 (SCL-90), using a special five-factor solution. Toxicological urinalyses were carried out for each patient during the treatment period. Results No statistically significant differences were detected in psychopathological symptoms, including 'worthlessness-being trapped', 'somatization', and 'panic-anxiety'. Methadone proved to be more effective on patients characterized by 'sensitivity-psychoticism', whereas buprenorphine was more effective on patients displaying a 'violence-suicide' symptomatology. Conclusions Heroin-dependent patients with psychiatric comorbidities may benefit from opioid agonist treatment not only because it targets their addictive problem, but also, precisely due to this, because it is effective against their mental disorder too. PMID:21569624

  20. An exploration of alcohol use severity and route of drug administration among persons that use heroin and cocaine.

    PubMed

    Scherer, Michael; Harrell, Paul T; Trenz, Rebecca C; Canham, Sarah; Latimer, William W

    2016-01-01

    Alcohol use is prevalent among populations of persons that use illicit drugs. Problematic alcohol use among persons that use heroin and cocaine has been associated with poor treatment adherence, abstinence maintenance, and mental health concerns. Fully exploring how alcohol use severity interacts with route of administration (ROA) may be of notable importance in development of treatment protocols for persons that use heroin and cocaine. Data from a neurological and sociobehavioral assessment of risk factors among injection and noninjection drug users known as the NEURO-HIV Epidemiologic Study was used in the analyses. Participants (N = 551) included those who reported their level of past-30-day alcohol use and past-6-month heroin and cocaine use. Multiple logistic regression analyses found that both problematic and moderate alcohol users were significantly less likely than abstainers to report injecting heroin and cocaine. Both problematic and moderate alcohol users were significantly more likely than abstainers to snort substances. Alcohol use may play a role in promoting or impeding the use of substances through certain ROAs. Treatment protocols that transition persons that use injection heroin and cocaine to noninjection use of these substances may be used in conjunction with treatments that reduce alcohol consumption as a means to reduce noninjection drug use.

  1. Cognitive-behavioural therapy for heroin and cocaine use: Ecological momentary assessment of homework simplification and compliance.

    PubMed

    Willner-Reid, Jessica; Whitaker, Damiya; Epstein, David H; Phillips, Karran A; Pulaski, Amber R; Preston, Kenzie L; Willner, Paul

    2016-09-01

    The purpose of this study was to evaluate the effects of homework-task difficulty and electronic-diary reminders on written homework completion during cognitive-behavioural therapy (CBT) for addiction. Completion of homework is an important element in CBT that may affect outcome. All participants received all combinations of our two interventions in a factorial 2 × 2 counterbalanced Latin-square design. Methadone-maintained cocaine and heroin users were given homework between each of 12 weekly CBT sessions and carried electronic diaries that collected ecological momentary assessment (EMA) data on craving and exposure to drug-use triggers in four 3-week blocks assessing two levels of homework difficulty and prompted and unprompted homework. Neither simplified (picture-based) homework nor electronic reminders increased homework completion. In EMA reports, standard but not simplified homework seemed to buffer the craving that followed environmental exposure to drug cues. EMA recordings before and after the CBT intervention confirmed a decrease over time in craving for cocaine and heroin. These findings demonstrate the utility of EMA to assess treatment effects. However, the hypothesis that simplified homework would increase compliance was not supported. Our simplifications of homework assignments for cognitive-behavioural therapy were mostly ineffective, or even counterproductive, perhaps because they did not engage sufficient depth of processing or because they were perceived as too simplistic. Our reminder beeps for homework were mostly ineffective, or even counterproductive, suggesting that mobile electronic interventions for substance-use disorders may need to be more interactive. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

  2. Dosing adjustments in postpartum patients maintained on buprenorphine or methadone.

    PubMed

    Jones, Hendrée E; Johnson, Rolley E; O'Grady, Kevin E; Jasinski, Donald R; Tuten, Michelle; Milio, Lorraine

    2008-06-01

    Scant scientific attention has been given to examining the need for agonist medication dose changes in the postpartum period. Study objectives were: 1) to determine the need for medication dose adjustments in participants stabilized on buprenorphine or methadone 3 weeks before and 4 weeks after delivery, and 2) to evaluate the need for methadone dose adjustments during the first 7 days in participants transferred from buprenorphine to methadone at 5 weeks postpartum. Participants were opioid-dependent pregnant women who had completed a randomized, double-blind, double-dummy, flexible dosing comparison of buprenorphine to methadone. Participants received a stable dose of methadone (N = 10) or buprenorphine (N = 8) before and 4 weeks after delivery. Buprenorphine-maintained participants were transferred to methadone at 5 weeks postpartum. There were no significant differences predelivery and/or postdelivery between the buprenorphine and methadone conditions in the mean ratings of dose adequacy, "liking," "hooked," and "craving" of heroin or cocaine. Patient response to the conversion from buprenorphine to methadone seems variable. Buprenorphine-maintained participants required dose changes postpartum only after they transferred to methadone. Regardless of type of medication, postpartum patients should be monitored for signs of overmedication.

  3. Ultrasonic vocalization in rats self-administering heroin and cocaine in different settings: evidence of substance-specific interactions between drug and setting.

    PubMed

    Avvisati, Riccardo; Contu, Laura; Stendardo, Emiliana; Michetti, Caterina; Montanari, Christian; Scattoni, Maria Luisa; Badiani, Aldo

    2016-04-01

    Clinical and preclinical evidence indicates that the setting of drug use affects drug reward in a substance-specific manner. Heroin and cocaine co-abusers, for example, indicated distinct settings for the two drugs: heroin being used preferentially at home and cocaine preferentially outside the home. Similar results were obtained in rats that were given the opportunity to self-administer intravenously both heroin and cocaine. The goal of the present study was to investigate the possibility that the positive affective state induced by cocaine is enhanced when the drug is taken at home relative to a non-home environment, and vice versa for heroin. To test this hypothesis, we trained male rats to self-administer both heroin and cocaine on alternate days and simultaneously recorded the emission of ultrasonic vocalizations (USVs), as it has been reported that rats emit 50-kHz USVs when exposed to rewarding stimuli, suggesting that these USVs reflect positive affective states. We found that Non-Resident rats emitted more 50-kHz USVs when they self-administered cocaine than when self-administered heroin whereas Resident rats emitted more 50-kHz USVs when self-administering heroin than when self-administering cocaine. Differences in USVs in Non-Resident rats were more pronounced during the first self-administration (SA) session, when the SA chambers were completely novel to them. In contrast, the differences in USVs in Resident rats were more pronounced during the last SA sessions. These findings indicate that the setting of drug taking exerts a substance-specific influence on the ability of drugs to induce positive affective states.

  4. [Characteristics of heroin dependent patients admitted to a methadone treatment program].

    PubMed

    Sanvisens, Arantza; Rivas, Inmaculada; Faure, Eva; Muñoz, Trinidad; Rubio, Manuela; Fuster, Daniel; Tor, Jordi; Muga, Robert

    2014-01-21

    Methadone is largely used as the primary opioid substitution therapy for the treatment of heroin addiction; the objective of the study was to describe the clinical characteristics of heroin abusers admitted into a methadone maintenance program (MMP) in metropolitan Barcelona. Cross-sectional study in patients enrolled in MMP since its introduction in 1992 through December 2010. Socio-demographic data, drug use characteristics, prevalence of blood-borne infections (human immunodeficiency virus [HIV], and hepatitis B [HBV] and C [HCV]) and psychiatric co-morbidity were assessed at entry. One thousand and six hundred seventy eight patients (82.8% male). A total of 608 (36.2%) patients were admitted during 1992-1996, 566 (33.7%) between 1997-2001, 305 (18.2%) between 2002-2006 and 199 (11.9%) in the last period. Age at admission to methadone increased significantly (28 years in period 1992-1996 vs. 37 years in the last period [P<.005]). The percentage of patients with a history of intravenous drug use decreased significantly (89.5% in first period vs. 56.4% in period 2007-2010 [P<.05]). Prevalence of HIV, HCV and HBV (HBcAb+) was 53.7, 73.6 and 61.3%, respectively. The prevalence of HIV decreased over time from 66.2% in first period to 43.5% in 2007-2010 (P<.05); the prevalence of HCV decreased significantly from 82.8% in 1992-1996 to 69.8% in last period (P<.05). Twenty five percent of patients had psychiatric co-morbidity at admission and the prevalence of psychiatric co-morbidity increased over time (21% in 1992-1996 and 32% in 2007-2010; P<.05). Age at first opioid substitution therapy is increasing over time, as well as the proportion of patients with psychiatric co-morbidity. There were significant reductions in blood-borne infections. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  5. The cutting of cocaine and heroin: A critical review.

    PubMed

    Broséus, Julian; Gentile, Natacha; Esseiva, Pierre

    2016-05-01

    The illicit drug cutting represents a complex problem that requires the sharing of knowledge from addiction studies, toxicology, criminology and criminalistics. Therefore, cutting is not well known by the forensic community. Thus, this review aims at deciphering the different aspects of cutting, by gathering information mainly from criminology and criminalistics. It tackles essentially specificities of cocaine and heroin cutting. The article presents the detected cutting agents (adulterants and diluents), their evolution in time and space and the analytical methodology implemented by forensic laboratories. Furthermore, it discusses when, in the history of the illicit drug, cutting may take place. Moreover, researches studying how much cutting occurs in the country of destination are analysed. Lastly, the reasons for cutting are addressed. According to the literature, adulterants are added during production of the illicit drug or at a relatively high level of its distribution chain (e.g. before the product arrives in the country of destination or just after its importation in the latter). Their addition seems hardly justified by the only desire to increase profits or to harm consumers' health. Instead, adulteration would be performed to enhance or to mimic the illicit drug effects or to facilitate administration of the drug. Nowadays, caffeine, diltiazem, hydroxyzine, levamisole, lidocaïne and phenacetin are frequently detected in cocaine specimens, while paracetamol and caffeine are almost exclusively identified in heroin specimens. This may reveal differences in the respective structures of production and/or distribution of cocaine and heroin. As the relevant information about cutting is spread across different scientific fields, a close collaboration should be set up to collect essential and unified data to improve knowledge and provide information for monitoring, control and harm reduction purposes. More research, on several areas of investigation, should be

  6. Self-administration of cocaine, cannabis and heroin in the human laboratory: benefits and pitfalls.

    PubMed

    Haney, Margaret

    2009-01-01

    The objective of this review is to describe self-administration procedures for modeling addiction to cocaine, cannabis and heroin in the human laboratory, the benefits and pitfalls of the approach, and the methodological issues unique to each drug. In addition, the predictive validity of the model for testing treatment medications will be addressed. The results show that all three drugs of abuse are reliably and robustly self-administered by non-treatment-seeking research volunteers. In terms of pharmacotherapies, cocaine use is extraordinarily difficult to disrupt either in the laboratory or in the clinic. A range of medications has been shown to significantly decrease cocaine's subjective effects and craving without decreasing either cocaine self-administration or cocaine abuse by patients. These negative data combined with recent positive findings with modafinil suggest that self-administration procedures are an important intermediary step between pre-clinical and clinical studies. In terms of cannabis, a recent study suggests that medications that improve sleep and mood during cannabis withdrawal decrease the resumption of marijuana self-administration in abstinent volunteers. Clinical data on patients seeking treatment for their marijuana use are needed to validate these laboratory findings. Finally, in contrast to cannabis or cocaine dependence, there are three efficacious Food and Drug Administration-approved medications to treat opioid dependence, all of which decrease both heroin self-administration and subjective effects in the human laboratory. In summary, self-administration procedures provide meaningful behavioral data in a small number of individuals. These studies contribute to our understanding of the variables maintaining cocaine, marijuana and heroin intake, and are important in guiding the development of more effective drug treatment programs.

  7. A randomized clinical trial of methadone maintenance for prisoners: results at 12 months postrelease.

    PubMed

    Kinlock, Timothy W; Gordon, Michael S; Schwartz, Robert P; Fitzgerald, Terrence T; O'Grady, Kevin E

    2009-10-01

    This study examined the impact of prison-initiated methadone maintenance at 12 months postrelease. Males with pre-incarceration heroin dependence (N = 204) were randomly assigned to (a) Counseling Only: counseling in prison, with passive referral to treatment upon release; (b) Counseling + Transfer: counseling in prison with transfer to methadone maintenance treatment upon release; and (c) Counseling + Methadone: counseling and methadone maintenance in prison, continued in the community upon release. The mean number of days in community-based drug abuse treatment were, respectively, Counseling Only, 23.1; Counseling + Transfer, 91.3; and Counseling + Methadone, 166.0 (p < .01); all pairwise comparisons were statistically significant (all ps < .01). Counseling + Methadone participants were also significantly less likely than participants in each of the other two groups to be opioid-positive or cocaine-positive according to urine drug testing. These results support the effectiveness of prison-initiated methadone for males in the United States. Further study is required to confirm the findings for women.

  8. [Evaluation of the Methadone Maintenance Program of the Risaralda Mental Hospital].

    PubMed

    Isaza, Carlos; Henao, Julieta; Velez, Juan; Rodríguez, Miguel A; Sierra, Juan; Beltrán, Leonardo; Sepúlveda, Ana

    2014-01-01

    Psychosocial care and methadone maintenance treatment (MMT) are the preferred strategies for the management of heroin addicts, but the results are still unsatisfactory, justifying the search and intervention of the factors influencing the response to treatment. In order to determine the contribution of demographic, clinical and genetic variables on serum concentrations and response to methadone, we investigated patients on MMT, who were receiving methadone in supervised and unchanged doses at least during the previous two weeks. The age, gender, body mass index (BMI), duration of heroin abuse, addiction to other drugs, criminal background, current daily methadone doses, time spent in the TMM, comorbidity and concomitant medication were recorded. Blood samples were taken for the determination of serum levels of racemic methadone and its R and S-enantiomers, and for typing of candidate alleles of POR, CYP2B6, ABCB1, GRIN1, OPRM1, SLC6A3, DßH and ARRB2 genes, all associated with the metabolism, tissue distribution and mechanism of action of methadone. Methadone quantification was by HPLC-DAD, and the detection of genetic markers by Real Time PCR and VNTR methods. A total of 80 subject volunteers were enrolled, with a mean age of 23.5 (5) years (86% male), all of them were addicts of multiple drugs, 60% with a criminal background, 5.1 (2.9) years taking heroin, and 5.3 (4) months on MMT, and taking a supervised dose of 41 (12) mg/day methadone. The (R), (S) and (R, S) methadone enantiomer trough plasma levels were, 84 (40), 84 (42), and 168 (77) ng/mL, respectively. All genotypes were in Hardy-Weinberg equilibrium. The two urine tests were negative for heroin in 61.3% (49/80) of the volunteers, the decline in cocaine/crack use was 83%, 30% of marijuana, and other psychoactives (inhalants, benzodiazepines, amphetamines) decreased to zero, while the consumption of snuff remained at 93.5% (75/80). Blood concentrations of racemic methadone and its enantiomers were

  9. Extended Heroin Access Increases Heroin Choices Over a Potent Nondrug Alternative

    PubMed Central

    Lenoir, Magalie; Cantin, Lauriane; Vanhille, Nathalie; Serre, Fuschia; Ahmed, Serge H

    2013-01-01

    Epidemiological research shows that the proportion of drug users who become addicted to heroin is higher than to cocaine. Here we tested whether this difference could be due to a difference in the addiction liability between the two drugs. Addiction liability was assessed under a discrete-trials choice procedure by measuring the proportion of rats that prefer the drug over a potent alternative reward (ie, water sweetened with saccharin). Previous research on choice between self-administration of i.v. cocaine or sweet water showed that the proportion of cocaine-preferring rats remains relatively low and invariable (ie, 15%), even after extended drug access and regardless of past drug consumption (ie, total drug use before choice testing). By contrast, the present study shows that under similar choice conditions, the proportion of heroin-preferring rats considerably increases with extended heroin access (6–9 h per day for several weeks) and with past heroin consumption, from 11 to 51% at the highest past drug consumption level. At this level, the proportion of drug-preferring rats was about three times higher with heroin than with cocaine (51% vs 15%). This increase in the rate of heroin preference after extended heroin access persisted even after recovery from acute heroin withdrawal. Overall, these findings show that choice procedures are uniquely sensitive to different drugs and suggest that heroin is more addictive than cocaine. This higher addiction liability may contribute to explain why more drug users become addicted to heroin than to cocaine in epidemiological studies. PMID:23322185

  10. A Randomized Clinical Trial of Methadone Maintenance for Prisoners: Results at Twelve-Months Post-Release

    PubMed Central

    Kinlock, Timothy W.; Gordon, Michael S.; Schwartz, Robert P.; Fitzgerald, Terrence T.; O’Grady, Kevin E.

    2009-01-01

    This study examined the impact of prison-initiated methadone maintenance at 12-months post-release. Males with pre-incarceration heroin dependence (n=204) were randomly assigned to: 1) Counseling Only: counseling in prison, with passive referral to treatment upon release; 2) Counseling+Transfer: counseling in prison with transfer to methadone maintenance treatment upon release; and 3) Counseling+Methadone: counseling and methadone maintenance in prison, continued in the community upon release. The mean number of days in community-based drug abuse treatment were, respectively, Counseling Only 23.1, Counseling+Transfer 91.3, and Counseling+Methadone 166.0, p <.01; all pairwise comparisons were statistically significant (all ps < .01). Counseling+Methadone participants were also significantly less likely than participants in each of the other two groups to be opioid-positive or cocaine-positive according to urine drug testing. These results support the effectiveness of prison-initiated methadone for males in the United States. Further study is required to confirm the findings for women. PMID:19339140

  11. Methadone overdose

    MedlinePlus

    ... please enable JavaScript. Methadone is a very strong painkiller. It is also used to treat heroin addiction. ... occur if a person takes methadone with certain painkillers. These painkillers include oxycontin, hydrocodone (Vicodin), or morphine. ...

  12. Simultaneous assay of cocaine, heroin and metabolites in hair, plasma, saliva and urine by gas chromatography-mass spectrometry.

    PubMed

    Wang, W L; Darwin, W D; Cone, E J

    1994-10-14

    As part of an ongoing research program on the development of drug detection methodology, we developed an assay for the simultaneous measurement of cocaine, heroin and metabolites in plasma, saliva, urine and hair by solid-phase extraction (SPE) and gas chromatography-mass spectrometry (GC-MS). The analytes that could be measured by this assay were the following: anhydroecgonine methyl ester; ecgonine methyl ester;. ecgonine ethyl ester; cocaine; cocaethylene; benzoylecgonine; cocaethylene; norcocaethylene; benzoylnorecgonine; codeine; morphine; norcodeine; 6-acetylmorphine; normorphine; and heroin. Liquid specimens were diluted, filtered and then extracted by SPE. Additional handling steps were necessary for the analysis of hair samples. An initial wash procedure was utilized to remove surface contaminants. Washed hair samples were extracted with methanol overnight at 40 degrees C. Both wash and extract fractions were collected, evaporated and purified by SPE. All extracts were evaporated, derivatized with N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) with 1% trimethylchlorosilane (TMCS) and analyzed by GC-MS. The limit of detection (LOD) for cocaine, heroin and metabolites in biological specimens was approximately 1 ng/ml with the exception of norcodeine, normorphine and benzoylnorecgonine (LOD = 5 ng/ml). The LOD for cocaine, heroin and metabolites in hair was approximately 0.1 ng/mg of hair with the exception of norcodeine (LOD = 0.3 ng/mg) and normorphine and benzoylnorecgonine (LOD = 0.5 ng/mg). Coefficients of variation ranged from 3 to 26.5% in the hair assay. This assay has been successfully utilized in research on the disposition of cocaine, heroin and metabolites in hair, plasma, saliva and urine and in treatment studies.

  13. Decrease of cocaine, but not heroin, self-administration and relapse by the tyrosine kinase inhibitor masitinib in male Sprague Dawley rats.

    PubMed

    Belin-Rauscent, A; Lacoste, J; Hermine, O; Moussy, A; Everitt, B J; Belin, David

    2018-05-01

    Accumulating evidence shows that cocaine, and also heroin, influence several tyrosine kinases, expressed in neurons and in non-neuronal populations such as microglia, astrocytes and mast-cells. Drug-induced activation of mast cells both triggers inflammatory processes in the brain mediated by the glial cells they activate, and facilitates histamine release which may directly influence the dopamine system. Thus, by triggering the activation and degranulation of mast cells dependent on the tyrosine kinase c-kit and Fyn, the latter being also involved in NMDA-dependent synaptic plasticity, cocaine and heroin may indirectly influence the neural mechanisms that mediate their reinforcing properties. Masitinib, a novel tyrosine kinase inhibitor with high selectivity for c-Kit, Fyn and Lyn, may alter the aberrant consequences of the activation of these tyrosine kinases by cocaine and heroin. We investigated in rats the effect of a chronic oral treatment with masitinib (20 mg/kg) on the reinforcing and motivational properties of self-administered cocaine (250 μg/infusion) and heroin (40 μg/infusion). Three different cohorts of rats were trained instrumentally to respond for cocaine, heroin or food under continuous reinforcement. In each group, we assessed the influence of chronic daily treatment with masitinib on the maintenance of instrumental responding and intake and the motivation for the reinforcer. Thus, masitinib and vehicle-treated rats were challenged to adapt to high behavioural demand, to respond under a progressive ratio schedule of reinforcement and to reinstate instrumental responding after extinction and/or abstinence. Masitinib selectively decreased cocaine intake, the motivation for cocaine and the subsequent propensity to respond for cocaine under extinction, while having no effect on instrumental responding for heroin or food. The present findings suggest masitinib, a drug with proven efficacy in CNS disorders, could represent a novel treatment for

  14. Disrupted white matter integrity in heroin dependence: a controlled study utilizing diffusion tensor imaging.

    PubMed

    Liu, Haihong; Li, Lin; Hao, Yihui; Cao, Dong; Xu, Lin; Rohrbaugh, Robert; Xue, Zhimin; Hao, Wei; Shan, Baoci; Liu, Zhening

    2008-01-01

    Fractional anisotropy (FA) via diffusion tensor imaging (DTI) can quantify the white matter integrity. Exposure to addictive drugs, such as alcohol, cocaine, methamphetamine, marijuana, and nicotine has been shown to alter FA. White matter abnormalities have been shown, but it remains unclear whether the white matter FA is altered in heroin dependence. Utilizing DTI, we investigated the FA difference between heroin-dependent and control subjects by a voxel-based strategy. The FA values of the identified regions were calculated from the FA image of each subject and were correlated with clinical features including months of heroin use, age, education, and dose of methadone. Reduced FA among 16 heroin dependent subjects was located in the bilateral frontal sub-gyral regions, right precentral and left cingulate gyrus. FA in the right frontal sub-gyral was negatively correlated with duration of heroin use. The disrupted white matter integrity in right frontal white matter may occur in continuous heroin abuse.

  15. Randomized Trial of Contingent Prizes versus Vouchers in Cocaine-Using Methadone Patients

    ERIC Educational Resources Information Center

    Petry, Nancy M.; Alessi, Sheila M.; Hanson, Tressa; Sierra, Sean

    2007-01-01

    Contingency management (CM) interventions frequently utilize vouchers as reinforcers, but a prize-based system is also efficacious. This study compared these approaches. Seventy-four cocaine-dependent methadone outpatients were randomly assigned to standard treatment (ST), ST plus a maximum of $585 in contingent vouchers, or ST plus an expected…

  16. Dysfunctional Default Mode Network in Methadone Treated Patients Who Have a Higher Heroin Relapse Risk.

    PubMed

    Li, Wei; Li, Qiang; Wang, Defeng; Xiao, Wei; Liu, Kai; Shi, Lin; Zhu, Jia; Li, Yongbin; Yan, Xuejiao; Chen, Jiajie; Ye, Jianjun; Li, Zhe; Wang, Yarong; Wang, Wei

    2015-10-15

    The purpose of this study was to identify whether heroin relapse is associated with changes in the functional connectivity of the default mode network (DMN) during methadone maintenance treatment (MMT). Resting-state functional magnetic resonance imaging (fMRI) data of chronic heroin relapsers (HR) (12 males, 1 female, age: 36.1 ± 6.9 years) and abstainers (HA) (11males, 2 female; age: 42.1 ± 8.1 years) were investigated with an independent component analysis to address the functional connectivity of their DMN. Group comparison was then performed between the relapsers and abstainers. Our study found that the left inferior temporal gyrus and the right superior occipital gyrus associated with DMN showed decreased functional connectivity in HR when compared with HA, while the left precuneus and the right middle cingulum had increased functional connectivity. Mean intensity signal, extracted from left inferior temporal gyrus of HR patients, showed a significant negative correlation corresponding to the degree of heroin relapse. These findings suggest that altered functional connectivity of DMN may contribute to the potential neurobiological mechanism(s) of heroin relapse and have a predictive value concerning heroin relapse under MMT.

  17. Abstinence symptomatology associated with cessation of chronic cocaine abuse among methadone-maintained patients.

    PubMed

    Margolin, A; Avants, S K; Kosten, T R

    1996-08-01

    We assessed cocaine abstinence symptomatology in a sample of 100 cocaine-abusing, methadone-maintained patients who completed an anonymous questionnaire retrospectively rating the intensity of 18 symptoms at six time points, from 30 minutes to 2 weeks, post-cocaine use. We found that a majority of patients endorsed symptoms related to dysphoria 24 hours post-binge. However, these symptoms tended to be mild to moderate in intensity and relatively short-lived. Principal components analyses extracted four factors accounting for 64% of the variance: psychoticism, exhaustion, agitation, recovery. Early post-binge period was dominated by psychoticism and agitation, followed by recovery for the duration of the period assessed.

  18. A Randomized Trial of Long-Term Reinforcement of Cocaine Abstinence in Methadone-Maintained Patients Who Inject Drugs

    ERIC Educational Resources Information Center

    Silverman, Kenneth; Robles, Elias; Mudric, Timothy; Bigelow, George E.; Stitzer, Maxine L.

    2004-01-01

    This study determined whether long-term abstinence reinforcement could maintain cocaine abstinence throughout a yearlong period. Patients who injected drugs and used cocaine during methadone treatment (n = 78) were randomly assigned to 1 of 2 abstinence-reinforcement groups or to a usual care control group. Participants in the 2…

  19. Proximity to the US-Mexico border: a key to explaining geographic variation in US methamphetamine, cocaine and heroin purity.

    PubMed

    Cunningham, James K; Maxwell, Jane Carlisle; Campollo, Octavio; Cunningham, Kathryn I; Liu, Lon-Mu; Lin, Hui-Lin

    2010-10-01

    Although illicit drug purity is a widely discussed health risk, research explaining its geographic variation within a country is rare. This study examines whether proximity to the US-Mexico border, the United States' primary drug import portal, is associated with geographic variation in US methamphetamine, heroin and cocaine purity. Distances (proximity) between the US-Mexico border and locations of methamphetamine, cocaine and heroin seizures/acquisitions (n = 239,070) recorded in STRIDE (System to Retrieve Information from Drug Evidence) were calculated for the period of 1990-2004. The association of drug purity with these distances and other variables, including time and seizure/acquisition size, was examined using hierarchical multivariate linear modeling (HMLM). Coterminous United States. Methamphetamine, cocaine and heroin purity generally decreased with distance from the US-Mexico border. Heroin purity, however, after initially declining with distance, turned upwards-a U-shaped association. During 2000-04, methamphetamine purity also had a U-shaped association with distance. For each of the three drugs, temporal changes in the purity of small acquisitions (<10 g) were typically more dynamic in areas closer to the US-Mexico border. Geographic variance in methamphetamine, cocaine and heroin purity throughout the coterminous United States was associated with US-Mexico border proximity. The U-shaped associations between border-distance and purity for heroin and methamphetamine may be due to imports of those drugs via the eastern United States and southeast Canada, respectively. That said, areas closer to the US-Mexico border generally had relatively high illicit drug purity, as well as more dynamic change in the purity of small ('retail level') drug amounts. © 2010 The Authors, Addiction © 2010 Society for the Study of Addiction.

  20. Comparison of self-administration behavior and responsiveness to drug-paired cues in rats running an alley for intravenous heroin and cocaine.

    PubMed

    Su, Zu-In; Wenzel, Jennifer; Baird, Rebeccah; Ettenberg, Aaron

    2011-04-01

    Evidence suggests that responsiveness to a drug-paired cue is predicted by the reinforcing magnitude of the drug during prior self-administration. It remains unclear, however, if this principle holds true when comparisons are made across drug reinforcers. The current study was therefore devised to test the hypothesis that differences in the animals' responsiveness to a cocaine- or heroin-paired cue presented during extinction would reflect differences in the patterns of prior cocaine and heroin runway self-administration. Rats ran a straight alley for single intravenous injections of either heroin (0.1 mg/kg/inj) or cocaine (1.0 mg/kg/inj) each paired with a distinct olfactory cue. Animals experienced 15 trials with each drug reinforcer in a counterbalanced manner. Start latencies, run times, and retreat behaviors (a form of approach-avoidance conflict) provided behavioral indices of the subjects' motivation to seek the reinforcer on each trial. Responsiveness to each drug-paired cue was assessed after 7, 14, or 21 days of non-reinforced extinction trials. Other animals underwent conditioned place preference (CPP) testing to ensure that the two drug reinforcers were capable of producing drug-cue associations. While both drugs produced comparable CPPs, heroin served as a stronger incentive stimulus in the runway as evidenced by faster start and run times and fewer retreats. In contrast, cocaine- but not heroin-paired cues produced increases in drug-seeking behavior during subsequent extinction trials. The subjects' responsiveness to drug-paired cues during extinction was not predicted by differences in the motivation to seek heroin versus cocaine during prior drug self-administration.

  1. Lesions of cholinergic pedunculopontine tegmental nucleus neurons fail to affect cocaine or heroin self-administration or conditioned place preference in rats.

    PubMed

    Steidl, Stephan; Wang, Huiling; Wise, Roy A

    2014-01-01

    Cholinergic input to the ventral tegmental area (VTA) is known to contribute to reward. Although it is known that the pedunculopontine tegmental nucleus (PPTg) provides an important source of excitatory input to the dopamine system, the specific role of PPTg cholinergic input to the VTA in cocaine reward has not been previously determined. We used a diphtheria toxin conjugated to urotensin-II (Dtx::UII), the endogenous ligand for urotensin-II receptors expressed by PPTg cholinergic but not glutamatergic or GABAergic cells, to lesion cholinergic PPTg neurons. Dtx::UII toxin infusion resulted in the loss of 95.78 (±0.65)% of PPTg cholinergic cells but did not significantly alter either cocaine or heroin self-administration or the development of cocaine or heroin conditioned place preferences. Thus, cholinergic cells originating in PPTg do not appear to be critical for the rewarding effects of cocaine or of heroin.

  2. Characteristics of Hidden Status Among Users of Crack, Powder Cocaine, and Heroin in Central Harlem

    PubMed Central

    Davis, W. Rees; Johnson, Bruce D.; Liberty, Hilary James; Randolph, Doris D.

    2007-01-01

    This article analyzes hidden status among crack, powder cocaine, and heroin users and setters, in contrast to more accessible users/sellers. Several sampling strategies acquired 657 users (N=559) and sellers (N=98). Indicators of hidden status were those who (1) paid rent in full in the last 30 days, (2) used nonstreet drug procurement. (3) had legal jobs, and (4) earned $1,000 or more in legal income in the last 30 days. Nearly half had at least one indicator: approximately 16% of users/sellers had two to four indicators. In logistic regression analyses, those who had not panhandled in the last 30 days, those who had used powder cocaine in the last 30 days, and those never arrested were the most likely to have hidden status, whether the analysis predicted those having any indicators or those having two to four indicators. The four indicators begin to operationally define hidden status among users of cocaine and heroin. PMID:17710217

  3. Methadone and illegal drugs in hair from children with parents in maintenance treatment or suspected for drug abuse in a German community.

    PubMed

    Pragst, Fritz; Broecker, Sebastian; Hastedt, Martin; Herre, Sieglinde; Andresen-Streichert, Hilke; Sachs, Hans; Tsokos, Michael

    2013-12-01

    Children living in homes with drug-addicted parents are in a steady danger of poisoning and may suffer from neglect, maltreatment, and lagging behind in development. Hair analysis could be a suitable way to examine this endangering exposure to drugs. Hair samples from 149 children (aged 1-14 years) living with parents substituted by methadone and/or suspected for abuse of illegal drugs, and from 124 of the parents in a German community were investigated by liquid chromatography-hybrid quadrupole time-of flight mass spectrometry and by headspace solid phase microextraction gas chromatography-mass spectrometry for methadone, heroin, cocaine, amphetamines, ecstasy, cannabinoids and benzodiazepines and their metabolites or degradation products (32 compounds). From the children's hair, only in 35 samples, no drugs were detected. Cannabinoids were found in 56 samples, in 20 of them as the only drug. In the remaining 95 samples, methadone was identified 35 times with additional use of illegal drugs in 28 cases. Drug use in the children's environment was obvious for heroin in 44 cases, cocaine in 73 cases, amphetamine or ecstasy in 6 cases, and diazepam in 8 cases. The concentrations varied from limit of quantification to 2.16 ng/mg of methadone, 11.1 ng/mg of 6-acetylmorphine, 17.8 ng/mg of cocaine, 3.29 ng/mg of amphetamine, and 0.72 ng/mg of Δ-tetrahydrocannabinol. In general, hair from younger children contained higher concentrations than from their elder siblings. Systemic incorporation of methadone, cocaine, or cannabinoids appeared likely from detection of the nonhydrolytic metabolites 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine in 11 cases, norcocaine in 16 cases, and 11-nor-9-carboxy-Δ-tetrahydrocannabinol in 9 cases. Within the families, hair samples of children and parents provided often the same drug pattern. External deposition from smoke and by contact with contaminated surfaces or parent's hands and systemic deposition after passive smoking

  4. Simultaneous Liquid Chromatography–Mass Spectrometry Quantification of Urinary Opiates, Cocaine, and Metabolites in Opiate-Dependent Pregnant Women in Methadone-Maintenance Treatment

    PubMed Central

    Shakleya, Diaa M.; Dams, Riet; Choo, Robin E.; Jones, Hendree; Huestis, Marilyn A.

    2011-01-01

    Opiates, cocaine, and metabolites were quantified by liquid chromatography–mass spectrometry (LC–MS) in 284 urine specimens, collected thrice weekly, to monitor possible drug relapse in 15 pregnant heroin-dependent women. Opiates were detected in 149 urine specimens (52%) with limits of quantification (LOQ) of 10–50 μg/L. Morphine, morphine-3-glucuronide, and/or morphine-6-glucuronide were positive in 121 specimens; 6-acetylmorphine, a biomarker of heroin ingestion, was quantifiable in only 7. No heroin, 6-acetylcodeine, papaverine, or noscapine were detected. One hundred and sixty-five urine specimens (58%) from all 15 participants were positive for one or more cocaine analytes (LOQ 10–100 μg/L). Ecgonine methylester (EME) and/or benzoylecgonine were the major cocaine biomarkers in 142. Anhydroecgonine methylester, a biomarker of smoked cocaine, was positive in six; cocaethylene and/or ecgonine ethylester, biomarkers of cocaine and ethanol co-ingestion, were found in 25. At the current Substance Abuse Mental Health Services Administration cutoffs for total morphine (2000 μg/L), codeine (2000 μg/L), 6-acetylmorphine (10 μg/L), and benzoylecgonine (100 μg/L), 16 opiate- and 29 cocaine-positive specimens were identified. Considering 100 μg/L EME as an additional urinary cocaine biomarker would identify 51 more positive cocaine specimens. Of interest is the differential pattern of opiate and cocaine biomarkers observed after LC–MS as compared to gas chromatography–mass spectrometry analysis. PMID:20109298

  5. Ethnic Differences in HIV Risk Behaviors Among Methadone-Maintained Women Receiving Contingency Management for Cocaine Use Disorders

    PubMed Central

    Barry, Danielle; Weinstock, Jeremiah; Petry, Nancy M.

    2008-01-01

    Objective To identify ethnic differences in HIV risk behaviors among cocaine using women receiving methadone maintenance for opioid dependence, and to evaluate the efficacy of contingency management (CM) for cocaine use disorders in reducing HIV risk behaviors. Methods African American (N=47), Hispanic (N=47), and White women (N = 29) were randomized to standard methadone treatment or standard methadone treatment plus a CM intervention. They completed the HIV Risk Behavior Scale (HRBS) indicating frequency of drug use and sexual behaviors across the lifetime, in the month before baseline, and in the 3 months following clinical trial participation. Ethnic group differences and the effect of CM on change in HIV risk behaviors between baseline and follow-up were evaluated. Results White women reported significantly higher lifetime rates of risky drug use and sexual behaviors on the HRBS than African American women; neither group differed significantly from Hispanic women. No ethnic group differences in HIV risk behaviors were identified in the month prior to baseline. At follow-up, African American women reported fewer high-risk drug use behaviors than White or Hispanic women, and Hispanic women reported more high-risk sexual behaviors than White or African American women. CM was associated with reduction in high-risk drug use behaviors regardless of ethnicity, but did not affect high-risk sexual behaviors. Conclusions White women receiving methadone maintenance engage in more lifetime HIV risk behaviors than African American women. CM for cocaine use reduces risky drug use behaviors, but certain ethnic groups may benefit from additional targeted HIV prevention efforts. PMID:18684571

  6. Attendance Rates in a Workplace Predict Subsequent Outcome of Employment-Based Reinforcement of Cocaine Abstinence in Methadone Patients

    ERIC Educational Resources Information Center

    Donlin, Wendy D.; Knealing, Todd W.; Needham, Mick; Wong, Conrad J.; Silverman, Kenneth

    2008-01-01

    This study assessed whether attendance rates in a workplace predicted subsequent outcome of employment-based reinforcement of cocaine abstinence. Unemployed adults in Baltimore methadone programs who used cocaine (N = 111) could work in a workplace for 4 hr every weekday and earn $10.00 per hour in vouchers for 26 weeks. During an induction…

  7. Value for money in drug treatment: economic evaluation of prison methadone.

    PubMed

    Warren, Emma; Viney, Rosalie; Shearer, James; Shanahan, Marian; Wodak, Alex; Dolan, Kate

    2006-09-15

    Although methadone maintenance treatment in community settings is known to reduce heroin use, HIV infection and mortality among injecting drug users (IDU), little is known about prison methadone programs. One reason for this is the complexity of undertaking evaluations in the prison setting. This paper estimates the cost-effectiveness of the New South Wales (NSW) prison methadone program. Information from the NSW prison methadone program was used to construct a model of the costs of the program. The information was combined with data from a randomised controlled trial of provision of prison methadone in NSW. The total program cost was estimated from the perspective of the treatment provider/funder. The cost per heroin free day, compared with no prison methadone, was estimated. Assumptions regarding resource use were tested through sensitivity analysis. The annual cost of providing prison methadone in NSW was estimated to be 2.9 million Australian dollars (or 3,234 Australian dollars per inmate per year). The incremental cost effectiveness ratio is 38 Australian dollars per additional heroin free day. From a treatment perspective, prison methadone is no more costly than community methadone, and provides benefits in terms of reduced heroin use in prisons, with associated reduction in morbidity and mortality.

  8. Heroin

    MedlinePlus

    ... an illegal narcotic because it has dangerous side effects and is very addictive. Sometimes Called: horse, smack, big H, black tar, caballo (Spanish), 8-ball (heroin mixed with crack cocaine), junk, TNT How It's Used: Heroin is usually ...

  9. Dysregulated post-synaptic density and endocytic zone in the amygdala of human heroin and cocaine abusers

    PubMed Central

    Ökvist, Anna; Fagergren, Pernilla; Whittard, John; Garcia-Osta, Ana; Drakenberg, Katarina; Horvath, Monika Cs.; Schmidt, Carl J.; Keller, Eva; Bannon, Michael J.; Hurd, Yasmin L.

    2010-01-01

    Background Glutamatergic transmission in the amygdala is hypothesized as an important mediator of stimulus-reward associations contributing to drug-seeking behavior and relapse. Insight is, however, lacking regarding the amygdala glutamatergic system in human drug abusers. Methods We examined glutamate receptors and scaffolding proteins associated with the post-synaptic density (PSD) of excitatory synapses in the human post-mortem amygdala. mRNA or protein levels were studied in a multi-drug (7 heroin, 8 cocaine, 7 heroin/cocaine and 7 control) or predominant heroin (29 heroin and 15 control) population of subjects. Results The amygdala of drug abusers was characterized by a striking positive correlation (r > 0.8) between AMPA GluA1 and post-synaptic protein-95 (PSD-95) mRNA levels, which was not evident in controls. Structural equation multi-group analysis of protein correlations also identified the relationship between GluA1 and PSD-95 protein levels as the distinguishing feature of abusers. In line with the GluA1—PSD-95 implications of enhanced synaptic plasticity, Homer 1b/c protein expression was significantly increased in both heroin and cocaine users as was its binding partner dynamin-3, localized to the endocytic zone. Furthermore, there was a positive relationship between Homer 1b/c and dynamin-3 in drug abusers that reflected an increase in the direct physical coupling between the proteins. A noted age-related decline of Homer 1b/c—dynamin-3 interactions, as well as GluA1 levels, was blunted in abusers. Conclusions Impairment of key components of the amygdala PSD and coupling to the endocytic zone, critical for the regulation of glutamate receptor cycling, may underlie heightened synaptic plasticity in human drug abusers. PMID:21126734

  10. Methadone maintenance treatment (MMT): a review of historical and clinical issues.

    PubMed

    Joseph, H; Stancliff, S; Langrod, J

    2000-01-01

    Methadone maintenance has been evaluated since its development in 1964 as a medical response to the post-World War II heroin epidemic in New York City. The findings of major early studies have been consistent. Methadone maintenance reduces and/or eliminates the use of heroin, reduces the death rates and criminality associated with heroin use, and allows patients to improve their health and social productivity. In addition, enrollment in methadone maintenance has the potential toreduce the transmission of infectious diseases associated with heroin injection, such as hepatitis and HIV. The principal effects of methadone maintenance are to relieve narcotic craving, suppress the abstinence syndrome, and block the euphoric effects associated with heroin. A majority of patients require 80-120 mg/d of methadone, or more, to achieve these effects and require treatment for an indefinite period of time, since methadone maintenance is a corrective but not a curative treatment for heroin addiction. Lower doses may not be as effective or provide the blockade effect. Methadone maintenance has been found to be medically safe and nonsedating. It is also indicated for pregnant women addicted to heroin. Reviews issued by the Institute of Medicine and the National Institutes of Health have defined narcotic addiction as a chronic medical disorder and have claimed that methadone maintenance coupled with social services is the most effective treatment for this condition. These agencies recommend reducing governmental regulation to facilitate patients access to treatment. In addition, they recommend that the number of programs be expanded, and that new models of treatment be implemented,if the nationwide problem of addiction is to be brought under control. The National Institutes of Health also recommend that methadone maintenance be available to persons under legal supervision, such as probationers, parolees and the incarcerated. However, stigma and bias directed at the programs and the

  11. Cocaine-related deaths.

    PubMed

    Lora-Tamayo, C; Tena, T; Rodriguez, A

    1994-07-15

    Cocaine availability has been increasing in Spain in the past few years. A review of all the toxicological analyses carried out at the Madrid Department of the Instituto Nacional de Toxicología, with subjects who had died of drugs from 1990 to 1992, found 533 persons who had cocaine in their blood and/or tissues; 450 (84%) deaths involved cocaine and heroin together whereas 83 (16%) deaths involved cocaine with an absence of heroin. This paper reports the circumstances, cocaine and benzoylecgonine concentrations in the blood and other toxicological findings for the two major groups of deaths where cocaine was found with an absence of heroin, i.e., possible overdose cases (35 cases) and traffic accidents (23 cases).

  12. Genetic variants associated with addictive behavior in Colombian addicted and non-addicted to heroin or cocaine.

    PubMed

    Isaza, Carlos; Henao, Julieta; Beltrán, Leonardo; Porras, Liliana; Gonzalez, Martha; Cruz, Raquel; Carracedo, Angel

    2013-01-01

    Determine the prevalence and compare some genetic markers involved in addictive behavior in a group of addicts to derivative of coca (cocaine/crack) or heroin and a control group of non-addicted people matched for gender, age and ethnicity. A 120 addicts and 120 non-addicts Colombian male were surveyed and genotyped for 18 polymorphism of the OPRM1, DRD2, DRD4, SLC6A3, SLC6A4, ABCB1, DβH and CYP2B6 genes. For the identification of alleles markers were used mini-sequencing and fragment multiplex PCR techniques; ethnicity of cases and controls was analyzed with 61 AIMs. The age of onset use of heroin or coca derivatives (cocaine/crack) was 16.5±6 years and 99.2% of them consume several illicit drugs. It showed that controls and addicts belong to the same ethnic group. Significant differences between addicts and controls in relation to schooling, marital status, social security family history of substance abuse (p <0.001), Int8-VNTR SLC6A3 gene (p= 0.015) and SNP 3435C>T ABCB1 gene (p= 0.001) were found. The present results indicate that the VNTR- 6R polymorphism of the gene SLC6A3 and the genotype 3435CC in the ABCB1 gene, are both associated with addictive behavior to heroin or cocaine.

  13. Brain-derived neurotrophic factor (BDNF) and oxidative stress in heroin-dependent male patients undergoing methadone maintenance treatment.

    PubMed

    Tsai, Meng-Chang; Huang, Tiao-Lai

    2017-03-01

    Brain-derived neurotrophic factor (BDNF) and oxidative stress may play a role in patients with heroin dependence. The aim of this study was to investigate the serum levels and activities of BDNF and oxidative stress markers, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), thiobarbituric acid reactive substances (TBARS), protein carbonyl content (PCC), and 8-hydroxy 2'-deoxyguanosine (8-OHdG), in heroin-dependent patients undergoing methadone maintenance treatment (MMT). 60 heroin-dependent male MMT patients and 30 healthy males were recruited for this study. The serum BDNF and oxidative stress markers of these subjects were measured with assay kits. Analyses of covariance (ANCOVAs) with age and body mass index adjustments indicated that the serum levels of BDNF in the MMT patients were significantly higher than those in the healthy controls (F=5.169; p=0.026). However, there were no significant differences between the heroin-dependent patients and the healthy controls in the serum levels or activities of oxidative stress markers (p>0.05). In conclusion, our results suggest that MMT increases BDNF levels in heroin-dependent patients, and that patients undergoing MMT might be in a balanced state of reduced oxidation. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  14. Association between cholesterol plasma levels and craving among heroin users.

    PubMed

    Lin, Shih-Hsien; Yang, Yen Kuang; Lee, Sheng-Yu; Hsieh, Pei Chun; Chen, Po See; Lu, Ru-Band; Chen, Kao Chin

    2012-12-01

    Lipids may play some roles in the central nervous system functions that are associated with drug addiction. To date, cholesterol is known to influence relapse of cocaine use. However, the relationship between cholesterol and heroin craving is unclear. This study examined the concurrent association between cholesterol and craving. The serum lipid levels of 70 heroin users who were undergoing or had undergone a methadone maintenance therapy were measured. Their craving and demographic data were assessed. Total cholesterol and low-density lipoprotein cholesterol are negatively associated with craving before (r = -0.33, P < 0.01, and r = -0.36, P < 0.01, respectively) and after controlling for the effects of potential confounders (β = -0.38, P < 0.01, and β = -0.42, P < 0.01, respectively). Cholesterol could be associated with the cognitive aspect of craving and may be a potential marker to predict risk of drug relapse.

  15. Effects of prior cocaine versus morphine or heroin self-administration on extinction learning driven by overexpectation versus omission of reward.

    PubMed

    Lucantonio, Federica; Kambhampati, Sarita; Haney, Richard Z; Atalayer, Deniz; Rowland, Neil E; Shaham, Yavin; Schoenbaum, Geoffrey

    2015-05-15

    Addiction is characterized by an inability to stop using drugs, despite adverse consequences. One contributing factor to this compulsive drug taking could be the impact of drug use on the ability to extinguish drug seeking after changes in expected outcomes. Here, we compared effects of cocaine, morphine, and heroin self-administration on two forms of extinction learning: standard extinction driven by reward omission and extinction driven by reward overexpectation. In experiment 1, we trained rats to self-administer cocaine, morphine, or sucrose for 3 hours per day (limited access). In experiment 2, we trained rats to self-administer heroin or sucrose for 12 hours per day (extended access). Three weeks later, we trained the rats to associate several cues with palatable food reward, after which we assessed extinction of the learned Pavlovian response, first by pairing two cues together in the overexpectation procedure and later by omitting the food reward. Rats trained under limited access conditions to self-administer sucrose or morphine demonstrated normal extinction in response to both overexpectation and reward omission, whereas cocaine-experienced rats or rats trained to self-administer heroin under extended access conditions exhibited normal extinction in response to reward omission but failed to show extinction in response to overexpectation. Here we show that cocaine and heroin can induce long-lasting deficits in the ability to extinguish reward seeking. These deficits were not observed in a standard extinction procedure but instead only affected extinction learning driven by a more complex phenomenon of overexpectation. Published by Elsevier Inc.

  16. Heroin and cocaine abusers have higher discount rates for delayed rewards than alcoholics or non-drug-using controls.

    PubMed

    Kirby, Kris N; Petry, Nancy M

    2004-04-01

    To test a prediction of the discounting model of impulsiveness that discount rates would be positively associated with addiction. The delay-discount rate refers to the rate of reduction in the present value of a future reward as the delay to that reward increases. We estimated participants' discount rates on the basis of their pattern of choices between smaller immediate rewards ($11-80) and larger, delayed rewards ($25-85; at delays from 1 week to 6 months) in a questionnaire format. Participants had a one-in-six chance of winning a reward that they chose on one randomly selected trial. Heroin (n = 27), cocaine (n = 41) and alcohol (n = 33) abusers and non-drug-using controls (n = 44) were recruited from advertisements. They were tested in a drug abuse research clinic at a medical school. On average, the cocaine and heroin groups had higher rates than controls (both P < 0.001), but alcoholics did not (P = 0.44). Abstinence was associated with lower rates for heroin abusers (P = 0.03), but not for cocaine or alcohol abusers (both P > 0.50). These data suggest that discount rates vary with the preferred drug of abuse, and that high discount rates should be considered in the development of substance abuse prevention and treatment efforts.

  17. Relationship between LAAM-methadone preference and treatment outcomes.

    PubMed

    White, Jason M; Danz, Cath; Kneebone, Joanne; La Vincente, Sophie F; Newcombe, David A L; Ali, Robert L

    2002-05-01

    Studies of relative LAAM-methadone preference have indicated that a significant proportion of patients prefer levo-alpha-acetylmethadol (LAAM). The present study was designed to determine whether this preference is associated with better treatment outcomes. Sixty-two stable methadone patients participated in a randomised crossover clinical trial. They received LAAM (alternate days) and methadone (daily) for 3 months each, followed by a further 6-month period during which they were free to choose between the drugs. LAAM maintenance was associated with a lower rate of heroin use than methadone maintenance based on analysis of morphine concentration in hair and equivalent health outcomes. The majority of subjects showed a preference for LAAM (n=27, 69.2%) rather than methadone (n=12, 30.8%). The main reasons given for the LAAM preference were that it produced less withdrawal (39.3%), fewer side effects (28.5%), less craving for heroin (17.9%), and entailed fewer pick-up days (14.3%). Those who chose LAAM had lower levels of heroin use during LAAM maintenance, significantly better outcomes on two sub-scales of the SF-36 (Vitality and Mental Health), and reported that they felt more normal and that they were 'held' better when on LAAM. For those who chose methadone, there were no differences in outcomes between the LAAM and methadone maintenance periods. Preference for LAAM is associated with treatment outcomes as good or better than those with methadone.

  18. Naltrexone implants compared to methadone: outcomes six months after prison release.

    PubMed

    Lobmaier, Philipp P; Kunøe, Nikolaj; Gossop, Michael; Katevoll, Tormod; Waal, Helge

    2010-01-01

    After prison release, offenders with heroin use problems are at high risk of relapse and overdose death. There is a particular need for treatments that can be initiated in prison and continued after release into the community. Methadone maintenance treatment has been shown to reduce heroin use, criminality and mortality. Naltrexone implant treatment has not previously been evaluated in prison settings. This study compares the effects of naltrexone implants and methadone treatment on heroin and other illicit drug use, and criminality among heroin-dependent inmates after release from prison. Forty-six volunteers were randomly allocated to naltrexone implants or methadone before release. Intention-to-treat analyses showed reductions in both groups in frequency of use of heroin and benzodiazepines, as well as criminality, 6 months after prison release. Naltrexone implants may be a valuable treatment option in prison settings. 2010 S. Karger AG, Basel.

  19. Acute heroin intoxication in a baby chronically exposed to cocaine and heroin: a case report

    PubMed Central

    2011-01-01

    Introduction Acute intoxication with drugs of abuse in children is often only the tip of the iceberg, actually hiding chronic exposure. Analysis using non-conventional matrices such as hair can provide long-term information about exposure to recreational drugs. Case presentation We report the case of a one-month-old Caucasian boy admitted to our pediatric emergency unit with respiratory distress and neurological abnormalities. A routine urine test was positive for opiates, suggesting an acute opiate ingestion. No other drugs of misuse, such as cocaine, cannabis, amphetamines or derivatives, were detected in the baby's urine. Subsequently, hair samples from the baby and the parents were collected to evaluate the possibility of chronic exposure to drug misuse by segmental analysis. Opiates and cocaine metabolites were detected in hair samples from the baby boy and his parents. Conclusions In light of these and previous results, we recommend hair analysis in babies and children from risky environments to detect exposure to heroin and other drug misuse, which could provide the basis for specific social and health interventions. PMID:21729296

  20. Profile of executive deficits in cocaine and heroin polysubstance users: common and differential effects on separate executive components.

    PubMed

    Verdejo-García, Antonio; Pérez-García, Miguel

    2007-03-01

    Structure of executive function was examined and we contrasted performance of substance dependent individuals (polysubstance users) and control participants on neuropsychological measures assessing the different executive components obtained. Additionally, we contrasted performance of polysubstance users with preference for cocaine vs heroin and controls to explore possible differential effects of the main substance abused on executive impairment. Two groups of participants were recruited: abstinent polysubstance users and controls. Polysubstance users were further subdivided based on their drug of choice (cocaine vs heroin). We administered to all participants a comprehensive protocol of executive measures, including tests of fluency, working memory, reasoning, inhibitory control, flexibility, and decision making. Consistent with previous models, the principal component analysis showed that executive functions are organized into four separate components, three of them previously described: updating, inhibition, and shifting; and a fourth component of decision making. Abstinent polysubstance users had clinically significant impairments on measures assessing these four executive components (with effect sizes ranging from 0.5 to 2.2). Cocaine polysubstance users had more severe impairments than heroin users and controls on measures of inhibition (Stroop) and shifting (go/no go and category test). Greater severity of drug use predicted poorer performance on updating measures. Executive functions can be fractionated into four relatively independent components. Chronic drug use is associated with widespread impairment of these four executive components, with cocaine use inducing more severe deficits on inhibition and shifting. These findings show both common and differential effects of two widely used drugs on different executive components.

  1. A 50-Year-Old Woman Addicted to Heroin

    PubMed Central

    O’Brien, Charles P.

    2011-01-01

    Heroin addiction is a complicated medical and psychiatric issue, with well-established as well as newer modes of treatment. The case of Ms W, a 50-year-old woman with a long history of opiate addiction who has been treated successfully with methadone for 9 years and who now would like to consider newer alternatives, illustrates the complex issues of heroin addiction. The treatment of heroin addiction as a chronic disease is reviewed, including social, medical, and cultural issues and pharmacologic treatment with methadone and the more experimental medication options of buprenorphine and naltrexone. PMID:18594026

  2. Professional Demeanor of Chronically Unemployed Cocaine-Dependent Methadone Patients in a Therapeutic Workplace

    PubMed Central

    Carpenedo, Carolyn M.; Needham, Mick; Knealing, Todd W.; Kolodner, Kenneth; Fingerhood, Michael; Wong, Conrad J.; Silverman, Kenneth

    2011-01-01

    This study assesses the frequency that users of illicit drugs display unprofessional behaviors in an employment setting. This research was conducted in the Therapeutic Workplace, a model employment-based treatment program for chronically unemployed adults with long-histories of illicit drug use. Unemployed adults in methadone treatment, who were opiate and cocaine dependent, showed signs of injection drug use, and recently used cocaine were hired to work for 4 hours every weekday for 7 months. Results show that while the overall incidence of many undesirable behaviors is low, a small percentage of participants had serious workplace behavior problems that might limit their success in community workplaces. This study suggests that unprofessional behavior in the workplace could contribute to chronic unemployment in this population. PMID:17668330

  3. Maternal Methadone Dose, Placental Methadone Concentrations, and Neonatal Outcomes

    PubMed Central

    de Castro, Ana; Jones, Hendreé E.; Johnson, Rolley E.; Gray, Teresa R.; Shakleya, Diaa M.; Huestis, Marilyn A.

    2015-01-01

    BACKGROUND Few investigations have used placenta as an alternative matrix to detect in utero drug exposure, despite its availability at the time of birth and the large amount of sample. Methadone-maintained opioid-dependent pregnant women provide a unique opportunity to examine the placental disposition of methadone and metabolite [2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP)], to explore their correlations with maternal methadone dose and neonatal outcomes, and to test the ability to detect in utero exposure to illicit drugs. METHODS We calculated the correlations of placental methadone and EDDP concentrations and their correlations with maternal methadone doses and neonatal outcomes. Cocaine- and opiate-positive placenta results were compared with the results for meconium samples and for urine samples collected throughout gestation. RESULTS Positive correlations were found between placental methadone and EDDP concentrations (r = 0.685), and between methadone concentration and methadone dose at delivery (r = 0.542), mean daily dose (r = 0.554), mean third-trimester dose (r = 0.591), and cumulative daily dose (r = 0.639). The EDDP/methadone concentration ratio was negatively correlated with cumulative daily dose (r = 0.541) and positively correlated with peak neonatal abstinence syndrome (NAS) score (r = 0.513). Placental EDDP concentration was negatively correlated with newborn head circumference (r = 0.579). Cocaine and opiate use was detected in far fewer placenta samples than in thrice-weekly urine and meconium samples, a result suggesting a short detection window for placenta. CONCLUSIONS Quantitative methadone and EDDP measurement may predict NAS severity. The placenta reflects in utero drug exposure for a shorter time than meconium but may be useful when meconium is unavailable or if documentation of recent exposure is needed. PMID:21245372

  4. Regional homogeneity changes between heroin relapse and non-relapse patients under methadone maintenance treatment: a resting-state fMRI study.

    PubMed

    Chang, Haifeng; Li, Wei; Li, Qiang; Chen, Jiajie; Zhu, Jia; Ye, Jianjun; Liu, Jierong; Li, Zhe; Li, Yongbin; Shi, Ming; Wang, Yarong; Wang, Wei

    2016-08-18

    Methadone maintenance treatment (MMT) is recognized as one of the most effective treatments for heroin addiction but its effect is dimmed by the high incidence of heroin relapse. However, underlying neurobiology mechanism of heroin relapse under MMT is still largely unknown. Here, we took advantage of a resting-state fMRI technique by analysis of regional homogeneity (ReHo), and tried to explore the difference of brain function between heroin relapsers and non-relapsers in MMT. Forty MMT patients were included and received a 12-month follow-up. All patients were given baseline resting-state fMRI scans by using a 3.0 T GE Signa Excite HD whole-body MRI system. Monthly self-report and urine test were used to assess heroin relapse or non-relapse. Subjective craving was measured with visual analog scale. The correlation between ReHo and the degree of heroin relapse was analyzed. Compared with the non-relapsers, ReHo values were increased in the bilateral medial orbitofrontal cortex, right caudate, and right cerebellum of the heroin relapsers while those in the left parahippocampal gyrus, left middle temporal gyrus, right lingual gyrus, and precuneus were decreased in heroin relapsers. Importantly, altered ReHo in the right caudate were positively correlated with heroin relapse rates or subjective craving response. Using the resting-state fMRI technique by analysis of ReHo, we provided the first resting-state fMRI evidence that right caudate may serve as a potential biomarker for heroin relapse prediction and also as a promising target for reducing relapse risk.

  5. Non-attendance at counselling therapy in cocaine-using methadone-maintained patients: lessons learnt from an abandoned randomised controlled trial.

    PubMed

    Darker, C; Sweeney, B; El Hassan, H; Kelly, A; O' Connor, S; Smyth, B; Barry, J

    2012-12-01

    Recently, the authors commenced a randomised controlled trial to study the effectiveness of cognitive behavioural coping skills (CBCS) to reduce cocaine usage in methadone-maintained patients' in a clinical setting by assessing attendance at treatment sessions and outcomes in terms of cocaine use. However, recruitment into the study stopped when it became apparent that attendance at counselling sessions was poor. The aim of the current study was to determine the reasons for both non-attendance and attendance from a patient's perspective at counselling sessions. A cross-sectional design was employed whereby participants who were recruited for the original study were interviewed utilising a semi-structured interview format. Motivational inconsistencies were most frequently cited as the reason for dropping out of counselling, whereas a good relationship with staff was cited by attenders as the most important factors which aided their attendance at counselling sessions. Selecting opiate-dependent methadone-maintained cocaine abusers on the basis of their urine toxicology and offering them counselling as a way of reducing their harmful drug use did not prove efficacious. Attempting to address cocaine misuse within this cohort may need a more stepped approach including brief interventions, such as motivational interviewing, or other enhancers of motivation before we can test the effectiveness of CBCS in this population.

  6. Methadone maintenance.

    PubMed

    Russell-Taylor, W J

    1975-07-01

    Management of heroin addiction with oral methadone continues to create controversy. Since the first Dole-Nyswander experiments were reported almost a decade ago, methadone maintenance programs have been started in every major city in North America at an estimated public cost in the hundreds of millions of tax dollars. By the end of 1972, the United States alone spending at an annual rate in excess of $250 million, and an expenditure rate in excess of one billion dollars was occurring by the end of 1973. Despite the FDA investigational New Drug status of methadone when used for this purpose, objective data have still not been generated to substantiate the worth of Narcotic Substitution Therapy. Iatrogenic consequences are on the increase, and scepticism is growing among most pharmacologists. A critical evaluation of the entire methadone maintenance approach is being advocated by many and being attempted by some. Data currently being generated at the Philadelphia General Hospital suggest that many patients may have been better managed without methadone.

  7. Opioid Agonist Treatments and Heroin Overdose Deaths in Baltimore, Maryland, 1995–2009

    PubMed Central

    Gryczynski, Jan; O’Grady, Kevin E.; Sharfstein, Joshua M.; Warren, Gregory; Olsen, Yngvild; Mitchell, Shannon G.; Jaffe, Jerome H.

    2013-01-01

    Objectives. We examined the association between the expansion of methadone and buprenorphine treatment and the prevalence of heroin overdose deaths in Baltimore, Maryland from 1995 to 2009. Methods. We conducted a longitudinal time series analysis of archival data using linear regression with the Newey–West method to correct SEs for heteroscedasticity and autocorrelation, adjusting for average heroin purity. Results. Overdose deaths attributed to heroin ranged from a high of 312 in 1999 to a low of 106 in 2008. While mean heroin purity rose sharply (1995–1999), the increasing number of patients treated with methadone was not associated with a change in the number of overdose deaths, but starting in 2000 expansion of opioid agonist treatment was associated with a decline in overdose deaths. Adjusting for heroin purity and the number of methadone patients, there was a statistically significant inverse relationship between heroin overdose deaths and patients treated with buprenorphine (P = .002). Conclusions. Increased access to opioid agonist treatment was associated with a reduction in heroin overdose deaths. Implementing policies that support evidence-based medication treatment of opiate dependence may decrease heroin overdose deaths. PMID:23488511

  8. Simultaneous Quantification of Methadone, Cocaine, Opiates, and Metabolites in Human Placenta by Liquid Chromatography–Mass Spectrometry*

    PubMed Central

    de Castro, Ana; Concheiro, Marta; Shakleya, Diaa M.; Huestis, Marilyn A.

    2011-01-01

    A validated method for quantifying methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine, cocaine, benzoylecgonine, 6-acetylmorphine, morphine, and codeine in human placenta by liquid chromatography–ion trap mass spectrometry is described. Specimens (1 g) were homogenized and subjected to solid-phase extraction. Chromatographic separation was performed on a Synergi Polar RP column with a gradient of 0.1% formic acid and acetonitrile. The method was linear from 10 to 2000 ng/g for methadone and 2.5 to 500 ng/g for other analytes. Limits of detection were 0.25–2.5 ng/g, imprecisions < 9.1%CV, analytical recoveries 84.4–113.3%, extraction efficiencies > 46%, matrix effects −8.0–129.9%, and process efficiencies 24.2–201.0%. Method applicability was demonstrated by analysis of five placenta specimens from opioid-dependent women receiving methadone pharmacotherapy, with methadone doses ranging from 65 to 95 mg on the day of delivery. These are the first data on placenta concentrations of methadone and metabolites after controlled drug administration. Detection of other common drugs of abuse in placenta will also improve our knowledge of the usefulness of this matrix for detecting in utero drug exposure and studying disposition of drugs in the maternal-fetal dyad. PMID:19671243

  9. Attendance rates in a workplace predict subsequent outcome of employment-based reinforcement of cocaine abstinence in methadone patients.

    PubMed

    Donlin, Wendy D; Knealing, Todd W; Needham, Mick; Wong, Conrad J; Silverman, Kenneth

    2008-01-01

    This study assessed whether attendance rates in a workplace predicted subsequent outcome of employment-based reinforcement of cocaine abstinence. Unemployed adults in Baltimore methadone programs who used cocaine (N=111) could work in a workplace for 4 hr every weekday and earn $10.00 per hour in vouchers for 26 weeks. During an induction period, participants provided urine samples but could work independent of their urinalysis results. After the induction period, participants had to provide urinalysis evidence of cocaine abstinence to work and maintain maximum pay. A multiple regression analysis showed that induction period attendance was independently associated with urinalysis evidence of cocaine abstinence under the employment-based abstinence reinforcement contingency. Induction period attendance may measure the reinforcing value of employment and could be used to guide the improvement of employment-based abstinence reinforcement.

  10. Characterizing longitudinal health state transitions among heroin, cocaine, and methamphetamine users

    PubMed Central

    Nosyk, B; Li, L; Evans, E; Huang, D; Min, J; Kerr, T; Brecht, ML; Hser, YI

    2014-01-01

    Aims Characterize longitudinal patterns of drug use careers and identify determinants of drug use frequency across cohorts of primary heroin, methamphetamine (MA) and cocaine users. Design Pooled analysis of prospective cohort studies. Settings Illicit drug users recruited from community, criminal justice and drug treatment settings in California, USA. Participants We used longitudinal data on from five observational cohort studies featuring primary users of heroin (N=629), cocaine (N=694) and methamphetamine (N=474). The mean duration of follow-up was 20.9 years. Measurements Monthly longitudinal data was arranged according to five health states (incarceration, drug treatment, abstinence, non-daily and daily use). We fitted proportional hazards (PH) frailty models to determine independent differences in successive episode durations. We then executed multi-state Markov (MSM) models to estimate probabilities of transitioning between health states, and the determinants of these transitions. Findings Across primary drug use types, PH frailty models demonstrated durations of daily use diminished in successive episodes over time. MSM models revealed primary stimulant users had more erratic longitudinal patterns of drug use, transitioning more rapidly between periods of treatment, abstinence, non-daily and daily use. MA users exhibited relatively longer durations of high-frequency use. Criminal engagement had a destabilizing effect on health state durations across drug types. Longer incarceration histories were associated with delayed transitions towards cessation. Conclusions PH frailty and MSM modeling techniques provided complementary information on longitudinal patterns of drug abuse. This information can inform clinical practice and policy, and otherwise be used in health economic simulation models, designed to inform resource allocation decisions. PMID:24837584

  11. Cocaine

    MedlinePlus

    ... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter ... The Brain & the Actions of Cocaine, Opioids and Marijuana The first in a 5-part series, offers ...

  12. A preliminary, controlled investigation of magnesium L-aspartate hydrochloride for illicit cocaine and opiate use in methadone-maintained patients.

    PubMed

    Margolin, Arthur; Kantak, Kathleen; Copenhaver, Michael; Avants, S Kelly

    2003-01-01

    Based on pre-clinical studies suggesting that magnesium (Mg) reduces cocaine self-administration and potentiates the antinociceptive effects of morphine, we conducted a preliminary randomized clinical trial investigating Mg for the treatment of illicit cocaine and opiate use. Eighteen methadone-maintained patients who used illicit opiates and cocaine received either Mg (732 mg/day) or placebo for 12 weeks. Overall, findings showed that the percentage of urine screens testing positive for opiates in the Mg group (22.6%) was half that of the placebo group (46.4%), p = .04; the difference was even greater in the "medication compliant" sample (Mg: 16.3%, placebo: 47.9%), p = .02. Cocaine craving was lower in the Mg compared to the placebo group, but there was no difference between groups in cocaine use. These preliminary findings suggest that Mg may have a beneficial effect for reducing illicit opiate use. It is possible that a higher dose of Mg than was used in this study may be needed to decrease cocaine use.

  13. The epidemiology of cocaine use in Spain.

    PubMed

    Barrio Anta, G; Vicente Orta, J; Bravo Portela, M J; de la Fuente de Hoz, L

    1993-12-01

    Trends and patterns of cocaine use in Spain are described with the aid of different information sources such as population surveys, the State Information System on Drug Abuse, and anthropological studies. In recent years the magnitude of cocaine supply indicators has increased greatly. High levels of last-month prevalence of cocaine use have been detected among the general population--consistently higher than those for heroin-- and cocaine consumption among heroin users has increased. Although the frequency of some health problems related to cocaine use--treatment admissions, hospital emergency admissions--has increased, it is still 30 times less than for heroin. Various hypotheses to explain these discrepancies are discussed.

  14. Improvements in Health-related Quality of Life among Methadone Maintenance Clients in Dar es Salaam, Tanzania

    PubMed Central

    Ubuguyu, Omary; Tran, Olivia C.; Bruce, R. Douglas; Masao, Frank; Nyandindi, Cassian; Sabuni, Norman; McCurdy, Sheryl; Mbwambo, Jessie

    2016-01-01

    Background Injection of heroin has become widespread in Dar es Salaam, Tanzania and is spreading throughout the country. To prevent potential bridging of HIV epidemics, the Tanzanian government established a methadone maintenance treatment (MMT) clinic in February 2011. We assess the effect of MMT on health-related quality of life (HRQOL) and examine factors, particularly HIV infection and methadone dose, associated with changes in HRQOL. Methods This study utilized routine data on clients enrolling in methadone from February 2011 to April 2012 at Muhimbili National Hospital. Change in physical (PCS) and mental health (MCS) composite scores, as measured by the SF-12 tool, were the primary outcomes. Backward stepwise linear regression, with a criterion of p<0.2 was used to identify baseline exposure variables for inclusion in multivariable models, while adjusting for baseline scores. Results A total of 288 MMT clients received baseline and follow-up assessments. Mean methadone dose administered was 45 mg (SD±25) and 76(27%) were confirmed HIV-positive. Significant improvements were observed in PCS and MCS, with mean increases of 15.7 and 3.3, respectively. In multivariable models, clients who had previous poly-substance use with cocaine [p=0.040] had a significantly higher mean change in PCS. Clients who were living with HIV [p=0.002]; satisfied with current marital situation [p=0.045]; had a history of suicidal thoughts [p=0.021]; and previously experienced cognitive difficulties [p=0.012] had significantly lower mean change in PCS. Clients with shorter history of heroin use [p=0.012] and who received higher methadone doses [p=0.028] had significantly higher mean change in MCS, compared to their counterparts. Discussion Aspects of mental and physical health, risk behaviors and quality of life among drug users are intertwined and complex. Our research revealed positive short-term effects of MMT on HRQOL and highlights the importance of sustained retention for

  15. Beneficial effects of co-treatment with dextromethorphan on prenatally methadone-exposed offspring.

    PubMed

    Chiang, Yao-Chang; Ye, Li-Ci; Hsu, Kuei-Ying; Liao, Chien-Wei; Hung, Tsai-Wei; Lo, Wan-Jou; Ho, Ing-Kang; Tao, Pao-Luh

    2015-03-20

    Heroin use among young women of reproductive age has drawn much attention around the world. Although methadone is widely used in maintenance therapy for heroin/morphine addiction, the long-term effects of prenatal exposure to methadone and preventative therapy remain unclear. For revealing this question, female pregnant Sprague-Dawley rats were sub-grouped to receive (1) vehicle, (2) methadone 5 mg/kg at embryonic day 3 (E3) and then 7 mg/kg from E4 to E20, (3) dextromethorphan (DM) 3 mg/kg, and (4) methadone + DM (the rats received methadone followed by DM treatment), subcutaneously, twice a day from E3 to E20. The body weight, natural withdrawal, pain sensitivity, ED50, conditioned place preference and water maze were conducted at different postnatal stages (P1 to P79) of offspring. The quantitative real-time RT-PCR and electrophysiology were also used to measure the gene expression of opioid receptors in the spinal cord and changes of LTP/LTD in the hippocampus, separately. Prenatal exposure to methadone or DM did not affect survival rate, body weight, water maze and LTP or LTD of offspring. However, prenatal methadone significantly increased the withdrawal symptoms, pain sensitivity, addiction liability and decreased the mRNA expression of pain related opioid receptors. Co-administration of DM with methadone in the maternal rats effectively prevented these abnormalities of offspring induced by methadone. Our study clearly showed that co-administration of dextromethorphan with methadone in the maternal rats prevented the adverse effects induced by prenatal methadone exposure. It implies that dextromethorphan may have a potential to be used in combination with methadone for maintenance treatment in pregnant heroin-addicted women to prevent the adverse effects induced by methadone on offspring.

  16. Supervised Injectable Heroin: A Clinical Perspective.

    PubMed

    Bell, James; Waal, Rob van der; Strang, John

    2017-07-01

    Six recent randomised control trials (RCTs) have suggested that supervised injectable heroin (SIH) can be effective in patients who persist in street heroin use during methadone treatment. However, short-term randomised control trials have limitations in assessing the effectiveness of treatments for addictive disorders, which are chronic and relapsing disorders of motivation. These RCTs particularly fail to capture the process of the SIH treatment and the diversity of influence and change over time. This narrative review is based on the analysis of published data. Conclusions are drawn from a process of reflection informed by experience in delivering one of the published trials, subsequent experiences in varying the way SIH is delivered, and through consideration of possible mechanisms of action of SIH. Many long-term, socially marginalised and demoralised people who are addicted to heroin experience few rewards from the stability afforded by methadone treatment. Supervised injected heroin is sufficiently reinforcing for many of these individuals to attend daily and participate in highly structured treatment. With an adequate daily dose of supervised methadone to avoid withdrawal dysphoria, occasional diamorphine injections-not necessarily twice daily, or even every day-is enough to hold people in treatment. Participation was associated with reduced amounts of non-prescribed drug use, a gradual change in self-image and attitude, and for some subjects, a movement towards social reintegration and eventual withdrawal from SIH. Prescribed heroin is sufficiently motivating to hold a proportion of recidivist addicts in long-term treatment. Participation in structured treatment provides respite from compulsive drug use, and a proportion of subjects develop sufficient rewards from social reintegration to successfully withdraw from treatment. Such change, when it occurs, is slow and stuttering.

  17. Associations among hypothalamus-pituitary-adrenal axis function, novelty seeking, and retention in methadone maintenance therapy for heroin dependency.

    PubMed

    Lin, Shih-Hsien; Chen, Wei Tseng; Chen, Kao Chin; Lee, Sheng-Yu; Lee, I Hui; Chen, Po See; Yeh, Tzung Lieh; Lu, Ru-Band; Yang, Yen Kuang

    2013-01-01

    The efficacy of methadone maintenance therapy for heroin dependence is compromised by the low retention rate. Hypothalamus-pituitary-adrenal (HPA) axis function, which is associated with stress response, and novelty seeking (NS), a personality trait associated with low dopaminergic activity, may play roles in retention. We conducted a prospective study in which HPA axis function and NS were assessed by the dexamethasone suppression test and the Tridimensional Personality Questionnaire at baseline, respectively. The retention rate was assessed at the half- and 1-year points of methadone maintenance therapy. A low suppression rate of dexamethasone suppression test (D%) was associated with a high level of NS. A low D% was associated with half-year dropout, whereas a high level of NS was associated with 1-year dropout. Survival analysis confirmed that D% and NS were significant time-dependent covariates for retention. The findings showed that HPA axis function and NA were associated with retention at different time points.

  18. The impact of law enforcement activity on a heroin market.

    PubMed

    Weatherburn, D; Lind, B

    1997-05-01

    It may be argued that seizing large quantities of heroin being imported into the country should decrease its supply and hence increase its price, resulting in a reduction in the quantity of the drug being purchased or consumed. To date, however, there has been no empirical evidence that heroin seizures in Australia have any effect on the price of heroin at street level. This article describes a 2-year research study during which the price and purity of street-level heroin were regularly monitored. It was found that heroin seizures had no effect on the price, purity or perceived availability of heroin at street level. It was further found that admissions to methadone treatment were not affected by the price or perceived availability of heroin or by local arrests for heroin use/possession, nor was any relationship found between these arrests and the price of street-level heroin. Nevertheless, two-thirds of those who sought entry to local methadone programmes indicated the price as a reason for stopping using heroin. This paper argues that supply-side law enforcement should only be used as a strategy for maintaining high heroin prices if the demand for heroin can be shown to be price-elastic and, further, that the costs of such a strategy need to be weighted against the benefits.

  19. Trends in Deaths Involving Heroin and Synthetic Opioids Excluding Methadone, and Law Enforcement Drug Product Reports, by Census Region - United States, 2006-2015.

    PubMed

    O'Donnell, Julie K; Gladden, R Matthew; Seth, Puja

    2017-09-01

    Opioid overdose deaths quadrupled from 8,050 in 1999 to 33,091 in 2015 and accounted for 63% of drug overdose deaths in the United States in 2015. During 2010-2015, heroin overdose deaths quadrupled from 3,036 to 12,989 (1). Sharp increases in the supply of heroin and illicitly manufactured fentanyl (IMF) are likely contributing to increased deaths (2-6). CDC examined trends in unintentional and undetermined deaths involving heroin or synthetic opioids excluding methadone (i.e., synthetic opioids)* by the four U.S. Census regions during 2006-2015. Drug exhibits (i.e., drug products) obtained by law enforcement and reported to the Drug Enforcement Administration's (DEA's) National Forensic Laboratory Information System (NFLIS) that tested positive for heroin or fentanyl (i.e., drug reports) also were examined. All U.S. Census regions experienced substantial increases in deaths involving heroin from 2006 to 2015. Since 2010, the South and West experienced increases in heroin drug reports, whereas the Northeast and Midwest experienced steady increases during 2006-2015. † In the Northeast, Midwest, and South, deaths involving synthetic opioids and fentanyl drug reports increased considerably after 2013. These broad changes in the U.S. illicit drug market highlight the urgent need to track illicit drugs and enhance public health interventions targeting persons using or at high risk for using heroin or IMF.

  20. Wheel running decreases the positive reinforcing effects of heroin.

    PubMed

    Smith, Mark A; Pitts, Elizabeth G

    2012-01-01

    The purpose of this study was to examine the effects of voluntary wheel running on the positive reinforcing effects of heroin in rats with an established history of drug self-administration. Rats were assigned to sedentary (no wheel) and exercise (wheel) conditions and trained to self-administer cocaine under positive reinforcement contingencies. Rats acquiring cocaine self-administration were then tested with various doses of heroin during daily test sessions. Sedentary rats self-administered more heroin than exercising rats, and this effect was greatest at low and moderate doses of heroin. These data suggest that voluntary wheel running decreases the positive reinforcing effects of heroin.

  1. Medically assisted recovery from opiate dependence within the context of the UK drug strategy: methadone and Suboxone (buprenorphine-naloxone) patients compared.

    PubMed

    McKeganey, Neil; Russell, Christopher; Cockayne, Lucinda

    2013-01-01

    The focus of drug policy in the UK has shifted markedly in the past 5 years to move beyond merely emphasising drug abstinence towards maximising individuals' opportunities for recovery. The UK government continues to recognise the prescribing of narcotic medications indicated for opiate dependence as a key element of these individuals' recovery journey. This article describes a small, naturalistic comparison of the efficacy of the two most commonly prescribed opiate substitute medications in the UK--methadone hydrochloride (methadone oral solution) and Suboxone (buprenorphine-naloxone sublingual tablets)--for reducing current heroin users' (n = 34) days of heroin use, and preventing short-term abstainers (n = 37) from relapsing to regular heroin use. All patients had been prescribed either methadone or Suboxone for maintenance for 6 months prior to intake. Results showed that when controlling for a number of patient-level covariates, both methadone and Suboxone significantly reduced current users' days of heroin use between the 90 days prior to intake and at the 8-month follow-up, with Suboxone yielding a significantly larger magnitude reduction in heroin use days than methadone. Methadone and Suboxone were highly and equally effective for preventing relapse to regular heroin use, with all but 3 of 37 (91.9%) patients who were abstinent at intake reporting past 90-day point prevalence heroin abstinence at the 8-month follow-up. Overall, prescribing methadone or Suboxone for eight continuous months was highly effective for initiating abstinence from heroin use, and for converting short-term abstinence to long-term abstinence. However, the study design, which was based on a relatively small sample size and was not able randomise patients to medication and so could not control for the effects of potential prognostic factors inherent within each patient group, means that these conclusions can only be made tentatively. These positive but preliminary indications of the

  2. Evaluation of poly-drug use in methadone-related fatalities using segmental hair analysis.

    PubMed

    Nielsen, Marie Katrine Klose; Johansen, Sys Stybe; Linnet, Kristian

    2015-03-01

    In Denmark, fatal poisoning among drug addicts is often related to methadone. The primary mechanism contributing to fatal methadone overdose is respiratory depression. Concurrent use of other central nervous system (CNS) depressants is suggested to heighten the potential for fatal methadone toxicity. Reduced tolerance due to a short-time abstinence period is also proposed to determine a risk for fatal overdose. The primary aims of this study were to investigate if concurrent use of CNS depressants or reduced tolerance were significant risk factors in methadone-related fatalities using segmental hair analysis. The study included 99 methadone-related fatalities collected in Denmark from 2008 to 2011, where both blood and hair were available. The cases were divided into three subgroups based on the cause of death; methadone poisoning (N=64), poly-drug poisoning (N=28) or methadone poisoning combined with fatal diseases (N=7). No significant differences between methadone concentrations in the subgroups were obtained in both blood and hair. The methadone blood concentrations were highly variable (0.015-5.3, median: 0.52mg/kg) and mainly within the concentration range detected in living methadone users. In hair, methadone was detected in 97 fatalities with concentrations ranging from 0.061 to 211ng/mg (median: 11ng/mg). In the remaining two cases, methadone was detected in blood but absent in hair specimens, suggesting that these two subjects were methadone-naive users. Extensive poly-drug use was observed in all three subgroups, both recently and within the last months prior to death. Especially, concurrent use of multiple benzodiazepines was prevalent among the deceased followed by the abuse of morphine, codeine, amphetamine, cannabis, cocaine and ethanol. By including quantitative segmental hair analysis, additional information on poly-drug use was obtained. Especially, 6-acetylmorphine was detected more frequently in hair specimens, indicating that regular abuse of

  3. Heroin purchasing is income and price sensitive.

    PubMed

    Roddy, Juliette; Steinmiller, Caren L; Greenwald, Mark K

    2011-06-01

    Semi-structured interviews were used to assess behavioral economic drug demand in heroin dependent research volunteers. Findings on drug price, competing purchases, and past 30-day income and consumption, established in a previous study, are replicated. We extended these findings by having participants indicate whether hypothetical environmental changes would alter heroin purchasing. Participants (n = 109) reported they would significantly (p < .005) decrease heroin daily purchasing amounts (DPA) from past 30-day levels (M = $60/day) if: (a) they encountered a 33% decrease in income (DPA = $34), (b) family/friends no longer paid their living expenses (DPA = $32), or (c) they faced four-fold greater likelihood of police arrest at their purchasing location (DPA = $42). Participants in higher income quartiles (who purchase more heroin) show greater DPA reductions (but would still buy more heroin) than those in lower income quartiles. For participants receiving government aid (n = 31), heroin purchasing would decrease if those subsidies were eliminated (DPA = $28). Compared to participants whose urine tested negative for cocaine (n = 31), cocaine-positive subjects (n = 32) reported more efficient heroin purchasing, that is, they live closer to their primary dealer; are more likely to have heroin delivered or walk to obtain it (and less likely to ride the bus), thus reducing purchasing time (52 vs. 31 min, respectively); and purchase more heroin per episode. These simulation results have treatment and policy implications: Daily heroin users' purchasing repertoire is very cost-effective, more so for those also using cocaine, and only potent environmental changes (income reductions or increased legal sanctions) may impact this behavior. (PsycINFO Database Record (c) 2011 APA, all rights reserved).

  4. The Textures of Heroin: User Perspectives on "Black Tar" and Powder Heroin in Two U.S. Cities.

    PubMed

    Mars, Sarah G; Bourgois, Philippe; Karandinos, George; Montero, Fernando; Ciccarone, Daniel

    2016-01-01

    Since the 1990s, U.S. heroin consumers have been divided from the full range of available products: east of the Mississippi River, Colombian-sourced powder heroin (PH) dominates the market while, to the west, Mexican-sourced "black tar" (BTH) is the main heroin available. By conducting qualitative research in two exemplar cities, Philadelphia (PH) and San Francisco (BTH), we compare users' experiences of heroin source-types, markets, health consequences, and consumption preferences. The strict division of heroin markets may be changing with novel forms of powder heroin appearing in San Francisco. Our researchers and interviewees perceived vein loss stemming from the injection of heroin alone to be a particular problem of BTH while, among the Philadelphia sample, those who avoided the temptations of nearby cocaine sales displayed healthier injecting sites and reported few vein problems. Abscesses were common across both sites, the Philadelphia sample generally blaming missing a vein when injecting cocaine and the San Francisco group finding several explanations, including the properties of BTH. Consumption preferences revealed a "connoisseurship of potency," with knowledge amassed and deployed to obtain the strongest heroin available. We discuss the reasons that their tastes take this narrow form and its relationship to the structural constraints of the heroin market.

  5. The Textures of Heroin: User Perspectives on “Black Tar” and Powder Heroin in Two US Cities

    PubMed Central

    Mars, Sarah G.; Bourgois, Philippe; Karandinos, George; Montero, Fernando; Ciccarone, Daniel

    2016-01-01

    Since the 1990s, US heroin consumers have been divided from the full range of available products: east of the Mississippi River, Colombian-sourced powder heroin (PH) dominates the market, while to the west, Mexican-sourced “black tar” (BTH) is the main heroin available. By conducting qualitative research in two exemplar cities, Philadelphia (PH) and San Francisco (BTH), we compare users’ experiences of heroin source-types, markets, health consequences and consumption preferences. The strict division of heroin markets may be changing with novel forms of powder heroin appearing in San Francisco. Our researchers and interviewees perceived vein loss stemming from the injection of heroin alone to be a particular problem of BTH while among the Philadelphia sample, those who avoided the temptations of nearby cocaine sales displayed healthier injecting sites and reported few vein problems. Abscesses were common across both sites, the Philadelphia sample generally blaming missing a vein when injecting cocaine and the San Francisco group finding several explanations, including the properties of BTH. Consumption preferences revealed a ‘connoisseurship of potency’, with knowledge amassed and deployed to obtain the strongest heroin available. We discuss the reasons that their tastes take this narrow form and its relationship to the structural constraints of the heroin market. PMID:27440088

  6. Improving psychosocial health and employment outcomes for individuals receiving methadone treatment: a realist synthesis of what makes interventions work.

    PubMed

    Jackson, Lois A; Buxton, Jane A; Dingwell, Julie; Dykeman, Margaret; Gahagan, Jacqueline; Gallant, Karen; Karabanow, Jeff; Kirkland, Susan; LeVangie, Dolores; Sketris, Ingrid; Gossop, Michael; Davison, Carolyn

    2014-01-01

    For over 50 years, methadone has been prescribed to opioid-dependent individuals as a pharmacological approach for alleviating the symptoms of opioid withdrawal. However, individuals prescribed methadone sometimes require additional interventions (e.g., counseling) to further improve their health. This study undertook a realist synthesis of evaluations of interventions aimed at improving the psychosocial and employment outcomes of individuals on methadone treatment, to determine what interventions work (or not) and why. The realist synthesis method was utilized because it uncovers the processes (or mechanisms) that lead to particular outcomes, and the contexts within which this occurs. A comprehensive search process resulted in 31 articles for review. Data were extracted from the articles, and placed in four templates to assist with analysis. Data analysis was an iterative process and involved comparing and contrasting data within and across each template, and cross checking with original articles to determine key patterns in the data. For individuals on methadone, engagement with an intervention appears to be important for improved psychosocial and/or employment outcomes. The engagement process involves attendance at interventions as well as an investment in what is offered. Three intervention contexts (often in some combination) support the engagement process: a) client-centered contexts (or those where clients' psychosocial and/or employment needs/issues/skills are recognized and/or addressed); b) contexts which address clients' socio-economic conditions and needs; and, c) contexts where there are positive client-counselor and/or peer relationships. There is some evidence that sometimes ongoing engagement is necessary to maintain positive outcomes. There is also some evidence that complete abstinence from drugs (e.g., cocaine, heroin) is not necessary for engagement. It is important to consider how the contexts of interventions might elicit and/or support

  7. Dextromethorphan attenuated inflammation and combined opioid use in humans undergoing methadone maintenance treatment.

    PubMed

    Chen, Shiou-Lan; Lee, Sheng-Yu; Tao, Pao-Luh; Chang, Yun-Hsuan; Chen, Shih-Heng; Chu, Chun-Hsien; Chen, Po See; Lee, I Hui; Yeh, Tzung Lieh; Yang, Yen Kuang; Hong, Jau-Shyong; Lu, Ru-Band

    2012-12-01

    Recent studies show that proinflammatory cytokines might be related to the development of opioid dependence (physiological, psychological, or both). In a double-blind, randomly stratified clinical trial investigating whether add-on dextromethorphan (60-120 mg/day) attenuated inflammation and the combined use of opioids in heroin-dependent patients undergoing methadone maintenance treatment, we evaluated whether inflammation is related to the progression of opioid dependence. All participants (107 heroin-dependent patients and 84 nondependent healthy controls) were recruited from National Cheng Kung University Hospital. Their plasma cytokine levels were measured to evaluate the effect of add-on dextromethorphan. Plasma TNF-α and IL-8 levels were significantly higher in long-term heroin-dependent patients than in healthy controls (p < 0.001). Chronic heroin-use-induced TNF-α and IL-8 levels were significantly (p < 0.05) attenuated in patients treated for 12 weeks with add-on dextromethorphan. Moreover, both tolerance to methadone and the combined use of opioids were significantly (p < 0.05) attenuated in patients taking dextromethorphan. We conclude that dextromethorphan might be a feasible adjuvant therapeutic for attenuating inflammation and inhibiting methadone tolerance and combined opioid use in heroin-dependent patients.

  8. Concurrent Heroin Use and Correlates among Methadone Maintenance Treatment Clients: A 12-Month Follow-up Study in Guangdong Province, China

    PubMed Central

    Luo, Xiaofeng; Zhao, Peizhen; Gong, Xiao; Zhang, Lei; Tang, Weiming; Zou, Xia; Chen, Wen; Ling, Li

    2016-01-01

    Objective: To assess concurrent heroin use and correlates among Methadone Maintenance Treatment (MMT) clients in Guangdong Province, China. Method: Demographic and drug use data were collected with a structured questionnaire, and MMT information was obtained from the MMT clinic registration system in Guangdong. Human immunodeficiency virus (HIV-) and hepatitis C virus (HCV) infected status and urine morphine results were obtained from laboratory tests. Logistic regressions were employed to investigate the factors associated with concurrent heroin use. Results: Among the 6848 participants, 75% continued using heroin more than once during the first 12 months after treatment initiation. Concurrent heroin use was associated with inharmonious family relationship (OR (odds ratio) = 1.49, 95% CI (confidence intervals): 1.24–1.78), HIV positivity (OR = 1.25, 95% CI: 1.01–1.55), having multiple sex partners (OR = 1.34, 95% CI: 1.07–1.69), having ever taken intravenous drugs (OR = 0.81, 95% CI: 0.69–0.95), higher maintenance dose (OR = 1.13, 95% CI: 1.01–1.28) and poorer MMT attendance (OR<20% = 1.32, 95% CI: 1.13–1.53; OR20%– = 1.33, 95% CI: 1.14–1.54; OR50%– = 1.69, 95% CI: 1.44–2.00). Among those who used heroin concurrently, the same factors, and additionally being older (OR35– = 1.26, 95% CI: 1.11–1.43; OR≥45 = 1.63, 95% CI: 1.30–2.05) and female (OR = 1.60, 95% CI: 1.28–2.00), contribute to a greater frequency of heroin use. Conclusions: Concurrent heroin use was prevalent among MMT participants in Guangdong, underscoring the urgent needs for tailored interventions and health education programs for this population. PMID:27005649

  9. Neural correlates of the severity of cocaine, heroin, alcohol, MDMA and cannabis use in polysubstance abusers: a resting-PET brain metabolism study.

    PubMed

    Moreno-López, Laura; Stamatakis, Emmanuel A; Fernández-Serrano, Maria José; Gómez-Río, Manuel; Rodríguez-Fernández, Antonio; Pérez-García, Miguel; Verdejo-García, Antonio

    2012-01-01

    Functional imaging studies of addiction following protracted abstinence have not been systematically conducted to look at the associations between severity of use of different drugs and brain dysfunction. Findings from such studies may be relevant to implement specific interventions for treatment. The aim of this study was to examine the association between resting-state regional brain metabolism (measured with 18F-fluorodeoxyglucose Positron Emission Tomography (FDG-PET) and the severity of use of cocaine, heroin, alcohol, MDMA and cannabis in a sample of polysubstance users with prolonged abstinence from all drugs used. Our sample consisted of 49 polysubstance users enrolled in residential treatment. We conducted correlation analyses between estimates of use of cocaine, heroin, alcohol, MDMA and cannabis and brain metabolism (BM) (using Statistical Parametric Mapping voxel-based (VB) whole-brain analyses). In all correlation analyses conducted for each of the drugs we controlled for the co-abuse of the other drugs used. The analysis showed significant negative correlations between severity of heroin, alcohol, MDMA and cannabis use and BM in the dorsolateral prefrontal cortex (DLPFC) and temporal cortex. Alcohol use was further associated with lower metabolism in frontal premotor cortex and putamen, and stimulants use with parietal cortex. Duration of use of different drugs negatively correlated with overlapping regions in the DLPFC, whereas severity of cocaine, heroin and alcohol use selectively impact parietal, temporal, and frontal-premotor/basal ganglia regions respectively. The knowledge of these associations could be useful in the clinical practice since different brain alterations have been associated with different patterns of execution that may affect the rehabilitation of these patients.

  10. The cocaine and heroin markets in the era of globalisation and drug reduction policies.

    PubMed

    Costa Storti, Cláudia; De Grauwe, Paul

    2009-11-01

    Despite the large volume of public effort devoted to restrain drug supply and the growing attention given to drug demand reduction policies, the use of cocaine and heroin remains steady. Furthermore, retail drug prices have fallen significantly in Europe and the US. This puzzling evidence leads us to develop a model aiming at systematically analysing illicit drug markets. We model the markets of cocaine and heroin from production to the final retail markets. One novelty of the analysis consists in characterising the retail market as a monopolistic competitive one. Then, upper level dealers have some market power in the retail market. This allows them to charge a markup and to earn extra profits. These extra profits attract newcomers so that profits tend to fall over time. Theoretical model was used to analyse the effect of supply containment policies on the retail market, the producer market and the export-import business. This introduces the discussion of the impact of demand reduction policies on the high level traffickers' profit. Finally, globalisation enters in the model. Law enforcement measures increase the risk premia received by the lower and higher level traffickers. Consequently, trafficking intermediation margins tend to increase. However, globalisation has the opposite effect. It lowers intermediation margins and, then, pushes retail prices down, thereby stimulating consumption. In doing so, globalisation offsets the effects of supply containment policies. Finally, we discuss how the effectiveness of supply containment policies can be enhanced by combining them with demand reduction policies.

  11. The impact of benzodiazepine use on methadone maintenance treatment outcomes.

    PubMed

    Brands, Bruna; Blake, Joan; Marsh, David C; Sproule, Beth; Jeyapalan, Renuka; Li, Selina

    2008-01-01

    The purposes of this study were to examine predictors of benzodiazepine use among methadone maintenance treatment patients, to determine whether baseline benzodiazepine use influenced ongoing use during methadone maintenance treatment, and to assess the effect of ongoing benzodiazepine use on treatment outcomes (i.e., opioid and cocaine use and treatment retention). A retrospective chart review of 172 methadone maintenance treatment patients (mean age = 34.6 years; standard deviation = 8.5 years; 64% male) from January 1997 to December 1999 was conducted. At baseline, 29% were "non-users" (past year) of benzodiazepine, 36% were "occasional users," and 35% were "regular/problem users." Regular/problem users were more likely to have started opioid use with prescription opioids, experienced more overdoses, and reported psychiatric comorbidity. Being female, more years of opioid use, and a history of psychiatric treatment were significant predictors of baseline benzodiazepine use. Ongoing benzodiazepine users were more likely to have opioid-positive and cocaine-positive urine screens during methadone maintenance treatment. Only ongoing cocaine use was negatively related to retention. Benzodiazepine use by methadone maintenance treatment patients is associated with a more complex clinical picture and may negatively influence treatment outcomes.

  12. A social network perspective on heroin and cocaine use among adults: evidence of bidirectional influences.

    PubMed

    Bohnert, Amy S B; Bradshaw, Catherine P; Latkin, Carl A

    2009-07-01

    While several studies have documented a relationship between initiation of drug use and social network drug use in youth, the direction of this association is not well understood, particularly among adults or for stages of drug involvement beyond initiation. The present study sought to examine two competing theories (social selection and social influence) in the longitudinal relationship between drug use (heroin and/or cocaine) and social network drug use among drug-experienced adults. Three waves of data came from a cohort of 1108 adults reporting a life-time history of heroin and/or cocaine use. Low-income neighborhoods with high rates of drug use in Baltimore, Maryland. Participants had weekly contact with drug users and were 18 years of age or older. Drug use data were self-report. Network drug use was assessed through a social network inventory. Close friends were individuals whom the participant reported seeing daily or rated as having the highest level of trust. Findings Structural equation modeling indicated significant bidirectional influences. The majority of change in network drug use over time was due to change in the composition of the network rather than change in friends' behavior. Drug use by close peers did not influence participant drug use beyond the total network. There is evidence of both social selection and social influence processes in the association between drug use and network drug use among drug-experienced adults.

  13. Ageing opioid users' increased risk of methadone-specific death in the UK.

    PubMed

    Pierce, Matthias; Millar, Tim; Robertson, J Roy; Bird, Sheila M

    2018-05-01

    The first evidence that the hazard ratio (HR) for methadone-specific death rises more steeply with age-group than for all drug-related deaths (DRDs) came from Scotland's cohort of 33,000 methadone-prescription clients. We aim to examine, for England, whether illicit opioid users' risk of methadone-specific death increases with age; and to pool age-related HRs for methadone-specific deaths with those for Scotland's methadone-prescription clients. The setting is all services in England that provide publicly-funded, structured treatment for illicit opioid users, the methodology linkage of the English National Drug Treatment Monitoring System and mortality database, and key measurements are DRDs, methadone-specific DRDs, or heroin-specific DRDs, by age-group and gender, with proportional hazards adjustment for substances used, injecting status and periods in/out of treatment. Linkage was achieved for 129,979 adults receiving prescribing treatment modalities for opioid dependence during April 2005 to March 2009 and followed-up for 378,009 person-years (pys). There were 1,266 DRDs: 271 methadone-specific (7 per 10,000 pys: irrespective of gender) and 473 heroin-specific (15 per 10,000 pys for males, 7 for females). Methadone-specific DRD-rate per 10,000 person-years was 3.5 (95% CI: 2.7-4.4) at 18-34 years, 8.9 (CI: 7.3-10.5) at 35-44 years and 18 (CI: 13.8-21.2) at 45+ years; heroin-specific DRD-rate was unchanged with age. Relative to 25-34 years, pooled HRs for UK clients' methadone-specific deaths were: 0.87 at <25 years (95% CI: 0.56-1.35); 2.14 at 35-44 years (95% CI: 1.76-2.60); 3.75 at 45+ years (95% CI: 2.99-4.70). International testing and explanation are needed of UK's sharp age-related increase in the risk of methadone-specific death. Clients should be alerted that their risk of methadone-specific death increases as they age. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  14. Patterns of Cognitive Impairments among Heroin and Cocaine Users: The Association with Self-Reported Learning Disabilities and Infectious Disease

    ERIC Educational Resources Information Center

    Severtson, Stevan G.; Hedden, Sarra L.; Martins, Silvia S.; Latimer, William W.

    2012-01-01

    This study used data from six neuropsychological measures of executive function (EF) and general intellectual functioning (GIF) administered to 303 regular users of heroin and/or cocaine as indicators in a latent profile analysis (LPA). Results indicated the presence of three profiles: impaired GIF and EF profile (30.8%), intact GIF and EF profile…

  15. A morphine/heroin vaccine with new hapten design attenuates behavioral effects in rats.

    PubMed

    Li, Qian-Qian; Luo, Yi-Xiao; Sun, Cheng-Yu; Xue, Yan-Xue; Zhu, Wei-Li; Shi, Hai-Shui; Zhai, Hai-Feng; Shi, Jie; Lu, Lin

    2011-12-01

    Heroin use has seriously threatened public heath in many countries, but the existing therapies continue to have many limitations. Recently, immunotherapy has shown efficacy in some clinical studies, including vaccines against nicotine and cocaine, but no opioid vaccines have been introduced in clinical studies. The development of a novel opioid antigen designed specifically for the prevention of heroin addiction is necessary. A morphine-keyhole limpet hemocyanin conjugate was prepared and administered subcutaneously in rats. Antibody titers in plasma were measured using an enzyme-linked immunosorbent assay (ELISA). Competitive ELISA was used to assess the selectivity of the antibodies. Dopamine concentrations in the nucleus accumbens in rats after vaccine administration were determined by high-performance liquid chromatography with electrochemical detection. The effects of the vaccine on the heroin-primed restatement of self-administration and locomotor sensitization were evaluated. A novel hapten, 6-glutarylmorphine, was produced, and the vaccine generated a high antibody titer response. This vaccine displayed specificity for both morphine and heroin, but the anti-morphine antibodies could not recognize dissimilar therapeutic opioid compounds, such as buprenorphine, methadone, naloxone, naltrexone, codeine, and nalorphine. The morphine antibody significantly decreased morphine-induced locomotor activity in rats after immunization. Importantly, rats immunized with this vaccine did not exhibit heroin-primed reinstatement of heroin seeking when antibody levels were sufficiently high. The vaccine reduced dopamine levels in the nucleus accumbens after morphine administration, which is consistent with its behavioral effects. These results suggest that immunization with a novel vaccine is an effective means of inducing a morphine-specific antibody response that is able to attenuate the behavioral and psychoactive effects of heroin. © 2011 The Authors. Journal of

  16. Gender Differences and Correlated Factors of Heroin Use Among Heroin Users.

    PubMed

    Zhou, Xiaobo; Yi, Zhihua; Yang, Xiaorong; Wang, Zhuo; Lyu, Xianxiang; Li, Jing

    2017-01-02

    Gender differences in illicit drug use are becoming increasingly recognized. However, there are few studies concerning differences between male and female heroin users in China. The study aimed to explore gender differences in terms of socio-demographic characteristics, drug-related behaviors, and treatment history among a heroin-using population in China. A cross-sectional study was conducted in four cities in December 2013. A total of 788 participants were recruited from several types of sites in each city: compulsory detoxification centers, methadone maintenance treatment clinics, and detention facilities. The data were collected via a self-administered questionnaire. Analysis of variance, chi-square test, and multivariate logistic regression analyses were conducted to examine gender differences in socio-demographic characteristics, drug-related behaviors, and treatment history. Female heroin users were more likely to be unemployed, have more education, and use heroin with their spouse/companion (p <.05). Male heroin users were more likely to be in detention facilities and MMT clinics, and relapse when they felt hopeless (p <.05). Conclusions/Importance: Although there were some similarities between male and female heroin users, significant gender differences do exist in some aspects of socio-demographic characteristics and heroin use. The data provide evidence that interventions aimed at preventing the initiation of heroin use and reducing relapse should take gender into account.

  17. Development and validation of a liquid chromatography mass spectrometry assay for the simultaneous quantification of methadone, cocaine, opiates and metabolites in human umbilical cord

    PubMed Central

    de Castro, Ana; Concheiro, Marta; Shakleya, Diaa M.; Huestis, Marilyn A.

    2011-01-01

    A liquid chromatography mass spectrometric selected reaction monitoring mode (SRM) method for methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), cocaine, benzoylecgonine (BE), 6-acetylmorphine, morphine and codeine quantification in human umbilical cord was developed and fully validated. Analytes were extracted from homogenized tissue (1 g) by solid phase extraction. Linearity was 2.5–500 ng/g, except for methadone (10–2000 ng/g). Method imprecision was <12.7%CV with analytical recovery 85.9–112.7%, extraction efficiency >59.2%, matrix effect 4.5–39.5%, process efficiency 48.6–92.6% and stability >84.6%. Analysis of an umbilical cord following controlled methadone administration and illicit drug use contained in ng/g, 40.3 morphine, 3.6 codeine, 442 BE, 186 methadone and 45.9 EDDP. PMID:19656745

  18. Methadone maintenance in prison: evaluation of a pilot program in Puerto Rico.

    PubMed

    Heimer, Robert; Catania, Holly; Newman, Robert G; Zambrano, John; Brunet, Arlyn; Ortiz, Arturo Marti

    2006-06-28

    To describe and evaluate a pilot methadone maintenance program for heroin-dependent inmates of Las Malvinas men's prison in San Juan, Puerto Rico. Data from self-report of inmates' drug use before and during incarceration, attitudes about drug treatment in general and methadone maintenance in particular, and expectations about behaviors upon release from prison and from testing inmates' urine were analyzed comparing program patients (n=20) and inmates selected at random from the prison population (n=40). Qualitative data obtained by interviewing program staff, the correctional officers and superintendent, and commonwealth officials responsible for establishing and operating the program were analyzed to identify attitudes about methadone and program effectiveness. Heroin use among prisoners not in treatment was common; 58% reported any use while incarcerated and 38% reported use in past 30 days. All patients in the treatment program had used heroin in prison in the 30 days prior to enrolling in treatment. While in treatment, the percentage of patients not using heroin was reduced, according to both self-report and urine testing, to one in 18 (94% reduction) and one in 20 (95% reduction), respectively. Participation in treatment was associated with an increased acceptance of methadone maintenance. Prison personnel and commonwealth officials were supportive of the program. The program appears to be a success, and prison officials have begun an expansion from the current ceiling of 24 inmates to treat 300 or more inmates.

  19. Alexithymia level and response to computer-based training in cognitive behavioral therapy among cocaine-dependent methadone maintained individuals.

    PubMed

    Morie, Kristen P; Nich, Charla; Hunkele, Karen; Potenza, Marc N; Carroll, Kathleen M

    2015-07-01

    Alexithymia, a characteristic marked by poor ability to identify, define and communicate emotions, has been associated with poorer treatment outcome, including traditional clinician delivered CBT. Computerized cognitive behavioral therapy (CBT4CBT), an effective adjunct to treatment, may provide a means of conveying skills without requiring interaction with a clinician. Seventy-three methadone maintained, cocaine dependent individuals participating in an 8-week randomized clinical trial comparing standard methadone maintenance to methadone maintenance plus CBT4CBT completed the Toronto Alexithymia Scale (TAS-20) at pretreatment, post-treatment, and follow-ups conducted one, two, and 6 months after treatment. There were no statistically significant differences on baseline TAS-20 scores by multiple demographic and substance use variables including gender and substance use severity. Higher TAS-20 scores were associated with somewhat higher levels of distress as measured by the Beck Depression Inventory and multiple Brief Severity Index scales. TAS-20 scores remained relatively stable throughout the duration of treatment and follow-up. Indicators of treatment process, including treatment retention, adherence and therapeutic alliance, were not significantly correlated with TAS-20 scores. There was a significant interaction of alexithymia and treatment condition, such that individuals with higher baseline scores on the TAS-20 submitted significantly higher percentages of cocaine-negative urine toxicology specimens and reported a higher percentage of abstinence days, and longer periods of consecutive abstinence within treatment when assigned to CBT4CBT compared with treatment as usual. These findings suggest that individuals with increased alexithymia may benefit from computerized CBT; possibly via reduced demands on interpersonal skills and interactions associated with computerized therapies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. Solid phase microextraction and gas chromatography-mass spectrometry methods for residual solvent assessment in seized cocaine and heroin.

    PubMed

    Cabarcos, Pamela; Herbello-Hermelo, Paloma; Álvarez-Freire, Iván; Moreda-Piñeiro, Antonio; Tabernero, María Jesús; Bermejo, Ana María; Bermejo-Barrera, Pilar

    2016-09-01

    A simple sample pre-treatment method based on solid phase microextraction (SPME) and gas chromatography-mass spectrometry (GC-MS) has been optimized and validated for the assessment of 15 residual solvents (2-propanol, 2-methylpentane, 3-methylpentane, acetone, ethyl acetate, benzene, hexane, methylcyclohexane, methylcyclopentane, m-xylene, propyl acetate, toluene, 1,2,4-trimethylbenzene, dichloromethane, and ethylbenzene) in seized illicit cocaine and heroin. DMSO and DMF as sample diluents were found to offer the best residual solvent transference to the head space for further adsorption onto the SPME fiber, and the developed method therefore showed high sensitivity and analytical recovery. Variables affecting SPME were fully evaluated by applying an experimental design approach. Best conditions were found when using an equilibration time of 5 min at 70 °C and headspace sampling of residual solvents at the same temperature for 15 min. Method validation, performed within the requirements of international guidelines, showed excellent sensitivity, as well as intra- and inter-day precision and accuracy. The proposed methodology was applied to 96 cocaine samples and 14 heroin samples seized in Galicia (northwestern Spain) within 2013 and 2014.

  1. Association between the DRD2 A1 allele and response to methadone and buprenorphine maintenance treatments.

    PubMed

    Barratt, Daniel T; Coller, Janet K; Somogyi, Andrew A

    2006-06-05

    The TaqI A polymorphism (A(1)) of the dopamine D(2) receptor gene (DRD2), although not a specific predictor of opioid dependence, has been strongly associated with high levels of prior heroin use and poor treatment outcomes among methadone maintenance patients. The aims of this study were to confirm these findings via a retrospective analysis of A(1) allele frequency in methadone (n = 46) and buprenorphine (n = 25) patients, and non-opioid-dependent controls (n = 95). Subjects were genotyped at the DRD2 TaqI A locus using PCR amplification followed by TaqI restriction enzyme digestion and gel electrophoresis. For methadone and buprenorphine subjects, heroin use (prior to treatment), treatment outcomes, and withdrawal occurrence were determined from comprehensive case notes. No significant differences in A(1) allele frequency (%) were observed between: methadone (19.6%), buprenorphine (18.0%), and control (17.9%) groups (P > 0.7); successful and poor treatment outcome groups, methadone: 20.0% and 19.2%, respectively (P = 1.0); buprenorphine: 18.4% and 20.0%, respectively (P = 1.0). Also, there were no significant relationships between TaqI A genotype and prior heroin use (P = 0.47). However, among the successful methadone subjects, significantly fewer A(1) allele carriers experienced withdrawal than non-A(1) carriers (P = 0.04). In conclusion, the DRD2 genotype effects did not affect opioid maintenance treatment outcomes. This suggests the need for a further prospective investigation into the role of the DRD2 A(1) allele in heroin use and response to maintenance pharmacotherapies for opioid dependence.

  2. Polydrug Use and HIV Risk Among People Who Inject Heroin in Tijuana, Mexico: A Latent Class Analysis.

    PubMed

    Meacham, Meredith C; Rudolph, Abby E; Strathdee, Steffanie A; Rusch, Melanie L; Brouwer, Kimberly C; Patterson, Thomas L; Vera, Alicia; Rangel, Gudelia; Roesch, Scott C

    2015-01-01

    Although most people who inject drugs (PWID) in Tijuana, Mexico, primarily inject heroin, injection and non-injection use of methamphetamine and cocaine is common. We examined patterns of polydrug use among heroin injectors to inform prevention and treatment of drug use and its health and social consequences. Participants were PWID residing in Tijuana, aged ≥18 years who reported heroin injection in the past six months and were recruited through respondent-driven sampling (n = 1,025). Latent class analysis was conducted to assign individuals to classes on a probabilistic basis, using four indicators of past six-month polydrug and polyroute use: cocaine injecting, cocaine smoking or snorting, methamphetamine injecting, and methamphetamine smoking or snorting. Latent class membership was regressed onto covariates in a multinomial logistic regression. Latent class analyses testing 1, 2, 3, and 4 classes were fit, with the 3-class solution fitting best. Class 1 was defined by predominantly heroin use (50.2%, n = 515); class 2 by methamphetamine and heroin use (43.7%, n = 448), and class 3 by methamphetamine, cocaine, and heroin use (6.0%, n = 62). Bivariate and multivariate analyses indicated a group of methamphetamine and cocaine users that exhibited higher-risk sexual practices and lower heroin injecting frequency, and a group of methamphetamine users who were younger and more likely to be female. Discrete subtypes of heroin PWID were identified based on methamphetamine and cocaine use patterns. These findings have identified subtypes of heroin injectors who require more tailored interventions to reduce the health and social harms of injecting drug use.

  3. Polydrug use and HIV risk among people who inject heroin in Tijuana, Mexico: A Latent class analysis

    PubMed Central

    Meacham, M.C.; Rudolph, A.E.; Strathdee, S.A.; Rusch, M.L.; Brouwer, K.C.; Patterson, T.L.; Vera, A.; Rangel, G.; Roesch, S.C.

    2016-01-01

    Background Although most people who inject drugs (PWID) in Tijuana, Mexico, primarily inject heroin, injection and non-injection use of methamphetamine and cocaine is common. We examined patterns of polydrug use among heroin injectors to inform prevention and treatment of drug use and its health and social consequences. Methods Participants were PWID residing in Tijuana aged ≥ 18 years who reported heroin injection in the past 6 months and were recruited through respondent driven sampling (n=1025). Latent class analysis was conducted to assign individuals to classes on a probabilistic basis, using four indicators of past 6 month polydrug and polyroute use: cocaine injecting, cocaine smoking or snorting, methamphetamine injecting, methamphetamine smoking or snorting. Latent class membership was regressed onto covariates in a multinomial logistic regression. Results Latent class analyses testing 1, 2, 3, and 4 classes were fit, with the 3-class solution fitting best. Class 1 was defined by predominantly heroin use (50.2%, n=515); class 2 by methamphetamine and heroin use (43.7%, n=448), and class 3 by methamphetamine, cocaine, and heroin use (6.0%, n=62). Bivariate and multivariate analyses indicated a group of methamphetamine and cocaine users that exhibited higher risk sexual practices and lower heroin injecting frequency, and a group of methamphetamine users who were younger and more likely to be female. Conclusions Discrete subtypes of heroin PWID were identified based on methamphetamine and cocaine use patterns. These findings have identified subtypes of heroin injectors who require more tailored interventions to reduce the health and social harms of injecting drug use. PMID:26444185

  4. Using Acceptance and Commitment Therapy during Methadone Dose Reduction: Rationale, Treatment Description, and a Case Report

    ERIC Educational Resources Information Center

    Stotts, Angela L.; Masuda, Akihiko; Wilson, Kelly

    2009-01-01

    Many clients who undergo methadone maintenance (MM) treatment for heroin and other opiate dependence prefer abstinence from methadone. Attempts at methadone detoxification are often unsuccessful, however, due to distressing physical as well as psychological symptoms. Outcomes from an MM client who voluntarily participated in an Acceptance and…

  5. What You Need to Know About Drugs: Heroin

    MedlinePlus

    ... illegal narcotic because it is has dangerous side effects and is very addictive. Sometimes Called: horse, smack, big H, black tar, caballo (Spanish), 8-ball (heroin mixed with crack cocaine), junk, TNT How It's Used: Heroin is usually ...

  6. Application of ToFSIMS to Studying Surface Diffusion: Do cocaine and heroin form a two-dimensional gas on surfaces?

    NASA Astrophysics Data System (ADS)

    Avci, Recep; Maccagnano, Sara; Bohannan, Gary; Gresham, Gary; Groenewold, Gary

    2001-03-01

    Imaging time-of-flight secondary ion mass spectroscopy ( ToFSIMS) is a practical tool for studying the movement of molecules on material surfaces as a function of time. The high detection sensitivity, rapid data acquisition and reasonable spatial resolution present ideal conditions for such studies. An application of ToFSIMS is presented characterizing the diffusion of large molecules on gold-coated Si wafers. Polydimethylsiloxane (PDMS) was selected for study because it contaminates material surfaces and can be detected easily. Also, the temperature dependent diffusion properties of hydrochlorinated heroin and cocaine are presented as part of a forensic application. While the PDMS diffusion could be explained by a two-dimensional ( 2-D) Brownian motion with a Gaussian probability distribution function (pdf) with a diffusion coefficient of 1.6 μ m^2/sec, the cocaine and to a lesser extent heroin were observed to move nearly freely on the surfaces as though they were part of a 2-D gas evaporating in 2-D from a condensed phase. The results could be described reasonably well using an extreme Lévi pdf with an index of stability α<= 0.01.

  7. An uncertain dominion: Irish psychiatry, methadone, and the treatment of opiate abuse.

    PubMed

    Saris, A Jamie

    2008-06-01

    This paper investigates some productive ambiguities around the medical administration of methadone in the Republic of Ireland. The tensions surrounding methadone maintenance therapy (MMT) are outlined, as well as the sociohistorical context in which a serious heroin addiction problem in Ireland developed. Irish psychiatry intervened in this situation, during a time of institutional change, debates concerning the nature of addiction, moral panics concerning heroin addiction in Irish society and the recent boom in the Irish economy, known popularly as the Celtic Tiger. A particular history of this sort illuminates how technologies like MMT become cosmopolitan, settling into, while changing, local contexts.

  8. Pleasure, power and dangerous substances: applying Foucault to the study of 'heroin dependence' in Germany.

    PubMed

    Bergschmidt, Viktoria B

    2004-04-01

    Taking the observation of disciplining and controlling everyday practices of methadone substitution as a point of departure, this paper explores the question of what exactly is so threatening or dangerous about heroin and heroin users. Drawing on the work of Michel Foucault and Judith Butler, the main argument of this article is that the danger of heroin use is a discursive construction in accordance with bio-power. On the one hand, the juridical governance of heroin dependence is shifting from punishment to therapy, and biomedical discourses proclaim the substitution of a moral notion of heroin dependence by a disease model. Nevertheless, in the context of the anxiety associated with HIV, heroin remains the dangerous drug par excellence, and heroin users are constructed as 'abject others', unable to subordinate to certain social norms. As a reaction to such injurious ascriptions, I argue, applicants to the methadone programme in their life stories intensely narrate a desire for normalization, which I read as a desire to emerge from the realm of the abject. Both the danger and the pleasure associated with heroin use are bound to fundamental processes of subject formation, which are often ignored in biomedical and anthropological discourses.

  9. Factors associated with concurrent heroin use among patients on methadone maintenance treatment in Vietnam: A 24-month retrospective analysis of a nationally representative sample.

    PubMed

    Hoang, Thai; Nguyen, Hong; Shiraishi, Ray W; Nguyen, Mai; Bingham, Trista; Nguyen, Diep; Nguyen, Tam; Duong, Hao; Lyss, Sheryl; Tran, Hien

    2018-05-01

    Methadone maintenance treatment (MMT) is highly effective for reducing heroin use and HIV transmission among people who inject opioids. We sought to measure and understand factors associated with continued heroin use, a critical factor affecting treatment outcome among MMT patients in Vietnam. We collected data from medical charts of a nationally representative sample of patients who were on MMT from May 2008 to December 2013. We selected 10 MMT clinics using probability proportional to size and 50 patients/clinic by systematic random sampling. Concurrent heroin use was defined by self-report/positive urine test recorded in patient charts during month 3, 6, 12, and 24 after MMT initiation. We used multivariable logistic regression to identify factors associated with concurrent heroin use over the first 24 months in treatment. All clients used heroin at baseline; concurrent heroin use was 55% at month 3; 19%, 14.6% and 15.2% at month 6, 12, and 24, respectively. Having no family emotional/financial support at baseline versus having this support (AOR = 2.03; 95% confidence interval [CI] = 1.17-3.53); using heroin for <15 years versus ≥15 years at baseline (AOR = 1.55; 95% CI = 1.01-2.38); being HIV-infected/not on antiretroviral treatment (ART; AOR = 1.79; 95% CI = 1.07-2.98) or being HIV infected/on ART (AOR = 2.39; 95% CI = 1.61-3.55), versus not being HIV infected; baseline methamphetamine use versus non-use (AOR = 2.68; 95% CI = 1.08-6.65), were associated with increased odds of concurrent heroin use among patients. The association between concurrent heroin use among MMT patients and lack of family emotional/financial support, highlights the critical importance of these types of support for successful treatment. Association with shorter heroin use history suggests motivational enhancement may reduce concurrent heroin use. Living with HIV, whether on ART or not, is associated with increased concurrent heroin use and

  10. Sex-Related Differences in Self-Reported Neurocognitive Impairment among High-Risk Cocaine Users in Methadone Maintenance Treatment Program.

    PubMed

    Shrestha, Roman; Huedo-Medina, Tania B; Copenhaver, Michael M

    2015-01-01

    Previous research has suggested possible sex-related differences in executive functioning among cocaine users; however, no studies specifically explain sex-related differences in neurocognitive impairment (NCI) among cocaine users receiving clinical care. Knowledge about this association can aid in the development of targeted prevention strategies to reduce adverse health outcomes. This study was designed to examine the sex-related differences in NCI among high-risk cocaine users receiving substance-abuse treatment. The Neuropsychological Impairment Scale (NIS) was administered to 199 cocaine users (98 men; 101 women), receiving methadone maintainance treatment, to assess self-reported NCI by identifying the patients' awareness of neuropsychological symptoms. We used T-test comparison to find differences in NCI between men and women and multiple regression analysis to explore the relative contribution of sex to NCI. Consistent with prior work, high NCI was evident within this sample, as indicated by high scores on most of the NIS subscales. Women reported greater impairment than men, as evidenced by significantly higher scores on several NIS subscales, after controlling for demographic and other confounding variables. Interestingly, cocaine craving significantly predicted NCI among men but not among women, as suggested by the significant association between cocaine craving and all except one of the NIS subscales. These findings suggest that cocaine users enter into treatment with a range of NCI - with women having significantly more neurocognitive deficits than men - that may contribute to differential treatment outcomes. This highlights the need to include additional services such as neuropsychological screening and sex-specific treatment programs to optimally reduce adverse health outcomes in these high-risk, cognitively impaired patients.

  11. Days of heroin use predict poor self-reported health in hospitalized heroin users

    PubMed Central

    Meshesha, Lidia Z.; Tsui, Judith I.; Liebschutz, Jane M.; Crooks, Denise; Anderson, Bradley J.; Herman, Debra S.; Stein, Michael D.

    2013-01-01

    This study examined associations between substance use behaviors and self-reported health among hospitalized heroin users. Of the 112 participants, 53 (47%) reported good or better health. In multivariable logistic regression models, each day of heroin use in the last month was associated with an 8% lower odds of reporting health as good or better (OR=.92; 95%CI 0.87, 0.97, p < .05). Cocaine, cannabis, cigarettes, alcohol use, unintentional overdose, nor injection drug use were associated with health status. PMID:24045030

  12. Pharmacogenetics and human molecular genetics of opiate and cocaine addictions and their treatments.

    PubMed

    Kreek, Mary Jeanne; Bart, Gavin; Lilly, Charles; LaForge, K Steven; Nielsen, David A

    2005-03-01

    Opiate and cocaine addictions are major social and medical problems that impose a significant burden on society. Despite the size and scope of these problems, there are few effective treatments for these addictions. Methadone maintenance is an effective and most widely used treatment for opiate addiction, allowing normalization of many physiological abnormalities caused by chronic use of short-acting opiates. There are no pharmacological treatments for cocaine addiction. Epidemiological, linkage, and association studies have demonstrated a significant contribution of genetic factors to the addictive diseases. This article reviews the molecular genetics and pharmacogenetics of opiate and cocaine addictions, focusing primarily on genes of the opioid and monoaminergic systems that have been associated with or have evidence for linkage to opiate or cocaine addiction. This evidence has been marshalled either through identification of variant alleles that lead to functional alterations of gene products, altered gene expression, or findings of linkage or association studies. Studies of polymorphisms in the mu opioid receptor gene, which encodes the receptor target of some endogenous opioids, heroin, morphine, and synthetic opioids, have contributed substantially to knowledge of genetic influences on opiate and cocaine addiction. Other genes of the endogenous opioid and monoaminergic systems, particularly genes encoding dopamine beta-hydroxylase, and the dopamine, serotonin, and norepinephrine transporters have also been implicated. Variants in genes encoding proteins involved in metabolism or biotransformation of drugs of abuse and also of treatment agents are reviewed.

  13. Lifetime history of insomnia and hypersomnia symptoms as correlates of alcohol, cocaine, and heroin use and relapse among adults seeking substance use treatment in the United States from 1991 to 1994

    PubMed Central

    Dolsen, Michael R.; Harvey, Allison G.

    2017-01-01

    Aims To examine the association between a lifetime history of insomnia and hypersomnia compared with no sleep disturbance and substance use patterns and amounts before and after a substance use treatment episode. Design Secondary analysis of data from the Drug Abuse Treatment Outcome Studies conducted from 1991 to 1994. Setting Data were collected at 96 substance use treatment programs in 11 United States cities including short-term in-patient, long-term residential, methadone maintenance, and outpatient drug-free treatment modalities. Participants Study samples included 7,168 adults at treatment entry and 2,965 at 12 months post-treatment entry whose primary substance use at entry was alcohol (14.7%), cocaine (62.7%), or heroin (22.6%). Measurements Lifetime history of insomnia and hypersomnia was assessed via self-report. Type and frequency of substance use were assessed at treatment entry. Substance use was also assessed 12 months following treatment completion. Associations were examined using linear and logistic regression with age, sex, race, education level, depression history, treatment modality, and in-treatment substance use as covariates. Findings Lifetime history of insomnia, hypersomnia, both or neither was reported by 26.3%, 9.5%, 28.0% and 36.2% of participants, respectively. Compared with no sleep disturbance, lifetime insomnia and hypersomnia were associated at treatment entry with unique substance use patterns and a higher frequency of any substance use (p < .001). All types of sleep disturbance were associated with higher rates of cocaine use at 12-month post-entry (ORs: 1.30–1.57). Conclusions There is evidence of an adverse association between substance use and sleep disturbance including higher frequency of all substance use before substance abuse treatment and higher rates of cocaine use after a treatment episode. PMID:28127809

  14. Loneliness and its impact on quality of life in Chinese heroin-dependent patients receiving methadone maintenance treatment.

    PubMed

    Yang, Ying-Jia; Xu, Yan-Min; Chen, Wen-Cai; Zhu, Jun-Hong; Lu, Jin; Zhong, Bao-Liang

    2017-10-03

    To date, no studies have examined loneliness in Chinese patients with substance use disorders. This study determined the prevalence and socio-demographic and clinical correlates of loneliness and its impact on quality of life (QOL) in Chinese heroin-dependent patients (HDPs) receiving methadone maintenance treatment (MMT). A total of 603 HDPs were consecutively recruited from three city-owned MMT clinics in Wuhan, China, and administered with a standardized questionnaire to collect socio-demographic and clinical data. Loneliness and QOL were assessed with a single-item self-report question and World Health Organization QOL Scale Brief Version, respectively. As high as 55.9% Chinese HDPs of MMT clinics endorsed loneliness. Multiple logistic regression found that non-married status, unemployment, religious beliefs, a history of injecting heroin, poor interpersonal relationship, and more depressive symptoms were significant contributors to loneliness. Lonely HDPs had significantly poorer physical and psychological QOL than not lonely HDPs. After controlling for the potential confounding effects of socio-demographic and clinical factors with analysis of covariance, these group-differences in physical (F = 127.169, P < 0.001) and psychological (F = 85.004, P < 0.001) QOL remained statistically significant. Loneliness is prevalent in HDPs receiving MMT and independently associated with poor QOL. To address this serious issue, psychosocial services, including the identification of psychosocial problems, expanded social supports that focus on promoting mental wellbeing, and, when necessary, psychiatric assessment and treatment, should be routinely provided in Chinese MMT settings.

  15. Loneliness and its impact on quality of life in Chinese heroin-dependent patients receiving methadone maintenance treatment

    PubMed Central

    Yang, Ying-Jia; Xu, Yan-Min; Chen, Wen-Cai; Zhu, Jun-Hong; Lu, Jin; Zhong, Bao-Liang

    2017-01-01

    To date, no studies have examined loneliness in Chinese patients with substance use disorders. This study determined the prevalence and socio-demographic and clinical correlates of loneliness and its impact on quality of life (QOL) in Chinese heroin-dependent patients (HDPs) receiving methadone maintenance treatment (MMT). A total of 603 HDPs were consecutively recruited from three city-owned MMT clinics in Wuhan, China, and administered with a standardized questionnaire to collect socio-demographic and clinical data. Loneliness and QOL were assessed with a single-item self-report question and World Health Organization QOL Scale Brief Version, respectively. As high as 55.9% Chinese HDPs of MMT clinics endorsed loneliness. Multiple logistic regression found that non-married status, unemployment, religious beliefs, a history of injecting heroin, poor interpersonal relationship, and more depressive symptoms were significant contributors to loneliness. Lonely HDPs had significantly poorer physical and psychological QOL than not lonely HDPs. After controlling for the potential confounding effects of socio-demographic and clinical factors with analysis of covariance, these group-differences in physical (F = 127.169, P < 0.001) and psychological (F = 85.004, P < 0.001) QOL remained statistically significant. Loneliness is prevalent in HDPs receiving MMT and independently associated with poor QOL. To address this serious issue, psychosocial services, including the identification of psychosocial problems, expanded social supports that focus on promoting mental wellbeing, and, when necessary, psychiatric assessment and treatment, should be routinely provided in Chinese MMT settings. PMID:29108361

  16. Effect of computerized cognitive behavioral therapy on acquisition of coping skills among cocaine-dependent individuals enrolled in methadone maintenance.

    PubMed

    Kiluk, Brian D; DeVito, Elise E; Buck, Matthew B; Hunkele, Karen; Nich, Charla; Carroll, Kathleen M

    2017-11-01

    The acquisition of coping skills has long been considered one of the putative mechanisms of cognitive behavioral therapy (CBT) for substance use disorders, yet consistent statistical support is lacking. This study sought to replicate and extend prior findings regarding the quality of coping skills as a mediator of abstinence outcomes from a computerized CBT program for substance users. Participants were methadone-maintained, cocaine dependent individuals enrolled in a clinical trial evaluating the efficacy of computer-based training for CBT ('CBT4CBT') as an add-on to treatment as usual (TAU+CBT4CBT) compared to TAU only. A subsample (N=71) completed a role play assessment to measure coping skills, the Drug Risk Response Test (DRRT), which was administered before, during (week 4), and after the 8-week treatment period. Participants' verbal responses to various high-risk situations for cocaine use were recorded and independent evaluators rated the quality of the coping responses. Results of repeated measures analyses revealed a main effect of time for the quality of overall responses [F(1, 141.26)=4.29, p<0.01], indicating improvement in the quality of coping skills across groups, yet no differential effect of treatment. Despite the significant association between coping responses and abstinence outcomes, analyses did not support the quality of coping skills as a mediator of treatment effects. However, among the high-risk situations wherein individuals provided lower quality responses at baseline, those assigned to TAU+CBT4CBT showed greater improvement compared to those assigned to TAU only [F(1, 697.65)=6.47, p=0.01]. This study failed to replicate the quality of coping skills as a mediator of CBT4CBT's effect on reducing drug use previously shown in a mixed outpatient substance use sample. However, in this methadone maintained sample, those with poorer quality skills in response to certain high-risk situations at baseline appeared to improve their coping

  17. Sustained Release d-Amphetamine Reduces Cocaine but not ‘Speedball'-Seeking in Buprenorphine-Maintained Volunteers: A Test of Dual-Agonist Pharmacotherapy for Cocaine/Heroin Polydrug Abusers

    PubMed Central

    Greenwald, Mark K; Lundahl, Leslie H; Steinmiller, Caren L

    2010-01-01

    The aim of this study was to determine whether oral sustained release d-amphetamine (SR-AMP) reduces cocaine and opioid/cocaine combination (‘speedball'-like) seeking in volunteers with current opioid dependence and cocaine dependence. Following outpatient buprenorphine (BUP) 8 mg/day stabilization without SR-AMP, eight participants completed a 3-week in-patient study with continued BUP 8 mg/day maintenance and double-blind ascending SR-AMP weekly doses of 0, 30, and 60 mg/day, respectively. After 3 days (Saturday–Monday) stabilization at each SR-AMP weekly dose (0, 15, or 30 mg administered at 0700 and 1225 each day), on Tuesday–Friday mornings (0900–1200 hours), participants sampled four drug combinations in randomized, counterbalanced order under double-blind, double-dummy (intranasal cocaine and intramuscular hydromorphone) conditions: cocaine (COC 100 mg+saline); hydromorphone (COC 4 mg+HYD 24 mg); ‘speedball' (COC 100 mg+HYD 24 mg); and placebo (COC 4 mg+saline). Subjective and physiological effects of these drug combinations were measured. From 1230 to 1530 hours, participants could respond on a choice, 12-trial progressive ratio schedule to earn drug units (1/12th of total morning dose) or money units (US$2). SR-AMP significantly reduced COC, but not HYD or speedball, choices and breakpoints. SR-AMP also significantly reduced COC subjective (eg, abuse-related) effects and did not potentiate COC-induced cardiovascular responses. This study shows the ability of SR-AMP to attenuate COC self-administration, as well as its selectivity, in cocaine/heroin polydrug abusers. Further research is warranted to ascertain whether SR-AMP combined with BUP could be a useful dual-agonist pharmacotherapy. PMID:20881947

  18. Loss of treatment benefit when heroin-assisted treatment is stopped after 12 months.

    PubMed

    Demaret, Isabelle; Quertemont, Etienne; Litran, Géraldine; Magoga, Cécile; Deblire, Clémence; Dubois, Nathalie; Charlier, Corinne; Lemaitre, André; Ansseau, Marc

    2016-10-01

    In 2013, during a recent heroin-assisted treatment trial, participants in heroin-assisted treatment (HAT) decreased significantly more their street heroin use than participants in oral methadone treatment. After the trial, HAT was discontinued. To examine whether the treatment benefits were sustained three months after the trial, the use of street heroin by the participants was analyzed in a follow-up study. At the follow-up assessment, street heroin use increased in the experimental group. The two groups no longer showed a significant difference (p=0.55) in the level of street heroin use. A predetermined and forced end of HAT was followed by a significant increase in the level of street level use. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Emergence of methadone as a street drug in St. Petersburg, Russia.

    PubMed

    Heimer, Robert; Lyubimova, Aleksandra; Barbour, Russell; Levina, Olga S

    2016-01-01

    The syndemic of opioid addiction, HIV, hepatitis, tuberculosis, imprisonment, and overdose in Russia has been worsened by the illegality of opioid substitution therapy. As part of on-going serial studies, we sought to explore the influence of opioid availability on aspects of the syndemic as it has affected the city of St. Petersburg. We employed a sequential approach in which quantitative data collection and statistical analysis were followed by a qualitative phase. Quantitative data were obtained in 2013-2014 from a respondent-driven sample (RDS) of people who inject drugs (PWID). Individuals recruited by RDS were tested for antibodies to HIV and interviewed about drug use and injection practices, sociodemographics, health status, and access to medical care. Subsequently, we collected in-depth qualitative data on methadone use, knowledge, and market availability from PWID recruited at nine different locations within St. Petersburg. Analysis of interview data from the sample revealed the percentage of PWID injecting methadone in the 30 days prior to interview increased from 3.6% in 2010 to 53.3% in 2012-2013. Injection of only methadone, as compared to injecting only heroin or both drugs, was associated with less frequent injection and reduced HIV-related injected risk, especially a lower rate of injecting with a previously used syringe. In-depth questioning of methadone injectors corroborated the finding from serial quantitative surveys of PWID that methadone's black market availability is a recent phenomenon. Spatial analysis revealed widespread methadone availability but no concentration in any specific districts of the city. Despite the prohibition of substitution therapy and demonization of methadone, the drug has emerged to rival heroin as the most commonly available opioid in St. Petersburg. Ironically, its use is associated with reduced injection-related HIV risk even when its use is illegal. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Sexually transmitted infections among pregnant heroin or cocaine addicted women in treatment: The significance of psychiatric comorbidity and sex trade

    PubMed Central

    Cavanaugh, Courtenay E.; Hedden, Sarra L.; Latimer, William W.

    2010-01-01

    Summary Psychiatric comorbidity and sex trade were tested as correlates of sexually transmitted infections (STIs) among 76 pregnant heroin or cocaine dependent women. Participants were recruited from a drug treatment program and attended a clinician-administered assessment including the Structured Clinical Interview for DSM-IV (SCID-IV-TR) and self report questionnaires about lifetime histories of sex trade and STIs (i.e. gonorrhea, syphilis, chlamydia, herpes, genital warts, or trichomonas). Lifetime and six month rates of STIs were 53.9% and 18.4% respectively. The majority of women also had lifetime histories of psychiatric comorbidity (61.8%) and/or sex trade (60.5%). Participants with psychiatric comorbidity (AOR 3.9; 95% CI 1.3–11.6) and/or sex trade (AOR 3.2; 95% CI 1.1–9.5) were more likely to report STIs during their lifetime compared to those without such histories while controlling for age, education, and race/ethnicity. Results suggest that as many as one-in-five pregnant heroin or cocaine dependent women in treatment have one or more STIs that are concurrent with their pregnancy and may contribute to risk for contracting HIV and pregnancy complications; psychiatric comorbidity and/or sex trade were associated with greater STI risk. Findings underscore the importance of identifying and addressing comorbid psychiatric disorders and sex trade behavior in this population. PMID:20090001

  1. A Randomized Clinical Trial of Methadone Maintenance for Prisoners: Prediction of Treatment Entry and Completion in Prison

    PubMed Central

    GORDON, MICHAEL S.; KINLOCK, TIMOTHY W.; COUVILLION, KATHRYN A.; SCHWARTZ, ROBERT P.; O’GRADY, KEVIN

    2014-01-01

    The present report is an intent-to-treat analysis involving secondary data drawn from the first randomized clinical trial of prison-initiated methadone in the United States. This study examined predictors of treatment entry and completion in prison. A sample of 211 adult male prerelease inmates with preincarceration heroin dependence were randomly assigned to one of three treatment conditions: counseling only (counseling in prison; n= 70); counseling plus transfer (counseling in prison with transfer to methadone maintenance treatment upon release; n= 70); and counseling plus methadone (methadone maintenance in prison, continued in a community-based methadone maintenance program upon release; n= 71). Entered prison treatment (p <. 01), and completed prison treatment (p< .001) were significantly predicted by the set of 10 explanatory variables and favored the treatment conditions receiving methadone. The present results indicate that individuals who are older in age and have longer prison sentences may have better outcomes than younger individuals with shorter sentences, meaning they are more likely to enter and complete prison-based treatment. Furthermore, implications for the treatment of prisoners with prior heroin dependence and for conducting clinical trials may indicate the importance of examining individual characteristics and the possibility of the examination of patient preference. PMID:25392605

  2. A Randomized Clinical Trial of Methadone Maintenance for Prisoners: Prediction of Treatment Entry and Completion in Prison.

    PubMed

    Gordon, Michael S; Kinlock, Timothy W; Couvillion, Kathryn A; Schwartz, Robert P; O'Grady, Kevin

    2012-05-01

    The present report is an intent-to-treat analysis involving secondary data drawn from the first randomized clinical trial of prison-initiated methadone in the United States. This study examined predictors of treatment entry and completion in prison. A sample of 211 adult male prerelease inmates with preincarceration heroin dependence were randomly assigned to one of three treatment conditions: counseling only (counseling in prison; n= 70); counseling plus transfer (counseling in prison with transfer to methadone maintenance treatment upon release; n= 70); and counseling plus methadone (methadone maintenance in prison, continued in a community-based methadone maintenance program upon release; n= 71). Entered prison treatment (p <. 01), and completed prison treatment (p< .001) were significantly predicted by the set of 10 explanatory variables and favored the treatment conditions receiving methadone. The present results indicate that individuals who are older in age and have longer prison sentences may have better outcomes than younger individuals with shorter sentences, meaning they are more likely to enter and complete prison-based treatment. Furthermore, implications for the treatment of prisoners with prior heroin dependence and for conducting clinical trials may indicate the importance of examining individual characteristics and the possibility of the examination of patient preference.

  3. Comparison of buprenorphine and methadone effects on opiate self-administration in primates.

    PubMed

    Mello, N K; Bree, M P; Mendelson, J H

    1983-05-01

    The effects of ascending and descending doses of buprenorphine (0.014-0.789 mg/kg/day) and methadone (0.179-11.86 mg/kg/day) on opiate and food intake were studied in Macaque monkeys over 195 to 245 days. Food (1-g banana pellets) and i.v. drug self-administration (heroin 0.01 or 0.02 mg/kg/injection or Dilaudid 0.02 mg/kg/injection) were maintained on a second-order schedule of reinforcement [FR 4 (VR 16:S)]. Buprenorphine (0.282-0.789 mg/kg/day) produced a significant suppression of opiate self-administration at 2.5 to 7 times the dose shown to be effective in human opiate abusers (P less than .05-.001). Methadone (1.43-11.86 mg/kg/day) did not suppress opiate self-administration in four of five monkeys across a dose range equivalent to 100 to 800 mg/day in man. The distribution of opiate self-administration across drug sessions did not account for the absence of methadone suppression as monkeys took 43% of the total daily opiate injections during the first daily drug session, 2.5 hr after methadone administration. During buprenorphine maintenance, food intake remained stable or increased significantly above base-line levels. Methadone maintenance was associated with significant decrements in food intake in four of five monkeys. Buprenorphine appeared to be significantly more effective in suppressing opiate self-administration than methadone across the dose range studied. Buprenorphine had none of the toxic side effects (seizures, respiratory depression, profound psychomotor retardation) associated with high doses of methadone over 6 to 8 months of daily drug treatment. These data are consistent with clinical studies of buprenorphine effects on heroin self-administration in human opiate addicts.

  4. Neuronal representation of individual heroin choices in the orbitofrontal cortex.

    PubMed

    Guillem, Karine; Brenot, Viridiana; Durand, Audrey; Ahmed, Serge H

    2018-05-01

    Drug addiction is a harmful preference for drug use over and at the expense of other non-drug-related activities. We previously identified in the rat orbitofrontal cortex (OFC) a mechanism that influences individual preferences between cocaine use and an alternative action rewarded by a non-drug reward (i.e. sweet water). Here, we sought to test the generality of this mechanism to a different addictive drug, heroin. OFC neuronal activity was recorded while rats responded for heroin or the alternative non-drug reward separately or while they chose between the two. First, we found that heroin-rewarded and sweet water-rewarded actions were encoded by two non-overlapping OFC neuronal populations and that the relative size of the heroin population represented individual drug choices. Second, OFC neurons encoding the preferred action-which was the non-drug action in the large majority of individuals-progressively fired more than non-preferred action-coding neurons 1 second after the onset of choice trials and around 1 second before the preferred action was actually chosen, suggesting a pre-choice neuronal competition for action selection. Together with a previous study on cocaine choice, the present study on heroin choice reveals important commonalities in how OFC neurons encode individual drug choices and preferences across different classes of drugs. It also reveals some drug-specific differences in OFC encoding activity. Notably, the proportion of neurons that non-selectively encode both the drug and the non-drug reward was higher when the drug was heroin (present study) than when it was cocaine (previous study). We will discuss the potential functional significance of these commonalities and differences in OFC neuronal activity across different drugs for understanding drug choice. © 2017 Society for the Study of Addiction.

  5. Prescription naloxone: a novel approach to heroin overdose prevention.

    PubMed

    Sporer, Karl A; Kral, Alex H

    2007-02-01

    The mortality and morbidity from heroin overdose have increased in the United States and internationally in the last decade. The lipid solubility allows the rapid deposition of heroin and its metabolites into the central nervous system and accounts for the "rush" experienced by users and for the toxicity. Risk factors for fatal and nonfatal heroin overdoses such as recent abstinence, decreased opiate tolerance, and polydrug use have been identified. Opiate substitution treatment such as methadone or buprenorphine is the only proven method of heroin overdose prevention. Death from a heroin overdose most commonly occurs 1 to 3 hours after injection at home in the company of other people. Numerous communities have taken advantage of this opportunity for treatment by implementing overdose prevention education to active heroin users, as well as prescribing naloxone for home use. Naloxone is a specific opiate antagonist without agonist properties or potential for abuse. It is inexpensive and nonscheduled and readily reverses the respiratory depression and sedation caused by heroin, as well as causing transient withdrawal symptoms. Program implementation considerations, legal ramifications, and research needs for prescription naloxone are discussed.

  6. Emergence of Methadone as a Street Drug in St. Petersburg, Russia

    PubMed Central

    Heimer, Robert; Lyubimova, Aleksandra; Barbour, Russell; Levina, Olga S.

    2015-01-01

    Background The syndemic of opioid addiction, HIV, hepatitis, tuberculosis, imprisonment, and overdose in Russia has been worsened by the illegality of opioid substitution therapy. As part of on-going serial studies, we sought to explore the influence of opioid availability on aspects of the syndemic as it has affected the city of St. Petersburg. Methods We employed a sequential approach in which quantitative data collection and statistical analysis were followed by a qualitative phase. Quantitative data were obtained from a respondent-driven sample (RDS) of people who inject drugs (PWID) obtained in 2012–13. Individuals recruited by RDS were tested for antibodies to HIV and interviewed about drug use and injection practices, sociodemographics, health status, and access to medical care. Subsequently, we collected in-depth qualitative data on methadone use, knowledge, and market availability from PWID recruited at nine different locations within St. Petersburg. Results Analysis of interview data from the sample revealed he percentage of PWID injecting methadone in the 30 days prior to interview increased from 3.6% in 2010 to 53.3% in 2012–13. Injection of only methadone, as compared to injecting only heroin or both drugs, was associated with less frequent injection and reduced HIV-related injected risk, especially a lower rate of injecting with a previously used syringe. In-depth questioning of methadone injectors corroborated the finding from serial quantitative surveys of PWID that methadone’s black market availability is a recent phenomenon. Spatial analysis revealed widespread methadone availability but no concentration in any specific districts of the city. Conclusion Despite the prohibition of substitution therapy and demonization of methadone, the drug has emerged to rival heroin as the most commonly available opioid in St. Petersburg. Ironically, its use is associated with reduced injection-related HIV risk even when its use is illegal. PMID:26573380

  7. Differences in Mortality among Heroin, Cocaine, and Methamphetamine Users: A Hierarchical Bayesian Approach

    PubMed Central

    Liang, Li-Jung; Huang, David; Brecht, Mary-Lynn; Hser, Yih-ing

    2010-01-01

    Studies examining differences in mortality among long-term drug users have been limited. In this paper, we introduce a Bayesian framework that jointly models survival data using a Weibull proportional hazard model with frailty, and substance and alcohol data using mixed-effects models, to examine differences in mortality among heroin, cocaine, and methamphetamine users from five long-term follow-up studies. The traditional approach to analyzing combined survival data from numerous studies assumes that the studies are homogeneous, thus the estimates may be biased due to unobserved heterogeneity among studies. Our approach allows us to structurally combine the data from different studies while accounting for correlation among subjects within each study. Markov chain Monte Carlo facilitates the implementation of Bayesian analyses. Despite the complexity of the model, our approach is relatively straightforward to implement using WinBUGS. We demonstrate our joint modeling approach to the combined data and discuss the results from both approaches. PMID:21052518

  8. Maintenance treatment for opioid dependence with slow-release oral morphine: a randomized cross-over, non-inferiority study versus methadone

    PubMed Central

    Beck, Thilo; Haasen, Christian; Verthein, Uwe; Walcher, Stephan; Schuler, Christoph; Backmund, Markus; Ruckes, Christian; Reimer, Jens

    2014-01-01

    Aims To compare the efficacy of slow-release oral morphine (SROM) and methadone as maintenance medication for opioid dependence in patients previously treated with methadone. Design Prospective, multiple-dose, open label, randomized, non-inferiority, cross-over study over two 11-week periods. Methadone treatment was switched to SROM with flexible dosing and vice versa according to period and sequence of treatment. Setting Fourteen out-patient addiction treatment centres in Switzerland and Germany. Participants Adults with opioid dependence in methadone maintenance programmes (dose ≥50 mg/day) for ≥26 weeks. Measurements The efficacy end-point was the proportion of heroin-positive urine samples per patient and period of treatment. Each week, two urine samples were collected, randomly selected and analysed for 6-monoacetyl-morphine and 6-acetylcodeine. Non-inferiority was concluded if the two-sided 95% confidence interval (CI) in the difference of proportions of positive urine samples was below the predefined boundary of 10%. Findings One hundred and fifty-seven patients fulfilled criteria to form the per protocol population. The proportion of heroin-positive urine samples under SROM treatment (0.20) was non-inferior to the proportion under methadone treatment (0.15) (least-squares mean difference 0.05; 95% CI = 0.02, 0.08; P > 0.01). The 95% CI fell within the 10% non-inferiority margin, confirming the non-inferiority of SROM to methadone. A dose-dependent effect was shown for SROM (i.e. decreasing proportions of heroin-positive urine samples with increasing SROM doses). Retention in treatment showed no significant differences between treatments (period 1/period 2: SROM: 88.7%/82.1%, methadone: 91.1%/88.0%; period 1: P = 0.50, period 2: P = 0.19). Overall, safety outcomes were similar between the two groups. Conclusions Slow-release oral morphine appears to be at least as effective as methadone in treating people with opioid use disorder. PMID:24304412

  9. Modeling the structure and operation of drug supply chains: The case of cocaine and heroin in Italy and Slovenia.

    PubMed

    Caulkins, Jonathan P; Disley, Emma; Tzvetkova, Marina; Pardal, Mafalda; Shah, Hemali; Zhang, Xiaoke

    2016-05-01

    Multiple layers of dealers connect international drug traffickers to users. The fundamental activity of these dealers is buying from higher-level dealers and re-selling in smaller quantities at the next lower market level. Each instance of this can be viewed as completing a drug dealing "cycle". This paper introduces an approach for combining isolated accounts of such cycles into a coherent model of the structure, span, and profitability of the various layers of the domestic supply chain for illegal drugs. The approach is illustrated by synthesizing data from interviews with 116 incarcerated dealers to elucidate the structure and operation of distribution networks for cocaine and heroin in Italy and Slovenia. Inmates' descriptions of cycles in the Italian cocaine market suggest fairly orderly networks, with reasonably well-defined market levels. The Italian heroin market appears to have more "level-jumpers" who skip a market level by making a larger number of sales per cycle, with each sale being of a considerably smaller weight. Slovenian data are sparser, but broadly consistent. Incorporating prices allows calculation of how much of the revenue from retail sales is retained by dealers at each market level. In the Italian cocaine market, both retail sellers and the international supply chain outside of Italy each appear to receive about 30-40% of what users spend, with the remaining 30% going to higher-level dealers operating in Italy (roughly 10% to those at the multi-kilo level and 20% to lower level wholesale dealers). Factoring in cycle frequencies permits rough estimation of the number of organizations at each market level per billion euros in retail sales, and of annual net revenues for organizations at each level. These analyses provide an approach to gaining insight into the structure and operation of the supply chain for illegal drugs. They also illustrate the value of two new graphical tools for describing illicit drug supply chains and hint at possible

  10. Use of Preclinical Drug vs. Food Choice Procedures to Evaluate Candidate Medications for Cocaine Addiction.

    PubMed

    Banks, Matthew L; Hutsell, Blake A; Schwienteck, Kathryn L; Negus, S Stevens

    2015-06-01

    Drug addiction is a disease that manifests as an inappropriate allocation of behavior towards the procurement and use of the abused substance and away from other behaviors that produce more adaptive reinforcers (e.g. exercise, work, family and social relationships). The goal of treating drug addiction is not only to decrease drug-maintained behaviors, but also to promote a reallocation of behavior towards alternative, nondrug reinforcers. Experimental procedures that offer concurrent access to both a drug reinforcer and an alternative, nondrug reinforcer provide a research tool for assessment of medication effects on drug choice and behavioral allocation. Choice procedures are currently the standard in human laboratory research on medications development. Preclinical choice procedures have been utilized in biomedical research since the early 1940's, and during the last 10-15 years, their use for evaluation of medications to treat drug addiction has increased. We propose here that parallel use of choice procedures in preclinical and clinical studies will facilitate translational research on development of medications to treat cocaine addiction. In support of this proposition, a review of the literature suggests strong concordance between preclinical effectiveness of candidate medications to modify cocaine choice in nonhuman primates and rodents and clinical effectiveness of these medications to modify either cocaine choice in human laboratory studies or metrics of cocaine abuse in patients with cocaine use disorder. The strongest evidence for medication effectiveness in preclinical choice studies has been obtained with maintenance on the monoamine releaser d -amphetamine, a candidate agonist medication for cocaine use analogous to use of methadone to treat heroin abuse or nicotine formulations to treat tobacco dependence.

  11. Use of Preclinical Drug vs. Food Choice Procedures to Evaluate Candidate Medications for Cocaine Addiction

    PubMed Central

    Banks, Matthew L; Hutsell, Blake A; Schwienteck, Kathryn L; Negus, S. Stevens

    2015-01-01

    Opinion Statement Drug addiction is a disease that manifests as an inappropriate allocation of behavior towards the procurement and use of the abused substance and away from other behaviors that produce more adaptive reinforcers (e.g. exercise, work, family and social relationships). The goal of treating drug addiction is not only to decrease drug-maintained behaviors, but also to promote a reallocation of behavior towards alternative, nondrug reinforcers. Experimental procedures that offer concurrent access to both a drug reinforcer and an alternative, nondrug reinforcer provide a research tool for assessment of medication effects on drug choice and behavioral allocation. Choice procedures are currently the standard in human laboratory research on medications development. Preclinical choice procedures have been utilized in biomedical research since the early 1940’s, and during the last 10–15 years, their use for evaluation of medications to treat drug addiction has increased. We propose here that parallel use of choice procedures in preclinical and clinical studies will facilitate translational research on development of medications to treat cocaine addiction. In support of this proposition, a review of the literature suggests strong concordance between preclinical effectiveness of candidate medications to modify cocaine choice in nonhuman primates and rodents and clinical effectiveness of these medications to modify either cocaine choice in human laboratory studies or metrics of cocaine abuse in patients with cocaine use disorder. The strongest evidence for medication effectiveness in preclinical choice studies has been obtained with maintenance on the monoamine releaser d-amphetamine, a candidate agonist medication for cocaine use analogous to use of methadone to treat heroin abuse or nicotine formulations to treat tobacco dependence. PMID:26009706

  12. Do painkillers serve as "hillbilly heroin" for rural adults with high levels of psychosocial stress?

    PubMed

    Black, Pamela; Hendy, Helen M

    2017-07-05

    Nonmedical use of painkillers has increased in recent years, with some authors suggesting that painkillers serve as "hillbilly heroin": a drug chosen by rural adults to cope with psychosocial stresses in their lives. The present study compared rural and urban adults for their reported use of 5 drugs during the past year (painkillers, marijuana, cocaine, methamphetamine, heroin) and for associations between these 5 drugs and their reported psychosocial stressors. This study conducted secondary analyses of anonymous survey data provided by the 2014 National Survey on Drug Use and Health with responses from 8,699 rural and 18,481 urban adults. The survey included demographics (gender, age, race, education, marital status, family income), reports of whether participants had used each of 5 illicit drugs during the past year, and measures of psychological distress and social functioning problems. Controlling for demographics, rural adults showed no greater prevalence of painkiller use than urban adults, but rural adults were more likely than urban adults to use methamphetamine and less likely to use marijuana, cocaine, and heroin. Controlling for demographics, rural adults showed no associations between psychological or social stressors and the use of painkillers, but such stressors were significantly associated with the use of marijuana, methamphetamine, and heroin. Urban adults showed significant associations of psychological and social stressors with the use of painkillers, as well as with the use of marijuana, cocaine, and heroin. Results suggest that painkillers are unlikely to serve as "hillbilly heroin" for rural adults, but they may serve as "big-city heroin" for urban adults.

  13. Overcoming obstacles to implementing methadone maintenance therapy for prisoners: Implications for policy and practice

    PubMed Central

    McKenzie, Michelle; Nunn, Amy; Zaller, Nickolas D.; Bazazi, Alexander R.; Rich, Josiah D.

    2010-01-01

    More than 2.4 million people are currently incarcerated in the United States, many as a result of drug-related offenses. In addition, more than 200,000 active heroin addicts pass through the correctional system annually. New evidence suggests that both providing prisoners with referrals for community-based methadone programs and providing methadone prior to release reduces recidivism and adverse health and social consequences associated with drug use. This article reports the programmatic challenges associated with initiating methadone treatment in the Rhode Island correctional system. Significant obstacles to implementing methadone treatment include: stigma associated with pharmacological treatment, misconceptions regarding the nature of opioid addiction, logistics of control and storage of methadone, increased work load for nursing staff, and general safety and control concerns. The authors discuss strategies to address these barriers and conclude that providing methadone prior to inmate release is a feasible intervention with the potential to mitigate drug-related health and social harms. PMID:19736902

  14. Retrospective case series analysis of characteristics and trends in unintentional pharmaceutical drug poisoning by methadone, opioid analgesics, antidepressants and benzodiazepines in Clark County, NV 2009-13.

    PubMed

    Bruno, Tamara; Pharr, Jennifer R

    2017-06-01

    Poisoning has become the leading cause of injury death in the USA-with opioid analgesic involved in more fatal poisonings than any other drug, including cocaine and heroin. The epidemic of prescription drug poisonings is a public health concern. This study aimed to define potential high-risk groups for unintentional prescription drug poisoning by methadone, opioid analgesics, antidepressants or benzodiazepines. A hospital-based retrospective case series analysis of admissions related to prescription drug poisonings associated with methadone, opioid analgesics, antidepressants or benzodiazepines for hospitals in Clark County, Nevada between 2009 and 2013 was employed. There were 7414 admissions with a primary diagnosis of an unintentional poisoning due to methadone, opioid analgesics, antidepressants or benzodiazepines. Women had the highest rate of admissions particularly in the 45-54 age group. Higher rates of admissions were also found among non-Hispanic whites, single and uninsured populations. There were concerning increases in admissions among 65+ and Native American/Alaskan Native subgroups in 2013. Benzodiazepines and opioid analgesics were the most prevalent drug categories for prescription drug poisoning admissions. Public health professionals can utilize hospital data to identify populations at risk and in need of targeted interventions. © The Author 2016. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  15. Demand Curves for Hypothetical Cocaine in Cocaine-Dependent Individuals

    PubMed Central

    Bruner, Natalie R.; Johnson, Matthew W.

    2013-01-01

    Rationale Drug purchasing tasks have been successfully used to examine demand for hypothetical consumption of abused drugs including heroin, nicotine, and alcohol. In these tasks drug users make hypothetical choices whether to buy drugs, and if so, at what quantity, at various potential prices. These tasks allow for behavioral economic assessment of that drug's intensity of demand (preferred level of consumption at extremely low prices) and demand elasticity (sensitivity of consumption to price), among other metrics. However, a purchasing task for cocaine in cocaine-dependent individuals has not been investigated. Objectives This study examined a novel Cocaine Purchasing Task and the relation between resulting demand metrics and self-reported cocaine use data. Methods Participants completed a questionnaire assessing hypothetical purchases of cocaine units at prices ranging from $0.01 to $1,000. Demand curves were generated from responses on the Cocaine Purchasing Task. Correlations compared metrics from the demand curve to measures of real-world cocaine use. Results Group and individual data were well modeled by a demand curve function. The validity of the Cocaine Purchasing Task was supported by a significant correlation between the demand curve metrics of demand intensity and Omax (determined from Cocaine Purchasing Task data) and self-reported measures of cocaine use. Partial correlations revealed that after controlling for demand intensity, demand elasticity and the related measure, Pmax, were significantly correlated with real-world cocaine use. Conclusions Results indicate that the Cocaine Purchasing Task produces orderly demand curve data, and that these data relate to real-world measures of cocaine use. PMID:24217899

  16. Demand curves for hypothetical cocaine in cocaine-dependent individuals.

    PubMed

    Bruner, Natalie R; Johnson, Matthew W

    2014-03-01

    Drug purchasing tasks have been successfully used to examine demand for hypothetical consumption of abused drugs including heroin, nicotine, and alcohol. In these tasks, drug users make hypothetical choices whether to buy drugs, and if so, at what quantity, at various potential prices. These tasks allow for behavioral economic assessment of that drug's intensity of demand (preferred level of consumption at extremely low prices) and demand elasticity (sensitivity of consumption to price), among other metrics. However, a purchasing task for cocaine in cocaine-dependent individuals has not been investigated. This study examined a novel Cocaine Purchasing Task and the relation between resulting demand metrics and self-reported cocaine use data. Participants completed a questionnaire assessing hypothetical purchases of cocaine units at prices ranging from $0.01 to $1,000. Demand curves were generated from responses on the Cocaine Purchasing Task. Correlations compared metrics from the demand curve to measures of real-world cocaine use. Group and individual data were well modeled by a demand curve function. The validity of the Cocaine Purchasing Task was supported by a significant correlation between the demand curve metrics of demand intensity and O max (determined from Cocaine Purchasing Task data) and self-reported measures of cocaine use. Partial correlations revealed that after controlling for demand intensity, demand elasticity and the related measure, P max, were significantly correlated with real-world cocaine use. Results indicate that the Cocaine Purchasing Task produces orderly demand curve data, and that these data relate to real-world measures of cocaine use.

  17. Opponent process properties of self-administered cocaine.

    PubMed

    Ettenberg, Aaron

    2004-01-01

    Over the past decade, data collected in our laboratory have demonstrated that self-administered cocaine produces Opponent-Process-like behavioral effects. Animals running a straight alley once each day for IV cocaine develop over trials an approach-avoidance conflict about re-entering the goal box. This conflict behavior is characterized by a stop in forward locomotion (usually at the very mouth of the goal box) followed by a turn and 'retreat' back toward the goal box. The results of a series of studies conducted over the past decade collectively suggest that the behavioral ambivalence exemplified by rats running the alley for IV cocaine stems from concurrent and opponent positive (rewarding) and negative (anxiogenic) properties of the drug--both of which are associated with the goal box. These opponent properties of cocaine have been shown to result from temporally distinct affective states. Using a conditioned place preference test, we have been able to demonstrate that while the initial immediate effects of IV cocaine are reinforcing, the state present 15 min post-injection is aversive. In our most recent work, the co-administration of IV cocaine with either oral ethanol or IV heroin was found to greatly diminish the development and occurrence of retreat behaviors in the runway. It may therefore be that the high incidence of co-abuse of cocaine with either ethanol or heroin, stems from the users' motivation to alleviate some of the negative side effects of cocaine. It would seem then that the Opponent Process Theory has provided a useful conceptual framework for the study of the behavioral consequences of self-administered cocaine including the notion that both positive and negative reinforcement mechanisms are involved in the development and maintenance of cocaine abuse.

  18. From heroin to methadone--social role changes and reinforcement differentials in relation to outcome on methadone. Part I. The study of reinforcement differentials.

    PubMed

    Cheek, F E; Holstein, C N; Fullam, F A; Arana, G; Tomarchio, T P; Mandell, S

    1976-01-01

    This study examines the relevance of reinforcements available to the addict in five critical stages of his career to his success on methadone maintenance. In-depth focused interviews were held with 30 addicts who had completed a program of methadone induction and who were characterized by social worker's evaluations as Successful, Marginally Adjusted, or Failures. The Successful group showed a higher initial negative reinforcement followed by higher positive reinforcement on methadone. The Moderately Successful group showed more negative reinforcement before treatment but continued to show negative reinforcements afterwards. The Failures were low on negative reinforcements earlier but negative reinforcements were high after treatment.

  19. [Use of methadone in the treatment of psychotic patients with heroin dependence].

    PubMed

    Walby, F A; Borg, P; Eikeseth, P H; Neegaard, E; Kjerpeseth, K; Bruvik, S; Waal, H

    2000-01-20

    Comorbidity of psychosis and substance abuse has gained increased attention for some time. However, pharmacological treatment for opioid dependence among psychotic patients is seldom described. We present the treatment of four opioid dependent psychotic patients with methadone and antipsychotic medication. Three of the four patients had initially a period of increased psychotic symptoms, but all four patients have shown marked improvement following the introduction of methadone. Compliance with treatment has increased, they have had enduring non-psychotic periods and a markedly reduced use of illegal substances. The results should obviously be interpreted with caution, given the small number of subjects. Further research is therefore important.

  20. Predictors of heroin relapse: Personality traits, impulsivity, COMT gene Val158met polymorphism in a 5-year prospective study in Shanghai, China.

    PubMed

    Su, Hang; Li, Zhibin; Du, Jiang; Jiang, Haifeng; Chen, Zhikang; Sun, Haiming; Zhao, Min

    2015-12-01

    Relapse is a typical feature of heroin addiction and rooted in genetic and psychological determinants. The aim of this study was to evaluate the effect of personality traits, impulsivity, and COMT gene polymorphism (rs4680) on relapse to heroin use during 5-year follow up. 564 heroin dependent patients were enrolled in compulsory drug rehabilitation center. 12 months prior to their release, personality traits were measured by BIS-11 (Barratt Impulsiveness Scale-11) and Temperament and Character Inventory (TCI). The COMT gene rs4680 polymorphism was genotyped using a DNA sequence detection system. The heroin use status was evaluated for 5 years after discharged. Among the 564 heroin-dependent patients, 500 were followed for 5 years after discharge and 53.0% (n = 265) were considered as relapsed to heroin use according to a strict monitor system. Univariate analysis showed that age, having ever been in methadone maintenance treatment (MMT), the total scores and non-planning scores of BIS-11, and the COMT rs4680 gene variants were different between relapse and abstinent groups. Logistic regression analysis showed higher BIS total score, having ever been in MMT and younger first heroin use age are the predictors of relapse to heroin use during 5 years follow-up, and the COMT rs4680 gene had an interaction with BIS scores. Our findings indicated that the impulsive personality traits, methadone use history, and onset age could predict relapse in heroin-dependent patients during 5 year's follow up. The COMT gene showed a moderational effect in part the relationship of impulsivity with heroin relapse. © 2015 Wiley Periodicals, Inc.

  1. A 5-year evaluation of a methadone medical maintenance program.

    PubMed

    Harris, Kenneth A; Arnsten, Julia H; Joseph, Herman; Hecht, Joe; Marion, Ira; Juliana, Patti; Gourevitch, Marc N

    2006-12-01

    Methadone medical maintenance (MMM) is a model for the treatment of opioid dependence in which a monthly supply of methadone is distributed in an office setting, in contrast to more highly regulated settings where daily observed dosing is the norm. We assessed patient characteristics and treatment outcomes of an MMM program initiated in the Bronx, New York, in 1999 by conducting a retrospective chart review. Participant characteristics were compared with those of patients enrolled in affiliated conventional methadone maintenance treatment programs. Patients had diverse ethnicities, occupations, educational backgrounds, and income levels. Urine toxicology testing detected illicit opiate and cocaine use in 0.8% and 0.4% of aggregate samples, respectively. The retention rate was 98%, which compares favorably with the four other MMM programs that have been reported in the medical literature. This study demonstrates that selected patients from a socioeconomically disadvantaged population remained clinically stable and engaged in treatment in a far less intensive setting than traditional methadone maintenance.

  2. A 5-year evaluation of a methadone medical maintenance program

    PubMed Central

    Harris, Kenneth A.; Arnsten, Julia H.; Joseph, Herman; Hecht, Joe; Marion, Ira; Juliana, Patti; Gourevitch, Marc N.

    2009-01-01

    Methadone medical maintenance (MMM) is a model for the treatment of opioid dependence in which a monthly supply of methadone is distributed in an office setting, in contrast to more highly regulated settings where daily observed dosing is the norm. We assessed patient characteristics and treatment outcomes of an MMM program initiated in the Bronx, New York, in 1999 by conducting a retrospective chart review. Participant characteristics were compared with those of patients enrolled in affiliated conventional methadone maintenance treatment programs. Patients had diverse ethnicities, occupations, educational backgrounds, and income levels. Urine toxicology testing detected illicit opiate and cocaine use in 0.8% and 0.4% of aggregate samples, respectively. The retention rate was 98%, which compares favorably with the four other MMM programs that have been reported in the medical literature. This study demonstrates that selected patients from a socioeconomically disadvantaged population remained clinically stable and engaged in treatment in a far less intensive setting than traditional methadone maintenance. PMID:17084798

  3. [Overdose of heroin and influencing factors in intravenous drug users in parts of Yunnan].

    PubMed

    Zhou, Y; Luo, W; Cao, X B; Zhang, B; Wu, Z Y

    2016-05-01

    To assess the prevalence of overdose of heroin and risk factors in intravenous drug users(IDUs)in Yunnan Province. During July-August of 2015, IDUs were recruited from four methadone maintenance treatment(MMT)clinics and two compulsory drug rehabilitation centers in Honghe and Dehong prefectures, Yunnan province. The information about IDUs ' demographic characteristics and drug use history, overdose of heroin in previous12 months and the latest overdose of heroin were collected through face to face questionnaire survey. The factors associated with overdose of heroin were evaluated with logistic regression models. Of the 340 IDUs surveyed, 85.3%(290/340)were males, the mean age was 37.7±8.7 years, 65.6%(223/340)were Han ethnicity, and 49.4%(167/338)were HIV positive, 22.6%(77/340)reported having used club-related drugs(such as ephedrine, methamphetamine, benzodiazepines and ketamine)in the previous 12 months. Of the 340 IDUs, 41.8%(142/340)had at least one overdose of heroin in their lifetime(median: 3 overdoses)and 15.6%(53/340)had at least one overdose of heroin(median : 1 overdose use)in previous 12 months. The mean age of the 53 IDUs was(36.7 ± 8.4)years, and 83.0%(44/53)of them were males, the average drug use history was(16.5 ± 7.6)years. Dosage increase(26.4%, 14/53)and multidrug use(28.3%, 15/53)were the main causes for overdose of heroin. Multiple logistic regression analysis indicated that methadone maintenance treatment during the past year(OR=0.534, 95%CI: 0.290-0.980)was independently associated with decreased risk of overdose of heroin, needle sharing in the past 6 months(OR=2.735, 95%CI: 1.383-5.407)and being forced to receive drug rehabilitation for less than one year(OR=2.881, 95% CI: 1.226-6.767)were independently associated with increased risk of overdose of heroin. Overdose of heroin is common among IDUs in Yunnan. It is necessary to encourage IDUs to receive MMT and strengthen the health education about the prevention of overdose of heroin

  4. Acute morphine and cocaine related death after trimethoprim-adultered cocaine abuse.

    PubMed

    Fucci, Nadia; Pascali, Vincenzo L

    2014-01-01

    Over the last few decades, cocaine and morphine (heroin) have been among the primary causes of deaths related to drug abuse. Cocaine is frequently altered by dilution, substitution, contamination, and adulteration. Trimethoprim has never been identified in the powders of cocaine, making this the first post-mortem case report in which the presence of this compound is described. The case reported here is that of a 46-year-old woman with a history of cocaine and morphine abuse who was found dead inside her bathroom. The police found the corpse next to a syringe, with a telephone card containing trace of cocaine on the sink. Toxicological analysis was performed, and drug levels were measured by means of gas chromatography/mass spectrometry. In addition to the presence of cocaine and smaller alkaloids, trimethoprim was also detected on the syringe and telephone card and in the woman's nasal mucosa. Trimethoprim analysis is very quick and easy and can be added to the routine analysis of drugs of abuse seized on the illicit market to obtain more information. © 2014 by the Association of Clinical Scientists, Inc.

  5. Intravenous heroin use in Haiphong, Vietnam: Need for comprehensive care including methamphetamine use-related interventions.

    PubMed

    Michel, Laurent; Des Jarlais, Don C; Duong Thi, Huong; Khuat Thi Hai, Oanh; Pham Minh, Khuê; Peries, Marianne; Vallo, Roselyne; Nham Thi Tuyet, Thanh; Hoang Thi, Giang; Le Sao, Mai; Feelemyer, Jonathan; Vu Hai, Vinh; Moles, Jean-Pierre; Laureillard, Didier; Nagot, Nicolas

    2017-10-01

    The aim of this study was to describe patterns among people who inject drugs (PWID), risk-related behaviours and access to methadone treatment, in order to design a large-scale intervention aiming to end the HIV epidemic in Haiphong, Vietnam. A respondent-driven sampling (RDS) survey was first conducted to identify profiles of drug use and HIV risk-related behaviour among PWID. A sample of PWID was then included in a one-year cohort study to describe access to methadone treatment and associated factors. Among the 603 patients enrolled in the RDS survey, 10% were female, all were injecting heroin and 24% were using methamphetamine, including 3 (0.5%) through injection. Different profiles of risk-related behaviours were identified, including one entailing high-risk sexual behaviour (n=37) and another involving drug-related high-risk practices (n=22). High-risk sexual activity was related to binge drinking and methamphetamine use. Among subjects with low sexual risk, sexual intercourse with a main partner with unknown serostatus was often unprotected. Among the 250 PWID included in the cohort, 55.2% initiated methadone treatment during the follow-up (versus 4.4% at RDS); methamphetamine use significantly increased. The factors associated with not being treated with methadone after 52 weeks were fewer injections per month and being a methamphetamine user at RDS. Heroin is still the main drug injected in Haiphong. Methamphetamine use is increasing markedly and is associated with delay in methadone initiation. Drug-related risks are low but sexual risk behaviours are still present. Comprehensive approaches are needed in the short term. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Oral Fluid as an Alternative Matrix to Monitor Opiate and Cocaine Use in Substance-Abuse Treatment Patients

    PubMed Central

    Dams, Riet; Choo, Robin E.; Lambert, Willy E.; Jones, Hendree; Huestis, Marilyn A.

    2007-01-01

    Interest in oral fluid as an alternative matrix for monitoring drug use is due to its ease-of-collection and non-invasiveness; however, limited data are available on the disposition of drugs into oral fluid. The objective of this research was to provide data on the presence and concentrations of heroin, cocaine and multiple metabolites in oral fluid after illicit opioid and cocaine use. Thrice weekly oral fluid specimens (N=403) from 16 pregnant opiate-dependent women were obtained with the Salivette® oral fluid collection device. Evidence of heroin (N=62) and cocaine (N=130) use was detected in oral fluid by LC-APCI-MS/MS. 6-Acetylmorphine (6-AM), heroin and morphine were the major opiates detected, with median concentrations of 5.2, 2.3, and 7.5 μg/L, respectively. Cocaine and benzoylecgonine (BE) had median concentrations of 6.4 and 3.4 μg/L. Application of the Substance Abuse Mental Health Services Administration (SAMHSA) recommended cutoffs for morphine and codeine (40 μg/L), 6-AM (4 μg/L) and cocaine and BE (8 μg/L), yielded 28 opiate- and 50 cocaine-positive specimens. Oral fluid is a promising alternative matrix to monitor opiate and cocaine use in drug testing programs. These data guide interpretation of oral fluid test results and evaluate currently proposed SAMHSA oral fluid testing cutoffs. PMID:17008030

  7. Recent Increases in Cocaine-Related Overdose Deaths and the Role of Opioids.

    PubMed

    McCall Jones, Christopher; Baldwin, Grant T; Compton, Wilson M

    2017-03-01

    To assess trends in cocaine overdose deaths and examine the role opioids play in these deaths. We used data on drug overdose deaths in the United States from 2000 to 2015 collected in the National Vital Statistics System to calculate annual rates and numbers of cocaine-related overdose deaths overall and deaths both involving and not involving opioids. We assessed statistically significant changes in trends with joinpoint regression. Rates of cocaine-related overdose deaths increased significantly from 1.26 to 2.50 per 100 000 population from 2000 to 2006, declined to 1.35 in 2010, and increased to 2.13 in 2015. Cocaine-related overdose deaths involving opioids increased from 0.37 to 0.91 from 2000 to 2006, declined to 0.57 in 2010, and then increased to 1.36 in 2015. Cocaine-related overdose deaths not involving opioids increased from 0.89 to 1.59 from 2000 to 2006 and then declined to 0.78 in 2015. Opioids, primarily heroin and synthetic opioids, have been driving the recent increase in cocaine-related overdose deaths. This corresponds to the growing supply and use of heroin and illicitly manufactured fentanyl in the United States.

  8. Forensic Toxicology Perspectives of Methadone-associated Deaths in Tehran, Iran, a 7-year Overview.

    PubMed

    Akhgari, Maryam; Amini-Shirazi, Noushin; Iravani, Fariba Sardari

    2018-04-01

    Methadone has a long history of pain relief and successful substitute for maintenance treatment in heroin and narcotic addiction. The aim of the study was to assess the trends of methadone-associated deaths in Tehran, Iran, in 2009-2015, from a forensic toxicology point of view. All methadone-associated deaths during this 7-year study period were evaluated according to demographic parameters and forensic toxicology analysis results. Results showed that 1274 cases of methadone-associated deaths were investigated during the study period. The incidence rate of methadone-associated deaths had risen 7.7 times in 2015 in comparison with 2009 (p < 0.05). The majority of cases were men (90.35%), aged from 20 to 40 years. About 80% of cases had shown positive results for other drugs and poisons in combination with methadone. Methamphetamine and tramadol were the most drugs detected in post-mortem samples. Death rates among methadone users in Tehran, Iran, increased year by year during 2009-2015. These findings raise the attention to the concomitant use of drugs with the need for changes in regulation and regulatory policy to restrict access and use of controlled drugs. © 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  9. Overdose Deaths Involving Opioids, Cocaine, and Psychostimulants - United States, 2015-2016.

    PubMed

    Seth, Puja; Scholl, Lawrence; Rudd, Rose A; Bacon, Sarah

    2018-03-30

    During 1999‒2015, 568,699 persons died from drug overdoses in the United States.* Drug overdose deaths in the United States increased 11.4% from 2014 to 2015 resulting in 52,404 deaths in 2015, including 33,091 (63.1%) that involved an opioid. The largest rate increases from 2014 to 2015 occurred among deaths involving synthetic opioids other than methadone (synthetic opioids) (72.2%) (1). Because of demographic and geographic variations in overdose deaths involving different drugs (2,3), † CDC examined age-adjusted death rates for overdoses involving all opioids, opioid subcategories (i.e., prescription opioids, heroin, and synthetic opioids), § cocaine, and psychostimulants with abuse potential (psychostimulants) by demographics, urbanization levels, and in 31 states and the District of Columbia (DC). There were 63,632 drug overdose deaths in 2016; 42,249 (66.4%) involved an opioid. ¶ From 2015 to 2016, deaths increased across all drug categories examined. The largest overall rate increases occurred among deaths involving cocaine (52.4%) and synthetic opioids (100%), likely driven by illicitly manufactured fentanyl (IMF) (2,3). Increases were observed across demographics, urbanization levels, and states and DC. The opioid overdose epidemic in the United States continues to worsen. A multifaceted approach, with faster and more comprehensive surveillance, is needed to track emerging threats to prevent and respond to the overdose epidemic through naloxone availability, safe prescribing practices, harm-reduction services, linkage into treatment, and more collaboration between public health and public safety agencies.

  10. Cocaine behavioral economics: From the naturalistic environment to the controlled laboratory setting

    PubMed Central

    Greenwald, Mark K.; Steinmiller, Caren L.

    2017-01-01

    Background We previously observed that behavioral economic factors predict naturalistic heroin seeking behavior that correlates with opioid seeking in the experimental laboratory. The present study sought to replicate and extend these prior findings with regular cocaine users. Methods Participants (N = 83) completed a semi-structured interview to establish income-generating and cocaine-purchasing/use repertoire during the past month. Questions addressed sources/amounts of income and expenditures; price (money and time) per purchase; and frequency/amounts of cocaine purchased and consumed. Naturalistic cocaine purchasing and use patterns were: (1) analyzed as a function of income quartile, (2) perturbed by hypothetical changes in cost factors to assess changes in purchasing/use habits, and (3) correlated with experimental cocaine seeking. Results Income was positively related to naturalistic cocaine seeking/use pattern (i.e., income elastic), and behaviors were cost-efficient and sensitive to supply chain. Income was unrelated to proportional expenditure on cocaine (≈55%) but inversely related to food expenditure. In all hypothetical scenarios (changes in income or dealer, loss of income assistance from government or family/friends, and increasing arrest risk when purchasing), the high-income group reported they would continue to use more cocaine daily than other groups. Number of laboratory cocaine choices significantly correlated with cocaine purchase time (positively) and purity of cocaine (negatively) in the naturalistic setting. Conclusions These results replicate and extend findings with regular heroin users, demonstrate the importance of income, cost-efficiency and supply-mindedness in cocaine seeking/use, and suggest that this interview-based approach has good external validity. PMID:24878248

  11. Randomized Trial Comparing Two Treatment Strategies Using Prize-Based Reinforcement of Abstinence in Cocaine and Opiate Users

    ERIC Educational Resources Information Center

    Preston, Kenzie L.; Ghitza, Udi E.; Schmittner, John P.; Schroeder, Jennifer R.; Epstein, David H.

    2008-01-01

    We compared two strategies of prize-based contingency management (CM) in methadone-maintained outpatients. Urine was tested thrice weekly for 5 weeks pre-CM, 12 weeks CM, and 8 weeks post-CM. Participants were randomly assigned to a cocaine contingency (four prize draws for each cocaine-negative urine, N = 29) or an opiate-cocaine contingency (one…

  12. Case report: quantification of methadone-induced respiratory depression using toxicokinetic/toxicodynamic relationships.

    PubMed

    Mégarbane, Bruno; Declèves, Xavier; Bloch, Vanessa; Bardin, Christophe; Chast, François; Baud, Frédéric J

    2007-01-01

    Methadone, the most widely delivered maintenance therapy for heroin addicts, may be responsible for life-threatening poisonings with respiratory depression. The toxicokinetics and the toxicokinetic/toxicodynamic (TK/TD) relationships of methadone enantiomers have been poorly investigated in acute poisonings. The aim of this study was to describe the relationships between methadone-related respiratory effects and their corresponding concentrations. We report a 44-year-old methadone-maintained patient who ingested a 240-mg dose of methadone. He was found comatose with pinpoint pupils and respiratory depression. He was successfully treated with intravenous naloxone infusion over the course of 31 hours at a rate adapted to maintain normal consciousness and respiratory rate. We performed a TK/TD analysis of the naloxone infusion rate needed to maintain his respiratory rate at more than 12 breaths per minute (as toxicodynamics parameter) versus plasma R,S- and R-methadone concentrations (as toxicokinetics parameter), determined using an enantioselective high-performance liquid chromatography assay. Initial plasma R,S-methadone concentration was 1,204 ng/ml. Decrease in plasma R- and S-methadone concentrations was linear and demonstrated a first-order pharmacokinetics (maximal observed concentrations 566 and 637 ng/ml, half-lives 16.1 and 13.2 hours, respectively). TK/TD correlation between naloxone infusion rate and R,S- and R-methadone concentrations fitted well a sigmoidal Emax model (concentration associated with a half-maximum effect [EC50] 334 and 173 ng/ml, Hill coefficient 10.0 and 7.8, respectively). In our chronically treated patient, EC50 values were in the range of previously reported values regarding methadone analgesic effects, suggesting that plasma methadone concentrations to prevent withdrawal are lower than those associated with methadone analgesic effects. After the ingestion of a toxic dose of a racemic mixture, plasma R- and S

  13. Stress-opioid interactions: a comparison of morphine and methadone.

    PubMed

    Taracha, Ewa; Mierzejewski, Paweł; Lehner, Małgorzata; Chrapusta, Stanisław J; Kała, Maria; Lechowicz, Wojciech; Hamed, Adam; Skórzewska, Anna; Kostowski, Wojciech; Płaźnik, Adam

    2009-01-01

    The utility of methadone and morphine for analgesia and of methadone for substitution therapy for heroin addiction is a consequence of these drugs acting as opioid receptor agonists.We compared the cataleptogenic and antinociceptive effects of single subcutaneous doses of methadone hydrochloride (1-4 mg/kg) and morphine sulfate (2.5-10 mg/kg) using catalepsy and hot-plate tests, and examined the effects of the highest doses of the drugs on Fos protein expression in selected brain regions in male Sprague-Dawley rats. Methadone had greater cataleptogenic and analgesic potency than morphine. Fos immunohistochemistry revealed substantial effects on the Fos response of both the stress induced by the experimental procedures and of the drug exposure itself. There were three response patterns identified: 1) drug exposure, but not stress, significantly elevated Fos-positive cell counts in the caudate-putamen; 2) stress alone and stress combined with drug exposure similarly elevated Fos-positive cell counts in the nucleus accumbens and cingulate cortex; and 3) methadone and morphine (to a lesser extent) counteracted the stimulatory effect of nonpharmacological stressors on Fos protein expression in the somatosensory cortex barrel field, and Fos-positive cell counts in this region correlated negatively with both the duration of catalepsy and the latency time in the hot-plate test. The overlap between brain regions reacting to nonpharmacological stressors and those responding to exogenous opioids suggests that stress contributes to opioid-induced neuronal activation.

  14. Self-identification of nonpharmaceutical fentanyl exposure following heroin overdose

    PubMed Central

    Griswold, Matthew K.; Chai, Peter R.; Krotulski, Alex J.; Friscia, Melissa; Chapman, Brittany; Boyer, Edward W.; Logan, Barry K.; Babu, Kavita M.

    2018-01-01

    Objective To compare user self-identification of nonpharmaceutical fentanyl exposure with confirmatory urine drug testing in emergency department (ED) patients presenting after heroin overdose. Methods This was a cross-sectional study of adult ED patients who presented after a heroin overdose requiring naloxone administration. Participants provided verbal consent after which they were asked a series of questions regarding their knowledge, attitudes and beliefs toward heroin and non-pharmaceutical fentanyl. Participants also provided urine samples, which were analyzed using liquid chromatography coupled to quadrupole time-of-flight mass spectrometry to identify the presence of fentanyl, heroin metabolites, other clandestine opioids, common pharmaceuticals and drugs of abuse. Results Thirty participants were enrolled in the study period. Ten participants (33%) had never required naloxone for an overdose in the past, 20 participants (67%) reported recent abstinence, and 12 participants (40%) reported concomitant cocaine use. Naloxone was detected in all urine drug screens. Heroin or its metabolites were detected in almost all samples (93.3%), as were fentanyl (96.7%) and its metabolite, norfentanyl (93.3%). Acetylfentanyl was identified in nine samples (30%) while U-47700 was present in two samples (6.7%). Sixteen participants self-identified fentanyl in their heroin (sensitivity 55%); participants were inconsistent in their qualitative ability to identify fentanyl in heroin. Conclusions Heroin users presenting to the ED after heroin overdose requiring naloxone are unable to accurately identify the presence of nonpharmaceutical fentanyl in heroin. Additionally, cutting edge drug testing methodologies identified fentanyl exposures in 96.7% of our patients, as well as unexpected clandestine opioids (like acetylfentanyl and U-47700). PMID:28681615

  15. Self-identification of nonpharmaceutical fentanyl exposure following heroin overdose.

    PubMed

    Griswold, Matthew K; Chai, Peter R; Krotulski, Alex J; Friscia, Melissa; Chapman, Brittany; Boyer, Edward W; Logan, Barry K; Babu, Kavita M

    2018-01-01

    To compare user self-identification of nonpharmaceutical fentanyl exposure with confirmatory urine drug testing in emergency department (ED) patients presenting after heroin overdose. This was a cross-sectional study of adult ED patients who presented after a heroin overdose requiring naloxone administration. Participants provided verbal consent after which they were asked a series of questions regarding their knowledge, attitudes and beliefs toward heroin and nonpharmaceutical fentanyl. Participants also provided urine samples, which were analyzed using liquid chromatography coupled to quadrupole time-of-flight mass spectrometry to identify the presence of fentanyl, heroin metabolites, other clandestine opioids, common pharmaceuticals and drugs of abuse. Thirty participants were enrolled in the study period. Ten participants (33%) had never required naloxone for an overdose in the past, 20 participants (67%) reported recent abstinence, and 12 participants (40%) reported concomitant cocaine use. Naloxone was detected in all urine drug screens. Heroin or its metabolites were detected in almost all samples (93.3%), as were fentanyl (96.7%) and its metabolite, norfentanyl (93.3%). Acetylfentanyl was identified in nine samples (30%) while U-47700 was present in two samples (6.7%). Sixteen participants self-identified fentanyl in their heroin (sensitivity 55%); participants were inconsistent in their qualitative ability to identify fentanyl in heroin. Heroin users presenting to the ED after heroin overdose requiring naloxone are unable to accurately identify the presence of nonpharmaceutical fentanyl in heroin. Additionally, cutting edge drug testing methodologies identified fentanyl exposures in 96.7% of our patients, as well as unexpected clandestine opioids (like acetylfentanyl and U-47700).

  16. Methadone induces CAD degradation and AIF-mediated necrotic-like cell death in neuroblastoma cells.

    PubMed

    Perez-Alvarez, Sergio; Iglesias-Guimarais, Victoria; Solesio, María E; Melero-Fernandez de Mera, Raquel María; Yuste, Víctor J; Galindo, María F; Jordán, Joaquín

    2011-04-01

    Methadone (d,l-methadone hydrochloride) is a full-opioid agonist, originally developed as a substitution for heroin or other opiates abusers. Nowadays methadone is also being applied as long-lasting analgesics in cancer, and it is proposed as a promising agent for leukemia therapy. Previously, we have demonstrated that high concentrations of methadone (0.5mM) induced necrotic-like cell death in SH-SY5Y cells. The pathway involved is caspase-independent but involves impairment of mitochondrial ATP synthesis and mitochondrial cytochrome c release. However, the downstream mitochondrial pathways remained unclear. Here, we studied the participation of apoptosis inducing factor (AIF) in methadone-induced cell death. Methadone resulted in a translocation of AIF from mitochondria to the nucleus. Translocation was inhibited by cyclosporine A, but not by lack of Bax protein. Therefore the effect seems mediated by the formation of the mitochondrial transition pore, but is apparently independent of Bax. Furthermore, methadone-treated SH-SY5Y nuclei show characteristics that are typical for stage I nuclear condensation. Methadone did not induce degradation of DNA into oligonucleosomal fragments or into high molecular weight DNA fragments. Absence of DNA fragmentation coincided with a considerable decrease in the levels of the caspase-actived endonuclase DNase and its chaperone-inhibitor ICAD. In conclusion, our results provide mechanistic insights into the molecular mechanisms that underlie methadone-induced cell death. This knowledge may prove useful to develop novel strategies to prevent toxic side-effects of methadone thereby sustaining its use as therapeutical agent against tumors. Copyright © 2010 Elsevier Ltd. All rights reserved.

  17. Wastewater-based assessment of regional and temporal consumption patterns of illicit drugs and therapeutic opioids in Croatia.

    PubMed

    Krizman, Ivona; Senta, Ivan; Ahel, Marijan; Terzic, Senka

    2016-10-01

    A comprehensive study of spatial and temporal consumption patterns of the selected illicit drugs (heroin, cocaine, amphetamine, MDMA, methamphetamine, cannabis) and therapeutic opioids (codeine, methadone) has been performed in six Croatian cities by applying wastewater-based epidemiology. The investigated cities (Bjelovar, Vinkovci, Varazdin, Karlovac, Zadar and Zagreb) varied widely in the population size (27,000-688,000 inhabitants) as well as in the number of registered drug consumers included in compulsory and voluntary medical treatment and rehabilitation programs (30-513 persons/100,000 inhabitants of age 15-64). The most consumed illicit drugs were cannabis (10-70doses/day/1000 inhabitants), heroin (<0.2-10doses/day/1000 inhabitants) and cocaine (0.2-8.7doses/day/1000 inhabitants), while the consumption of amphetamine-type drugs was much lower (<0.01-4.4doses/day/1000 inhabitants). Enhanced consumption of illegal drugs was generally associated with larger urban centers (Zagreb and Zadar) however comparatively high consumption rate of cocaine, MDMA and methadone was determined in some smaller cities as well. The overall average dose number of 3 major illegal stimulants (cocaine, MDMA, amphetamine) was rather similar to the number of corresponding heroin doses, which is in disagreement with a comparatively much higher proportion of heroin users in the total number of registered drug users in Croatia. Furthermore, the illicit drug consumption pattern in the large continental city (Zagreb) was characterized by a significant enhancement of the consumption of all stimulants during the weekend, which could not be confirmed neither for the coastal city of Zadar nor for the remaining small continental cities. On the other hand, the city of Zadar exhibited a significant increase of stimulant drug usage during summer vacation period, as a result of pronounced seasonal changes of the population composition and lifestyle in coastal tourist centers. The obtained results

  18. Neurobiology of addictive behaviors and its relationship to methadone maintenance.

    PubMed

    Stimmel, B; Kreek, M J

    2000-01-01

    Scientific information about the neurobiology of addictive behaviors provides an increasingly important rationale to support opioid agonist pharmacotherapy, primarily methadone maintenance treatment, for long-term heroin addiction. In late 1963 and 1964, the first research was performed at The Rockefeller Institute for Medical Research by Dole, Nyswander, and Kreek in an attempt to develop a new pharmacotherapy for opiate addiction. The hypothesis underlying that research was that heroin addiction was a disease. However, the evidence for heroin addiction being a disease was based primarily on clinical anecdotes and the natural history of opiate addiction. Until then chronic addiction was managed primarily using abstinence-based, medication-free behavioral approaches. Such approaches were uniformly successful in only a small percent of long-term heroin addicts. Subsequent research, both clinical research as well as laboratory-based research, using a variety of appropriate animal models as well as in vitro techniques, has shown that drugs of abuse in general, and specifically the short-acting opiates, such as heroin, may profoundly alter molecular and neurochemical indices, and thus physiologic functions. Also, research has shown that after chronic exposure to a short-acting opiate,these alterations may be persistent, or even permanent, and may contribute directly to the perpetuation of self-administration of opiates, and even the return to opiate use after achieving a drug-free and medication-free state. There is ample evidence now that disruption of several components of the endogenous opioid system, ranging from changes in gene expression to changes in behavior, may occur during cycles of short-acting opiate abuse. Also, there are very convincing studies that suggest that stress responsivity is profoundly altered by chronic abuse of short-acting opiates including: documentation of atypical hypo-responsivity to stressors during cycles of heroin addiction; evidence

  19. [Study on incidence of HIV infection among heroin addicts receiving methadone maintenance treatment in Dehong prefecture, Yunnan province].

    PubMed

    Duan, Song; Yang, Yue-cheng; Han, Jing; Yang, Shun-sheng; Yang, Ying-bo; Long, Yu-cun; Li, Guo-qiang; Yin, Jin-song; Xiang, Li-fen; Ye, Run-hua; Gao, Jie; Tang, Ren-hai; Pang, Lin; Rou, Ke-ming; Wu, Zun-you; He, Na

    2011-12-01

    To determine the incidence and risk factors of HIV infection among heroin addicts receiving methadone maintenance treatment (MMT) in Dehong prefecture, Yunnan province. All heroin addicts who were HIV negative at the initiation of MMT in June 2005 and through June 2011, in Dehong prefecture were included in the cohort analysis. HIV incidence was calculated and related risk factors determined by using Cox proportional hazard regression model. A total of 3154 MMT clinic attendants were qualified for this cohort study. By June 2011, 1023 (32.4%) of them had never received any follow-up HIV testing so were thus referred as loss to follow-up. The other 2131 (67.6%) members had received at least one follow-up HIV testing and were observed for a total of 4615.86 person-years. During the period, 22 new HIV infections or seroconverters were identified, making the overall HIV incidence as 0.48/100 person-years. The HIV incidence was higher among those who were unemployed, never married, self-reported being injecting drug users (IDUs) and HCV positive at entry into the MMT program. None of those who were always negative on follow-up-urine-testing of morphine was discovered as HIV newly infected during the follow-up period. Data from multiple regression analysis under Cox proportional hazard model indicated that after controlling for confounding variables, non-IDUs at the entry point for the MMT program, were less likely to be HIV newly-infected or seroconverted than IDUs (HR = 0.29, 95%CI: 0.11 - 0.76). MMT program in Dehong prefecture was demonstrated to be fairly effective in reducing HIV transmission through drug use. Those HIV negative attendants at the MMT clinic who were IDUs or keep using drugs during the treatment, were at higher risk of HIV seroconvertion. More efforts were needed to improve the follow-up and HIV testing programs for the MMT clinic attendants.

  20. [Postpartum risk factors in the development of children born to opiate-addicted mothers; comparison between mothers with and without methadone substitution].

    PubMed

    Ziegler, M; Poustka, F; von Loewenich, V; Englert, E

    2000-09-01

    In a retrospective case control study at the University of Frankfurt, Germany, 101 babies born to opiate-addicted mothers were identified from birth charts from 1988 to 1995. After birth, they developed a withdrawal syndrome (neonatal abstinence syndrome). Fifty control infants and their mothers were selected from neonatal wards. The group of opiate-exposed babies was subdivided into a group born to mothers without methadone treatment (n = 48) and a group born to mothers who were enrolled in a methadone program (n = 51). The methadone infants had a significantly higher mean birth weight (2822 g) than children in the group without methadone (2471 g). The abstinence syndrome was much more intense in the methadone group (convulsions 47.1%) than in heroin-exposed babies without methadone treatment (convulsions 27.1%). Women in methadone maintenance programs lived in more stable socioeconomic conditions than opiate-addicted women without methadone substitution. Moreover, they cared significantly better for their babies: 81.3% of the methadone mothers visited their children on a regular basis and 90.9% cared adequately. The data emphasize the need in future research to look more closely at the role of methadone treatment programs in the development of opiate-exposed babies.

  1. Drug Abuse: The Crack Cocaine Epidemic Health Consequences and Treatment.

    DTIC Science & Technology

    1991-01-01

    addicts . Buackground Once considered to be nonaddictive, recent studies show that cocaine is one of the most potent drugs of abuse. Cocaine is a...responsibility for addiction prevention and treatment programs. The agencies we contacted include NIDA, the Alcohol, Drug Abuse, and Mental Health Administration...heroin addicts for Treating Crack are being used to treat many crack addicts . Meanwhile, drug treatment Addicts researchers are experimenting with new

  2. Patient perspectives on choosing buprenorphine over methadone in an urban, equal-access system.

    PubMed

    Gryczynski, Jan; Jaffe, Jerome H; Schwartz, Robert P; Dušek, Kristi A; Gugsa, Nishan; Monroe, Cristin L; O'Grady, Kevin E; Olsen, Yngvild K; Mitchell, Shannon Gwin

    2013-01-01

    Recent policy initiatives in Baltimore City, MD significantly reduced access disparities between methadone and buprenorphine in the publicly funded treatment sector. This study examines reasons for choosing buprenorphine over methadone among patients with access to both medications. This study was embedded within a larger clinical trial conducted at two outpatient substance abuse treatment programs offering buprenorphine. Qualitative and quantitative data on treatment choice were collected for new patients starting buprenorphine treatment (n = 80). The sample consisted of predominantly urban African American (94%) heroin users who had prior experience with non-prescribed street buprenorphine (85%), and opioid agonist treatment (68%). Qualitative data were transcribed and coded for themes, while quantitative data were analyzed using descriptive and bivariate statistics. Participants typically conveyed their choice of buprenorphine treatment as a decision against methadone. Buprenorphine was perceived as a helpful medication while methadone was perceived as a harmful narcotic with multiple unwanted physical effects. Positive experiences with non-prescribed "street buprenorphine" were a central factor in participants' decisions to seek buprenorphine treatment. Differences in service structure between methadone and buprenorphine did not strongly influence treatment-seeking decisions in this sample. Personal experiences with medications and the street narrative surrounding them play an important role in treatment selection decisions. This study characterizes important decision factors that underlie patients' selection of buprenorphine over methadone treatment. Copyright © American Academy of Addiction Psychiatry.

  3. Patient Perspectives on Choosing Buprenorphine over Methadone in an Urban Equal Access System

    PubMed Central

    Gryczynski, Jan; Jaffe, Jerome H.; Schwartz, Robert P.; Dušek, Kristi A.; Gugsa, Nishan; Monroe, Cristin L.; O'Grady, Kevin E.; Olsen, Yngvild K.; Mitchell, Shannon Gwin

    2014-01-01

    Background Recent policy initiatives in Baltimore City, MD significantly reduced access disparities between methadone and buprenorphine in the publicly-funded treatment sector. Objectives This study examines reasons for choosing buprenorphine over methadone among patients with access to both medications. Methods This study was embedded within a larger clinical trial conducted at two outpatient substance abuse treatment programs offering buprenorphine. Qualitative and quantitative data on treatment choice were collected for new patients starting buprenorphine treatment (n=80). The sample consisted of predominantly urban African American (94%) heroin users who had prior experience with non-prescribed street buprenorphine (85%) and opioid agonist treatment (68%). Qualitative data were transcribed and coded for themes, while quantitative data were analyzed using descriptive and bivariate statistics. Results Participants typically conveyed their choice of buprenorphine treatment as a decision against methadone. Buprenorphine was perceived as a helpful medication while methadone was perceived as a harmful narcotic with multiple unwanted physical effects. Positive experiences with non-prescribed “street buprenorphine” were a central factor in participants’ decisions to seek buprenorphine treatment. Conclusions Differences in service structure between methadone and buprenorphine did not strongly influence treatment-seeking decisions in this sample. Personal experiences with medications and the street narrative surrounding them play an important role in treatment selection decisions. Scientific Significance This study characterizes important decision factors that underlie patients’ selection of buprenorphine over methadone treatment. PMID:23617873

  4. NPS and the methadone queue: Spillages of space and time.

    PubMed

    Alexandrescu, Liviu

    2017-02-01

    Between 2008 and 2013, powder-stimulants sold by 'head shops' as novel psychoactive substances (NPS) or 'legal highs' have displaced heroin among groups of injecting substance users in Bucharest, Romania. Rising HIV-infection rates and other medical or social harms have been reported to follow this trend. The study builds on two sets of original (N=30) and existing (N=20) interview data and on observations collected mainly at the site of a methadone substitution treatment facility. By disentangling the space-time continuum of the methadone queue, this paper argues that injecting drug users' (IDUs) passage from opiates to amphetamine-type stimulants (ATS) can be understood as 'spillages' of space and time. IDUs thus 'spill' out of the disciplinary flows of methadone treatment in two ways. The first is that of space and materiality. Drawing on actor-network theory (ANT), ATS/NPS appear embedded in reconfigured practices and rituals of injecting use. Such spillages see the pleasure-seeking self being fluidised in forming connections with, or spilling into, nonhuman actants such as substances, settings or objects. The second dimension of spilling is that of time. In this sense, heroin use is a 'cryogenic strategy' of inhabiting history and facing the transition to the market society that Romanian opiate injectors spill out of, not able to appropriate choice and legitimate consumption. The phenomenological qualities of stimulants that seem to accelerate lived time and generalise desire thus present them with an opportunity to alleviate a form of what a post-communist moral imaginary of transition frames as debilitating nostalgia. ATS/NPS are revealed as fluid entities that do not only shape risk conditions but also alter shared meanings and contextual configurations of bodies, substances and disciplinary regimes in unpredictable ways. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Prescription opioid mortality trends in New York City, 1990–2006: Examining the emergence of an epidemic☆

    PubMed Central

    Ransome, Yusuf; Keyes, Katherine M.; Koenen, Karestan C.; Tracy, Melissa; Tardiff, Kenneth J.; Vlahov, David; Galea, Sandro

    2013-01-01

    Background The drug overdose mortality rate tripled between 1990 and 2006; prescription opioids have driven this epidemic. We examined the period 1990–2006 to inform our understanding of how the current prescription opioid overdose epidemic emerged in urban areas. Methods We used data from the Office of the Chief Medical Examiner to examine changes in demographic and spatial patterns in overdose fatalities induced by prescription opioids (i.e., analgesics and methadone) in New York City (NYC) in 1990–2006, and what factors were associated with death from prescription opioids vs. heroin, historically the most prevalent form of opioid overdose in urban areas. Results Analgesic-induced overdose fatalities were the only types of overdose fatalities to increase in 1990–2006 in NYC; the fatality rate increased sevenfold from 0.39 in 1990 to 2.7 per 100,000 persons in 2006. Whites and Latinos were the only racial/ethnic groups to exhibit an increase in overdose-related mortality. Relative to heroin overdose decedents, analgesic and methadone overdose decedents were more likely to be female and to concurrently use psychotherapeutic drugs, but less likely to concurrently use alcohol or cocaine. Analgesic overdose decedents were less likely to be Black or Hispanic, while methadone overdose decedents were more likely to be Black or Hispanic in contrast to heroin overdose decedents. Conclusions The distinct epidemiologic profiles exhibited by analgesic and methadone overdose fatalities highlight the need to define drug-specific public health prevention efforts. PMID:23357743

  6. A Randomized Clinical Trial of Methadone Maintenance for Prisoners: Prediction of Treatment Entry and Completion in Prison

    ERIC Educational Resources Information Center

    Gordon, Michael S.; Kinlock, Timothy W.; Couvillion, Kathryn A.; Schwartz, Robert P.; O'Grady, Kevin

    2012-01-01

    The present report is an intent-to-treat analysis involving secondary data drawn from the first randomized clinical trial of prison-initiated methadone in the United States. This study examined predictors of treatment entry and completion in prison. A sample of 211 adult male prerelease inmates with preincarceration heroin dependence were randomly…

  7. Youth, Heroin, Crack: A Review of Recent British Trends

    ERIC Educational Resources Information Center

    Seddon, Toby

    2008-01-01

    Purpose: The purpose of this paper is to review the research evidence on recent British trends in the use of heroin and/or crack-cocaine by young people in order to appraise the scale and nature of the contemporary health problem they pose. Design/methodology/approach: The approach consists of a narrative review of the main current data sources on…

  8. Gender and Age Effects on the Trajectory of Depression in Opioid Users during Methadone Maintenance Treatment.

    PubMed

    Wang, Peng-Wei; Lin, Huang-Chi; Yang, Yi-Hsin Connie; Hsu, Chih-Yao; Chung, Kuan-Sheng; Wu, Hung-Chi; Yen, Cheng-Fang

    2017-01-01

    Both heroin use and depression are significant health problems. Methadone maintenance treatment (MMT) can be of great benefit to heroin users. However, changes in the level of depression in heroin users during MMT are not clear. Gender and age are also important factors in the development of depression, and whether gender and age moderate changes in depression in heroin users during MMT warrants further study. This study aimed to explore: (1) the trajectory of depression in opioid users during MMT and (2) the moderating effects of gender and age on the trajectory of depression in opioid users receiving MMT. A total of 294 intravenous heroin users were recruited into this 9-month observational study. The level of depression was measured at the intake interview and at follow-up interviews every 3 months. A latent growth model was used to analyze the trajectory of the level of depression among the participants. Depression improved rapidly during the first 3 months of MMT and slowly after the first 3 months in both the female and male heroin users. There was no gender difference in the level of depression at each follow-up point. The level of depression in the female heroin users decreased faster than that in the male heroin users. In addition, the level of depression in the younger heroin users decreased faster than that in the older subjects. Depression in female and younger heroin users improved more rapidly than in male and older subjects, respectively.

  9. A study on photodegradation of methadone, EDDP, and other drugs of abuse in hair exposed to controlled UVB radiation.

    PubMed

    Favretto, Donata; Tucci, Marianna; Monaldi, Alice; Ferrara, Santo Davide; Miolo, Giorgia

    2014-06-01

    The drug content of hair may be affected by washing, chemical or thermal treatments, the use of cosmetics, or exposure to the environment. Knowledge concerning the effect of natural or artificial light on drug content in hair can be helpful to the forensic toxicologist, in particular when investigating drug concentrations above or below pre-determined cut-offs. The photodegradation of methadone and its metabolite, 2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) was studied in authentic positive hair samples by comparing drug concentrations determined by liquid chromatrography-high resolution mass spectrometry before and after exposure to UVB light (in vivo study). The same approach was applied in order to investigate the light sensitivity of opiates (6-monoacetylmorphine and morphine) and cocainics (cocaine and benzoylecgonine) in true positive hair. The yields of photodegradation were calculated for each drug class in eight different positive hair samples irradiated by UVB at 300 J/cm(2) obtaining averages, ranges and standard deviations. In parallel, the photostability of all the compounds as 10(-5) -10(-4)  M standard solutions in methanol were examined by means of UVB light irradiation in the range 0-100 J/cm(2) followed by UV/Vis spectroscopic analysis and direct infusion electrospray ionization-high resolution mass spectrometry (in vitro study). In hair, methadone was shown to be significantly affected by light (photodegradation of 55% on average), while its metabolite EDDP proved to be more photostable (17%). 6-monoacetylmorphine, morphine, benzoylecgonine, and cocaine were more photostable than methadone in vivo (on average, 21%, 17%, 20%, and 11% of degradation, respectively). When irradiated in standard solutions, the target molecules exhibited a larger photodegradation than in vivo with the exception of cocaine (photodegradation for methadone up to 70%, 6-monoacetylmorphine and morphine up to 90%, benzoylecgonine up to 67%, cocaine up to 15

  10. The cost-effectiveness of methadone maintenance as a health care intervention.

    PubMed

    Barnett, P G

    1999-04-01

    Cost-effectiveness analysis using life-years of survival as the measure of treatment benefit is widely used in the economic evaluation of health care interventions but has not been applied to substance abuse treatment. The cost-effectiveness of methadone maintenance was evaluated to demonstrate the feasibility of applying this method to substance abuse treatment. A literature review was undertaken to determine the effect of methadone treatment on the rate of mortality associated with opiate addiction. Information was also obtained on the average cost and duration of treatment. A two-state Markov model was used to estimate the incremental effect of methadone on the life span and treatment cost of a cohort of 25-year-old heroin users. Providing opiate addicts with access to methadone maintenance has an incremental cost-effectiveness ratio of $5915 per life-year gained (that is, for every year of life that is saved by providing methadone to opiate addicts, an additional $5915 in treatment costs are incurred). One-way sensitivity analysis determined that the ratio was less than $10,000 per-life year over a wide range of modeling assumptions. The ratio determined for methadone is lower than that of many common medical therapies, and well within the $50,000 threshold for judging cost-effectiveness. Even if decision makers do not wish use the same ratio that is applied to the general population, this method allows substance abuse treatment enhancements to be compared to improvements in health services offered to individuals with substance abuse disorders. Future work will require information on the impact of methadone treatment on the cost of health care and public programs, the indirect costs incurred by patients, and adjustments to reflect quality of life.

  11. Porous silicon mass spectrometry as an alternative confirmatory assay for compliance testing of methadone.

    PubMed

    Guinan, Taryn M; Neldner, Declan; Stockham, Peter; Kobus, Hilton; Della Vedova, Christopher B; Voelcker, Nicolas H

    2017-05-01

    Porous silicon based surface-assisted laser desorption ionization mass spectrometry (pSi SALDI-MS) is an analytical technique well suited for high throughput analysis of low molecular weight compounds from biological samples. A potential application of this technology is the compliance monitoring of opioid addiction programmes, where methadone is used as a pharmacological treatment for drugs such as heroin. Here, we present the detection and quantification of methadone and 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) from water and clinical samples (saliva, urine, and plasma) from opioid dependent participants using pSi SALDI-MS. A one-step solvent phase extraction using chloroform was developed for the detection of methadone from clinical samples for analysis by pSi SALDI-MS. Liquid chromatography-mass spectrometry (LC-MS) was used as a comparative technique for the quantification of methadone from clinical saliva and plasma samples. In all cases, we obtained a good correlation of pSi SALDI-MS and LC-MS results, suggesting that pSi SALDI-MS may be an alternative procedure for high-throughput screening and quantification for application in opioid compliance testing. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  12. Can a rapid measure of self-exposure to drugs of abuse provide dimensional information on depression comorbidity?

    PubMed

    Butelman, Eduardo Roque; Bacciardi, Silvia; Maremmani, Angelo Giovanni Icro; Darst-Campbell, Maya; Correa da Rosa, Joel; Kreek, Mary Jeanne

    2017-09-01

    Addictions to heroin or to cocaine are associated with substantial psychiatric comorbidity, including depression. Poly-drug self-exposure (eg, to heroin, cocaine, cannabis, or alcohol) is also common, and may further affect depression comorbidity. This case-control study examined the relationship of exposure to the above drugs and depression comorbidity. Participants were recruited from methadone maintenance clinics, and from the community. Adult male and female participants (n = 1,201) were ascertained consecutively by experienced licensed clinicians. The instruments used were the SCID-I, and Kreek-McHugh-Schluger-Kellogg (KMSK) scales, which provide a rapid dimensional measure of maximal lifetime self-exposure to each of the above drugs. This measure ranges from no exposure to high unit dose, high frequency, and long duration of exposure. A multiple logistic regression with stepwise variable selection revealed that increasing exposure to heroin or to cocaine was associated greater odds of depression, with all cases and controls combined. In cases with an opioid dependence diagnosis, increasing cocaine exposure was associated with a further increase in odds of depression. However, in cases with a cocaine dependence diagnosis, increasing exposure to either cannabis or alcohol, as well as heroin, was associated with a further increase in odds of depression. This dimensional analysis of exposure to specific drugs provides insights on depression comorbidity with addictive diseases, and the impact of poly-drug exposure. A rapid analysis of exposure to drugs of abuse reveals how specific patterns of drug and poly-drug exposure are associated with increasing odds of depression. This approach detected quantitatively how different patterns of poly-drug exposure can result in increased odds of depression comorbidity, in cases diagnosed with opioid versus cocaine dependence. (Am J Addict 2017;26:632-639). © 2017 American Academy of Addiction Psychiatry.

  13. Gender differences among older heroin users.

    PubMed

    Hamilton, Alison B; Grella, Christine E

    2009-01-01

    This purpose of this study was to explore the following question: Are there gender differences among older individuals with a history of heroin addiction with regard to social and family relationships and health problems? Eight gender-specific focus groups were conducted with 38 (19 women, 19 men) older (50+ years) individuals with long-term histories of heroin dependence. Four groups were conducted in a methadone maintenance (MM) clinic and four groups were derived from the Los Angeles community. Modest gender differences were observed, but mainly in the focus-group dynamics. Women typically described the impact of their addiction on their families, while men typically described their surprise at still being alive. Hepatitis C was the primary health concern in all groups; mental health issues were also discussed. Remarkable gender differences were not apparent in the qualitative experiences of these participants. Instead, we found overriding similarities related to the interactive effects of drug use and aging. Longitudinal studies of this population as they age and interact with the health-care system and other social systems will help to untangle the complicated relationship between aging, drug addiction, gender, and health.

  14. Evidence-based drug treatment practice and the child welfare system: the example of methadone.

    PubMed

    Lundgren, Lena M; Schilling, Robert F; Peloquin, Susan D

    2005-01-01

    This article examined the extent to which methadone maintenance (MM) is considered a treatment alternative for drug-dependent parents, as reflected in the social work and child welfare literature and in child welfare policies. Findings were derived from a review of 15 social work journals published from 1996 through 2002 and from a review of child welfare policies in 27 states in regard to treatment recommendations for substance-abusing parents. These reviews found that 23 articles focused on child welfare-substance abuse issues; no article specifically discussed MM as a treatment option for heroin-using parents; and of the 27 states, only three included methadone as a treatment option in their child welfare policy recommendations. Practice and policy recommendations are discussed.

  15. Employment-based abstinence reinforcement promotes opiate and cocaine abstinence in out-of-treatment injection drug users.

    PubMed

    Holtyn, August F; Koffarnus, Mikhail N; DeFulio, Anthony; Sigurdsson, Sigurdur O; Strain, Eric C; Schwartz, Robert P; Silverman, Kenneth

    2014-01-01

    We examined the use of employment-based abstinence reinforcement in out-of-treatment injection drug users, in this secondary analysis of a previously reported trial. Participants (N = 33) could work in the therapeutic workplace, a model employment-based program for drug addiction, for 30 weeks and could earn approximately $10 per hr. During a 4-week induction, participants only had to work to earn pay. After induction, access to the workplace was contingent on enrollment in methadone treatment. After participants met the methadone contingency for 3 weeks, they had to provide opiate-negative urine samples to maintain maximum pay. After participants met those contingencies for 3 weeks, they had to provide opiate- and cocaine-negative urine samples to maintain maximum pay. The percentage of drug-negative urine samples remained stable until the abstinence reinforcement contingency for each drug was applied. The percentage of opiate- and cocaine-negative urine samples increased abruptly and significantly after the opiate- and cocaine-abstinence contingencies, respectively, were applied. These results demonstrate that the sequential administration of employment-based abstinence reinforcement can increase opiate and cocaine abstinence among out-of-treatment injection drug users. © Society for the Experimental Analysis of Behavior.

  16. EMPLOYMENT-BASED ABSTINENCE REINFORCEMENT PROMOTES OPIATE AND COCAINE ABSTINENCE IN OUT-OF-TREATMENT INJECTION DRUG USERS

    PubMed Central

    Holtyn, August F.; Koffarnus, Mikhail N.; DeFulio, Anthony; Sigurdsson, Sigurdur O.; Strain, Eric C.; Schwartz, Robert P.; Silverman, Kenneth

    2016-01-01

    We examined the use of employment-based abstinence reinforcement in out-of-treatment injection drug users, in this secondary analysis of a previously reported trial. Participants (N = 33) could work in the therapeutic workplace, a model employment-based program for drug addiction, for 30 weeks and could earn approximately $10 per hr. During a 4-week induction, participants only had to work to earn pay. After induction, access to the workplace was contingent on enrollment in methadone treatment. After participants met the methadone contingency for 3 weeks, they had to provide opiate-negative urine samples to maintain maximum pay. After participants met those contingencies for 3 weeks, they had to provide opiate- and cocaine-negative urine samples to maintain maximum pay. The percentage of drug-negative urine samples remained stable until the abstinence reinforcement contingency for each drug was applied. The percentage of opiate- and cocaine-negative urine samples increased abruptly and significantly after the opiate- and cocaine-abstinence contingencies, respectively, were applied. These results demonstrate that the sequential administration of employment-based abstinence reinforcement can increase opiate and cocaine abstinence among out-of-treatment injection drug users. PMID:25292399

  17. Prenatal drug exposure: infant and toddler outcomes.

    PubMed

    Bandstra, Emmalee S; Morrow, Connie E; Mansoor, Elana; Accornero, Veronica H

    2010-04-01

    This manuscript provides an overview of the current scientific literature on the impact of maternal drug use, specifically opioids and cocaine, during pregnancy on the acute and long-term outcomes of infants and toddlers from birth through age 3 years. Emphasis with regard to opioids is placed on heroin and opioid substitutes used to treat opioid addiction, including methadone, which has long been regarded as the standard of care in pregnancy, and buprenorphine, which is increasingly being investigated and prescribed as an alternative to methadone. Controlled studies comparing methadone at high and low doses, as well as those comparing methadone with buprenorphine, are highlighted and the diagnosis and management of neonatal abstinence syndrome is discussed. Over the past two decades, attention of the scientific and lay communities has also been focused on the potential adverse effects of cocaine and crack cocaine, especially during the height of the cocaine epidemic in the United States. Herein, the findings are summarized from prospective studies comparing cocaine-exposed with non-cocaine-exposed infants and toddlers with respect to anthropometric growth, infant neurobehavior, visual and auditory function, and cognitive, motor, and language development. The potentially stigmatizing label of the so-called "crack baby" preceded the evidence now accumulating from well-designed prospective investigations that have revealed less severe sequelae in the majority of prenatally exposed infants than originally anticipated. In contrast to opioids, which may produce neonatal abstinence syndrome and infant neurobehavioral deficits, prenatal cocaine exposure appears to be associated with what has been described as statistically significant but subtle decrements in neurobehavioral, cognitive, and language function, especially when viewed in the context of other exposures and the caregiving environment which may mediate or moderate the effects. Whether these early findings may

  18. The Association between the Level of Plasma Oxytocin and Craving among Former Heroin Users.

    PubMed

    Lin, Shih-Hsien; Chen, Po See; Lee, Lan-Ting; Lee, Sheng-Yu; Tsai, Hsin Chun; Chen, Wei Tseng; Chen, Kao Chin; Lee, I Hui; Lu, Ru-Band; Yang, Yen Kuang

    2018-06-14

    Animal studies have demonstrated that oxytocin can influence addiction behaviors and might interact with the dopaminergic system, which is a key component of addiction behaviors. However, related evidence from clinical studies is scarce. The aim of our study was to explore the relationship between plasma oxytocin level and heroin craving among patients receiving methadone maintenance treatment, and to ascertain whether this relationship is moderated by novelty-seeking. The study was conducted in a methadone maintenance therapy clinic of a medical center in Taiwan. Seventy-seven patients with heroin addiction were enrolled. Plasma oxytocin was measured using an ELISA kit. Craving was assessed using an established instrument, the Chinese Craving Scale. A significant negative association was found between the plasma oxytocin level and craving score, which remained robust after controlling the effects of social support and low-density lipoprotein cholesterol. An interaction between oxytocin and novelty-seeking indicated that this relationship was stronger among patients with a lower level of novelty-seeking. This finding may be taken into account in future studies and may provide a basis for the development of potential treatment for addiction. The effect of oxytocin for the treatment of opioid dependence might be modulated by some psychological factors. © 2018 S. Karger AG, Basel.

  19. The selective dopamine D3 receptor antagonist, SR 21502, reduces cue-induced reinstatement of heroin seeking and heroin conditioned place preference in rats.

    PubMed

    Galaj, Ewa; Manuszak, Monica; Babic, Sandra; Ananthan, Subramaniam; Ranaldi, Robert

    2015-11-01

    Because the role of dopamine (DA) D3 receptors has been investigated primarily in relation to cocaine-related behaviors little is known of the role of these receptors in heroin seeking. To investigate the effect of the selective DA D3 receptor antagonist, SR 21502, on cue-induced reinstatement of heroin seeking and heroin conditioned place preference (CPP). In experiment 1, rats were trained to self-administer intravenous heroin for 15 days followed by extinction. Following extinction animals were treated with one of several SR 21502 doses (0, 7.5, 10 or 15mg/kg) and a cue-induced reinstatement test was conducted. In experiment 2, animals were conditioned to experience heroin in one compartment of a CPP apparatus and saline in the other. On the test day animals were treated with 0, 3.75, 7.5, 10 or 15mg/kg of SR 21502 and tested for their CPP. The results from experiment 1 showed a significant dose-related reduction in cue-induced reinstatement of active lever pressing in the 7.5 and 10mg groups and an absence of the reinstatement effect in the 15mg group. In experiment 2, animals treated with vehicle or 3.75mg of SR 21502 showed significant heroin place preferences but those treated with the higher doses showed no CPP. Our findings suggest that DA D3 receptors play a significant role in heroin approach behaviors driven by conditioned stimuli. As such, we propose that SR 21502 holds potential as an effective pharmacotherapeutic agent for relapse prevention and should be studied further. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. Orthoptic status before and immediately after heroin detoxification

    PubMed Central

    Firth, A Y; Pulling, S; Carr, M P; Beaini, A Y

    2004-01-01

    Aim: To determine whether changes in orthoptic status take place during withdrawal from heroin and/or methadone. Method: A prospective study of patients, using a repeated measures design, attending a 5 day naltrexone compressed opiate detoxification programme. Results: 83 patients were seen before detoxification (mean age 27.1 (SD 4.6) years) and 69 after detoxification. The horizontal angle of deviation became less exo/more eso at distance (p<0.001) but no significant change was found at near (p = 0.069). Stereoacuity, visual acuity, and convergence were found to be reduced in the immediate post-detoxification period. Prism fusion range, refractive error, subjective accommodation, and objective accommodation at 33 cm did not reduce but a small decrease was found in objective accommodation at 20 cm. Conclusions: The eso trend found in these patients may be responsible for the development of acute concomitant esotropia in some patients undergoing heroin detoxification. However, the mechanism for this trend does not appear to be caused by divergence insufficiency or sixth nerve palsy. PMID:15317713

  1. Acute recreational drug toxicity

    PubMed Central

    Liakoni, Evangelia; Yates, Christopher; Dines, Alison M.; Dargan, Paul I.; Heyerdahl, Fridtjof; Hovda, Knut Erik; Wood, David M.; Eyer, Florian; Liechti, Matthias E.

    2018-01-01

    Abstract The aim of the study was to compare self-reported and analytically confirmed substance use in cases of acute recreational drug toxicity. We performed a retrospective analysis of emergency department presentations of acute recreational drug toxicity over 2 years (October 2013 to September 2015) within the European Drug Emergencies Network Plus project. Among the 10,956 cases of acute recreational drug toxicity during the study period, 831 could be included. Between the self-reported substance use and the toxicological results, the highest agreement was found for heroin (86.1%) and cocaine (74.1%), whereas inhalants, poppers, and magic mushrooms were self-reported but not analytically detected. Cathinones and other new psychoactive substances (NPS) could be detected using additional analytical methods. Among cases with both immunoassay (IA) and confirmation with mass spectrometry (MS), the results were consistent for methadone (100%) and cocaine (95.5%) and less consistent for amphetamines (81.8%). In cases with a positive IA for amphetamines (n = 54), MS confirmed the presence of 3,4-methylenedioxymethamphetamine (MDMA), amphetamine, methamphetamine, and NPS in 37, 20, 10, and 6 cases, respectively, also revealing use of more than 1 substance in some cases. MS yielded positive results in 21 cases with a negative IA for amphetamines, including amphetamine, MDMA, methamphetamine, and NPS, in 14, 7, 2, and 2 cases, respectively. In conclusion, the highest agreement was found between self-reports and analytical findings for heroin and cocaine. The diagnosis of NPS use was mainly based on self-report. The IAs accurately identified methadone and cocaine, and MS had advantages for the detection of NPS and amphetamine derivatives. PMID:29384873

  2. Epidemiologic trends and geographic patterns of fatal opioid intoxications in Connecticut, USA: 1997-2007.

    PubMed

    Green, Traci C; Grau, Lauretta E; Carver, H Wayne; Kinzly, Mark; Heimer, Robert

    2011-06-01

    The leading cause of injury death among adults in Connecticut (CT), USA is drug poisonings. We analyzed the epidemiology and geographic distribution of opioid-involved accidental drug-involved intoxication deaths ("overdoses") in CT over an 11-year period. We reviewed data from 1997 to 2007 on all adult accidental/undetermined drug intoxication deaths in CT that were referred to the Office of the Chief Medical Examiner (OCME). Regression analyses were conducted to uncover risk factors for fatal opioid-involved intoxications and to compare heroin- to prescription opioid- and methadone-involved deaths. Death locations were mapped to visualize differences in the geographic patterns of overdose by opioid type. Of the 2900 qualifying deaths, 2231 (77%) involved opioids. Trends over time revealed increases in total opioid-related deaths although heroin-related deaths remained constant. Methadone, oxycodone and fentanyl, the most frequently cited prescription opioids, exhibited significant increases in opioid deaths. Prescription opioid-only deaths were more likely to involve other medications (e.g., benzodiazepines) and to have occurred among residents of a suburban or small town location, compared to heroin-involved or methadone-involved deaths. Heroin-only deaths tended to occur among non-Whites, were more likely to involve alcohol or cocaine and to occur in public locations and large cities. The epidemiology of fatal opioid overdose in CT exhibits distinct longitudinal, risk factor, and geographic differences by opioid type. Each of these trends has implications for public health and prevention efforts. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  3. Risks associated with crack cocaine smoking among exotic dancers in Baltimore, MD.

    PubMed

    Sherman, Susan G; Reuben, Jacqueline; Chapman, Chris Serio; Lilleston, Pamela

    2011-04-01

    There is a dearth of research focusing on sex work in exotic dance clubs. We conducted a cross-sectional study to examine the prevalence and correlates of crack cocaine smoking among a sample of exotic dancers. The "block," a historical red-light district in downtown Baltimore, MD, is comprised of 30 adult-entertainment establishments. Between 01/09 and 08/09, we conducted a survey with exotic dancers (N=98). The survey explored demographic, and drug and sexual/drug risk behaviors. Bivariate and multivariate analysis was conducted using Poisson regression with robust variance estimates to examine correlates of current crack smoking. Crack cocaine smokers compared to non-crack cocaine smokers were significantly more likely to report: older age (29 vs. 23 years, respectively, p<0.0001); being White (79% vs. 50%, respectively, p=0.008); having been arrested (93% vs. 67%, respectively, p=0.008); daily alcohol consumption (36% vs. 17%, p=0.047); current heroin injection (57% vs. 13%, p<0.001); and current sex exchange (79% vs. 30%, p<0.001). In the presence of other variables, crack cocaine smokers compared to non-crack cocaine smokers were significantly older, more likely to report current heroin injection, and more likely to report current sex exchange. We found high levels of drug use and sexual risk behaviors as well as a number of risks behaviors associated with crack cocaine smoking among this very under-studied population. Targeted interventions are greatly needed. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  4. Altered gray matter volume and disrupted functional connectivity of dorsolateral prefrontal cortex in men with heroin dependence.

    PubMed

    Lin, Huang-Chi; Wang, Peng-Wei; Wu, Hung-Chi; Ko, Chih-Hung; Yang, Yi-Hsin; Yen, Cheng-Fang

    2018-03-27

    Chronic heroin use can cause various neuropathological characteristics that may compromise brain function. The present study evaluated the alteration of gray matter volume (GMV) and its resting-state functional connectivity (rsFC) over the dorsolateral prefrontal cortex (DLPFC) among male heroin users. Thirty heroin-dependent men undergoing methadone maintenance therapy and 30 educational-level- and age-matched male controls were recruited for this study. To assess their GMV and rsFC, the participants were evaluated using spoiled gradient echo and gradient-recalled echo planar imaging sequences with a 3-Tesla General Electric MR scanner under resting state. The heroin-dependent men showed lower GMV over the right DLPFC in comparison with the controls. Further evaluation of the rsFC of the right DLPFC revealed a marked decrease in interhemispheric DLPFC connectivity among those with heroin dependence under control of head movement and GMV of the right DLPFC. Although the mechanism remains unclear, the present study shows that chronic heroin use is associated with alteration of morphology as well as rsFC over the right DLPFC. As the DLPFC plays an imperative role in various domains of cognitive function, service providers for heroin users should consider the impacts of possible DLPFC-related cognitive deficits on treatment effectiveness. © 2018 The Authors. Psychiatry and Clinical Neurosciences © 2018 Japanese Society of Psychiatry and Neurology.

  5. Buprenorphine Outpatient Outcomes Project: can Suboxone be a viable outpatient option for heroin addiction?

    PubMed Central

    Sittambalam, Charmian D.; Vij, Radhika; Ferguson, Robert P.

    2014-01-01

    Background Opioid dependence treatment traditionally involves methadone clinics, for which dispensing schedules can be cumbersome. Buprenorphine, a partial agonist of the mu receptor and antagonist of the kappa receptor, is a potential outpatient alternative to methadone. Funded by a grant from the State of Maryland's Community Health Resources Commission (CHRC), the Buprenorphine Outpatient Outcomes Project (BOOP) evaluates the outcome of Suboxone (buprenorphine/naloxone) treatment on abstinence from heroin use, rates of emergency room visits and hospitalizations, legal issues, and quality of life. Methods Active heroin users were recruited between June 2007 and June 2010 and induction therapy with Suboxone was instituted during hospitalization. Once discharged, patients were followed as outpatients for maintenance treatment and counseling. Data were collected from electronic medical records, Maryland state legal records, and SF-36® Health Surveys regarding several parameters and patients were categorized according to duration of treatment with Suboxone into one of three groups: <1 month, 1–3 months, and >3 months. Results A total of 220 participants were included in the study. The age range of participants was 18–67 years with most being African American males. Eighty-three (38%) remained in the study for at least 1 month, with 37 of the 83 (45%) remaining in treatment for >3 months. Ten of the 37 (27%) never relapsed after their longest period of abstinence from heroin. During the first year after initiating treatment with Suboxone, hospitalization and emergency room visit rates for all 220 participants decreased by 45 and 23%, respectively, as compared to the year prior to starting treatment. The number of legal charges for drug possession decreased from 70 to 62. Anecdotally, the quality of life seemed to improve in those who were treated with Suboxone for longer periods of time and received regular counseling. Conclusion Overall, Suboxone is an effective

  6. Can methadone maintenance for heroin-dependent patients retained in general practice reduce criminal conviction rates and time spent in prison?

    PubMed Central

    Keen, J; Rowse, G; Mathers, N; Campbell, M; Seivewright, N

    2000-01-01

    A retrospective analysis was made of the criminal records of 57 patients successfully retained in methadone maintenance at two general practices in Sheffield. Their criminal conviction rates and time spent in prison per year were compared for the periods before and after the start of their methadone programme. Overall, patients retained on methadone programmes in the general practices studied had significantly fewer convictions and cautions, and spent significantly less time in prison than they had before the start of treatment. PMID:10695069

  7. Validation of an automated solid-phase extraction method for the analysis of 23 opioids, cocaine, and metabolites in urine with ultra-performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Ramírez Fernández, María del Mar; Van Durme, Filip; Wille, Sarah M R; di Fazio, Vincent; Kummer, Natalie; Samyn, Nele

    2014-06-01

    The aim of this work was to automate a sample preparation procedure extracting morphine, hydromorphone, oxymorphone, norcodeine, codeine, dihydrocodeine, oxycodone, 6-monoacetyl-morphine, hydrocodone, ethylmorphine, benzoylecgonine, cocaine, cocaethylene, tramadol, meperidine, pentazocine, fentanyl, norfentanyl, buprenorphine, norbuprenorphine, propoxyphene, methadone and 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine from urine samples. Samples were extracted by solid-phase extraction (SPE) with cation exchange cartridges using a TECAN Freedom Evo 100 base robotic system, including a hydrolysis step previous extraction when required. Block modules were carefully selected in order to use the same consumable material as in manual procedures to reduce cost and/or manual sample transfers. Moreover, the present configuration included pressure monitoring pipetting increasing pipetting accuracy and detecting sampling errors. The compounds were then separated in a chromatographic run of 9 min using a BEH Phenyl analytical column on a ultra-performance liquid chromatography-tandem mass spectrometry system. Optimization of the SPE was performed with different wash conditions and elution solvents. Intra- and inter-day relative standard deviations (RSDs) were within ±15% and bias was within ±15% for most of the compounds. Recovery was >69% (RSD < 11%) and matrix effects ranged from 1 to 26% when compensated with the internal standard. The limits of quantification ranged from 3 to 25 ng/mL depending on the compound. No cross-contamination in the automated SPE system was observed. The extracted samples were stable for 72 h in the autosampler (4°C). This method was applied to authentic samples (from forensic and toxicology cases) and to proficiency testing schemes containing cocaine, heroin, buprenorphine and methadone, offering fast and reliable results. Automation resulted in improved precision and accuracy, and a minimum operator intervention, leading to safer sample

  8. ABCB1 genetic variability and methadone dosage requirements in opioid-dependent individuals.

    PubMed

    Coller, Janet K; Barratt, Daniel T; Dahlen, Karianne; Loennechen, Morten H; Somogyi, Andrew A

    2006-12-01

    The most common treatment for opioid dependence is substitution therapy with another opioid such as methadone. The methadone dosage is individualized but highly variable, and program retention rates are low due in part to nonoptimal dosing resulting in withdrawal symptoms and further heroin craving and use. Methadone is a substrate for the P-glycoprotein transporter, encoded by the ABCB1 gene, which regulates central nervous system exposure. This retrospective study aimed to investigate the influence of ABCB1 genetic variability on methadone dose requirements. Genomic deoxyribonucleic acid was isolated from opioid-dependent subjects (n = 60) and non-opioid-dependent control subjects (n = 60), and polymerase chain reaction-restriction fragment length polymorphism and allele-specific polymerase chain reaction were used to determine the presence of single nucleotide polymorphisms at positions 61, 1199, 1236, 2677, and 3435. ABCB1 haplotypes were inferred with PHASE software (version 2.1). There were no significant differences in the allele or genotype frequencies of the individual single nucleotide polymorphisms or haplotypes between the 2 populations. ABCB1 genetic variability influenced daily methadone dose requirements, such that subjects carrying 2 copies of the wild-type haplotype required higher doses compared with those with 1 copy and those with no copies (98.3 +/- 10.4, 58.6 +/- 20.9, and 55.4 +/- 26.1 mg/d, respectively; P = .029). In addition, carriers of the AGCTT haplotype required significantly lower doses than noncarriers (38.0 +/- 16.8 and 61.3 +/- 24.6 mg/d, respectively; P = .04). Although ABCB1 genetic variability is not related to the development of opioid dependence, identification of variant haplotypes may, after larger prospective studies have been performed, provide clinicians with a tool for methadone dosage individualization.

  9. When is coercive methadone therapy justified?

    PubMed

    D'Hotman, Daniel; Pugh, Jonathan; Douglas, Thomas

    2018-06-08

    Heroin use poses a significant health and economic burden to society, and individuals with heroin dependence are responsible for a significant amount of crime. Owing to its efficacy and cost-effectiveness, methadone maintenance therapy (MMT) is offered as an optional alternative to imprisonment for drug offenders in several jurisdictions. Some object to such 'MMT offers' on the basis that they involve coercion and thus invalidate the offender's consent to MMT. While we find these arguments unpersuasive, we do not attempt to build a case against them here. Instead, we explore whether administration of MMT following acceptance of an MMT offer might be permissible even on the assumption that MMT offers are coercive, and in such a way that the resulting MMT is non-consensual. We argue that non-consensual MMT following an MMT offer is typically permissible. We first offer empirical evidence to demonstrate the substantial benefits to the offender and society of implementing non-consensual MMT in the criminal justice system. We then explore and respond to potential objections to such uses of MMT. These appeal respectively to harm, autonomy, bodily and mental interference, and penal theoretic considerations. Finally, we introduce and dismiss a potential response to our argument that takes a revisionist position, rejecting prevailing incarceration practices. © 2018 John Wiley & Sons Ltd.

  10. Relationship between alcohol consumption, whether linked to other substance use or not, and antiretroviral treatment adherence in HIV+ patients.

    PubMed

    González-Álvarez, Sara; Madoz-Gúrpide, Agustín; Parro-Torres, Carlos; Hernández-Huerta, Daniel; Ochoa Mangado, Enriqueta

    2017-07-14

    Hazardous alcohol consumption is a common diagnosis among people living with HIV infection. The relationship between alcohol consumption and poor adherence to antiretroviral therapy has been highlighted in different studies, yet few of them performed a parallel analysis of other substance use. In Spain, alcohol consumption is frequently associated with other substance use, mainly cannabis and cocaine. The aim of this study is to assess the influence of hazardous alcohol consumption both combined with other substances (cocaine, heroin, methadone and/or cannabis) or alone on antiretroviral therapy adherence in our social environment. We performed an observational case-control study including 119 HIV+ individuals. We recruited 40 non-adherent patients, defined by less than 90% compliance according to hospital pharmacy refill data, and corroborated by the Simplified Medication Adherence Questionnaire (SMAQ) and referring professional's opinion. Control cases (n=79) were defined as those patients with similar characteristics but considered adherent according to the same parameters. Data collection took place between May 2013 and September 2015. Statistical analysis was performed using a binary logistic regression model. Our results indicate that alcohol consumption decreases adherence to antiretroviral therapy. The use of methadone represents a statistically significant increased risk of poor adherence. No significant differences were found between adherent and non-adherent groups regarding cocaine, heroin or cannabis use in this study. In summary, the detection of substance use and especially alcohol consumption in HIV+ patients can improve the effectiveness of antiretroviral therapy by identifying and treating at-risk individuals for a poor therapeutic adherence.

  11. The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS) project: an open-label pragmatic randomised control trial comparing the efficacy of differing therapeutic agents for primary care detoxification from either street heroin or methadone [ISRCTN07752728].

    PubMed

    Oldham, Nicola S; Wright, Nat M J; Adams, Clive E; Sheard, Laura; Tompkins, Charlotte N E

    2004-04-29

    Heroin is a synthetic opioid with an extensive illicit market leading to large numbers of people becoming addicted. Heroin users often present to community treatment services requesting detoxification and in the UK various agents are used to control symptoms of withdrawal. Dissatisfaction with methadone detoxification 8 has lead to the use of clonidine, lofexidine, buprenorphine and dihydrocodeine; however, there remains limited evaluative research. In Leeds, a city of 700,000 people in the North of England, dihydrocodeine is the detoxification agent of choice. Sublingual buprenorphine, however, is being introduced. The comparative value of these two drugs for helping people successfully and comfortably withdraw from heroin has never been compared in a randomised trial. Additionally, there is a paucity of research evaluating interventions among drug users in the primary care setting. This study seeks to address this by randomising drug users presenting in primary care to receive either dihydrocodeine or buprenorphine. The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS) project is a pragmatic randomised trial which will compare the open use of buprenorphine with dihydrocodeine for illicit opiate detoxification, in the UK primary care setting. The LEEDS project will involve consenting adults and will be run in specialist general practice surgeries throughout Leeds. The primary outcome will be the results of a urine opiate screening at the end of the detoxification regimen. Adverse effects and limited data to three and six months will be acquired.

  12. The effect of a jail methadone maintenance therapy (MMT) program on inmate recidivism.

    PubMed

    McMillan, Garnett P; Lapham, Sandra; Lackey, Michael

    2008-12-01

    To evaluate the effects of a jail-based continuation of methadone maintenance therapy (MMT) on subsequent inmate recidivism risks. Prospective, longitudinal, observational study. A large, Southwestern United States jail that continues MMT for heroin-addicted inmates on MMT at the time of booking. A total of 589 inmates booked between 22 November 2005 (the start date for the MMT program) and 31 October 2006. The outcome measure was time from release to subsequent re-booking in the jail. Predictors included binary dosing with methadone in the jail, final dose received (mg), age, gender, race/ethnicity, previous bookings and days in jail. Random effects Weibull proportional hazards models were fit to the recidivism times to estimate the impact of treatment with MMT in the jail on re-booking risks. There was no statistically significant effect of receiving methadone in the jail or dosage on subsequent recidivism risks (hazard ratio = 1.16; 95% confidence interval = 0.8-1.68). Offering jail-based MMT does not increase recidivism risks by eliminating the deterrent effect of imposed withdrawal, nor does it reduce recidivism in this high-risk population.

  13. The drug use behaviour of cocaine users.

    PubMed

    Moosburger, R; Plant, A J; Pierce, J P

    1990-01-01

    We interviewed 50 current cocaine users with the aim of providing insights into cocaine use in Sydney. The study sample was obtained by one researcher using a chain referral technique. Appointments were made for interview and the interview aimed to determine the quantity, frequency, pattern and circumstances of drug use in the respondents. The study sample included people with a wide range of incomes and occupations; all but one person were employed. Extensive current drug use was reported; 78% smoked tobacco, 98% drank alcohol with 36% having more than two drinks per day, 96% used marijuana with 40% smoking marijuana at least 5 times per week, 65% used amphetamines, 36% used hallucinogens and 10% used heroin. Ten per cent were unable to name one health risk of cocaine. When asked about the image of a cocaine user, 42% thought of a rock star, film industry worker or someone involved in the arts and entertainment world. The information obtained from a study such as this provides important data for targeting of people in anti-drug campaigns.

  14. Monitoring Pregnant Women’s Illicit Opiate and Cocaine Use With Sweat Testing

    PubMed Central

    Brunet, Bertrand R.; Barnes, Allan J.; Choo, Robin E.; Mura, Patrick; Jones, Hendrée E.; Huestis, Marilyn A.

    2011-01-01

    Dependence on illicit drugs during pregnancy is a major public health concern as there may be associated adverse maternal, fetal, and neonatal consequences. Sweat patches (n = 389) were collected from 39 pregnant volunteers who provided written informed consent for this Institutional Review Board-approved protocol and wore patches, replaced approximately weekly, from study entry until delivery. Patches were analyzed for opiates (heroin, 6-acetylmor-phine, 6-acetylcodeine, morphine and codeine) and cocaine (cocaine, benzoylecgonine, ecgonine methyl ester, anhydroecgonine methyl ester) by solid phase extraction and gas chromatography mass spectrometry. Seventy-one percent (276) of collected sweat patches were ≥5 ng per patch (limit of quantification) for one or more analytes. Cocaine was present in 254 (65.3%) patches in concentrations ranging from 5.2 to 11,835 ng per patch with 154 of these high enough to satisfy the proposed Substance Abuse and Mental Health Services Administration guidelines for a confirmatory drug test (25 ng per patch). Interestingly, 6-acetylmorphine was the most prominent opiate analyte documented in 134 patches (34.4%) with 11.3% exceeding the proposed opiate Substance Abuse and Mental Health Services Administration cut-off (25 ng per patch). Heroin was identified in fewer patches (77), but in a similar concentration range (5.3–345.4 ng per patch). Polydrug use was evident by the presence of both cocaine and opiate metabolites in 136 (35.0%) patches. Sweat testing is an effective method for monitoring abstinence or illicit drug use relapse in this high-risk population of pregnant opiate- and/or cocaine-dependent women. PMID:19927046

  15. TGI Monday?: drug-dependent outpatients report lower stress and more happiness at work than elsewhere.

    PubMed

    Epstein, David H; Preston, Kenzie L

    2012-01-01

    In the general population, experience-sampling studies show that work is the aspect of daily life most associated with momentary unhappiness and a desire to be elsewhere. We assessed whether this holds true for urban outpatients in treatment for heroin and cocaine dependence. In a 25-week natural-history study, 79 employed methadone-maintained misusers of heroin and cocaine carried electronic diaries on which mood and behavior were assessed up to five times per day. Being at work was associated with lower stress, greater happiness, and lower drug craving. Work accounted for 14% of the variance in stress, 30% of the variance in happiness, and 50% of the variance in cocaine craving. Participants with skilled jobs reported more positive and less negative mood states (and lower cocaine craving) at all times compared to participants with semi/unskilled jobs, although the latter reported greater mood improvement at work. In all participants, mood improvements occurred specifically in the presence of coworkers (not other companions). Our seemingly unusual findings might be specific to substance-disorder patients (for whom work may be a respite from drug-using companions), but might also hold for other urban dwellers of similar socioeconomic backgrounds (for whom work may be a respite from environmental stressors). Copyright © American Academy of Addiction Psychiatry.

  16. TGI Monday?: Drug-Dependent Outpatients Report Lower Stress and More Happiness at Work than Elsewhere

    PubMed Central

    Epstein, David H.; Preston, Kenzie L.

    2013-01-01

    In the general population, experience-sampling studies show that work is the aspect of daily life most associated with momentary unhappiness and a desire to be elsewhere. We assessed whether this holds true for urban outpatients in treatment for heroin and cocaine dependence. In a 25-week natural-history study, 79 employed methadone-maintained misusers of heroin and cocaine carried electronic diaries on which mood and behavior were assessed up to five times per day. Being at work was associated with lower stress, greater happiness, and lower drug craving. Work accounted for 14% of the variance in stress, 30% of the variance in happiness, and 50% of the variance in cocaine craving. Participants with skilled jobs reported more positive and less negative mood states (and lower cocaine craving) at all times compared to participants with semi/unskilled jobs, although the latter reported greater mood improvement at work. In all participants, mood improvements occurred specifically in the presence of coworkers (not other companions). Our seemingly unusual findings might be specific to substance-disorder patients (for whom work may be a respite from drug-using companions), but might also hold for other urban dwellers of similar socioeconomic backgrounds (for whom work may be a respite from environmental stressors). PMID:22494220

  17. Methadone and buprenorphine prescribing and referral practices in US prison systems: results from a nationwide survey.

    PubMed

    Nunn, Amy; Zaller, Nickolas; Dickman, Samuel; Trimbur, Catherine; Nijhawan, Ank; Rich, Josiah D

    2009-11-01

    More than 50% of incarcerated individuals have a history of substance use, and over 200,000 individuals with heroin addiction pass through American correctional facilities annually. Opiate replacement therapy (ORT) with methadone or buprenorphine is an effective treatment for opiate dependence and can reduce drug-related disease and recidivism for inmates. Provision of ORT is nevertheless a frequently neglected intervention in the correctional setting. We surveyed the 50 state; Washington, District of Columbia (DC); and Federal Department of Corrections' medical directors or their equivalents about their facilities' ORT prescribing policies and referral programs for inmates leaving prison. We received responses from 51 of 52 prison systems nationwide. Twenty-eight prison systems (55%) offer methadone to inmates in some situations. Methadone use varies widely across states: over 50% of correctional facilities that offer methadone do so exclusively for pregnant women or for chronic pain management. Seven states' prison systems (14%) offer buprenorphine to some inmates. The most common reason cited for not offering ORT was that facilities "prefer drug-free detoxification over providing methadone or buprenorphine." Twenty-three states' prison systems (45%) provide referrals for some inmates to methadone maintenance programs after release, which increased from 8% in 2003; 15 states' prison systems (29%) provide some referrals to community buprenorphine providers. Despite demonstrated social, medical, and economic benefits of providing ORT to inmates during incarceration and linkage to ORT upon release, many prison systems nationwide still do not offer pharmacological treatment for opiate addiction or referrals for ORT upon release.

  18. Methadone and Buprenorphine Prescribing and Referral Practices in US Prison Systems: Results from a Nationwide Survey

    PubMed Central

    Nunn, Amy; Zaller, Nickolas; Dickman, Samuel; Trimbur, Catherine; Nijhawan, Ank; Rich, Josiah D.

    2009-01-01

    Background More than 50% of incarcerated individuals have a history of substance use, and over 200,000 individuals with heroin addiction pass through American correctional facilities annually. Opiate replacement therapy (ORT) with methadone or buprenorphine is an effective treatment for opiate dependence and can reduce drug-related disease and recidivism for inmates. Provision of ORT is nevertheless a frequently neglected intervention in the correctional setting. Objective and Methods We surveyed the 50 state; Washington, District of Columbia (DC); and Federal Department of Corrections' medical directors or their equivalents about their facilities' ORT prescribing policies and referral programs for inmates leaving prison. Results We received responses from 51 of 52 prison systems nationwide. Twenty-eight prison systems (55%) offer methadone to inmates in some situations. Methadone use varies widely across states: over 50% of correctional facilities that offer methadone do so exclusively for pregnant women or for chronic pain management. Seven states' prison systems (14%) offer buprenorphine to some inmates. The most common reason cited for not offering ORT was that facilities “prefer drug-free detoxification over providing methadone or buprenorphine.” Twenty-three states' prison systems (45%) provide referrals for some inmates to methadone maintenance programs after release, which increased from 8% in 2003; 15 states' prison systems (29%) provide some referrals to community buprenorphine providers. Conclusion Despite demonstrated social, medical, and economic benefits of providing ORT to inmates during incarceration and linkage to ORT upon release, many prison systems nationwide still do not offer pharmacological treatment for opiate addiction or referrals for ORT upon release. PMID:19625142

  19. Sleep in lonely heroin-dependent patients receiving methadone maintenance treatment: longer sleep latency, shorter sleep duration, lower sleep efficiency, and poorer sleep quality.

    PubMed

    Li, Hong-Jie; Zhong, Bao-Liang; Xu, Yan-Min; Zhu, Jun-Hong; Lu, Jin

    2017-10-24

    Given the socially isolated status of Chinese heroin-dependent patients (HDPs) and the significant association between loneliness and sleep problem in the general population, the impact of loneliness on sleep of HDPs is potentially substantial. The study aimed to test whether loneliness is associated with poor sleep in terms of quantity and quality in a consecutive sample of Chinese HDPs receiving methadone maintenance treatment (MMT). The study participants were 603 HDPs of three MMT clinics in Wuhan, China. Data on socio-demographic and clinical characteristics were collected by a standardized self-administered questionnaire. Sleep outcomes included sleep latency, sleep duration, sleep efficiency, and sleep quality. We measured depressive symptoms, loneliness, and sleep quality by using Zung's Self-rating Depression Scale, the single-item self-report of loneliness, and the Pittsburgh Sleep Quality Index, respectively. Multiple linear regression was used to examine whether loneliness is independently associated with sleep measures. After controlling for the confounding effects of potential socio-demographic and clinical variables, loneliness was significantly associated with longer sleep latency, shorter sleep duration, lower sleep efficiency, and poorer sleep quality. Loneliness may exacerbate sleep disturbance in Chinese HDPs of MMT clinics. Psychosocial interventions aimed at reducing loneliness in MMT clinics would improve the sleep of HDPs.

  20. Extensive Necrotic Purpura in Levamisole-Adulterated Cocaine Abuse - A Case Report.

    PubMed

    Le Garff, Erwan; Tournel, Gilles; Becquart, Coralie; Cottencin, Olivier; Dupin, Nicolas; Delaporte, Emmanuel; Hedouin, Valéry

    2016-11-01

    Levamisole, which is used as an adulterated compound of cocaine, is currently being seen year after year in cocaine intoxication. For a few cases in the last decade, necrotic purpura and neutropenia after levamisole/cocaine intoxication have been described in the medical community. Herein, we present an original case of levamisole intoxication of a 40-year-old woman who smoked heroin and cocaine few during a month. She rapidly presented an extensive necrotic purpura of the nose, cheeks and extremities (lower and upper), and immunologic reactions (positive anti-MPO and anti-HNE). Levamisole was detected on hairs with ultra-high performance liquid chromatography and tandem mass spectrometry. The case reports also a probable cocaine supplier deceit, which bring pure drug for hospital investigation after the intoxication of his client. The intoxicated woman had survived with several skin and chronic pain complications. That case recalls the knowledge about levamisole with a short review of the forensic literature. © 2016 American Academy of Forensic Sciences.

  1. Substitution of (R,S)-methadone by (R)-methadone: Impact on QTc interval.

    PubMed

    Ansermot, Nicolas; Albayrak, Ozgür; Schläpfer, Jürg; Crettol, Séverine; Croquette-Krokar, Marina; Bourquin, Michel; Déglon, Jean-Jacques; Faouzi, Mohamed; Scherbaum, Norbert; Eap, Chin B

    2010-03-22

    Methadone is administered as a chiral mixture of (R,S)-methadone. The opioid effect is mainly mediated by (R)-methadone, whereas (S)-methadone blocks the human ether-à-go-go-related gene (hERG) voltage-gated potassium channel more potently, which can cause drug-induced long QT syndrome, leading to potentially lethal ventricular tachyarrhythmias. To investigate whether substitution of (R,S)-methadone by (R)-methadone could reduce the corrected QT (QTc) interval, (R,S)-methadone was replaced by (R)-methadone (half-dose) in 39 opioid-dependent patients receiving maintenance treatment for 14 days. (R)-methadone was then replaced by the initial dose of (R,S)-methadone for 14 days (n = 29). Trough (R)-methadone and (S)-methadone plasma levels and electrocardiogram measurements were taken. The Fridericia-corrected QT (QTcF) interval decreased when (R,S)-methadone was replaced by a half-dose of (R)-methadone; the median (interquartile range [IQR]) values were 423 (398-440) milliseconds (ms) and 412 (395-431) ms (P = .06) at days 0 and 14, respectively. Using a univariate mixed-effect linear model, the QTcF value decreased by a mean of -3.9 ms (95% confidence interval [CI], -7.7 to -0.2) per week (P = .04). The QTcF value increased when (R)-methadone was replaced by the initial dose of (R,S)-methadone for 14 days; median (IQR) values were 424 (398-436) ms and 424 (412-443) ms (P = .01) at days 14 and 28, respectively. The univariate model showed that the QTcF value increased by a mean of 4.7 ms (95% CI, 1.3-8.1) per week (P = .006). Substitution of (R,S)-methadone by (R)-methadone reduces the QTc interval value. A safer cardiac profile of (R)-methadone is in agreement with previous in vitro and pharmacogenetic studies. If the present results are confirmed by larger studies, (R)-methadone should be prescribed instead of (R,S)-methadone to reduce the risk of cardiac toxic effects and sudden death.

  2. Humanizing folk devils using ethnography.

    PubMed

    Myers, Peter L

    2018-01-01

    The sociological concepts of the "moral panic" and the deviant "folk devil" apply to the drug panics in the United States over methamphetamine, heroin, and crack cocaine. Mothers or pregnant women who smoke crack cocaine, and their babies, are assigned exaggerated "demonic" attributes that result in stigma and societal rejection. Otherwise, ethnographic studies of drug users demonstrate realities that are other than what might be considered were one to merely look at their use and the consequences. These considerations are examined with respect to the image of folk devils, methadone program attendees, smokers of "blunts," opium den habitués, and others grouped together as negative influences as a result of their drug habits.

  3. Noni (Morinda citrifolia L.) fruit extract attenuates the rewarding effect of heroin in conditioned place preference but not withdrawal in rodents

    PubMed Central

    Narasingam, Megala; Pandy, Vijayapandi; Mohamed, Zahurin

    2016-01-01

    The present study was designed to investigate the effect of a methanolic extract of Morinda citrifolia Linn. fruit (MMC) on the rewarding effect of heroin in the rat conditioned place preference (CPP) paradigm and naloxone-precipitated withdrawal in mice. In the first experiment, following a baseline preference test (preconditioning score), the rats were subjected to conditioning trials with five counterbalanced escalating doses of heroin versus saline followed by a preference test conducted under drug-free conditions (post-conditioning score) using the CPP test. Meanwhile, in the second experiment, withdrawal jumping was precipitated by naloxone administration after heroin dependence was induced by escalating doses for 6 days (3×/ day). The CPP test results revealed that acute administration of MMC (1, 3, and 5 g/kg body weight (bw), p.o.), 1 h prior to the CPP test on the 12th day significantly reversed the heroin-seeking behavior in a dose-dependent manner, which was similar to the results observed with a reference drug, methadone (3 mg/kg bw, p.o.). On the other hand, MMC (0.5, 1, and 3 g/kg bw, p.o.) did not attenuate the heroin withdrawal jumps precipitated by naloxone. These findings suggest that the mechanism by which MMC inhibits the rewarding effect of heroin is distinct from naloxone-precipitated heroin withdrawal. PMID:26744024

  4. Noni (Morinda citrifolia L.) fruit extract attenuates the rewarding effect of heroin in conditioned place preference but not withdrawal in rodents.

    PubMed

    Narasingam, Megala; Pandy, Vijayapandi; Mohamed, Zahurin

    2016-05-20

    The present study was designed to investigate the effect of a methanolic extract of Morinda citrifolia Linn. fruit (MMC) on the rewarding effect of heroin in the rat conditioned place preference (CPP) paradigm and naloxone-precipitated withdrawal in mice. In the first experiment, following a baseline preference test (preconditioning score), the rats were subjected to conditioning trials with five counterbalanced escalating doses of heroin versus saline followed by a preference test conducted under drug-free conditions (post-conditioning score) using the CPP test. Meanwhile, in the second experiment, withdrawal jumping was precipitated by naloxone administration after heroin dependence was induced by escalating doses for 6 days (3×/ day). The CPP test results revealed that acute administration of MMC (1, 3, and 5 g/kg body weight (bw), p.o.), 1 h prior to the CPP test on the 12th day significantly reversed the heroin-seeking behavior in a dose-dependent manner, which was similar to the results observed with a reference drug, methadone (3 mg/kg bw, p.o.). On the other hand, MMC (0.5, 1, and 3 g/kg bw, p.o.) did not attenuate the heroin withdrawal jumps precipitated by naloxone. These findings suggest that the mechanism by which MMC inhibits the rewarding effect of heroin is distinct from naloxone-precipitated heroin withdrawal.

  5. Methadone and Metabolites in Hair of Methadone-Assisted Pregnant Women and Their Infants

    PubMed Central

    Himes, Sarah K; Goodwin, Robert S; Rock, Colleen M; Jones, Hendrée E; Johnson, Rolley E; Wilkins, Diana G; Huestis, Marilyn A

    2012-01-01

    Methadone is the recommended pharmacotherapy for opioid-dependent pregnant women. The primary aims of this study were to determine whether a dose-concentration relationship exists between cumulative maternal methadone dose, methadone and metabolite concentrations in maternal hair during pregnancy and whether maternal hair methadone and metabolite concentrations predict neonatal outcomes. Materials and Methods Hair specimens were collected monthly from opioid-dependent mothers enrolled in methadone treatment and 4 of their infants. Hair specimens were segmented (3cm), washed (maternal hair only) and analyzed for methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) and 2-ethyl-5-methyl-3,3-diphenylpyrroline (EMDP) by liquid chromatography tandem mass spectrometry. Results There was large inter-subject variability and no dose-concentration relationship for cumulative methadone dose and methadone, EDDP, EMDP or total concentrations in hair. For individual women, a positive trend was noted for cumulative methadone dose and methadone and EDDP concentrations in hair. There was a positive linear trend for cumulative methadone dose and EDDP/methadone ratio in maternal hair, perhaps reflecting methadone’s induction of its own metabolism. Maternal methadone concentrations were higher than those in infant hair, and infant EDDP hair concentrations were higher than those in maternal hair. Maternal methadone dose, and methadone and EDDP hair concentrations were not correlated with peak infant neonatal abstinence syndrome (NAS) scores, days to peak NAS, duration of NAS, time to NAS onset, birth length, head circumference or amount of neonatal morphine pharmacotherapy. Maternal cumulative 3rd trimester methadone dose was positively correlated with infant birth weight. Conclusion Methadone and EDDP in pregnant women’s hair are markers of methadone exposure and do not predict total methadone dose, nor neonatal outcomes from in utero methadone exposure. PMID

  6. Neuropsychological functioning in buprenorphine maintained patients versus abstinent heroin abusers on naltrexone hydrochloride therapy.

    PubMed

    Messinis, Lambros; Lyros, Epameinondas; Andrian, Virginia; Katsakiori, Paraskevi; Panagis, George; Georgiou, Vasileios; Papathanasopoulos, Panagiotis

    2009-10-01

    Methadone and buprenorphine are among the most widely employed pharmacological treatments currently available for opioid addiction. Cognitive effects of buprenorphine in abstinent heroin abusers are nevertheless far from being understood. Neuropsychological performance of 18 buprenorphine-maintained patients (BMP) was evaluated relative to that of 32 currently abstinent heroin abusers on naltrexone hydrochloride therapy (FHAN), and 34 non-drug dependent controls. The three groups were demographically balanced. Clinical groups reported histories of similar patterns of drug use and had increased periods of abstinence from any illicit substance use including heroin. The BMP group performed poorer than controls on the RAVLT (encoding and delayed recall of verbal information), CTT (conceptual flexibility, executive functions) and the RBANS figure copy (visual perception) and delayed recall of visual information. There were no significant differences in any of the cognitive measures between the BMP and FHAN groups or between the FHAN group and controls. Furthermore, the non-differing percentage of abnormal cases between the two patient groups led us to infer that treatment with either BPM or FHAN is not accompanied by qualitative differences in the cognitive profiles of these patients. Overall, results suggest that treatment with naltrexone in abstinent heroin abusers may result in less impairment of cognitive functions compared to treatment with buprenorphine. These findings are relevant for improved prognosis and treatment strategies in opioid dependence.

  7. Acute effects of heroin on emotions in heroin-dependent patients.

    PubMed

    Blum, Julia; Gerber, Hana; Gerhard, Urs; Schmid, Otto; Petitjean, Sylvie; Riecher-Rössler, Anita; Wiesbeck, Gerhard A; Borgwardt, Stefan J; Walter, Marc

    2013-01-01

    Euphoria has been described in heroin-dependent individuals after heroin administration. However, affective disturbances and disorders are common in heroin dependence. The present study examined the acute effects of heroin on emotions in heroin-dependent patients. This randomized controlled crossover trial included 28 heroin-dependent patients (67.9% male, n = 19) in stable heroin-assisted treatment and 20 healthy controls. The patients were administered heroin or saline (placebo), the controls were administered saline. Data measuring mood, affects and heroin craving (BDI, AMRS, STAI, STAXI, and HCQ) were assessed before and 60 minutes after substance injection. Before substance injection, heroin-dependent patients showed significantly higher levels of anxiety and depression than healthy controls (p < .0001). Heroin administration-but not placebo administration-was associated with a significant decrease in all negative emotions, including craving, and a significant increase in emotional well-being (p < .0001), irrespective of perceived intoxication and sedation. After the experiment, the patients did not differ from healthy controls in their emotions, once they had received heroin. Heroin dampens craving, negative emotions, and increases positive emotions. These findings indicate that heroin regulates emotions and underscore the clinical benefit of opioid substitution treatment for heroin-dependent patients. Copyright © American Academy of Addiction Psychiatry.

  8. Immunological screening of drugs of abuse and gas chromatographic-mass spectrometric confirmation of opiates and cocaine in hair.

    PubMed

    Segura, J; Stramesi, C; Redón, A; Ventura, M; Sanchez, C J; González, G; San, L; Montagna, M

    1999-03-05

    The work presents an analytical strategy to detect drugs of abuse in hair. It involves two sequential steps: a screening by a simple enzyme-linked immunosorbent assay (ELISA) methodology to detect opiates, cocaine and its metabolites, and benzodiacepines, followed by confirmation of opiates and cocaine metabolites in positive samples by gas chromatography coupled to mass spectrometry (GC-MS). In the same GC-MS run other drugs for substitution therapy (e.g. methadone and its main metabolite) can also be detected. After a double washing of hair samples with dichloromethane, hair specimens were cut into small pieces and 10 mg samples were incubated in 2 ml of methanol-trifluoroacetic acid (9:1) mixture, overnight at 37 degrees C. Aliquots of the extract were then evaporated, reconstituted in buffer and analysed according to the ELISA procedure. Confirmation involved solid-phase extraction of another fraction of the extract kept at -20 degrees C, derivatization with heptafluorobutyric anhydride and hexafluoroisopropanol and detection of cocaine, benzoylecgonine, ecgonine methylester, cocaethylene, morphine, codeine, 6-monoacetylmorphine, methadone and 2-ethylidene-1.5-dimethyl-3,3-diphenylpirrolidine (methadone metabolite) by selective ion monitoring after gas chromatographic separation. During the development of the method it was verified that no more than 10% of cocaine, opiates and benzodiacepines were lost when dichloromethane was used to wash real samples. The results also confirmed the increase of extractability power of TFA when it was added to methanol: the recovery for the analytes (cocaine and its metabolites and opiates) added to methanol-TFA alone was of the order of 90% except for benzoylecgonine (75%), and the recovery for the analytes added to methanol-TFA extract of drug-free hair was about 90% for all analytes except for benzoylecgonine and 6-MAM (around 70%). Regarding the stability of labile compounds, only small amounts of ecgonine methylester (2

  9. Methadone.

    PubMed

    Chhabra, Shalini; Bull, Janet

    2008-01-01

    Methadone hydrochloride is an old drug that has been in vogue off and on. It has complex pharmacodynamics and can be potentially fatal in inexperienced settings. Drug switching from an opioid to methadone or vice versa requires knowledge of equianalgesic dosing. It is critical when using the drug to monitor for signs and symptoms of toxicity so that overdosing or toxicity can be identified in a timely manner. This review discusses these important topics so that methadone can be used safely and effectively.

  10. Activation of AMPA receptor in the infralimbic cortex facilitates extinction and attenuates the heroin-seeking behavior in rats.

    PubMed

    Chen, Weisheng; Wang, Yiqi; Sun, Anna; Zhou, Linyi; Xu, Wenjin; Zhu, Huaqiang; Zhuang, Dingding; Lai, Miaojun; Zhang, Fuqiang; Zhou, Wenhua; Liu, Huifen

    2016-01-26

    Infralimbic cortex (IL) is proposed to suppress cocaine seeking after extinction, but whether the IL regulates the extinction and reinstatement of heroin-seeking behavior is unknown. To address this issue, the male SD rats were trained to self-administer heroin under a FR1 schedule for consecutive 14 days, then the rats underwent 7 daily 2h extinction session in the operant chamber. The activation of IL by microinjection PEPA, an allosteric AMPA receptor potentiator into IL before each of extinction session facilitated the extinction responding after heroin self-administration, but did not alter the locomotor activity in an open field testing environment. Other rats were first trained under a FR1 schedule for heroin self-administration for 14 days, followed by 14 days of extinction training, and reinstatement of heroin-seeking induced by cues was measured for 2h. Intra-IL microinjecting of PEPA at 15min prior to test inhibited the reinstatement of heroin-seeking induced by cues. Moreover, the expression of GluR1 in the IL and NAc remarkably increased after treatment with PEPA during the reinstatement. These finding suggested that activation of glutamatergic projection from IL to NAc shell may be involved in the extinction and reinstatement of heroin-seeking. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. Steady-state pharmacokinetics of (R)- and (S)-methadone in methadone maintenance patients

    PubMed Central

    Foster, David J R; Somogyi, Andrew A; Dyer, Kyle R; White, Jason M; Bochner, Felix

    2000-01-01

    Aims To investigate the steady-state pharmacokinetics of (R)- and (S)-methadone in a methadone maintenance population. Methods Eighteen patients recruited from a public methadone maintenance program underwent an interdosing interval pharmacokinetic study. Plasma and urine samples were collected and analysed for methadone and its major metabolite (EDDP) using stereoselective h.p.l.c. Methadone plasma protein binding was examined using ultrafiltration, and plasma α1-acid glycoprotein concentrations were quantified by radial immunoassay. Results (R)-methadone had a significantly (P < 0.05) greater unbound fraction (mean 173%) and total renal clearance (182%) compared with (S)-methadone, while maximum measured plasma concentrations (83%) and apparent partial clearance of methadone to EDDP (76%) were significantly (P < 0.001) lower. When protein binding was considered (R)-methadone plasma clearance of the unbound fraction (59%) and apparent partial intrinsic clearance to EDDP (44%) were significantly (P < 0.01) lower than for (S)-methadone, while AUCτSS, (167%) was significantly (P < 0.001) greater. There were no significant (P > 0.2) differences between the methadone enantiomers for AUCτSS, steady-state plasma clearance, trough plasma concentrations and unbound renal clearance. Patients excreted significantly (P < 0.0001) more (R)-methadone and (S)-EDDP than the corresponding enantiomers. Considerable interindividual variability was observed for the pharmacokinetic parameters, with coefficients of variation of up to 70%. Conclusions Steady-state pharmacokinetics of unbound methadone are stereoselective, and there is large interindividual variability consistent with CYP3A4 mediated metabolism to the major metabolite EDDP; the variability did not obscure a significant dose-plasma concentration relationship. Stereoselective differences in the pharmacokinetics of methadone may have important implications for pharmacokinetic-pharmacodynamic modelling but is unlikely to

  12. Medicaid Coverage of Methadone Maintenance and the Use of Opioid Agonist Therapy Among Pregnant Women in Specialty Treatment.

    PubMed

    Bachhuber, Marcus A; Mehta, Pooja K; Faherty, Laura J; Saloner, Brendan

    2017-12-01

    Opioid agonist therapy (OAT) is the standard of care for pregnant women with opioid use disorder (OUD). Medicaid coverage policies may strongly influence OAT use in this group. To examine the association between Medicaid coverage of methadone maintenance and planned use of OAT in the publicly funded treatment system. Retrospective cross-sectional analysis of treatment admissions in 30 states extracted from the Treatment Episode Data Set (2013 and 2014). Medicaid-insured pregnant women with OUD (n=3354 treatment admissions). The main outcome measure was planned use of OAT on admission. The main exposure was state Medicaid coverage of methadone maintenance. Using multivariable logistic regression models adjusting for sociodemographic, substance use, and treatment characteristics, we compared the probability of planned OAT use in states with Medicaid coverage of methadone maintenance versus states without coverage. A total of 71% of pregnant women admitted to OUD treatment were 18-29 years old, 85% were white non-Hispanic, and 56% used heroin. Overall, 74% of admissions occurred in the 18 states with Medicaid coverage of methadone maintenance and 53% of admissions involved planned use of OAT. Compared with states without Medicaid coverage of methadone maintenance, admissions in states with coverage were significantly more likely to involve planned OAT use (adjusted difference: 32.9 percentage points, 95% confidence interval, 19.2-46.7). Including methadone maintenance in the Medicaid benefit is essential to increasing OAT among pregnant women with OUD and should be considered a key policy strategy to enhance outcomes for mothers and newborns.

  13. Simultaneous determination of opiates, cocaine and major metabolites of cocaine in human hair by gas chromotography/mass spectrometry (GC/MS).

    PubMed

    Kintz, P; Mangin, P

    1995-05-22

    A procedure is presented for the simultaneous identification and quantification of morphine (MOR), codeine (COD), ethylmorphine (EM), 6-monoacetylmorphine (6-MAM), cocaine (COC), benzoylecgonine (BZE), ecgonine methylester (EME) and cocaethylene (CE), contained in the hair of opiates and cocaine addicts. The method involves decontamination in dichloromethane, pulverization in a ball mill, heat-acid hydrolysis, addition of deuterated internal standards, liquid-liquid extraction and gas chromatography/mass spectrometry (GC/MS) after silylation. The limit of detection (LOD) was approximately 0.1-0.8 ng/mg for each drug, using a 30-mg hair sample. The method is reproductible, with a coefficient of variation (CV) of approximately 8-17%. Cocaine and 6-monoacetylmorphine were the major compounds detected in cases of cocaine (14 cases) and heroin (68 cases) intake. Concentrations were in the range 0.4-78.4 ng/mg (COC), 0.0-36.3 ng/mg (BZE), 0.0-1.6 ng/mg (EME), 0.0-2.1 ng/mg (CE), 0.0-84.3 ng/mg (6-MAM), 0.2-27.1 ng/mg (MOR) and 0.1-19.6 ng/mg (COD). An application in forensic sciences, involving multi-sectional analysis, is given.

  14. Analysis of drugs of abuse in human plasma by dispersive liquid-liquid microextraction and high-performance liquid chromatography.

    PubMed

    Fernández, P; Regenjo, M; Bermejo, A M; Fernández, A M; Lorenzo, R A; Carro, A M

    2015-04-01

    Opioids and cocaine are widely used at present, both for recreational purposes and as drugs of abuse. This raises the need to develop new analytical methods specifically designed for the simultaneous detection of several drugs of abuse in biological samples. In this work, dispersive liquid-liquid microextraction (DLLME) was assessed as a new sample treatment for the simultaneous extraction of morphine (MOR), 6-acetylmorphine (6AM), cocaine (COC), benzoylecgonine (BZE) and methadone (MET) from human plasma. Preliminary assays were done before developing an experimental design based on a Uniform Network Doehlert which allowed the optimum extraction conditions to be identified, namely: a volume of extractant solvent (chloroform) and dispersant solvent (acetonitrile) of 220 µl and 3.2 ml, respectively; 0.2 g of NaCl as a salting-out additive; pH 10.6 and ultrasound stirring for 3.5 min. The resulting extracts were analyzed by high-performance liquid chromatography with photodiode array detection (HPLC-PDA), using an XBridge® RP18 column (250 × 4.6 mm i.d., 5 µm particle size). Calibration graphs were linear over the concentration range 0.1-10 µg ml⁻¹, and detection limits ranged from 13.9 to 28.5 ng ml⁻¹. Precision calculated at three different concentration levels in plasma was included in the range 0.1-6.8% RSD. Recoveries of the five drugs were all higher than 84% on average. Finally the proposed method was successfully applied to 22 plasma samples from heroin, cocaine and/or methadone users, and the most frequently detected drug was benzoylecgonine, followed by methadone, cocaine and morphine. Copyright © 2014 John Wiley & Sons, Ltd.

  15. Patterns of pre-treatment drug abuse, drug treatment history and characteristics of addicts in methadone maintenance treatment in Iran

    PubMed Central

    2012-01-01

    Background Opiates are the main drugs of abuse, and Methadone Maintenance Treatment (MMT) is the most widely administered drug addiction treatment program in Iran. Our study aimed to investigate patterns of pre-treatment drug abuse, addiction treatment history and characteristics of patients in MMT in Tehran. Methods We applied a stratified cluster random sampling technique and conducted a cross-sectional survey utilizing a standard patient characteristic and addiction history form with patients (n = 810) in MMT. The Chi-square test and t-test served for statistical analyses. Results A clear majority of the participants were men (96%), more than 60% of whom were between 25 and 44 years of age, educated (89% had more than elementary education), and employed (>70%). The most commonly reported main drugs of abuse prior to MMT entry were opium (69%) and crystalline heroin (24%). The patients’ lifetime drug experience included opium (92%), crystalline heroin (28%), cannabis (16%), amphetamines (15%), and other drugs (33%). Crystalline heroin abusers were younger than opium users, had begun abusing drugs earlier, and reported a shorter history of opiate addiction. Conclusion Opium and crystalline heroin were the main drugs of abuse. A high rate of addiction using more dangerous opiate drugs such as crystalline heroin calls for more preventive efforts, especially among young men. PMID:22676557

  16. Heroin uncertainties: Exploring users' perceptions of fentanyl-adulterated and -substituted 'heroin'.

    PubMed

    Ciccarone, Daniel; Ondocsin, Jeff; Mars, Sarah G

    2017-08-01

    The US is experiencing an unprecedented opioid overdose epidemic fostered in recent years by regional contamination of the heroin supply with the fentanyl family of synthetic opioids. Since 2011 opioid-related overdose deaths in the East Coast state of Massachusetts have more than tripled, with 75% of the 1374 deaths with an available toxicology positive for fentanyl. Fentanyl is 30-50X more potent than heroin and its presence makes heroin use more unpredictable. A rapid ethnographic assessment was undertaken to understand the perceptions and experiences of people who inject drugs sold as 'heroin' and to observe the drugs and their use. A team of ethnographers conducted research in northeast Massachusetts and Nashua, New Hampshire in June 2016, performing (n=38) qualitative interviews with persons who use heroin. (1) The composition and appearance of heroin changed in the last four years; (2) heroin is cheaper and more widely available than before; and (3) heroin 'types' have proliferated with several products being sold as 'heroin'. These consisted of two types of heroin (alone), fentanyl (alone), and heroin-fentanyl combinations. In the absence of available toxicological information on retail-level heroin, our research noted a hierarchy of fentanyl discernment methods, with embodied effects considered most reliable in determining fentanyl's presence, followed by taste, solution appearance and powder color. This paper presents a new 'heroin' typology based on users' reports. Massachusetts' heroin has new appearances and is widely adulterated by fentanyl. Persons who use heroin are trying to discern the substances sold as heroin and their preferences for each form vary. The heroin typology presented is inexact but can be validated by correlating users' discernment with drug toxicological testing. If validated, this typology would be a valuable harm reduction tool. Further research on adaptations to heroin adulteration could reduce risks of using heroin and

  17. Unintended impacts of regulatory changes to British Columbia Methadone Maintenance Program on addiction and HIV-related outcomes: an interrupted time series analysis

    PubMed Central

    Socías, M. Eugenia; Wood, Evan; McNeil, Ryan; Kerr, Thomas; Dong, Huiru; Shoveller, Jean; Montaner, Julio; Milloy, M-J

    2018-01-01

    Background In February 2014, several regulatory reforms were introduced to the methadone maintenance treatment (MMT) program in British Columbia, Canada, including a switch to a ten-times more concentrated methadone formulation and restrictions in pharmacy delivery services. We evaluated possible unintended effects of these changes on illicit drug use patterns and HIV treatment outcomes among HIV-positive opioid users. Methods Data was drawn from ACCESS, a prospective community-recruited cohort of HIV-positive people who use illicit drugs in Vancouver, Canada. Interrupted time series analyses were used to evaluate impacts of the policy change on monthly rates of MMT enrollment, illicit heroin injection, antiretroviral therapy (ART) adherence, and HIV viral suppression among HIV-positive opioid users between November 2012 and May 2015. Results A total of 331 HIV-positive opioid users were included. The MMT policy change led to a significant immediate 11.5% increase in heroin injection, and 15.9% drop in optimal ART adherence. A gradual increase in the prevalence of MMT enrolment after the policy change was also documented (0.9% per month). No changes in viral suppression rates were observed. Conclusions We observed immediate increases in illicit heroin injection and decreases in ART adherence in the wake of regulatory changes to the local MMT program. These findings underscore the need to consider potential unintended effects of altering health programmes for vulnerable populations, the need to develop appropriate mitigation strategies, as well as to involve all relevant stakeholders in the planning and implementations of new policies. PMID:28454044

  18. Unintended impacts of regulatory changes to British Columbia Methadone Maintenance Program on addiction and HIV-related outcomes: An interrupted time series analysis.

    PubMed

    Socías, M Eugenia; Wood, Evan; McNeil, Ryan; Kerr, Thomas; Dong, Huiru; Shoveller, Jean; Montaner, Julio; Milloy, M-J

    2017-07-01

    In February 2014, several regulatory reforms were introduced to the methadone maintenance treatment (MMT) program in British Columbia, Canada, including a switch to a ten-times more concentrated methadone formulation and restrictions in pharmacy delivery services. We evaluated possible unintended effects of these changes on illicit drug use patterns and HIV treatment outcomes among HIV-positive opioid users. Data was drawn from ACCESS, a prospective community-recruited cohort of HIV-positive people who use illicit drugs in Vancouver, Canada. Interrupted Time Series Analyses were used to evaluate impacts of the policy change on monthly rates of MMT enrolment, illicit heroin injection, antiretroviral therapy (ART) adherence, and HIV viral suppression among HIV-positive opioid users between November 2012 and May 2015. A total of 331 HIV-positive opioid users were included. The MMT policy change led to a significant immediate 11.5% increase in heroin injection, and 15.9% drop in optimal ART adherence. A gradual increase in the prevalence of MMT enrolment after the policy change was also documented (0.9% per month). No changes in viral suppression rates were observed. We observed immediate increases in illicit heroin injection and decreases in ART adherence in the wake of regulatory changes to the local MMT program. These findings underscore the need to consider potential unintended effects of altering health programmes for vulnerable populations, the need to develop appropriate mitigation strategies, as well as to involve all relevant stakeholders in the planning and implementations of new policies. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Clinical use of methadone.

    PubMed

    Layson-Wolf, Cherokee; Goode, Jean-Venable; Small, Ralph E

    2002-01-01

    Methadone hydrochloride is a mu-opioid agonist that has been used for the treatment of pain and for the management and maintenance of opioid withdrawal for over 50 years. Several characteristics make methadone a useful drug. However, these same characteristics and wide interpatient variability can make methadone difficult to use safely. A MEDLINE search was conducted on publications between January 1996 and May 2001 to identify literature relevant to this subject. Those publications were reviewed, and from them, other literature was identified and reviewed. Published studies demonstrate methadone's efficacy in pain management and in opioid withdrawal. However, interpatient variability in pharmacokinetic variables of methadone produces difficulties in developing guidelines for methadone use. Clinicians should not be deterred from use of this drug which has been shown to benefit patients in both pain management and methadone maintenance, but an individualized patient approach must be taken to use methadone safely.

  20. Variants of opioid system genes are associated with non-dependent opioid use and heroin dependence.

    PubMed

    Randesi, Matthew; van den Brink, Wim; Levran, Orna; Blanken, Peter; Butelman, Eduardo R; Yuferov, Vadim; da Rosa, Joel Correa; Ott, Jurg; van Ree, Jan M; Kreek, Mary Jeanne

    2016-11-01

    Heroin addiction is a chronic, relapsing brain disease. Genetic factors are involved in the development of drug addiction. The aim of this study was to determine whether specific variants in genes of the opioid system are associated with non-dependent opioid use and heroin dependence. Genetic information from four subject groups was collected: non-dependent opioid users (NOD) [n=163]; opioid-dependent (OD) patients in methadone maintenance treatment (MMT) [n=143]; opioid-dependent MMT-resistant patients in heroin-assisted treatment (HAT) [n=138]; and healthy controls with no history of opioid use (HC) [n=153]. Eighty-two variants in eight opioid system genes were studied. To establish the role of these genes in (a) non-dependent opioid use, and (b) heroin dependence, the following groups were compared: HC vs. NOD; HC vs. OD (MMT+HAT); and NOD vs. OD (MMT+HAT). Five unique SNPs in four genes showed nominally significant associations with non-dependent opioid use and heroin dependence. The association of the delta opioid receptor (OPRD1) intronic SNP rs2236861 with non-dependent opioid use (HC vs. NOD) remained significant after correction for multiple testing (OR=0.032; p corrected =0.015). This SNP exhibited a significant gene-gene interaction with prepronociceptin (PNOC) SNP rs2722897 (OR=5.24; p corrected =0.041) (HC vs. NOD). This study identifies several new and some previously reported associations of variants with heroin dependence and with non-dependent opioid use, an important and difficult to obtain group not extensively studied previously. Further studies are warranted to confirm and elucidate the potential roles of these variants in the vulnerability to illicit drug use and drug addiction. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. Impact of methamphetamine precursor chemical legislation, a suppression policy, on the demand for drug treatment.

    PubMed

    Cunningham, James K; Liu, Lon-Mu

    2008-04-01

    Research is needed to help treatment programs plan for the impacts of drug suppression efforts. Studies to date indicate that heroin suppression may increase treatment demand. This study examines whether treatment demand was impacted by a major US methamphetamine suppression policy -- legislation regulating precursor chemicals. The precursors ephedrine and pseudoephedrine, in forms used by large-scale methamphetamine producers, were regulated in August 1995 and October 1997, respectively. ARIMA-intervention time-series analysis was used to examine the impact of each precursor's regulation on monthly voluntary methamphetamine treatment admissions (a measure of treatment demand), including first-time admissions and re-admissions, in California (1992-2004). Cocaine, heroin, and alcohol treatment admissions were used as quasi-control series. The 1995 regulation of ephedrine was found to be associated with a significant reduction in methamphetamine treatment admissions that lasted approximately 2 years. The 1997 regulation of pseudoephedrine was associated with a significant reduction that lasted approximately 4 years. First-time admissions declined more than re-admissions. Cocaine, heroin, and alcohol admissions were generally unaffected. While heroin suppression may be associated with increased treatment demand as suggested by research to date, this study indicates that methamphetamine precursor regulation was associated with decreases in treatment demand. A possible explanation is that, during times of suppression, heroin users may seek treatment to obtain substitute drugs (e.g., methadone), while methamphetamine users have no comparable incentive. Methamphetamine suppression may particularly impact treatment demand among newer users, as indicated by larger declines in first-time admissions.

  2. A randomized trial of employment-based reinforcement of cocaine abstinence in injection drug users.

    PubMed

    Silverman, Kenneth; Wong, Conrad J; Needham, Mick; Diemer, Karly N; Knealing, Todd; Crone-Todd, Darlene; Fingerhood, Michael; Nuzzo, Paul; Kolodner, Kenneth

    2007-01-01

    High-magnitude and long-duration abstinence reinforcement can promote drug abstinence but can be difficult to finance. Employment may be a vehicle for arranging high-magnitude and long-duration abstinence reinforcement. This study determined if employment-based abstinence reinforcement could increase cocaine abstinence in adults who inject drugs and use cocaine during methadone treatment. Participants could work 4 hr every weekday in a workplace where they could earn about $10.00 per hour in vouchers; they were required to provide routine urine samples. Participants who attended the workplace and provided cocaine-positive urine samples during the initial 4 weeks were invited to work 26 weeks and were randomly assigned to an abstinence-and-work (n = 28) or work-only (n = 28) group. Abstinence-and-work participants had to provide urine samples showing cocaine abstinence to work and maintain maximum pay. Work-only participants could work independent of their urinalysis results. Abstinence-and-work participants provided more (p = .004; OR = 5.80, 95% CI = 2.03-16.56) cocaine-negative urine samples (29%) than did work-only participants (10%). Employment-based abstinence reinforcement can increase cocaine abstinence.

  3. Is the New Heroin Epidemic Really New? Racializing Heroin.

    PubMed

    Bowser, Benjamin; Fullilove, Robert; Word, Carl

    2017-01-01

    Heroin abuse as an outcome of the prior use of painkillers increased rapidly over the past decade. This "new epidemic" is unique because the new heroin users are primarily young White Americans in rural areas of virtually every state. This commentary argues that the painkiller-to-heroin transition could not be the only cause of heroin use on such a scale and that the new and old heroin epidemics are linked. The social marketing that so successfully drove the old heroin epidemic has innovated and expanded due to the use of cell-phones, text messaging and the "dark web" which requires a Tor browser, and software that allows one to communicate with encrypted sites without detection. Central city gentrification has forced traffickers to take advantage of larger and more lucrative markets. A second outcome is that urban black and Latino communities are no longer needed as heroin stages areas for suburban and exurban illicit drug distribution. Drug dealing can be done directly in predominantly white suburbs and rural areas without the accompanying violence associated with the old epidemic. Denial of the link between the new and old heroin epidemics racially segregates heroin users and more proactive prevention and treatment in the new epidemic than in the old. It also cuts off a half-century of knowledge about the supply-side of heroin drug dealing and the inevitable public policy measures that will have to be implemented to effectively slow and stop both the old and new epidemic. Copyright © 2016 National Medical Association. Published by Elsevier Inc. All rights reserved.

  4. Heroin and Pregnancy

    MedlinePlus

    ... Home > Pregnancy > Is it safe? > Heroin and pregnancy Heroin and pregnancy E-mail to a friend Please ... way that’s safe for your baby. What is heroin? Heroin (also called smack or junk) is an ...

  5. Differences in methylphenidate abuse rates among methadone maintenance treatment patients in two clinics.

    PubMed

    Peles, Einat; Schreiber, Shaul; Linzy, Shirley; Domani, Yoav; Adelson, Miriam

    2015-07-01

    Methylphenidate, an amphetamine-like prescription medication for attention deficit hyperactivity disorder (ADHD) was suspected as being abused among methadone maintenance treatment (MMT) patients. We tested its presence in the routine urine monitoring of all patients in both Tel Aviv and Las Vegas MMT clinics. Data on demographic and addiction history, ADHD (Wender Utah Rating Scale), cognitive impairment (Mini Mental State Exam), and lifetime DSM-IV-TR psychiatric diagnosis from admission were retrieved, and retention following 6 months. None of the 190 patients in Las Vegas tested positive for methylphenidate, while 14.7% (45/306) did in Tel Aviv. Abusers were less educated (p = 0.01), had higher ADHD scores (p = 0.02), lower cognitive scores (p = 0.05), and a higher benzodiazepine (BDZ) abuse rate (p < 0.0005), with no difference in age, gender, duration in MMT, cannabis, opiates, and cocaine abuse and infectious disease. Of the methylphenidate abuse 42.2% have take-home methadone dose privileges. Not like opiate use, being methylphenidate positive did not relate to 6-months retention. Compared to Tel Aviv, Las Vegas patients were more educated, with lower BDZ, and cocaine abuse. The greater abuse of methylphenidate among ADHD subjects might indicate their using it as self-medication, raising a possible indication for its prescription for that subgroup of MMT patients. The high rate of methylphenidate abuse in Israel needs future study. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Association of time-dependent changes in mu opioid receptor mRNA, but not BDNF, TrkB, or MeCP2 mRNA and protein expression in the rat nucleus accumbens with incubation of heroin craving.

    PubMed

    Theberge, Florence R M; Pickens, Charles L; Goldart, Evan; Fanous, Sanya; Hope, Bruce T; Liu, Qing-Rong; Shaham, Yavin

    2012-12-01

    Responding to heroin cues progressively increases after cessation of heroin self-administration (incubation of heroin craving). We investigated whether this incubation is associated with time-dependent changes in brain-derived neurotrophic factor (BDNF) and methyl-CpG binding protein 2 (MeCP2) signaling and mu opioid receptor (MOR) expression in nucleus accumbens (NAc), dorsal striatum (DS), and medial prefrontal cortex (mPFC). We also investigated the effect of the preferential MOR antagonist naloxone on cue-induced heroin seeking during abstinence. We trained rats to self-administer heroin or saline for 9-10 days and then dissected the NAc, DS, and mPFC at different abstinence days and measured mRNA and protein levels of BDNF, TrkB, and MeCP2, as well as MOR mRNA (Oprm1). In other groups, we assessed cue-induced heroin seeking in extinction tests after 1, 11, and 30 abstinence days, and naloxone's (0-1.0 mg/kg) effect on extinction responding after 1 and 15 days. Cue-induced heroin seeking progressively increased or incubated during abstinence. This incubation was not associated with changes in BDNF, TrkB, or MeCP2 mRNA or protein levels in NAc, DS, or mPFC; additionally, no molecular changes were observed after extinction tests on day 11. In NAc, but not DS or mPFC, MOR mRNA decreased on abstinence day 1 and returned to basal levels over time. Naloxone significantly decreased cue-induced heroin seeking after 15 abstinence days but not 1 day. Results suggest a role of MOR in incubation of heroin craving. As previous studies implicated NAc BDNF in incubation of cocaine craving, our data suggest that different mechanisms contribute to incubation of heroin versus cocaine craving.

  7. Association of time-dependent changes in mu opioid receptor mRNA, but not BDNF, TrkB, or MeCP2 mRNA and protein expression in the rat nucleus accumbens with incubation of heroin craving

    PubMed Central

    Theberge, Florence R. M.; Pickens, Charles L.; Goldart, Evan; Fanous, Sanya; Hope, Bruce T.; Liu, Qing-Rong

    2013-01-01

    Rationale and objectives Responding to heroin cues progressively increases after cessation of heroin self-administration (incubation of heroin craving). We investigated whether this incubation is associated with time-dependent changes in brain-derived neurotrophic factor (BDNF) and methyl-CpG binding protein 2 (MeCP2) signaling and mu opioid receptor (MOR) expression in nucleus accumbens (NAc), dorsal striatum (DS), and medial pre-frontal cortex (mPFC). We also investigated the effect of the preferential MOR antagonist naloxone on cue-induced heroin seeking during abstinence. Methods We trained rats to self-administer heroin or saline for 9–10 days and then dissected the NAc, DS, and mPFC at different abstinence days and measured mRNA and protein levels of BDNF, TrkB, and MeCP2, as well as MOR mRNA (Oprm1). In other groups, we assessed cue-induced heroin seeking in extinction tests after 1, 11, and 30 abstinence days, and naloxone’s (0–1.0 mg/kg) effect on extinction responding after 1 and 15 days. Results Cue-induced heroin seeking progressively increased or incubated during abstinence. This incubation was not associated with changes in BDNF, TrkB, or MeCP2 mRNA or protein levels in NAc, DS, or mPFC; additionally, no molecular changes were observed after extinction tests on day 11. In NAc, but not DS or mPFC, MOR mRNA decreased on abstinence day 1 and returned to basal levels over time. Naloxone significantly decreased cue-induced heroin seeking after 15 abstinence days but not 1 day. Conclusions Results suggest a role of MOR in incubation of heroin craving. As previous studies implicated NAc BDNF in incubation of cocaine craving, our data suggest that different mechanisms contribute to incubation of heroin versus cocaine craving. PMID:22790874

  8. Impact of South American heroin on the US heroin market 1993-2004.

    PubMed

    Ciccarone, Daniel; Unick, George J; Kraus, Allison

    2009-09-01

    The past two decades have seen an increase in heroin-related morbidity and mortality in the United States. We report on trends in US heroin retail price and purity, including the effect of entry of Colombian-sourced heroin on the US heroin market. The average standardized price ($/mg-pure) and purity (% by weight) of heroin from 1993 to 2004 was from obtained from US Drug Enforcement Agency retail purchase data for 20 metropolitan statistical areas. Univariate statistics, robust Ordinary Least Squares regression and mixed fixed and random effect growth curve models were used to predict the price and purity data in each metropolitan statistical area over time. Over the 12 study years, heroin price decreased 62%. The median percentage of all heroin samples that are of South American origin increased an absolute 7% per year. Multivariate models suggest percent South American heroin is a significant predictor of lower heroin price and higher purity adjusting for time and demographics. These analyses reveal trends to historically low-cost heroin in many US cities. These changes correspond to the entrance into and rapid domination of the US heroin market by Colombian-sourced heroin. The implications of these changes are discussed.

  9. Heroin Addicts Reporting Previous Heroin Overdoses Also Report Suicide Attempts

    ERIC Educational Resources Information Center

    Bradvik, Louise; Frank, Arne; Hulenvik, Per; Medvedeo, Alvaro; Berglund, Mats

    2007-01-01

    Nonfatal heroin overdoses and suicide attempts are both common among heroin addicts, but there is limited knowledge about the association between them. The sample in the present study consisted of 149 regular heroin users in Malmo, Sweden. Out of these 98 had taken an unintentional heroin overdose at some time and 51 had made at least one attempt…

  10. Heroin Addiction and Methadone Treatment in America: Using Our Heads in the Search for Solutions

    ERIC Educational Resources Information Center

    Basham, Richard

    1977-01-01

    An examination of America's attempts to cope with the problem of heroin (and other drug) addiction must proceed through an analysis of the basic responses to the problem--penal, behavioral and medical--from two quite different, and frequently conflicting, vantage points: that of the individual addict and that of the society as a whole. (Author/NQ)

  11. Prescription Opioid Use, Misuse, and Diversion among Street Drug Users in New York City

    PubMed Central

    Rees Davis, W.; Johnson, Bruce D.

    2008-01-01

    Objective The use of heroin, cocaine, and other drugs is well researched in New York City, but prescription opioids (POs) have been overlooked. This study documents patterns of PO use, misuse, and diversion among street drug users, and begins to indicate how drug culture practices interact with the legitimate therapeutic goals of PO prescriptions (e.g. pain management). Methods Staff completed interviews inquiring about the reasons for use of POs and illicit drugs with 586 street drug users. Ethnographers wrote extensive field notes about subjects’ complex patterns of PO use. Results Methadone was used (71.9%) and sold (64.7%) at a higher level than OxyContin, Vicodin, and Percocet, used by between 34% and 38% of the users and sold by between 28% and 41% of the sellers. Recent PO use is associated with the recency of using heroin and cocaine (p<.001). Half of the heroin/cocaine sellers sold POs, and one quarter of the PO sellers only sold POs. Subjects were classified into four groups by whether they diverted POs or used POs to relieve pain or withdrawal rather than for euphoria. This classification was associated with frequency of PO use, whether POs were obtained from doctors/pharmacies or from drug dealers and family members, and those mostly likely to use POs for pain and withdrawal. Conclusions POs are an important component of street drug users’ drug-taking regimes, especially those who are Physically III Chemical Abusers (PICA). Future research is needed to model PO use, misuse, and diversion among this population. PMID:17913395

  12. Prescription opioid use, misuse, and diversion among street drug users in New York City.

    PubMed

    Davis, W Rees; Johnson, Bruce D

    2008-01-01

    The use of heroin, cocaine, and other drugs is well researched in New York City, but prescription opioids (POs) have been overlooked. This study documents patterns of PO use, misuse, and diversion among street drug users, and begins to indicate how drug culture practices interact with the legitimate therapeutic goals of PO prescriptions (e.g. pain management). Staff completed interviews inquiring about the reasons for use of POs and illicit drugs with 586 street drug users. Ethnographers wrote extensive field notes about subjects' complex patterns of PO use. Methadone was used (71.9%) and sold (64.7%) at a higher level than OxyContin, Vicodin, and Percocet, used by between 34% and 38% of the users and sold by between 28% and 41% of the sellers. Recent PO use is associated with the recency of using heroin and cocaine (p<.001). Half of the heroin/cocaine sellers sold POs, and one quarter of the PO sellers only sold POs. Subjects were classified into four groups by whether they diverted POs or used POs to relieve pain or withdrawal rather than for euphoria. This classification was associated with frequency of PO use, whether POs were obtained from doctors/pharmacies or from drug dealers and family members, and those mostly likely to use POs for pain and withdrawal. POs are an important component of street drug users' drug-taking regimes, especially those who are Physically Ill Chemical Abusers (PICA). Future research is needed to model PO use, misuse, and diversion among this population.

  13. Heroin

    MedlinePlus

    ... DEA Museum and Visitors' Center National Prevention Week Heroin Last Updated: Wednesday, December 27, 2017 What is ... from morphine and extracted from certain poppy plants. Heroin comes in a white or brownish powder, or ...

  14. Fatal poisoning in drug addicts in the Nordic countries in 2012.

    PubMed

    Simonsen, K Wiese; Edvardsen, H M E; Thelander, G; Ojanperä, I; Thordardottir, S; Andersen, L V; Kriikku, P; Vindenes, V; Christoffersen, D; Delaveris, G J M; Frost, J

    2015-03-01

    This report is a follow-up to a study on fatal poisoning in drug addicts conducted in 2012 by a Nordic working group. Here we analyse data from the five Nordic countries: Denmark, Finland, Iceland, Norway and Sweden. Data on sex, number of deaths, places of death, age, main intoxicants and other drugs detected in the blood were recorded. National data are presented and compared between the Nordic countries and with data from similar studies conducted in 1991, 1997, 2002 and 2007. The death rates (number of deaths per 100,000 inhabitants) increased in drug addicts in Finland, Iceland and Sweden but decreased in Norway compared to the rates in earlier studies. The death rate was stable in Denmark from 1991 to 2012. The death rate remained highest in Norway (5.79) followed by Denmark (5.19) and Iceland (5.16). The differences between the countries diminished compared to earlier studies, with death rates in Finland (4.61) and Sweden (4.17) approaching the levels in the other countries. Women accounted for 15-27% of the fatal poisonings. The median age of the deceased drug addicts was still highest in Denmark, and deaths of addicts >45 years old increased in all countries. Opioids remained the main cause of death, but medicinal opioids like methadone, buprenorphine, fentanyl and tramadol mainly replaced heroin. Methadone was the main intoxicant in Denmark and Sweden, whereas heroin/morphine caused the most deaths in Norway. Finland differed from the other Nordic countries in that buprenorphine was the main intoxicant with only a few heroin/morphine and methadone deaths. Deaths from methadone, buprenorphine and fentanyl increased immensely in Sweden compared to 2007. Poly-drug use was widespread in all countries. The median number of drugs per case varied from 4 to 5. Heroin/morphine, medicinal opioids, cocaine, amphetamines, benzodiazepines and alcohol were the main abused drugs. However, less widely used drugs, like gamma-hydroxybutyric acid (GHB), methylphenidate

  15. Association of testosterone levels and heroin usage characteristics in male heroin users.

    PubMed

    Wang, Zhuo; Zhou, Xiao-Bo; Yang, Xiao-Rong; Song, Hui; Cao, Bing-Rong; Yin, Fei; Kang, Lin; An, Zhen-Mei; Li, Jing

    2017-05-01

    Previous studies have shown that heroin abuse can alter the gonadal functions. Few studies examined the association between testosterone levels and heroin use in the existing literature. We aimed to determine the association between gonadal hormones and heroin usage characteristics over 12 weeks of abstinence in heroin users. We collected data on patient demographics and heroin use patterns for 65 men aged 18 to 45 and for 29 age-matched healthy controls. Serum levels of total testosterone, estradiol, and prolactin were assessed at 5 time points. Testosterone levels gradually increased and prolactin levels decreased in heroin users in this study. In heroin users, a significant positive correlation was observed between the way of using drug and the testosterone levels, the way of using drug and the estradiol levels, between the duration of heroin dependence and the testosterone levels, between the duration of heroin dependence and the estradiol levels on D0, and between relapse time and testosterone levels on D84. Our data reveal testosterone might promote injection drug use and repeated relapse in male heroin users.

  16. A Randomized Trial of Employment-Based Reinforcement of Cocaine Abstinence in Injection Drug Users

    PubMed Central

    Silverman, Kenneth; Wong, Conrad J; Needham, Mick; Diemer, Karly N; Knealing, Todd; Crone-Todd, Darlene; Fingerhood, Michael; Nuzzo, Paul; Kolodner, Kenneth

    2007-01-01

    High-magnitude and long-duration abstinence reinforcement can promote drug abstinence but can be difficult to finance. Employment may be a vehicle for arranging high-magnitude and long-duration abstinence reinforcement. This study determined if employment-based abstinence reinforcement could increase cocaine abstinence in adults who inject drugs and use cocaine during methadone treatment. Participants could work 4 hr every weekday in a workplace where they could earn about $10.00 per hour in vouchers; they were required to provide routine urine samples. Participants who attended the workplace and provided cocaine-positive urine samples during the initial 4 weeks were invited to work 26 weeks and were randomly assigned to an abstinence-and-work (n  =  28) or work-only (n  =  28) group. Abstinence-and-work participants had to provide urine samples showing cocaine abstinence to work and maintain maximum pay. Work-only participants could work independent of their urinalysis results. Abstinence-and-work participants provided more (p  =  .004; OR  =  5.80, 95% CI  =  2.03–16.56) cocaine-negative urine samples (29%) than did work-only participants (10%). Employment-based abstinence reinforcement can increase cocaine abstinence. PMID:17970256

  17. "Every 'never' I ever said came true": transitions from opioid pills to heroin injecting.

    PubMed

    Mars, Sarah G; Bourgois, Philippe; Karandinos, George; Montero, Fernando; Ciccarone, Daniel

    2014-03-01

    This qualitative study documents the pathways to injecting heroin by users in Philadelphia and San Francisco before and during a pharmaceutical opioid pill epidemic. Data was collected through in-depth, semi-structured interviews (conducted between 2010 and 2012) that were, conducted against a background of longer-term participant-observation, ethnographic studies of street-based drug users and dealers in Philadelphia (2007-12) and San Francisco (1994-2007, 2012). Philadelphia and San Francisco were selected for their contrasting political economies, immigration patterns and source type of heroin. In Philadelphia the ethnographers found heroin injectors, usually white users, who had started their opiate using careers with prescription opioids rather than transitioning from other drugs. In both Philadelphia and San Francisco, most of the young heroin injectors interviewed began, their drug-use trajectories with opioid pills--usually Percocet (oxycodone and acetaminophen), generic short acting oxycodone or, OxyContin (long-acting oxycodone)--before transitioning to heroin, usually by nasal inhalation (sniffing) or smoking at first, followed by injecting. While most of the Philadelphia users were born in the city or its suburbs and had started using both opioid pills and heroin there, many of the San Francisco users had initiated their pill and sometimes heroin use elsewhere and had migrated to the city from around the country. Nevertheless, patterns of transition of younger injectors were similar in both cities suggesting an evolving national pattern. In contrast, older users in both Philadelphia and San Francisco were more likely to have graduated to heroin injection from non-opiate drugs such as cannabis, methamphetamine and cocaine. Pharmaceutical opioid initiates typically reported switching to heroin for reasons of cost and ease-of-access to supply after becoming physically and emotionally dependent on opioid pills. Many expressed surprise and dismay at their

  18. The relationship between US heroin market dynamics and heroin-related overdose, 1992-2008.

    PubMed

    Unick, George; Rosenblum, Daniel; Mars, Sarah; Ciccarone, Daniel

    2014-11-01

    Heroin-related overdose is linked to polydrug use, changes in physiological tolerance and social factors. Individual risk can also be influenced by the structural risk environment including the illicit drug market. We hypothesized that components of the US illicit drug market, specifically heroin source/type, price and purity, will have independent effects on the number of heroin-related overdose hospital admissions. Yearly, from 1992 to 2008, Metropolitan Statistical Area (MSA) price and purity series were estimated from the US Drug Enforcement Administration data. Yearly heroin overdose hospitalizations were constructed from the Nationwide Inpatient Sample. Socio-demographic variables were constructed using several databases. Negative binomial models were used to estimate the effect of price, purity and source region of heroin on yearly hospital counts of heroin overdoses controlling for poverty, unemployment, crime, MSA socio-demographic characteristics and population size. Purity was not associated with heroin overdose, but each $100 decrease in the price per pure gram of heroin resulted in a 2.9% [95% confidence interval (CI) = 4.8%, 1.0%] increase in the number of heroin overdose hospitalizations (P = 0.003). Each 10% increase in the market share of Colombian-sourced heroin was associated with a 4.1% (95% CI = 1.7%, 6.6%) increase in number of overdoses reported in hospitals (P = 0.001) independent of heroin quality. Decreases in the price of pure heroin in the United States are associated with increased heroin-related overdose hospital admissions. Increases in market concentration of Colombian-source/type heroin is also associated with an increase in heroin-related overdose hospital admissions. Increases in US heroin-related overdose admissions appear to be related to structural changes in the US heroin market. © 2014 Society for the Study of Addiction.

  19. Methadone adverse reaction presenting with large increase in plasma methadone binding: a case series

    PubMed Central

    2011-01-01

    Introduction The use of methadone as an analgesic is on the increase, but it is widely recognized that the goal of predictable and reproducible dosing is confounded by considerable variability in methadone pharmacokinetics, and unpredictable side effects that include sedation, respiratory depression and cardiac arrhythmias. The mechanisms underlying these unpredictable effects are frequently unclear. Here, to the best of our knowledge we present the first report of an association between accidental methadone overexposure and increased plasma protein binding, a new potential mechanism for drug interactions with methadone. Case presentation We describe here the cases of two patients who experienced markedly different responses to the same dose of methadone during co-administration of letrozole. Both patients were post-menopausal Caucasian women who were among healthy volunteers participating in a clinical trial. Under the trial protocol both patients received 6 mg of intravenous methadone before and then after taking letrozole for seven days. One woman (aged 59) experienced symptoms consistent with opiate overexposure after the second dose of methadone that were reversed by naloxone, while the other (aged 49) did not. To understand the etiology of this event, we measured methadone pharmacokinetics in both patients. In our affected patient only, a fourfold to eightfold increase in methadone plasma concentrations after letrozole treatment was observed. Detailed pharmacokinetic analysis indicated no change in metabolism or renal elimination in our patient, but the percentage of unbound methadone in the plasma decreased 3.7-fold. As a result, the volume of distribution of methadone decreased approximately fourfold. The increased plasma binding in our affected patient was consistent with observed increases in plasma protein concentrations. Conclusions The marked increase in the total plasma methadone concentration observed in our patient, and the enhanced pharmacodynamic

  20. Impact of South American heroin on the US heroin market 1993–2004

    PubMed Central

    Ciccarone, Daniel; Unick, George J; Kraus, Allison

    2008-01-01

    Background The past two decades have seen an increase in heroin-related morbidity and mortality in the United States. We report on trends in US heroin retail price and purity, including the effect of entry of Colombian-sourced heroin on the US heroin market. Methods The average standardized price ($/mg-pure) and purity (% by weight) of heroin from 1993 to 2004 was from obtained from US Drug Enforcement Agency retail purchase data for 20 metropolitan statistical areas. Univariate statistics, robust Ordinary Least Squares regression and mixed fixed and random effect growth curve models were used to predict the price and purity data in each metropolitan statistical area over time. Results Over the 12 study years, heroin price decreased 62%. The median percentage of all heroin samples that are of South American origin increased an absolute 7% per year. Multivariate models suggest percent South American heroin is a significant predictor of lower heroin price and higher purity adjusting for time and demographics. Conclusion These analyses reveal trends to historically low-cost heroin in many US cities. These changes correspond to the entrance into and rapid domination of the US heroin market by Colombian-sourced heroin. The implications of these changes are discussed. PMID:19201184

  1. African American Patients Seeking Treatment in the Public Sector: Characteristics of Buprenorphine v. Methadone Patients

    PubMed Central

    Mitchell, Shannon Gwin; Kelly, Sharon M.; Gryczynski, Jan; Myers, C. Patrick; Jaffe, Jerome H.; O’Grady, Kevin E.; Olsen, Yngvild K.; Schwartz, Robert P.

    2011-01-01

    Background To expand its public-sector treatment capacity, Baltimore City made buprenorphine treatment accessible to low-income, largely African American residents. This study compares the characteristics of patients entering methadone treatment v. buprenorphine treatment to determine whether BT was attracting different types of patients. Methods Participants consisted of two samples of adult heroin-dependent African Americans. The first sample was newly-admitted to a health center or a mental health center providing buprenorphine (N=200), and the second sample was newly-admitted to one of two hospital-based methadone programs (N=178). The Addiction Severity Index (ASI) and the Friends Supplemental Questionnaire were administered at treatment entry and data were analyzed with logistic regression. Results BT participants were more likely to be female (p=.017) and less likely to inject (p=.001). Participants with only prior buprenorphine treatment experience were nearly five time more likely to enter buprenorphine than methadone treatment (p<.001). Those with experience with both treatments were more than twice as likely to enter BT (OR=2.7, 95% CI=1.11–6.62; p=.028). In the 30 days prior to treatment entry, BT participants reported more days of medical problems (p=.002) and depression (p=.044), and were more likely to endorse a lifetime history of depression (p<.001). Conclusion Methadone and buprenorphine treatment provided in the public sector may attract different patient subpopulations. Providing buprenorphine treatment through drug treatment programs co-located with a health and mental health center may have accounted for their higher rates of medical and psychiatric problems and appears to be useful in attracting a diverse group of patients into public-sector funded treatment. PMID:21962726

  2. The safety of methadone hydrochloride.

    PubMed

    Swegle, John M; Wensel, David D

    2008-01-01

    Methadone is an interesting analgesic for multiple reasons. The unique properties of the agent, low cost and widespread availability have led to increases in methadone prescribing. Despite advantages, methadone is challenging to work with, particularly in patients with high opioid requirements. Recent concerns regarding cardiac arrhythmias and respiratory depression have led to changes in the labeling of methadone. This editorial highlights some of these concerns and provides some recommendations for the appropriate use of methadone in the setting of pain.

  3. The reductions in monetary cost and gains in productivity with methadone maintenance treatment: one year follow-up.

    PubMed

    Hsiao, Chih Yin; Chen, Kao Chin; Lee, Lan-Ting; Tsai, Hsin Chun; Chang, Wei Hung; Lee, I Hui; Chen, Po See; Lu, Ru-Band; Yang, Yen Kuang

    2015-02-28

    While methadone maintenance treatment (MMT) is beneficial for heroin dependence, there is little information regarding the reductions in monetary cost and gains in productivity following MMT. The aim of this study was to evaluate the changes in the monetary cost of heroin addiction and productivity after one year of MMT. Twenty-nine participants from an MMT clinic were included. The monetary cost, productivity, quality of life (QOL) and mental health status were assessed at both baseline and one year follow-up. The average annual total cost was approximately US$26,485 (1.43 GDP per capita in 2010) at baseline, and decreased by 59.3% to US$10,784 (0.58 GDP) at follow-up. The mean number of months of unemployment dropped from 6.03 to 2.79, the mean income increased to exceed the basic salary, but only reached 45.3% of the national average monthly earnings. The participants׳ mental health improved, but their QOL scores did not increase significantly. After one year of MMT, the monetary cost of heroin addiction fell, both the productivity and mental health of the participants׳ improved, but limited gains were seen with regard to their QOL. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  4. US federal cocaine essential (‘precursor’) chemical regulation impacts on US cocaine availability: an intervention time–series analysis with temporal replication

    PubMed Central

    Callaghan, Russell C.; Liu, Lon‐Mu

    2015-01-01

    Abstract Background and Aims Research shows that essential/precursor chemical controls have had substantial impacts on US methamphetamine and heroin availability. This study examines whether US federal essential chemical regulations have impacted US cocaine seizure amount, price and purity—indicators of cocaine availability. Design Autoregressive integrated moving average (ARIMA)‐intervention time–series analysis was used to assess the impacts of four US regulations targeting cocaine manufacturing chemicals: potassium permanganate/selected solvents, implemented October 1989 sulfuric acid/hydrochloric acid, implemented October 1992; methyl isobutyl ketone, implemented May 1995; and sodium permanganate, implemented December 2006. Of these chemicals, potassium permanganate and sodium permanganate are the most critical to cocaine production. Setting Conterminous United States (January 1987—April 2011). Measurements Monthly time–series: purity‐adjusted cocaine seizure amount (in gross weight seizures < 6000 grams), purity‐adjusted price (all available seizures), and purity (all available seizures). Data source: System to Retrieve Information from Drug Evidence. Findings The 1989 potassium permanganate/solvents regulation was associated with a seizure amount decrease (change in series level) of 28% (P < 0.05), a 36% increase in price (P < 0.05) and a 4% decrease in purity (P < 0.05). Availability recovered in 1–2 years. The 2006 potassium permanganate regulation was associated with a 22% seizure amount decrease (P < 0.05), 100% price increase (P < 0.05) and 35% purity decrease (P < 0.05). Following the 2006 regulation, essentially no recovery occurred to April 2011. The other two chemical regulations were associated with statistically significant but lesser declines in indicated availability. Conclusions In the United States, essential chemical controls from 1989 to 2006 were associated with pronounced downturns in cocaine availability. PMID:25559418

  5. Cue-induced activation of implicit affective associations with heroin use in abstinent heroin abusers.

    PubMed

    Chen, Jianyong; Wang, Xuan; Zhang, Meng; Zhang, Feng; Shen, Mowei

    2015-06-01

    While drug-related contexts have been shown to influence drug users' implicit and explicit drug-related cognitions, this has been minimally explored in heroin abusers. This study examined the effect of heroin-related cue exposure on implicit and explicit valence and arousal-sedation associations with heroin use for abstinent heroin abusers. In Experiment 1, 39 male abstinent heroin abusers were exposed to heroin-related words and reported cravings before and after cue exposure. They subsequently performed two Extrinsic Affective Simon Tasks (EASTs), which were used to assess implicit valence and arousal-sedation associations with heroin use. Thirty-six male abstinent heroin abusers (controls) only performed the two EASTs. All participants completed measures of explicit expectancy regarding heroin use. In Experiment 2, twenty-eight newly recruited abstinent heroin abusers were exposed to heroin-related pictures, and completed the same implicit and explicit measures used in Experiment 1. A non-significant increase in craving after cue exposure was observed. While participants exposed to heroin-related words or pictures exhibited more positive implicit heroin use associations (relative to negative associations), and such trend was not observed in controls, this difference was not significant across groups. Participants still indicated negative explicit associations with heroin use after cue exposure. Exposure to cues significantly accelerated arousal and sedation responses. Whether cue exposure could change self-reported craving requires further study in abstinent heroin abusers. The exclusively male sample limits generalization of the results. The present findings extend the evidence on whether implicit and explicit heroin-related cognitions are susceptible to context. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Heroin (Smack, Junk) Facts

    MedlinePlus

    ... That People Abuse » Heroin (Smack, Junk) Facts Heroin (Smack, Junk) Facts Listen ©istock.com/ Bestfotostudio Heroin ... 301.56 KB) (301.56 KB) "I needed heroin just to get by." ©istock.com/ pixelheadphoto Deon ...

  7. Substance use, childhood sexual abuse, and sexual risk behavior among women in methadone treatment.

    PubMed

    Cohen, Lisa R; Tross, Susan; Pavlicova, Martina; Hu, Mei-Chen; Campbell, Aimee N; Nunes, Edward V

    2009-01-01

    Substance use and a history of childhood sexual abuse (CSA) are risk factors for unprotected sex among women, yet questions remain as to how their combined influence may differentially affect sexual risk. The current study investigated how complex relationships among drug use and CSA may contribute to unprotected sexual occasions (USO). A Generalized Linear Mixed Model was used to examine the interaction between current cocaine/stimulants and opioid use and CSA on number of USOs in a sample of 214 sexually active women in outpatient methadone maintenance treatment. For women with CSA, an increase in days of cocaine/stimulant use was associated with a significant increase in USOs. In contrast, an increase in days of opiate use was associated with a significant decrease in USOs. For the group of women who did not report CSA, there was a significant increase in USOs with increased opiate use. Findings indicate that CSA is related to unprotected sexual occasions depending on drug type and severity of use. Women with CSA using cocaine are at particularly high risk for having unprotected sex and should be specifically targeted for HIV prevention interventions.

  8. Anticonvulsants for cocaine dependence.

    PubMed

    Minozzi, Silvia; Cinquini, Michela; Amato, Laura; Davoli, Marina; Farrell, Michael F; Pani, Pier Paolo; Vecchi, Simona

    2015-04-17

    Cocaine dependence is a major public health problem that is characterised by recidivism and a host of medical and psychosocial complications. Although effective pharmacotherapy is available for alcohol and heroin dependence, none is currently available for cocaine dependence, despite two decades of clinical trials primarily involving antidepressant, anticonvulsivant and dopaminergic medications. Extensive consideration has been given to optimal pharmacological approaches to the treatment of individuals with cocaine dependence, and both dopamine antagonists and agonists have been considered. Anticonvulsants have been candidates for use in the treatment of addiction based on the hypothesis that seizure kindling-like mechanisms contribute to addiction. To evaluate the efficacy and safety of anticonvulsants for individuals with cocaine dependence. We searched the Cochrane Drugs and Alcohol Group Trials Register (June 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 6), MEDLINE (1966 to June 2014), EMBASE (1988 to June 2014), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to June 2014), Web of Science (1991 to June 2014) and the reference lists of eligible articles. All randomised controlled trials and controlled clinical trials that focus on the use of anticonvulsant medications to treat individuals with cocaine dependence. We used the standard methodological procedures expected by The Cochrane Collaboration. We included a total of 20 studies with 2068 participants. We studied the anticonvulsant drugs carbamazepine, gabapentin, lamotrigine, phenytoin, tiagabine, topiramate and vigabatrin. All studies compared anticonvulsants versus placebo. Only one study had one arm by which the anticonvulsant was compared with the antidepressant desipramine. Upon comparison of anticonvulsant versus placebo, we found no significant differences for any of the efficacy and safety measures. Dropouts: risk ratio (RR) 0.95, 95

  9. Do Young Heroin Users in Madrid, Barcelona and Seville have Sufficient Knowledge of the Risk Factors for Unintentional Opioid Overdose?

    PubMed Central

    Barrio, Gregorio; Brugal, M. Teresa; de la Fuente, Luis; Ballesta, Rosario; Bravo, María J.; Silva, Teresa C.; Rodríguez-Martos, Alicia

    2006-01-01

    To identify the self-perceived reasons for unintentional opioid overdose of young heroin users in three Spanish cities and their agreement with objective risk factors for overdose. Computer-Assisted Personal Interviews (CAPI) were held with 991 street-recruited current heroin users aged 18–30. The general reasons for overdose and the reasons for the last overdose suffered were explored with open-ended (OEQs) and pre-coded questions (PCQs). Limited knowledge of overdose risk factors was defined as mention of fewer than two objective risk factors for unintentional overdose in the OEQ. Univariate, bivariate, and logistic regression methods were used. 77.8% (Seville), 64.9% (Madrid) and 57.2% (Barcelona) of participants have limited knowledge of overdose risk factors. Residence in Seville and not having attended courses or meetings on overdoses were significantly associated with limited knowledge, after adjusting for other factors. The most frequently identified general reasons in OEQ or PCQ were using heroin in large amounts (66.8%), together with tranquilizers (62.0%), adulterated (60.7%), or purer than usual (57.6%). Most reasons were selected more frequently in PCQ than in OEQ, especially rapid injection of the entire dose and using heroin shortly after using tranquilizers or alcohol, by injection, or after a period of abstinence. The results were similar for overdoses suffered by participants. Most young heroin users do not have sufficient knowledge of overdose risk factors, especially the use of heroin by injection, after a period of abstinence, or together with alcohol or methadone. Specific informational or educational programs adapted to the local context are critically needed. PMID:16739049

  10. Risks for HIV infection among users and sellers of crack, powder cocaine and heroin in central Harlem: Implications for interventions

    PubMed Central

    DAVIS, W. REES; JOHNSON, B. D.; RANDOLPH, D.; LIBERTY, H. J.

    2007-01-01

    This article investigates behaviours that may be associated HIV infection among users and sellers of crack, powder cocaine and heroin in central Harlem. Chain referral sampling and other strategies were combined to acquire a sample of 637 (Users = 546; Sellers = 91) who provided urine specimens that were tested for the presence of drugs and HIV. Nearly a quarter (23.9%) of all respondents were HIV positive. Drug injectors were more than 2.5 times more likely to have HIV infections than other respondents (OR = 2.66; 95% CI 1.66–4.26). Those involved in frauds/cons were almost as likely to be HIV positive (OR = 2.58; 95% CI 1.64–4.06). Those with a marital status of being separated, divorced or widowed were twice as likely to be HIV infected (OR 2.16; 95% CI 1.43–3.25). Respondents currently having multiple partner sex (OR = 1.66; 95% CI 1.1–2.51) or who were female (OR = 1.66; 95% CI 1.12–2.45) were more than 1.5 times more likely to be HIV positive. Thus, controlling for lifetime drug injection and current multiple partner sex, other factors, such as participating in frauds/cons, as well as relationship status and being female, were also associated with HIV infection. PMID:16338774

  11. The relationship between US heroin market dynamics and heroin-related overdose, 1992–2008

    PubMed Central

    Unick, George; Rosenblum, Daniel; Mars, Sarah; Ciccarone, Daniel

    2017-01-01

    Background and Aims Heroin-related overdose is linked to polydrug use, changes in physiological tolerance and social factors. Individual risk can also be influenced by the structural risk environment including the illicit drug market. We hypothesized that components of the US illicit drug market, specifically heroin source/type, price and purity, will have independent effects on the number of heroin-related overdose hospital admissions. Methods Yearly, from 1992 to 2008, Metropolitan Statistical Area (MSA) price and purity series were estimated from the US Drug Enforcement Administration data. Yearly heroin overdose hospitalizations were constructed from the Nationwide Inpatient Sample. Socio-demographic variables were constructed using several databases. Negative binomial models were used to estimate the effect of price, purity and source region of heroin on yearly hospital counts of heroin overdoses controlling for poverty, unemployment, crime, MSA socio-demographic characteristics and population size. Results Purity was not associated with heroin overdose, but each $100 decrease in the price per pure gram of heroin resulted in a 2.9% [95% confidence interval (CI) = 4.8%, 1.0%] increase in the number of heroin overdose hospitalizations (P = 0.003). Each 10% increase in the market share of Colombian-sourced heroin was associated with a 4.1% (95% CI = 1.7%, 6.6%) increase in number of overdoses reported in hospitals (P = 0.001) independent of heroin quality. Conclusions Decreases in the price of pure heroin in the United States are associated with increased heroin-related overdose hospital admissions. Increases in market concentration of Colombian-source/type heroin is also associated with an increase in heroin-related overdose hospital admissions. Increases in US heroin-related overdose admissions appear to be related to structural changes in the US heroin market. PMID:24938727

  12. Effects of incentives for naltrexone adherence on opiate abstinence in heroin-dependent adults

    PubMed Central

    Jarvis, Brantley P.; Holtyn, August F.; DeFulio, Anthony; Dunn, Kelly E.; Everly, Jeffrey J.; Leoutsakos, Jeannie-Marie S.; Umbricht, Annie; Fingerhood, Michael; Bigelow, George E.; Silverman, Kenneth

    2017-01-01

    Aim To test whether an incentive-based intervention that increased adherence to naltrexone also increased opiate abstinence. Design Post-hoc combined analysis of three earlier randomized controlled trials that individually showed that incentives for adherence to oral and to extended-release injection naltrexone dosing schedules increased naltrexone adherence but not opiate abstinence. Setting Outpatient therapeutic workplace in Baltimore, MD, USA. Participants 140 unemployed heroin-dependent adults participating from 2006–2010. Interventions Participants were hired in a model workplace for 26 weeks and randomized to a Contingency (n=72) or Prescription (n=68) group. Both groups were offered naltrexone. Contingency participants were required to take scheduled doses of naltrexone in order to work and earn wages. Prescription participants could earn wages independent of naltrexone adherence. Measures Thrice-weekly and monthly urine samples tested for opiates and cocaine and measures of naltrexone adherence (percentage of monthly urine samples positive for naltrexone or percentage of scheduled injections received). All analyses included prerandomization attendance, opiate use, and cocaine use as covariates. Additional analyses controlled for cocaine use and naltrexone adherence during the intervention. Findings Contingency participants had more opiate abstinence than Prescription participants (68.1% vs. 52.9% opiate-negative thrice-weekly urine samples, respectively; and 71.9% vs. 61.7% opiate-negative monthly urine samples, respectively) based on initial analyses (thrice-weekly samples, OR = 3.3, 95% CI = 1.7–6.5, p < .01; monthly samples, OR = 2.6, 95% CI = 1.0–7.1, p = .06) and on analyses that controlled for cocaine use (thrice-weekly samples, OR = 3.9, 95% CI = 3.3–4.5, p < .01; monthly samples, OR = 3.4, 95% CI = 1.1–11.1, p =.04), which was high and associated with opiate use. The difference in opiate abstinence rates between Contingency participants

  13. US federal cocaine essential ('precursor') chemical regulation impacts on US cocaine availability: an intervention time-series analysis with temporal replication.

    PubMed

    Cunningham, James K; Callaghan, Russell C; Liu, Lon-Mu

    2015-05-01

    Research shows that essential/precursor chemical controls have had substantial impacts on US methamphetamine and heroin availability. This study examines whether US federal essential chemical regulations have impacted US cocaine seizure amount, price and purity-indicators of cocaine availability. Autoregressive integrated moving average (ARIMA)-intervention time-series analysis was used to assess the impacts of four US regulations targeting cocaine manufacturing chemicals: potassium permanganate/selected solvents, implemented October 1989 sulfuric acid/hydrochloric acid, implemented October 1992; methyl isobutyl ketone, implemented May 1995; and sodium permanganate, implemented December 2006. Of these chemicals, potassium permanganate and sodium permanganate are the most critical to cocaine production. Conterminous United States (January 1987-April 2011). Monthly time-series: purity-adjusted cocaine seizure amount (in gross weight seizures < 6000 grams), purity-adjusted price (all available seizures), and purity (all available seizures). System to Retrieve Information from Drug Evidence. The 1989 potassium permanganate/solvents regulation was associated with a seizure amount decrease (change in series level) of 28% (P < 0.05), a 36% increase in price (P < 0.05) and a 4% decrease in purity (P < 0.05). Availability recovered in 1-2 years. The 2006 potassium permanganate regulation was associated with a 22% seizure amount decrease (P < 0.05), 100% price increase (P < 0.05) and 35% purity decrease (P < 0.05). Following the 2006 regulation, essentially no recovery occurred to April 2011. The other two chemical regulations were associated with statistically significant but lesser declines in indicated availability. In the United States, essential chemical controls from 1989 to 2006 were associated with pronounced downturns in cocaine availability. © 2015 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.

  14. Characterization of the Antinociceptive Effects of the Individual Isomers of Methadone Following Acute and Chronic Administration

    PubMed Central

    Morgan, Richard W.; Nicholson, Katherine L.

    2011-01-01

    Methadone is a long-acting opioid used in the treatment of various pain states and substitution therapy in heroin addiction. Extensive behavioral characterization has been carried out utilizing the racemate, but limited investigation has been performed with the individual isomers. While the l-isomer is a potent opioid agonist, the d-isomer has weak μ opioid activity and has also been shown to possess N-methyl-d-aspartate (NMDA) antagonist properties in vitro. The acute antinociceptive effects of the isomers were evaluated in rats using a warm water tail withdrawal procedure at two stimulus intensities (50° and 55° C). Increasing dose ratios of d- to l-methadone were administered chronically to determine the ability of the d-isomer to modulate antinociceptive tolerance to the l-isomer. Acutely, both l- (0.1-5.6 mg/kg, sc) and d- (3.0-56.0 mg/kg, sc) methadone produced antinociception though the efficacy of the d-isomer was limited at 55° C. These effects were dose-dependently blocked by naltrexone (0.01-1.0 mg/kg, sc). Administered chronically, d-methadone (1.7-10 mg/kg, sc) dose-dependently blocked tolerance development to the l-isomer (1.7 mg/kg, sc). These findings support the antinociceptive effects of the isomers being opioid receptor mediated with the l-isomer functioning as a full efficacy agonist whereas the d-isomer appears to have lower efficacy. The ability of nonracemic doses of the d-isomer to prevent tolerance development to the l-isomer may be attributed to partial μ agonist activity however NMDA antagonist activity cannot be discounted. PMID:21836464

  15. Pharmacokinetic Correlates of the Effects of a Heroin Vaccine on Heroin Self-Administration in Rats

    PubMed Central

    Raleigh, Michael D.; Pentel, Paul R.; LeSage, Mark G.

    2014-01-01

    The purpose of this study was to evaluate the effects of a morphine-conjugate vaccine (M-KLH) on the acquisition, maintenance, and reinstatement of heroin self-administration (HSA) in rats, and on heroin and metabolite distribution during heroin administration that approximated the self-administered dosing rate. Vaccination with M-KLH blocked heroin-primed reinstatement of heroin responding. Vaccination also decreased HSA at low heroin unit doses but produced a compensatory increase in heroin self-administration at high unit doses. Vaccination shifted the heroin dose-response curve to the right, indicating reduced heroin potency, and behavioral economic demand curve analysis further confirmed this effect. In a separate experiment heroin was administered at rates simulating heroin exposure during HSA. Heroin and its active metabolites, 6-acetylmorphine (6-AM) and morphine, were retained in plasma and metabolite concentrations were reduced in brain in vaccinated rats compared to controls. Reductions in 6-AM concentrations in brain after vaccination were consistent with the changes in HSA rates accompanying vaccination. These data provide evidence that 6-AM is the principal mediator of heroin reinforcement, and the principal target of the M-KLH vaccine, in this model. While heroin vaccines may have potential as therapies for heroin addiction, high antibody to drug ratios appear to be important for obtaining maximal efficacy. PMID:25536404

  16. Monitoring cocaine use in substance-abuse-treatment patients by sweat and urine testing.

    PubMed

    Preston, K L; Huestis, M A; Wong, C J; Umbricht, A; Goldberger, B A; Cone, E J

    1999-09-01

    Sweat and urine specimens were collected from 44 methadone-maintenance patients to evaluate the use of sweat testing to monitor cocaine use. Paired sweat patches that were applied and removed weekly (on Tuesdays) were compared with 3-5 consecutive urine specimens collected Mondays, Wednesdays, and Fridays. All patches (N = 930) were extracted in 2.5 mL of solvent and analyzed by ELISA immunoassay (cutoff concentration 10 ng/mL); a subset of patches (N = 591) was also analyzed by gas chromatography-mass spectrometry (GC-MS) for cocaine, benzoylecgonine (BZE), and ecgonine methyl ester (EME) (cutoff concentration 5 ng/mL). Urine specimens were subjected to qualitative analysis by EMIT (cutoff 300 ng/mL) and subsets were analyzed by TDx (semiquantitative, LOD 30 ng/mL) and by GC-MS for cocaine (LOD 5 ng/mL). Results were evaluated to (1) determine the relative amounts of cocaine and its metabolites in sweat; (2) assess replicability in duplicate patches; (3) compare ELISA and GC-MS results for cocaine in sweat; and (4) compare the detection of cocaine use by sweat and urine testing. Cocaine was detected by GC-MS in 99% of ELISA-positive sweat patches; median concentrations of cocaine, BZE, and EME were 378, 78.7, and 74 ng/mL, respectively. Agreement in duplicate patches was approximately 90% by ELISA analysis. The sensitivity, specificity, and efficiency of sweat ELISA cocaine results as compared with sweat GC-MS results were 93.6%, 91.3%, and 93.2%, respectively. The sensitivity, specificity, and efficiency between ELISA sweat patch and EMIT urine results were 97.6%, 60.5%, and 77.7%, respectively. These results support the use of sweat patches for monitoring cocaine use, though further evaluation is needed.

  17. A placebo-controlled trial of dextromethorphan as an adjunct in opioid-dependent patients undergoing methadone maintenance treatment.

    PubMed

    Lee, Sheng-Yu; Chen, Shiou-Lan; Chang, Yun-Hsuan; Chu, Chun-Hsien; Chen, Shih-Heng; Chen, Po See; Huang, San-Yuan; Tzeng, Nian-Sheng; Wang, Liang-Jen; Lee, I Hui; Wang, Tzu-Yun; Chen, Kao Chin; Yang, Yen Kuang; Hong, Jau-Shyong; Lu, Ru-Band

    2015-02-25

    Low-dose dextromethorphan (DM) might have anti-inflammatory and neurotrophic effects mechanistically remote from an NMDA receptor. In a randomized, double-blind, controlled 12 week study, we investigated whether add-on dextromethorphan reduced cytokine levels and benefitted opioid-dependent patients undergoing methadone maintenance therapy (MMT). Patients were randomly assigned to a group: DM60 (60mg/day dextromethorphan; n = 65), DM120 (120mg/day dextromethorphan; n = 65), or placebo (n = 66). Primary outcomes were the methadone dose required, plasma morphine level, and retention in treatment. Plasma tumor necrosis factor (TNF)-α, C-reactive protein, interleukin (IL)-6, IL-8, transforming growth factor-β1, and brain-derived neurotrophic factor (BDNF) levels were examined during weeks 0, 1, 4, 8, and 12. Multiple linear regressions with generalized estimating equation methods were used to examine the therapeutic effect. After 12 weeks, the DM60 group had significantly longer treatment retention and lower plasma morphine levels than did the placebo group. Plasma TNF-α was significantly decreased in the DM60 group compared to the placebo group. However, changes in plasma cytokine levels, BDNF levels, and the methadone dose required in the three groups were not significantly different. We provide evidence-decreased concomitant heroin use-of low-dose add-on DM's efficacy for treating opioid-dependent patients undergoing MMT. © The Author 2015. Published by Oxford University Press on behalf of CINP.

  18. A Placebo-Controlled Trial of Dextromethorphan as an Adjunct in Opioid-Dependent Patients Undergoing Methadone Maintenance Treatment

    PubMed Central

    Lee, Sheng-Yu; Chen, Shiou-Lan; Chang, Yun-Hsuan; Chu, Chun-Hsien; Chen, Shih-Heng; Chen, Po See; Huang, San-Yuan; Tzeng, Nian-Sheng; Wang, Liang-Jen; Lee, I Hui; Wang, Tzu-Yun; Chen, Kao Chin; Yang, Yen Kuang; Hong, Jau-Shyong

    2015-01-01

    Background: Low-dose dextromethorphan (DM) might have anti-inflammatory and neurotrophic effects mechanistically remote from an NMDA receptor. In a randomized, double-blind, controlled 12 week study, we investigated whether add-on dextromethorphan reduced cytokine levels and benefitted opioid-dependent patients undergoing methadone maintenance therapy (MMT). Methods: Patients were randomly assigned to a group: DM60 (60mg/day dextromethorphan; n = 65), DM120 (120mg/day dextromethorphan; n = 65), or placebo (n = 66). Primary outcomes were the methadone dose required, plasma morphine level, and retention in treatment. Plasma tumor necrosis factor (TNF)-α, C-reactive protein, interleukin (IL)-6, IL-8, transforming growth factor–β1, and brain-derived neurotrophic factor (BDNF) levels were examined during weeks 0, 1, 4, 8, and 12. Multiple linear regressions with generalized estimating equation methods were used to examine the therapeutic effect. Results: After 12 weeks, the DM60 group had significantly longer treatment retention and lower plasma morphine levels than did the placebo group. Plasma TNF-α was significantly decreased in the DM60 group compared to the placebo group. However, changes in plasma cytokine levels, BDNF levels, and the methadone dose required in the three groups were not significantly different. Conclusions: We provide evidence—decreased concomitant heroin use—of low-dose add-on DM’s efficacy for treating opioid-dependent patients undergoing MMT. PMID:25716777

  19. Perioperative pharmacokinetics of methadone in adolescents.

    PubMed

    Sharma, Anshuman; Tallchief, Danielle; Blood, Jane; Kim, Thomas; London, Amy; Kharasch, Evan D

    2011-12-01

    Methadone is frequently administered to adults experiencing anesthesia and receiving pain treatment. Methadone pharmacokinetics in adults are well characterized, including the perioperative period. Methadone is also used in children. There is, however, no information on methadone pharmacokinetics in children of any age. The purpose of this investigation was to determine the pharmacokinetics of intravenous methadone in children undergoing surgery. Perioperative opioid-sparing effects were also assessed. Eligible subjects were children 5-18 yr undergoing general anesthesia and surgery, with an anticipated postoperative inpatient stay exceeding 3 days. Three groups of 10 to 11 patients each received intravenous methadone hydrochloride after anesthetic induction in ascending dose groups of 0.1, 0.2, and 0.3 mg/kg (up to 20 mg). Anesthetic care was not otherwise changed. Venous blood was obtained for 4 days, for stereoselective determination of methadone and metabolites. Pain assessments were made each morning. Daily and total opioid consumption was determined. Perioperative opioid consumption and pain was determined in a second cohort, which was matched to age, sex, race, ethnicity, surgical procedure, and length of stay, but not receiving methadone. The final methadone study cohort was 31 adolescents (14 ± 2 yr, range 10-18) undergoing major spine surgery for a diagnosis of scoliosis. Methadone pharmacokinetics were linear over the dose range 0.1-0.3 mg/kg. Disposition was stereoselective. Methadone administration did not dose-dependently affect postoperative pain scores, and did not dose-dependently decrease daily or total postoperative opioid consumption in spinal fusion patients. Methadone enantiomer disposition in adolescents undergoing surgery was similar to that in healthy adults.

  20. Heroin overdose deaths and heroin purity between 1990 and 2000 in Istanbul, Turkey*.

    PubMed

    Toprak, Sadik; Cetin, Ilhan

    2009-09-01

    Turkey has continuously experienced problems with abuse of, and addiction to, opium derivatives. In this study, we analyzed the relationship between heroin overdose deaths and the characteristics of seized opium derivatives. Data were gathered from the Council of Forensic Medicine of the Ministry of Justice in Istanbul from 1990 to 2000. There were 636 heroin-related deaths during this period, 595 of which were classified as heroin overdose deaths. Mean crude and weighted heroin purities remained relatively constant and were calculated to be 46% (57-34%) and 51% (39-59%), respectively. The weight of heroin and the number of heroin seizures, but not the heroin purity, were significantly associated with the number of heroin-related deaths. Prevention strategies are needed to reduce the number of deaths caused by overdoses in countries situated on drug trafficking routes. These strategies should focus on drug trafficking, by providing increased levels of, and support for, law enforcement, stopping the supply of precursor chemicals, and combating corruption among border officials.

  1. Detecting cocaine use? The autobiographical implicit association test (aIAT) produces false positives in a real-world setting

    PubMed Central

    2013-01-01

    Background The autobiographical Implicit Association Test (aIAT) is a novel application of the implicit association concept for detecting life events. It has been used to reveal concealed knowledge in clinical and forensic settings, including detecting drug use. In this study, we aimed to explore the functionality of the aIAT to identify drug use in real-world settings. Methods The study used mixed methodology with known groups of drug users and nonusers. Recreational cocaine users (n = 23) and non-users (n = 23) were recruited through ethnographic methodology and assessed using a bespoke brief aIAT for cocaine use. An identical aIAT test for heroin detection was also administered to a sub-sample of 10 cocaine users and 13 nonusers. The accuracy of the cocaine aIAT was measured through ROC analysis. Paradoxical aIAT results were explored by integrating craving, consumption measures and life-story interviews into the analysis. Results Whilst the two brief aIATs showed good concurrent validity for cocaine users by accurately detecting drug using status for 18 of the 23 users (78.3%), the test falsely reported 61% cocaine users in the non-user comparison group. The average D-scores were 0.257±0.246 for the cocaine users and 0.134±0.367 for the non-users, showing no discriminatory power (t(44) = 1.339, p = 0.187; AUC = 0.605, p = 0.223). Results were independent from craving and recent cocaine use. The comparison group’s cocaine and heroin aIAT scores correlated significantly (r(13) = 0.776, p = 0.002) whilst an accurate absence of such relationship was evidenced in the cocaine using sample (r(10) = 0.061, p = 0.866). Triangulation with life-story interviews suggests that in the absence of an autobiographical event, this test may measure an alternative cognitive construct linked to the Self-concept. Conclusion The aIAT is a variant of an attitude measure and can be better rationalized if propositional thinking is implied to explain outcomes. The Relational Frame

  2. Sex work involvement among women with long-term opioid injection drug dependence who enter opioid agonist treatment.

    PubMed

    Marchand, Kirsten; Oviedo-Joekes, Eugenia; Guh, Daphne; Marsh, David C; Brissette, Suzanne; Schechter, Martin T

    2012-01-25

    Substitution with opioid-agonists (e.g., methadone) has shown to be an effective treatment for chronic long-term opioid dependency. Survival sex work, very common among injection drug users, has been associated with poor Opioid Agonist Treatment (OAT) engagement, retention and response. Therefore, this study was undertaken to determine factors associated with engaging in sex work among long-term opioid dependent women receiving OAT. Data from a randomized controlled trial, the North American Opiate Medication Initiative (NAOMI), conducted in Vancouver and Montreal (Canada) between 2005-2008, was analyzed. The NAOMI study compared the effectiveness of oral methadone to injectable diacetylmorphine or injectable hydromorphone, the last two on a double blind basis, over 12 months. A research team, independent of the clinic services, obtained outcome evaluations at baseline and follow-up (3, 6, 9, 12, 18 and 24 months). A total 53.6% of women reported engaging in sex work in at least one of the research visits. At treatment initiation, women who were younger and had fewer years of education were more likely to be engaged in sex work. The multivariate logistic generalized estimating equation regression analysis determined that psychological symptoms, and high illicit heroin and cocaine use correlated with women's involvement in sex work during the study period. After entering OAT, women using injection drugs and engaging in sex work represent a particularly vulnerable group showing poorer psychological health and a higher use of heroin and cocaine compared to women not engaging in sex work. These factors must be taken into consideration in the planning and provision of OAT in order to improve treatment outcomes. NCT00175357.

  3. Heroin. Specialized Information Service.

    ERIC Educational Resources Information Center

    Do It Now Foundation, Phoenix, AZ.

    The document presents a collection of articles about heroin. Article 1 provides general information on heroin identification, drug dependence, effects of abuse, cost, source of supply, and penalties for illegal heroin use. Article 2 gives statistical information on heroin-related deaths in the District of Columbia between 1971 and 1982. Article 3…

  4. Epidemiology of Pain among Outpatients in Methadone Maintenance Treatment Programs*

    PubMed Central

    Dhingra, Lara; Masson, Carmen; Perlman, David C.; Seewald, Randy M.; Katz, Judith; McKnight, Courtney; Homel, Peter; Wald, Emily; Jordan, Ashly E.; Young, Christopher; Portenoy, Russell K.

    2012-01-01

    BACKGROUND This analysis explored the prevalence and correlates of pain in patients enrolled in methadone maintenance treatment (MMT). METHODS Patients in two MMT programs starting a hepatitis care coordination randomized controlled trial completed the Brief Pain Inventory Short-Form and other questionnaires. Associations between clinically significant pain (average daily pain ≥ 5 or mean pain interference ≥ 5 during the past week) and sociodemographic data, medical status, depressive symptoms, and health-related quality of life, and current substance use were evaluated in multivariate analyses. RESULTS The 489 patients included 31.8% women; 30.3% Hispanics, 29.4% non-Hispanic blacks, and 36.0% non-Hispanic whites; 60.1% had hepatitis C, 10.6% had HIV, and 46.8% had moderate or severe depressive symptomatology. Mean methadone dose was 95.7 mg (SD 48.9) and urine drug screening (UDS) was positive for opiates, cocaine, and amphetamines in 32.9%, 40.1%, and 2.9%, respectively. Overall, 237 (48.5%) reported clinically significant pain. Pain treatments included prescribed opioids (38.8%) and non-opioids (48.9%), and self-management approaches (60.8%), including prayer (33.8%), vitamins (29.5%), and distraction (12.7%). Pain was associated with higher methadone dose, more medical comorbidities, prescribed opioid therapy, and more severe depressive symptomatology; it was not associated with UDS or self-reported substance use. CONCLUSIONS Clinically significant pain was reported by almost half of the patients in MMT programs and was associated with medical and psychological comorbidity. Pain was often treated with opioids and was not associated with measures of drug use. Studies are needed to further clarify these associations and determine their importance for pain treatment strategies. PMID:22951068

  5. Opioids in oral fluid of Spanish drivers.

    PubMed

    Herrera-Gómez, Francisco; García-Mingo, Mercedes; Colás, Mónica; González-Luque, Juan Carlos; Álvarez, F Javier

    2018-06-01

    Driving under the influence of certain drugs is not allowed, and roadside drug testing is being considered an important tool for deterring driving under the influence of them. This study aimed to assess the presence and concentration of opioids, as well as their combined use with other drugs (laboratory confirmation after the on-road screening) in Spanish drivers between 2011 and 2016. In Spain, mandatory roadside breath alcohol and oral fluid drug testing (screening) are carried out by the Traffic Police using Dräger Alcotest ® 6810 device, and Dräger DrugTest ® 5000, DrugWipe ® , or Alere™ DDS ® 2 Mobile Test System. For positive cases in the period covered, 65,244, confirmation analysis and quantification using chromatographic techniques were performed. Opioids were confirmed in 8.6% of positive cases, being 7.2% positives to 6-acetylmorphine (6-AM), 6.5% to morphine, 5.4% to codeine, and 4.1% to methadone. The majority of the confirmed tests for morphine (96.5%), codeine (88.4%) and methadone (81.9) were also positive for 6-AM. The presence of other drugs, particularly cocaine and cannabis, was very common. Concentration values reached important levels. Positive results for morphine (0.1%), codeine (0.6%) or methadone (0.4%) alone were very infrequent. Drivers with a confirmed positive roadside test for morphine, codeine, and methadone had also consumed heroin and/or other illicit drugs, such as cocaine and/or THC, and at relevant concentrations. Improving interventions to combat the problem of driving under the influence of driving-impairing substances is a priority. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. Aripiprazole for cocaine abstinence: a randomized controlled trial with ecological momentary assessment

    PubMed Central

    Moran, Landhing M.; Phillips, Karran A.; Kowalczyk, William J.; Ghitza, Udi E.; Agage, Daniel A.; Epstein, David H.; Preston, Kenzie L.

    2016-01-01

    Objectives. Aripiprazole blocks psychostimulant seeking in a rat model of relapse. However, in humans, it may increase ongoing use. We tested aripiprazole specifically for relapse prevention. Methadone-maintained outpatients who were abstinent from cocaine in weeks 11-12 were randomized to double-blind aripiprazole (15/mg daily) or placebo in weeks 13-27, after 12 weeks of contingency management. Participants reported craving via ecological momentary We stopped the trial because too few (18 of 41) participants met the abstinence criterion. The results were suggestive that aripiprazole delayed lapse (HR = 0.45, CI95 = 0.14 – 1.42, p = 0.17) and relapse (HR = 0.31. CI95 = 0.07 – 1.27, p = 0.10), but the effects did not reach statistical significance. Unexpectedly, the proportion of participants reporting cocaine craving was higher in the aripiprazole group (Fisher exact p = .026), though frequency of craving was similar in the aripiprazole and placebo groups (1.89% vs. 1.16%, reffect = .43, CI95 = −.08 - .76). The results suggest that in recently abstinent cocaine users, aripiprazole might delay relapse, but might also slightly increase craving. Difficulty in trial implementation underscores the fact that initial abstinence from cocaine is not a trivial hurdle. PMID:27755017

  7. Aripiprazole for cocaine abstinence: a randomized-controlled trial with ecological momentary assessment.

    PubMed

    Moran, Landhing M; Phillips, Karran A; Kowalczyk, William J; Ghitza, Udi E; Agage, Daniel A; Epstein, David H; Preston, Kenzie L

    2017-02-01

    Aripiprazole blocks psychostimulant seeking in a rat model of relapse. However, in humans, it may increase ongoing use. We tested aripiprazole specifically for relapse prevention. Methadone-maintained outpatients who were abstinent from cocaine in weeks 11-12 were randomized to double-blind aripiprazole (15 mg daily) or placebo in weeks 13-27 after 12 weeks of contingency management. Participants reported craving through ecological momentary assessment. We stopped the trial because very few (18/41) participants fulfilled the abstinence criterion. The results suggested that aripiprazole delayed lapse [hazard ratio (HR)=0.45, 95% confidence interval (CI)=0.14-1.42, P=0.17] and relapse (HR=0.31, 95% CI=0.07-1.27, P=0.10), but the effects did not reach statistical significance. Unexpectedly, the proportion of participants reporting cocaine craving was higher in the aripiprazole group (Fisher's exact P=0.026), although the frequency of craving was similar in the aripiprazole and placebo groups (1.89 vs. 1.16%, reffect=0.43, 95% CI=-0.08-0.76). The results suggest that in recently abstinent cocaine users, aripiprazole might delay relapse, but might also slightly increase craving. Difficulty in trial implementation underscores the fact that initial abstinence from cocaine is not a trivial hurdle.

  8. Long term outcomes of pharmacological treatments for opioid dependence: does methadone still lead the pack?

    PubMed Central

    Garcia-Portilla, Maria Paz; Bobes-Bascaran, Maria Teresa; Bascaran, Maria Teresa; Saiz, Pilar Alejandra; Bobes, Julio

    2014-01-01

    The aim of this review was to update and summarize the scientific knowledge on the long term outcomes of the different pharmacological treatment options for opioid dependence currently available and to provide a critical discussion on the different treatment options based on these results. We performed a literature search using the PubMed databases and the reference lists of the identified articles. Data from research show that the three pharmacological options reviewed are effective treatments for opioid dependence with positive long term outcomes. However, each one has its specific target population and setting. While methadone and buprenorphine are first line options, heroin-assisted treatment is a second line option for those patients refractory to treatment with methadone with concomitant severe physical, mental, social and/or functional problems. Buprenorphine seems to be the best option for use in primary care offices. The field of opioid dependence treatment is poised to undergo a process of reinforcement and transformation. Further efforts from researchers, clinicians and authorities should be made to turn new pharmacological options into clinical reality and to overcome the structural and functional obstacles that maintenance programmes face in combatting opioid dependence. PMID:23145768

  9. Methadone Treatment: Overview and Bibliography.

    ERIC Educational Resources Information Center

    Greenfield, Lawrence; Tang, Beth Archibald

    This overview focuses on methadone treatment. Briefly, it describes the clinical uses of methadone for substance abuse treatment, explores dosage guidelines, and discusses counseling components. This overview also reviews research data on the application of methadone treatment to special populations, such as pregnant women, polydrug users, and…

  10. Heroin in brown, black and white: structural factors and medical consequences in the US heroin market.

    PubMed

    Ciccarone, Daniel

    2009-05-01

    Heroin coming into the United States historically comes from three widely dispersed geographical regions: Southwest Asia, Southeast Asia and Mexico. A fourth source of US-bound heroin, from Colombia, originated in the early 1990s. The fact that the four heroin sources produce differing morphologies and qualities of heroin has not been critically examined. In addition, it is not well established how the contemporary competing dynamics of interdiction, or restriction of heroin flows across international boundaries, and neoliberal, e.g., global expansion of free trade, policies are affecting heroin markets. This paper will highlight changes in the US heroin market, including source trends, the political economy of the now dominant source and the resultant effects on the heroin risk environment by US region. Using a structural and historical framework this paper examines two decades of secondary data sources, including government and drug control agency documents, on heroin flows together with published work on the political and economic dynamics in Latin America. Co-occurring neoliberal economic reforms may have contributed to paradoxical effects of US/Colombian interdiction efforts. Since entering the US market, heroin from Colombia has been distributed at a much higher quality and lower retail price. An increasingly exclusive market has developed with Mexican and Colombian heroin gaining market share and displacing Asian heroin. These trends have had dramatic effects on the risk environment for heroin consumers. An intriguing factor is that different global sources of heroin produce substantially different products. Plausible associations exist between heroin source/form and drug use behaviours and harms. For example, cold water-soluble powdered heroin (sources: Asia, Colombia) may be associated with higher HIV prevalence in the US, while low-solubility "black tar" heroin (BTH; source: Mexico) is historically used in areas with reduced HIV prevalence. BTH is

  11. Heroin in brown, black and white: Structural factors and medical consequences in the US heroin market

    PubMed Central

    Ciccarone, Daniel

    2009-01-01

    Background Heroin coming into the United States historically comes from three widely dispersed geographical regions: Southwest Asia, Southeast Asia and Mexico. A fourth source of US-bound heroin, from Colombia, originated in the early 1990s. The fact that the four heroin sources produce differing morphologies and qualities of heroin has not been critically examined. In addition, it is not well established how the contemporary competing dynamics of interdiction, or restriction of heroin flows across international boundaries, and neoliberal, e.g., global expansion of free trade, policies are affecting heroin markets. This paper will highlight changes in the US heroin market, including source trends, the political economy of the now dominant source and the resultant effects on the heroin risk environment by US region. Methods Using a structural and historical framework this paper examines two decades of secondary data sources, including government and drug control agency documents, on heroin flows together with published work on the political and economic dynamics in Latin America. Results Co-occurring neoliberal economic reforms may have contributed to paradoxical effects of US/Colombian interdiction efforts. Since entering the US market, heroin from Colombia has been distributed at a much higher quality and lower retail price. An increasingly exclusive market has developed with Mexican and Colombian heroin gaining market share and displacing Asian heroin. These trends have had dramatic effects on the risk environment for heroin consumers. An intriguing factor is that different global sources of heroin produce substantially different products. Plausible associations exist between heroin source/form and drug use behaviours and harms. For example, cold water-soluble powdered heroin (sources: Asia, Colombia) may be associated with higher HIV prevalence in the US, while low-solubility “black tar” heroin (BTH; source: Mexico) is historically used in areas with reduced

  12. A follow-up study of heroin addicts (VEdeTTE2): study design and protocol

    PubMed Central

    Vigna-Taglianti, Federica D; Mathis, Federica; Diecidue, Roberto; Burroni, Paola; Iannaccone, Antonio; Lampis, Fabio; Zuccaro, Piergiorgio; Pacifici, Roberta; Versino, Elisabetta; Davoli, Marina; Faggiano, Fabrizio

    2007-01-01

    Background In Italy, a large cohort study (VEdeTTE1) was conducted between 1998–2001 to evaluate the effectiveness of treatments in reducing mortality and increasing treatment retention among heroin addicts. The follow-up of this cohort (VEdeTTE2) was designed to evaluate the effectiveness of treatments on long-term outcomes, such as rehabilitation and social re-integration. The purpose of this paper is to describe the protocol of the VEdeTTE2 study, and to present the results of the pilot study carried out to assess the feasibility of the study and to improve study procedures. Methods The source population for the VEdeTTE2 study was the VEdeTTE1 cohort, from which a sample of 2,200 patients, traced two or more years after enrolment in the cohort, were asked to participate. An interview investigates drug use; overdose; family and social re-integration. Illegal activity are investigated separately in a questionnaire completed by the patient. Patients are also asked to provide a hair sample to test for heroin and cocaine use. Information on treatments and HIV, HBV and HCV morbidity are obtained from clinical records. A pilot phase was planned and carried out on 60 patients. Results The results of the pilot phase pointed out the validity of the procedures designed to limit attrition: the number of traced subjects was satisfactory (88%). Moreover, the pilot phase was very useful in identifying possible causes of delays and attrition, and flaws in the instruments. Improvements to the procedures and the instruments were subsequently implemented. Sensitivity of the biological test was quite good for heroin (78%) but lower for cocaine (42.3%), highlighting the need to obtain a hair sample from all patients. Conclusion In drug addiction research, studies investigating health status and social re-integration of subjects at long-term follow-up are lacking. The VEdeTTE2 study aims to investigate these outcomes at long-term follow-up. Results of the pilot phase underline the

  13. Roadside opioid testing of drivers using oral fluid: the case of a country with a zero tolerance law, Spain.

    PubMed

    Fierro, Inmaculada; Colás, Mónica; González-Luque, Juan Carlos; Álvarez, F Javier

    2017-05-10

    Opioids can impair psychomotor performance, and driving under the influence of opioids is associated with an increased risk of accidents. The goals of this study were i) to determine the prevalence of opioids (heroin, morphine, codeine, methadone and tramadol) in Spanish drivers and ii) to explore the presence of opioids, more specifically whether they are used alone or in combination with other drugs. The 2008/9 DRUID database regarding Spain was used, which provided information on 3302 drivers. All drivers included in the study provided a saliva sample and mass-chromatographic analyses were carried out in all cases. To determine the prevalence, the sample was weighted according to traffic intensity. In the case of opioid use combinations, the sample was not weighted. The detection limit for each substance was considered a positive result. The prevalence of opioids in Spanish drivers was 1.8% (95% CI, 1.4-2.3). Polydrug detection was common (56.2%): of these, in two out of three cases, two opioids were detected and cocaine was also detected in 86% of the cases. The concentration (median [Q1-Q3] ng/ml) of the substances was low: methadone 1.71 [0.10-15.30], codeine 40.55 [2.10-120.77], 6-acetylmorphine 5.71 [1.53-84.05], and morphine 37.40 [2.84-200.00]. Morphine was always detected with 6-acetylmorphine (heroin use). Driving under the influence of opioids is relatively infrequent, but polydrug use is common. Our study shows that 6 out of 10 drivers with methadone in their OF (likely in methadone maintenance programs) are using other substances. This should be taken into account by health professionals in order to properly inform patients about the added risks of mixing substances when driving.

  14. Effects of methadone hydrochloride on the growth of organotypic cerebellar cultures prepared from methadone-tolerant and control rats.

    PubMed

    Willson, N J; Schneider, J F; Roizin, L; Fleiss, J F; Rivers, W; Demartini, J E

    1976-11-01

    Male and female Sprague-Dawley rats were given dl-methadone (5 mg/kg) for at least 3 months and then mated. The drug was continued throughout pregnancy and after delivery. The newly born pups were divided into two groups. One group was tested for in vivo methadone tolerance, while the animals in the othergroup were used to prepare organotypic cerebellar cultures. Various amounts of dl-methadone were added to the media of half of these cerebellum cultures. The effect of the drug in the medium was assessed by measuring explant outgrowth. Similar experiments were carried out with control animals. Statistical analysis of the data obtained in the in vivo portion of the experiment indicates that the pups of methadone-treated mothers tolerate methadone better than those of untreated mothers. The culture experiments revealed that the addition of methadone to the medium reduced explant outgrowth size and this was a dose-related effect. Also, there was significantly less outgrowth from explants prepared using pups of methadone-treated mothers as compared to the controls. There was no significant difference in the effect of methadone on the growth of cultures prepared from the methadone-tolerant and control animals.

  15. N-acetylaspartylglutamate Inhibits Heroin Self-Administration and Heroin-Seeking Behaviors Induced by Cue or Priming in Rats.

    PubMed

    Zhu, Huaqiang; Lai, Miaojun; Chen, Weisheng; Mei, Disen; Zhang, Fuqiang; Liu, Huifeng; Zhou, Wenhua

    2017-08-01

    Activation of presynaptic group II metabotropic glutamate receptors (mGluR2/3) inhibits drug reward and drug-seeking behavior, but the role of N-acetylaspartylglutamate (NAAG), an agonist of endogenous mGluR2/3, in heroin reward and heroin-seeking behavior remained unclear. Here, we aimed to explore the effects of exogenous NAAG on heroin self-administration and heroin-seeking behavior. First, rats were trained to self-administer heroin under a fixed ratio 1 (FR1) schedule for 10 days, then received NAAG (50 or 100 μg/10 μL in each nostril) in the absence or presence of LY341495 (1 mg/kg, i.p.), an antagonist of mGluR2/3, on day 11 and the effects of NAAG on heroin self-administration under FR1 were recorded for 3 consecutive days. Motivation was assessed in heroin self-administration under a progressive ratio schedule on day 11 in another 5 groups with the same doses of NAAG. Additional rats were withdrawn for 14 days after 14 days of heroin self-administration, then received the same pharmacological pretreatment and were tested for heroin-seeking behaviors induced by heroin priming or cues. The results showed that intranasal administration of NAAG significantly decreased intravenous heroin self-administration on day 12, but not on day 11. Pretreatment with LY341495 prior to testing on day 12 prevented the inhibitory effect of NAAG on heroin reinforcement. The break-point for reward motivation was significantly reduced by NAAG. Moreover, NAAG also significantly inhibited the heroin-seeking behaviors induced by heroin priming or cues and these were restored by pretreatment with LY341495. These results demonstrated that NAAG, via activation of presynaptic mGluR2/3, attenuated the heroin reinforcement, heroin motivational value, and heroin-seeking behavior, suggesting that it may be used as an adjunct treatment for heroin addiction.

  16. Co-occurring Attention Deficit Hyperactivity Disorder symptoms in adults affected by heroin dependence: Patients characteristics and treatment needs.

    PubMed

    Lugoboni, Fabio; Levin, Frances Rudnick; Pieri, Maria Chiara; Manfredini, Matteo; Zamboni, Lorenzo; Somaini, Lorenzo; Gerra, Gilberto; Gruppo InterSert Collaborazione Scientifica Gics

    2017-04-01

    Attention Deficit Hyperactivity Disorder (ADHD) is a risk for substance use disorders. The aim of this study was to investigate the association between adult ADHD symptoms, opioid use disorder, life dysfunction and co-occurring psychiatric symptoms. 1057 heroin dependent patients on opioid substitution treatment participated in the survey. All patients were screened for adult ADHD symptoms using the Adult ADHD Self-Report Scale (ASRS-v1.1). 19.4% of the patients screened positive for concurrent adult ADHD symptoms status and heroin dependence. Education level was lower among patients with ADHD symptoms, but not significant with respect to non-ADHD patients. Patients with greater ADHD symptoms severity were less likely to be employed. A positive association was observed between ADHD symptoms status and psychiatric symptoms. Patients with ADHD symptoms status were more likely to be smokers. Patients on methadone had a higher rate of ADHD symptoms status compared to buprenorphine. Those individuals prescribed psychoactive drugs were more likely to have ADHD symptoms. In conclusion, high rate of ADHD symptoms was found among heroin dependent patients, particularly those affected by the most severe form of addiction. These individuals had higher rates of unemployment, other co-morbid mental health conditions, heavy tobacco smoking. Additional psychopharmacological interventions targeting ADHD symptoms, other than opioid substitution, is a public health need. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  17. Linking drugs of abuse in wastewater to contamination of surface and drinking water.

    PubMed

    Rodayan, Angela; Afana, Shadi; Segura, Pedro A; Sultana, Tamanna; Metcalfe, Chris D; Yargeau, Viviane

    2016-04-01

    The concentrations of 17 drugs of abuse, including cocaine, several amphetamines, opioid drugs, and 2 metabolites--benzoylecgonine, a metabolite of cocaine, and 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrolidine, a metabolite of methadone--were investigated in an urban watershed that is heavily impacted by discharges of municipal wastewater. The artificial sweetener sucralose was also monitored as a persistent tracer of contamination from municipal wastewater. Monitoring was conducted in a municipal wastewater treatment plant (WWTP) and at sites upstream and downstream of the WWTP discharge, as well as in a drinking water treatment plant (DWTP) located 19 km downstream of the WWTP discharge that withdraws raw water from the river. Drug concentrations were monitored with polar organic chemical integrative samplers deployed for 2 wk in the river and in the WWTP and DWTP. Several of the investigated compounds exhibited a decrease in concentration with distance downstream from the wastewater discharge into the river, but there was little attenuation of sucralose, cocaine, benzoylecgonine, morphine, acetylmorphine, acetylcodeine, and oxycodone. Heroin and methadone were not detected at any sample locations. Amphetamine, methamphetamine, 3,4-methylenedioxy-methamphetamine, and 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrolidine were not detected in the samples collected at the drinking water intake. Many of the drugs of abuse were not removed effectively in the DWTP, including cocaine, benzoylecgonine, methylenedioxyamphetamine, ephedrine, and several prescription opioids, most probably because the DWTP was operating at or above its rated treatment capacity. These data indicate that there can be transport of drugs of abuse from wastewater sources into drinking water in urban watersheds. © 2015 SETAC.

  18. From gold-medal glory to prohibition: the early evolution of cocaine in the United Kingdom and the United States

    PubMed Central

    Gilchrist, Dawna

    2013-01-01

    As reported in the 2011 World Drug Report, cocaine is likely to be the most problematic drug worldwide in terms of trafficking-related violence and second only to heroin in terms of negative health consequences and drug deaths. Over a period of 60 years, cocaine evolved from the celebrated panacea of the 1860s to outlawed street drug of the 1920s. As demonstrated by the evolution of cocaine use and abuse in the United Kingdom and United States during this time period, cultural attitudes influenced both the acceptance of cocaine into the medical field and the reaction to the harmful effects of cocaine. Our review of articles on cocaine use in the United Kingdom and the United States from 1860 to 1920 reveals an attitude of caution in the United Kingdom compared with an attitude of progressivism in the United States. When the trends in medical literature are viewed in the context of the development of drug regulations, our analysis provides insight into the relationship between cultural attitudes and drug policy, supporting the premise that it is cultural and social factors which shape drug policy, rather than drug regulations changing culture. PMID:23772315

  19. HIV seroprevalence among street-recruited injection drug and crack cocaine users in 16 US municipalities.

    PubMed Central

    Kral, A H; Bluthenthal, R N; Booth, R E; Watters, J K

    1998-01-01

    OBJECTIVES: This study deter- mined human immunodeficiency virus (HIV) seroprevalence and factors associated with HIV infection among street-recruited injection drug users and crack cocaine smokers. METHODS: An analysis was performed on HIV serologies and risk behaviors of 6402 injection drug users and 3383 crack smokers in 16 US municipalities in 1992 and 1993. RESULTS: HIV seroprevalence was 12.7% among injection drug users and 7.5% among crack smokers. Most high-seroprevalence municipalities (>25%) were located along the eastern seaboard of the United States. In high-seroprevalence municipalities, but not in others, HIV seroprevalence was higher for injection drug users than for crack smokers. Among injection drug users, cocaine injection, use of speedballs (cocaine or amphetamines with heroin), and sexual risk behaviors were independently associated with HIV infection. Among crack smokers, sexual risk behaviors were associated with HIV infection. CONCLUSIONS: Injection drug users and crack smokers are at high risk for HIV infection. PMID:9584014

  20. Clinical pharmacology of methadone in dogs.

    PubMed

    Ingvast-Larsson, Carina; Holgersson, Anja; Bondesson, Ulf; Lagerstedt, Anne-Sofie; Olsson, Kerstin

    2010-01-01

    To investigate the pharmacokinetics and effects of methadone on behaviour and plasma concentrations of cortisol and vasopressin in healthy dogs. Randomized, cross-over, experimental trial. Nine adult dogs (beagle and beagle cross breeds), four males and five females. Methadone hydrochloride, 0.4 mg kg(-1), was administered intravenously (IV) and subcutaneously (SC) with a crossover design. Drug and hormone analyses in plasma were performed using Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry and radioimmunoassay respectively. Behavioural data were collected using a standardized protocol. After IV administration, the plasma concentration of methadone at 10 minutes was 82.1 +/- 9.2 ng mL(-1) (mean +/- SD), the terminal half-life was 3.9 +/- 1.0 hours, the volume of distribution 9.2 +/- 3.3 L kg(-1) and plasma clearance 27.9 +/- 7.6 mL minute(-1) kg(-1). After SC administration, time to maximal plasma concentration was 1.26 +/- 1.04 hours and maximal plasma concentration of methadone was 23.9 +/- 14.4 ng mL(-1), the terminal half-life was 10.7 +/- 4.3 hours and bioavailability was 79 +/- 22%. Concentrations of both cortisol and vasopressin were increased for an hour following IV methadone. The observed behavioural effects of methadone were decreased licking and swallowing and an increase in whining after SC administration. The latter finding is notable as it can be misinterpreted as pain when methadone is used as an analgesic. When methadone was administered by the SC route, the half-life was longer, but the individual variation in plasma concentrations was greater compared with IV administration. Increased frequency of whining occurred after administration of methadone and may be a drug effect and not a sign of pain. Cortisol and vasopressin concentrations in plasma may not be suitable for evaluating analgesia after methadone treatment.

  1. Day treatment versus enhanced standard methadone services for opioid-dependent patients: a comparison of clinical efficacy and cost.

    PubMed

    Avants, S K; Margolin, A; Sindelar, J L; Rounsaville, B J; Schottenfeld, R; Stine, S; Cooney, N L; Rosenheck, R A; Li, S H; Kosten, T R

    1999-01-01

    This study examined the differential efficacy and relative costs of two intensities of adjunctive psychosocial services--a day treatment program and enhanced standard care--for the treatment of opioid-dependent patients maintained on methadone hydrochloride. A 12-week randomized clinical trial with 6-month follow-up was conducted in a community-based methadone maintenance program. Of the 308 patients who met inclusion criteria, 291 began treatment (day treatment program: N=145; enhanced standard care: N=146), and 237 completed treatment (82% of those assigned to the day treatment program and 81% of those receiving enhanced standard care). Two hundred twenty of the patients participated in the 6-month follow-up (75% of those in the day treatment program and 73% of those in enhanced standard care provided a follow-up urine sample for screening). Both interventions were 12 weeks in duration, manual-guided, and provided by master's-level clinicians. The day treatment was an intensive, 25-hour-per-week program. The enhanced standard care was standard methadone maintenance plus a weekly skills training group and referral to on- and off-site services. Outcome measures included twice weekly urine toxicology screens, severity of addiction-related problems, prevalence of HIV risk behaviors, and program costs. Although the cost of the day treatment program was significantly higher, there was no significant difference in the two groups' use of either opiates or cocaine. Over the course of treatment, drug use, drug-related problems, and HIV risk behaviors decreased significantly for patients assigned to both treatment intensities. Improvements were maintained at follow-up. Providing an intensive day treatment program to unemployed, inner-city methadone patients was not cost-effective relative to a program of enhanced methadone maintenance services, which produced comparable outcomes at less than half the cost.

  2. Heroin: MedlinePlus Health Topic

    MedlinePlus

    ... flashes with goose bumps. NIH: National Institute on Drug Abuse Start Here DrugFacts: Heroin (National Institute on Drug Abuse) Also in Spanish Heroin (Drug Enforcement Administration) Heroin ( ...

  3. DrugFacts: Heroin

    MedlinePlus

    ... White matter impairment in chronic heroin dependence: a quantitative DTI study. Brain Res . 2013;1531:58-64. ... Minneapolis/St.Paul, Minn." Watch video (1:08) Research Report Heroin Offers the latest scientific information on ...

  4. Investigation of the Interactions between Methadone and Elvitegravir-Cobicistat in Subjects Receiving Chronic Methadone Maintenance

    PubMed Central

    Winkle, P.; Custodio, J. M.; Wei, X.; Rhee, M. S.; Kearney, B. P.; Ramanathan, S.; Friedland, Gerald H.

    2013-01-01

    Interactions between HIV and opioid dependence therapies are known to occur. We sought to determine if such interactions occurred between methadone and elvitegravir boosted with cobicistat (EVG/COBI). We performed a within-subject open-label pharmacokinetic and pharmacodynamic study of 11 HIV-seronegative subjects stabilized on at least 2 weeks of methadone. Subjects underwent baseline and steady-state evaluation of the effect of elvitegravir 150 mg once a day (QD) boosted with 150 mg QD of cobicistat (EVG/COBI) on methadone pharmacokinetic parameters. Safety and pharmacodynamics were monitored throughout the study. Compared to baseline values, the R-methadone mean area under the concentration-time curve to the end of the dosing period (AUCtau) (5,550 versus 6,210 h · ng/ml) and mean maximum concentration of drug in serum (Cmax) (316 versus 337 ng/ml) did not significantly increase in the presence of EVG/COBI. Compared to baseline values, the S-methadone mean AUCtau (7,040 versus 7,540 h · ng/ml) and mean Cmax (446 versus 452 ng/ml) did not significantly increase in the presence of EVG/COBI. The AUCtau, Cmax, and Ctau of elvitegravir and cobicistat did not significantly differ from those of historical controls. Opioid withdrawal or overdose was not observed among subjects in this study. The addition of EVG/COBI to stabilized patients receiving methadone did not affect methadone pharmacokinetics and pharmacodynamics. These two agents can be safely coadministered. PMID:24080665

  5. Research Reports: Heroin

    MedlinePlus

    ... areas west of the Mississippi River. 3 The dark color associated with black tar heroin results from ... have shown some deterioration of the brain’s white matter due to heroin use, which may affect decision- ...

  6. CDC Vital Signs: Today's Heroin Epidemic

    MedlinePlus

    ... is increasing, and so are heroin-related overdose deaths. How is heroin harmful? Heroin is an illegal, ... can cause slow and shallow breathing, coma, and death. People often use heroin along with other drugs ...

  7. Psychological Functioning of Women Taking Illicit Drugs during Pregnancy and the Growth and Development of Their Offspring in Early Childhood.

    PubMed

    Serino, Dana; Peterson, Bradley S; Rosen, Tove S

    2018-04-25

    Assess psychosocial history and psychological functioning in women who use drugs during pregnancy and determine how drug exposure affects child development. Pregnant marijuana (n = 38), cocaine (n = 35), methadone-maintained (n = 24), and control (n = 49) group women were enrolled and followed every 6 months through 18-24 months postnatally. There was a significantly higher incidence of mental illness in mothers in the drug groups. Prenatal stress and late-term drug severity scores were significantly higher in the cocaine and methadone mothers, who were also more likely to have abuse and incarceration histories. At 12 months, there were significantly higher rates of drug use in the marijuana group. Anxiety scores were highest in the methadone group. At 18-24 months, the methadone group reported significantly more stress, and methadone and marijuana groups had significantly higher anxiety and depression scores. At birth, methadone and marijuana neonates had significantly smaller head circumferences, with shorter lengths in the marijuana group. At one year, children in the cocaine group had significantly lower Bayley-III Cognitive and Motor scores. At 18-24 months, children in the methadone group had significantly smaller head circumferences and Cognitive scores. Children in the methadone and cocaine groups had a significantly higher incidence of atypical neurological examinations at 6-9 and 18-24 months. Methadone and cocaine group mothers presented with more severe prenatal drug use and psychosocial risk factors relative to women who used primarily marijuana. Children in the cocaine and methadone groups were neurologically atypical relative to others at study end. Mothers in the marijuana group reported chronic drug use as well as anxiety and depression in follow-up. At birth, children in the marijuana group were smaller, but this resolved with time. Similarly, children in the cocaine group had motor and cognitive delays which resolved by age two. Children in the

  8. The effect of stimulant and sedative use on treatment outcome of patients admitted to methadone maintenance treatment.

    PubMed

    DeMaria, P A; Sterling, R; Weinstein, S P

    2000-01-01

    While methadone maintenance treatment (MMT) has been demonstrated to be an effective treatment for opiate dependence, its impact on the treatment outcome of other illicit drug abuse is not as clear. Using the initial urine drug screen (UDS) and follow-up UDS at 1, 6, 12, and 24 months, 167 patients consecutively admitted to MMT were evaluated for opiate, sedative (predominantly benzodiazepine), and stimulant (predominantly cocaine) use. Retention for the opiate only group was 97.32 days longer on average than for patients using opiates along with stimulants, sedatives, or both stimulants and sedatives. Patients abusing opiates only had the greatest decrease in drug use; however, MMT was also associated with decreases in cocaine and sedative use over the 24 month follow-up period. There was no evidence that patients "switched" their drugs of abuse with time in treatment. The negative impact of non-opiate drug use on outcome in MMT and its implications for treatment planning are discussed.

  9. Development and validation of a Client Problem Profile and Index for drug treatment.

    PubMed

    Joe, George W; Simpson, D Dwayne; Greener, Jack M; Rowan-Szal, Grace A

    2004-08-01

    The development of the Client Problem Profile and Index are described, and initial concurrent and predictive validity data are presented for a sample of 547 patients in outpatient methadone treatment. Derived from the TCU Brief Intake for drug treatment admissions, the profile covers 14 problem areas related to drug use (particularly cocaine, heroin/opiate, marijuana, other illegal drugs, and multiple drug use), HIV risks, psychosocial-functioning, health, employment, and criminality. Analyses of predictive validity show the profile and its index (number of problem areas) were significantly related to therapeutic engagement, during-treatment performance, and posttreatment follow-up outcomes. Low moderate to high moderate effect sizes were observed in analyses of the index's discrimination.

  10. Enantiomeric metabolic interactions and stereoselective human methadone metabolism.

    PubMed

    Totah, Rheem A; Allen, Kyle E; Sheffels, Pamela; Whittington, Dale; Kharasch, Evan D

    2007-04-01

    Methadone is administered as a racemate, although opioid activity resides in the R-enantiomer. Methadone disposition is stereoselective, with considerable unexplained variability in clearance and plasma R/S ratios. N-Demethylation of methadone in vitro is predominantly mediated by cytochrome P450 CYP3A4 and CYP2B6 and somewhat by CYP2C19. This investigation evaluated stereoselectivity, models, and kinetic parameters for methadone N-demethylation by recombinant CYP2B6, CYP3A4, and CYP2C19, and the potential for interactions between enantiomers during racemate metabolism. CYP2B6 metabolism was stereoselective. CYP2C19 was less active, and stereoselectivity was opposite that for CYP2B6. CYP3A4 was not stereoselective. With all three isoforms, enantiomer N-dealkylation rates in the racemate were lower than those of (R)-(6-dimethyamino-4,4-diphenyl-heptan-3-one) hydrochloride (R-methadone) or (S)-(6-dimethyamino-4,4-diphenyl-heptan-3-one) hydrochloride (S-methadone) alone, suggesting an enantiomeric interaction and mutual metabolic inhibition. For CYP2B6, the interaction between enantiomers was stereoselective, with S-methadone as a more potent inhibitor of R-methadone N-demethylation than R-of S-methadone. In contrast, enantiomer interactions were not stereoselective with CYP2C19 or CYP3A4. For all three cytochromes P450, methadone N-demethylation was best described by two-site enzyme models with competitive inhibition. There were minor model differences between cytochromes P450 to account for stereoselectivity of metabolism and enantiomeric interactions. Changes in plasma R/S methadone ratios observed after rifampin or troleandomycin pretreatment in humans in vivo were successfully predicted by CYP2B6- but not CYP3A4-catalyzed methadone N-demethylation. CYP2B6 is a predominant catalyst of stereoselective methadone metabolism in vitro. In vivo, CYP2B6 may be a major determinant of methadone metabolism and disposition, and CYP2B6 activity and stereoselective metabolic

  11. Signs of Heroin Abuse and Addiction

    MedlinePlus

    ... Signs of Heroin Use and Addiction Signs of Heroin Use and Addiction Listen Heroin can give you ... Previous Index Next Español English Español "I needed heroin just to get by." ©istock.com/ pixelheadphoto Deon ...

  12. Carrier-mediated cocaine transport at the blood-brain barrier as a putative mechanism in addiction liability.

    PubMed

    Chapy, Hélène; Smirnova, Maria; André, Pascal; Schlatter, Joël; Chiadmi, Fouad; Couraud, Pierre-Olivier; Scherrmann, Jean-Michel; Declèves, Xavier; Cisternino, Salvatore

    2014-10-31

    The rate of entry of cocaine into the brain is a critical factor that influences neuronal plasticity and the development of cocaine addiction. Until now, passive diffusion has been considered the unique mechanism known by which cocaine crosses the blood-brain barrier. We reassessed mechanisms of transport of cocaine at the blood-brain barrier using a human cerebral capillary endothelial cell line (hCMEC/D3) and in situ mouse carotid perfusion. Both in vivo and in vitro cocaine transport studies demonstrated the coexistence of a carrier-mediated process with passive diffusion. At pharmacological exposure level, passive diffusion of cocaine accounted for only 22.5% of the total cocaine influx in mice and 5.9% in hCMEC/D3 cells, whereas the carrier-mediated influx rate was 3.4 times greater than its passive diffusion rate in vivo. The functional identification of this carrier-mediated transport demonstrated the involvement of a proton antiporter that shared the properties of the previously characterized clonidine and nicotine transporter. The functionnal characterization suggests that the solute carrier (SLC) transporters Oct (Slc22a1-3), Mate (Slc47a1) and Octn (Slc22a4-5) are not involved in the cocaine transport in vivo and in vitro. Diphenhydramine, heroin, tramadol, cocaethylene, and norcocaine all strongly inhibited cocaine transport, unlike benzoylecgonine. Trans-stimulation studies indicated that diphenhydramine, nicotine, 3,4-methylenedioxyamphetamine (ecstasy) and the cathinone compound 3,4-methylenedioxypyrovalerone (MDPV) were also substrates of the cocaine transporter. Cocaine transport at the BBB involves a proton-antiporter flux that is quantitatively much more important than its passive diffusion. The molecular identification and characterization of this transporter will provide new tools to understand its role in addictive mechanisms. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e

  13. Carrier-Mediated Cocaine Transport at the Blood-Brain Barrier as a Putative Mechanism in Addiction Liability

    PubMed Central

    Chapy, Hélène; Smirnova, Maria; André, Pascal; Schlatter, Joël; Chiadmi, Fouad; Couraud, Pierre-Olivier; Scherrmann, Jean-Michel; Declèves, Xavier

    2015-01-01

    Background: The rate of entry of cocaine into the brain is a critical factor that influences neuronal plasticity and the development of cocaine addiction. Until now, passive diffusion has been considered the unique mechanism known by which cocaine crosses the blood-brain barrier. Methods: We reassessed mechanisms of transport of cocaine at the blood-brain barrier using a human cerebral capillary endothelial cell line (hCMEC/D3) and in situ mouse carotid perfusion. Results: Both in vivo and in vitro cocaine transport studies demonstrated the coexistence of a carrier-mediated process with passive diffusion. At pharmacological exposure level, passive diffusion of cocaine accounted for only 22.5% of the total cocaine influx in mice and 5.9% in hCMEC/D3 cells, whereas the carrier-mediated influx rate was 3.4 times greater than its passive diffusion rate in vivo. The functional identification of this carrier-mediated transport demonstrated the involvement of a proton antiporter that shared the properties of the previously characterized clonidine and nicotine transporter. The functionnal characterization suggests that the solute carrier (SLC) transporters Oct (Slc22a1-3), Mate (Slc47a1) and Octn (Slc22a4-5) are not involved in the cocaine transport in vivo and in vitro. Diphenhydramine, heroin, tramadol, cocaethylene, and norcocaine all strongly inhibited cocaine transport, unlike benzoylecgonine. Trans-stimulation studies indicated that diphenhydramine, nicotine, 3,4-methylenedioxyamphetamine (ecstasy) and the cathinone compound 3,4-methylenedioxypyrovalerone (MDPV) were also substrates of the cocaine transporter. Conclusions: Cocaine transport at the BBB involves a proton-antiporter flux that is quantitatively much more important than its passive diffusion. The molecular identification and characterization of this transporter will provide new tools to understand its role in addictive mechanisms. PMID:25539501

  14. Measuring the incentive value of escalating doses of heroin in heroin-dependent Fischer rats during acute spontaneous withdrawal

    PubMed Central

    Reed, Brian; Ho, Ann; Kreek, Mary Jeanne

    2011-01-01

    Rationale/objectives Although continued heroin use and relapse are thought to be motivated, in part, by the positive incentive-motivational value attributed to heroin, little is understood about heroin’s incentive value during the relapse-prone state of withdrawal. This study uses place preference to measure the incentive value attributed to escalating-dose heroin in the context of heroin dependence. Methods Male Fischer rats were exposed chronically to escalating doses of heroin in the homecage and during place preference conditioning sessions. Conditioned preference for the context paired with escalating-dose heroin was tested after homecage exposure was discontinued and rats entered acute spontaneous withdrawal. Individuals’ behavioral and locomotor responses to heroin and somatic withdrawal signs were recorded. Results Conditioned preference for the heroin-paired context was strong in rats that received chronic homecage exposure to escalating-dose heroin and were tested in acute withdrawal. Behavioral responses to heroin (e.g., stereotypy) varied widely across individuals, with rats that expressed stronger heroin preference also expressing stronger behavioral activation in response to heroin. Individual differences in preference were also related to locomotor responses to heroin but not to overt somatic withdrawal signs. Conclusions Escalating doses of heroin evoked place preference in rats, suggesting that positive incentive-motivational value is attributed to this clinically relevant pattern of drug exposure. This study offers an improved preclinical model for studying dependence and withdrawal and provides insight into individual vulnerabilities to addiction-like behavior. PMID:21748254

  15. Pharmacokinetics and pharmacodynamics of smoked heroin.

    PubMed

    Jenkins, A J; Keenan, R M; Henningfield, J E; Cone, E J

    1994-10-01

    Despite the current popularity of smoking as a route of drug self-administration, there have been few human studies characterizing the pharmacokinetics and pharmacodynamics of smoked drugs of abuse. A variety of technological difficulties are encountered in the design of smoking studies, such as delivering reproducible doses and limiting the amount of pyrolysis of parent drug. As part of a concerted research effort to deliver precise, smoked doses of drug, a computer-assisted smoking device was utilized that delivered single puffs of heroin vapor to human subjects under controlled clinical conditions. Recovery studies indicated that the smoking device delivered approximately 89% of parent heroin to subjects. Although only two qualified heroin smokers could be identified as eligible volunteers, their participation provided the unique opportunity to study the pharmacokinetics and pharmacodynamics of smoked heroin. The two subjects were administered four smoked heroin doses in ascending order. In addition, four intravenous doses of heroin were administered for comparison of effects and estimation of bioavailability. Concurrent physiological, behavioral, and performance measures were collected along with blood samples. Blood was analyzed for heroin, 6-acetylmorphine, and morphine by solid-phase extraction gas chromatography-mass spectrometry. Heroin appeared rapidly in blood after administration and peaked 1-5 minutes after smoking, which is similar to that observed following intravenous administration. Heroin concentrations declined rapidly to the limit of detection (1.0 ng/mL) by 30 minutes. 6-Acetylmorphine blood concentrations also peaked and declined rapidly after smoked heroin with peak concentrations occurring at 1-2 minutes after smoking. Morphine levels rose and decayed more slowly. Mean elimination half-lives for heroin, 6-acetylmorphine, and morphine were 3.3 min, 5.4 min, and 18.8 min, respectively, by the smoked route. The bioavailability of smoked heroin

  16. Neural correlates of adherence to extended-release naltrexone pharmacotherapy in heroin dependence

    PubMed Central

    Wang, A-L; Elman, I; Lowen, S B; Blady, S J; Lynch, K G; Hyatt, J M; O'Brien, C P; Langleben, D D

    2015-01-01

    Injectable extended-release naltrexone (XRNTX) presents an effective therapeutic strategy for opioid addiction, however its utility could be hampered by poor adherence. To gain a better insight into this phenomenon, we utilized blood oxygenation level-dependent functional magnetic resonance imaging (fMRI) in conjunction with a validated cue-induced craving procedure to examine neural correlates of XRNTX adherence. We operationalized treatment adherence as the number of monthly XRNTX injections (range: 0–3) administered to a group of fully detoxified heroin-dependent subjects (n=32). Additional outcomes included urine toxicology screening and self-reported tobacco use. The presented heroin-related visual cues reliably elicited heroin craving in all tested subjects. Nine, five, three and 15 of the participants, respectively, received zero, one, two and three XRNTX injections, predicted by the individual baseline fMRI signal change in response to the cues in the medial prefrontal cortex, a brain region involved in inhibitory self-control and emotional appraisal. The incidence of opioid-positive urines during the XRNTX therapy was low and remained about half the pre-treatment rate after the XRNTX ended. During the treatment, cigarette smoking behaviors followed patterns of opioid use, while cocaine consumption was increased with reductions in opioid use. The present data support the hypothesis that medial prefrontal cortex functions are involved in adherence to opioid antagonist therapy. A potential role of concurrent non-opioid addictive substances consumption during the XRNTX pharmacotherapy warrants further investigation. Our findings set the stage for further bio-behavioral investigations of the mechanisms of relapse prevention in opioid dependence. PMID:25781230

  17. [Methods of use and behavior of cocaine addicts consulting medical-legal emergency units in Paris. Clinical aspects and urinary toxicology profile].

    PubMed

    Bécour, Bertrand; Menet, Marie-Claude; Questel, Frank; Guyon, François; Diamant-Berger, Odile

    2003-03-01

    Establish the epidemiological characteristics and urinary toxicological profiles of a population of cocaine addicts under police custody. A series of 60 cocaine addicts consulting the medico-legal emergency unit of the Hôtel-Dieu hospital in Paris was studied prospectively on the following elements: clinical characteristics, method of cocaine administration and association with other licit or illicit substances. Urinary toxicological analysis, using immuno-chemistry and chromatography linked to a mass spectrometer was systematically proposed to each patient. Half of the 17 to 26 year-old patients declared having consumed cocaine for the past 2 to 5 years. Inhalation of the vapours and the intravenous route were used more than the cigarette or nasal route. The majority of 26 to 35 year-olds were multi-drug addicted, generally associating cocaine, heroine and tobacco. Analysis of the urine provided an objective assessment of the cocaine consumption of these persons under police custody in Paris. Screening for urinary toxicity gives better knowledge on the consumption of addictive products by the person in whom urine was sampled. This study was conducted in cocaine addicts under police custody, and for the majority were social misfits. In this population, the consumption of crack by inhalation predominated.

  18. The relationship between initial route of heroin administration and speed of transition to daily heroin use.

    PubMed

    Hines, Lindsey A; Lynskey, Michael; Morley, Katherine I; Griffiths, Paul; Gossop, Michael; Powis, Beverly; Strang, John

    2017-09-01

    The effect of heroin administration route on speed of transition to regular use is unknown. This paper aims to determine whether the speed of transition from initiation of heroin use to daily heroin use differs by route of administration (injecting, chasing/inhaling or snorting). Privileged access interviewer survey of purposively selected sample of 395 current people who use heroin (both in and not in treatment) in London, UK (historical sample from 1991). Data on age and year of initiation, time from initiation to daily use and routes of administration were collected by means of a structured questionnaire. Generalised ordered logistic models were used to test the relationship between route of initial administration of heroin and speed of transition to daily heroin use. Analyses were adjusted for gender, ethnicity, daily use of other drug(s) at time of initiation, year of initiation and treatment status at interview. After adjustment, participants whose initial administration route was injecting had a 4.71 (95% confidence interval 1.34-16.5) increase in likelihood of progressing to daily use within 1-3 weeks of initiation, compared to those whose initial administration route was non-injecting. The speed of transition from first use to daily heroin use is faster if the individual injects heroin at initiation of use. Those who initiate heroin use through injecting have a shorter time frame for intervention before drug use escalation. [Hines LA, Lynskey M, Morley KI, Griffiths P, Gossop M, Powis B, Strang J. The relationship between initial route of heroin administration and speed of transition to daily heroin use. Drug Alcohol Rev 2017;00:000-000]. © 2017 Australasian Professional Society on Alcohol and other Drugs.

  19. Heroin crystal nephropathy

    PubMed Central

    Bautista, Josef Edrik Keith; Merhi, Basma; Gregory, Oliver; Hu, Susie; Henriksen, Kammi; Gohh, Reginald

    2015-01-01

    In this paper we present an interesting case of acute kidney injury and severe metabolic alkalosis in a patient with a history of heavy heroin abuse. Urine microscopy showed numerous broomstick-like crystals. These crystals are also identified in light and electron microscopy. We hypothesize that heroin crystalizes in an alkaline pH, resulting in tubular obstruction and acute kidney injury. Management is mainly supportive as there is no known specific therapy for this condition. This paper highlights the utility of urine microscopy in diagnosing the etiology of acute kidney injury and proposes a novel disease called heroin crystal nephropathy. PMID:26034599

  20. Biased and less sensitive: A gamified approach to delay discounting in heroin addiction.

    PubMed

    Scherbaum, Stefan; Haber, Paul; Morley, Kirsten; Underhill, Dylan; Moustafa, Ahmed A

    2018-03-01

    People with addiction will continue to use drugs despite adverse long-term consequences. We hypothesized (a) that this deficit persists during substitution treatment, and (b) that this deficit might be related not only to a desire for immediate gratification, but also to a lower sensitivity for optimal decision making. We investigated how individuals with a history of heroin addiction perform (compared to healthy controls) in a virtual reality delay discounting task. This novel task adds to established measures of delay discounting an assessment of the optimality of decisions, especially in how far decisions are influenced by a general choice bias and/or a reduced sensitivity to the relative value of the two alternative rewards. We used this measure of optimality to apply diffusion model analysis to the behavioral data to analyze the interaction between decision optimality and reaction time. The addiction group consisted of 25 patients with a history of heroin dependency currently participating in a methadone maintenance program; the control group consisted of 25 healthy participants with no history of substance abuse, who were recruited from the Western Sydney community. The patient group demonstrated greater levels of delay discounting compared to the control group, which is broadly in line with previous observations. Diffusion model analysis yielded a reduced sensitivity for the optimality of a decision in the patient group compared to the control group. This reduced sensitivity was reflected in lower rates of information accumulation and higher decision criteria. Increased discounting in individuals with heroin addiction is related not only to a generally increased bias to immediate gratification, but also to reduced sensitivity for the optimality of a decision. This finding is in line with other findings about the sensitivity of addicts in distinguishing optimal from nonoptimal choice options.

  1. [Fatal toxic leukoencephalopathy associated with consumption of pasta base of cocaine: Report of three cases].

    PubMed

    Cartier R, Luis; González L, Daniela; Harán D, Jorge

    2015-11-01

    The prevalence of drug-associated toxic encephalopathy is unknown, but it is an uncommon condition. Toxic leukoencephalopathy was described associated with heroin consumption, it has been less commonly described with the use of cocaine and there are no reports of its association with consumption pasta base of cocaine (PBC). We report two females aged 31 years and a male aged 19 years, consumers of PBC who developed a fatal toxic leukoencephalopathy. They initiated their disease with severe and persistent headache, sequential focal neurologic deficits and a progressive impairment of consciousness that culminated with their death. Laboratory parameters such as blood count, cerebrospinal fluid analyses or infectious biological indices were normal. MRI showed multifocal lesions in brain white matter of both hemispheres confirming the leukoencephalopathy. There was no response to the use of methylprednisolone.

  2. Harm reduction program use, psychopathology and medical severity in patients with methadone maintenance treatment.

    PubMed

    Martínez-Luna, Nieves Gudelia; Rodríguez-Cintas, Laia; Esojo, Abderraman; Palma-Álvarez, Raúl Felipe; Robles-Martínez, María; Grau-López, Lara; Perea, Marta; Roncero, Carlos

    2018-01-15

    Methadone maintenance programs (MMP) for opioid dependence treatment have been widely used due to their effective therapeutic outcomes. Harm reduction programs (HRP) are complementary programs for severe patients with high risk behaviors and when abstinence is not possible. This study aims to compare patients in MMP that use HRP (MMP-HRP) and patients in MMP who do not use HRP (MMP-NO HRP). The sample was composed of 143 patients (MMP-HRP = 42 vs. MMP-NO HRP = 101). An additional subanalysis was performed with patients under 45 years of age (n = 116; MMP-HRP = 38 vs. MMP-NO HRP = 78). All patients were assessed with an ad hoc socio-demographic questionnaire, EuropASI, SCID-I, and SCID-II. Results show that MMP-HRP patients were younger with more frequent use of intravenous drugs and with a high prevalence of Cluster B personality disorders. MMP-NO HRP patients had lower methadone doses compared to MMP-HRP patients and preferred to use drugs by smoked route more frequently. In the subanalysis of patients under 45, MMP-HRP patients were younger, had a higher prevalence of liver diseases, more intravenous drug use, greater severity on the drug use scale, less social and family support in the suescales of EUROP-ASI than compared to patients under 45 years in the group MMP-NO HRP. In conclusion, MMP-HRP patients are younger compared to MMP-NO HRP patients, they also receive higher doses of methadone and had more intravenous use. The above findings imply that the early onset of high risk drug use and long-term exposure to heroin have more severe outcomes such as higher comorbidities (e.g. infectious diseases, medical and psychiatric disorders), and consequently, these patients are a more vulnerable group with a worse prognosis.

  3. Employment-based abstinence reinforcement as a maintenance intervention for the treatment of cocaine dependence: post-intervention outcomes.

    PubMed

    DeFulio, Anthony; Silverman, Kenneth

    2011-05-01

    Due to the chronicity of cocaine dependence, practical and effective maintenance interventions are needed to sustain long-term abstinence. We sought to assess the effects of long-term employment-based reinforcement of cocaine abstinence after discontinuation of the intervention. Participants who initiated sustained opiate and cocaine abstinence during a 6-month abstinence reinforcement and training program worked as data entry operators and were randomly assigned to a group that could work independently of drug use (control, n = 24), or an abstinence-contingent employment (n = 27) group that was required to provide cocaine- and opiate-negative urine samples to work and maintain maximum rate of pay. A non-profit data entry business. Unemployed welfare recipients who persistently used cocaine while in methadone treatment. Urine samples and self-reports were collected every 6 months for 30 months. During the employment year, abstinence-contingent employment participants provided significantly more cocaine-negative samples than controls (82.7% and 54.2%; P = 0.01, OR = 4.61). During the follow-up year, the groups had similar rates of cocaine-negative samples (44.2% and 50.0%; P = 0.93) and human immunodeficiency virus risk behaviors. Participants' social, employment, economic and legal conditions were similar in the two groups across all phases of the study. Employment-based reinforcement effectively maintains long-term cocaine abstinence, but many patients relapse to use when the abstinence contingency is discontinued, even after a year of abstinence-contingent employment. Relapse could be prevented in many patients by leaving employment-based abstinence reinforcement in place indefinitely, which could be facilitated by integrating it into typical workplaces. © 2011 The Authors, Addiction © 2011 Society for the Study of Addiction.

  4. The therapeutic workplace to promote treatment engagement and drug abstinence in out-of-treatment injection drug users: a randomized controlled trial.

    PubMed

    Holtyn, August F; Koffarnus, Mikhail N; DeFulio, Anthony; Sigurdsson, Sigurdur O; Strain, Eric C; Schwartz, Robert P; Leoutsakos, Jeannie-Marie S; Silverman, Kenneth

    2014-11-01

    Determine if employment-based reinforcement can increase methadone treatment engagement and drug abstinence in out-of-treatment injection drug users. This study was conducted from 2008 to 2012 in a therapeutic workplace in Baltimore, MD. After a 4-week induction, participants (N=98) could work and earn pay for 26 weeks and were randomly assigned to Work Reinforcement, Methadone & Work Reinforcement, and Abstinence, Methadone & Work Reinforcement conditions. Work Reinforcement participants had to work to earn pay. Methadone & Work Reinforcement and Abstinence, Methadone, & Work Reinforcement participants had to enroll in methadone treatment to work and maximize pay. Abstinence, Methadone, & Work Reinforcement participants had to provide opiate- and cocaine-negative urine samples to maximize pay. Most participants (92%) enrolled in methadone treatment during induction. Drug abstinence increased as a graded function of the addition of the methadone and abstinence contingencies. Abstinence, Methadone & Work Reinforcement participants provided significantly more urine samples negative for opiates (75% versus 54%) and cocaine (57% versus 32%) than Work Reinforcement participants. Methadone & Work Reinforcement participants provided significantly more cocaine-negative samples than Work Reinforcement participants (55% versus 32%). The therapeutic workplace can promote drug abstinence in out-of-treatment injection drug users. Clinical trial registration number: NCT01416584. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. The Therapeutic Workplace to Promote Treatment Engagement and Drug Abstinence in Out-of-Treatment Injection Drug Users: A Randomized Controlled Trial

    PubMed Central

    Holtyn, August F.; Koffarnus, Mikhail N.; DeFulio, Anthony; Sigurdsson, Sigurdur O.; Strain, Eric C.; Schwartz, Robert P.; Leoutsakos, Jeannie-Marie S.; Silverman, Kenneth

    2014-01-01

    Objective Determine if employment-based reinforcement can increase methadone treatment engagement and drug abstinence in out-of-treatment injection drug users. Method This study was conducted from 2008–2012 in a therapeutic workplace in Baltimore, MD. After a 4-week induction, participants (N=98) could work and earn pay for 26 weeks and were randomly assigned to Work Reinforcement, Methadone & Work Reinforcement, and Abstinence, Methadone & Work Reinforcement conditions. Work Reinforcement participants had to work to earn pay. Methadone & Work Reinforcement, and Abstinence, Methadone, & Work Reinforcement participants had to enroll in methadone treatment to work and maximize pay. Abstinence, Methadone, & Work Reinforcement participants had to provide opiate- and cocaine-negative urine samples to maximize pay. Results Most participants (92%) enrolled in methadone treatment during induction. Drug abstinence increased as a graded function of the addition of the methadone and abstinence contingencies. Abstinence, Methadone & Work Reinforcement participants provided significantly more urine samples negative for opiates (75% versus 54%) and cocaine (57% versus 32%) than Work Reinforcement participants. Methadone & Work Reinforcement participants provided significantly more cocaine-negative samples than Work Reinforcement participants (55% versus 32%). Conclusion The therapeutic workplace can promote drug abstinence in out-of-treatment injection drug users. PMID:24607365

  6. Implicit processing of heroin and emotional cues in abstinent heroin users: early and late event-related potential effects.

    PubMed

    Yang, Ling; Zhang, Jianxun; Zhao, Xin

    2015-05-01

    The abnormal cognitive processing of drug cues is a core characteristic of drug dependence. Previous research has suggested that the late positive potential (LPP) of heroin users is increased by heroin-related stimuli because of the attention-grabbing nature of such stimuli. The present research used a modified emotional Stroop (eStroop) task to examine whether there was an early posterior negativity (EPN) modulation to heroin cues compared with emotional or neutral stimuli in heroin dependent subjects. Fifteen former heroin users and 15 matched controls performed the eStroop task, which was composed of positive, negative, heroin-related, and neutral pictures with superimposed color squares. Participants responded to the color of the square and not to the picture while behavioral data and event-related potentials were recorded. There were no significant differences of EPN amplitudes to emotional and neutral stimuli between heroin users and controls. However, heroin users displayed increased EPN modulation for heroin cues, whereas this modulation was absent in controls. Drug-related cues acquire motivational salience and automatically capture the attention of heroin users at early processing stages, even when engaged in a non-drug-related task. The EPN to heroin cues could represent a novel electrophysiological index with clinical implications for selecting abstinent drug users who are at increased risk of relapse or to evaluate treatment interventions.

  7. Heroin - Multiple Languages

    MedlinePlus

    ... Spanish) PDF The basics - Opioids, part 1 - English MP3 The basics - Opioids, part 1 - español (Spanish) MP3 The basics - Opioids, part 1 - English MP4 The ... Spanish) PDF Heroin - Opioid addiction, part 7 - English MP3 Heroin - Opioid addiction, part 7 - español (Spanish) MP3 ...

  8. The North American Opiate Medication Initiative (NAOMI): Profile of Participants in North America’s First Trial of Heroin-Assisted Treatment

    PubMed Central

    Nosyk, Bohdan; Brissette, Suzanne; Chettiar, Jill; Schneeberger, Pascal; Marsh, David C.; Krausz, Michael; Anis, Aslam; Schechter, Martin T.

    2008-01-01

    The North American Opiate Medication Initiative (NAOMI) is a randomized controlled trial evaluating the feasibility and effectiveness of heroin-assisted treatment (HAT) in the Canadian context. Our objective is to analyze the profile of the NAOMI participant cohort in the context of illicit opioid use in Canada and to evaluate its comparability with patient profiles of European HAT studies. Recruitment began in February 2005 and ended in March 2007. Inclusion criteria included opioid dependence, 5 or more years of opioid use, regular opioid injection, and at least two previous opiate addiction treatment attempts. Standardized assessment instruments such as the European Addiction Severity Index and the Maudsley Addiction Profile were employed. A total of 251 individuals were randomized from Vancouver, BC (192, 76.5%), and Montreal, Quebec (59, 23.5%); 38.5% were female, the mean age was 39.7 years (SD:8.6), and participants had injected drugs for 16.5 years (SD:9.9), on average. In the prior month, heroin was used a mean of 26.5 days (SD:7.4) and cocaine 16 days (SD;12.6). Vancouver had significantly more patients residing in unstable housing (88.5 vs. 22%; p < 0.001) and higher use of smoked crack cocaine (16.9 days vs. 2.3 days in the prior month; p < 0.001), while a significantly higher proportion of Montreal participants reported needle sharing in the prior 6 months (25% vs. 3.7%; p < 0.001). In many respects, the patient cohort was similar to the European trials; however, NAOMI had a higher proportion of female participants and participants residing in unstable housing. This study suggests that the NAOMI study successfully recruited participants with a profile indicated for HAT. It also raises concern about the high levels of crack cocaine use and social marginalization. PMID:18758964

  9. Prevalence and correlates of fentanyl-contaminated heroin exposure among young adults who use prescription opioids non-medically.

    PubMed

    Macmadu, Alexandria; Carroll, Jennifer J; Hadland, Scott E; Green, Traci C; Marshall, Brandon D L

    2017-05-01

    The rate of overdose deaths caused by fentanyl-contaminated heroin (FCH) use is increasing rapidly in the United States. We examined risk factors for exposure to FCH and experiences with FCH use among young adult non-medical prescription opioids (NMPO) users. We analyzed data from the Rhode Island Young Adult Prescription Drug Study (RAPiDS), which enrolled young adults aged 18 to 29 reporting prior 30day NMPO use between January 2015 and February 2016. Participants completed questionnaires ascertaining drug use patterns and risk behaviors, including FCH exposure. Logistic regression was used to assess factors associated with known or suspected FCH exposure. Of 199 participants, the median age was 25 (IQR: 22, 27), 130 (65.3%) were male, and 122 (61.3%) were of White, non-Hispanic race/ethnicity. In total, 22 (11%) reported known or suspected FCH exposure in the prior six months. Several drug use patterns and risk behaviors were associated with FCH exposure, including: regular heroin and cocaine use; diverted pharmaceutical fentanyl use in the prior six months; NMPO use to avoid withdrawal symptoms; longer duration of NMPO use; regular injection drug use; and prior overdose (all p<0.001). Among participants who reported FCH exposure, 59% were unaware that their heroin was contaminated with fentanyl prior to last use, 59% reported that FCH provides a better high, and all recognized that fentanyl increases overdose risk. Exposure to fentanyl-contaminated heroin is an emerging trend among young adult NMPO users in Rhode Island. Overdose prevention programs addressing FCH use are urgently needed. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Heroin shortage in Coastal Kenya: A rapid assessment and qualitative analysis of heroin users’ experiences

    PubMed Central

    Mital, Sasha; Miles, Gillian; McLellan-Lemal, Eleanor; Muthui, Mercy; Needle, Richard

    2016-01-01

    Introduction While relatively rare events, abrupt disruptions in heroin availability have a significant impact on morbidity and mortality risk among those who are heroin dependent. A heroin shortage occurred in Coast Province, Kenya from December 2010 to March 2011. This qualitative analysis describes the shortage events and consequences from the perspective of heroin users, along with implications for health and other public sectors. Methods As part of a rapid assessment, 66 key informant interviews and 15 focus groups among heroin users in Coast Province, Kenya were conducted. A qualitative thematic analysis was undertaken in Atlas.ti. to identify salient themes related to the shortage. Results Overall, participant accounts were rooted in a theme of desperation and uncertainty, with emphasis on six sub-themes: (1) withdrawal and strategies for alleviating withdrawal, including use of medical intervention and other detoxification attempts; (2) challenges of dealing with unpredictable drug availability, cost, and purity; (3) changes in drug use patterns, and actions taken to procure heroin and other drugs; (4) modifications in drug user relationship dynamics and networks, including introduction of risky group-level injection practices; (5) family and community response; and (6) new challenges with the heroin market resurgence. Conclusions The heroin shortage led to a series of consequences for drug users, including increased risk of morbidity, mortality and disenfranchisement at social and structural levels. Availability of evidence-based services for drug users and emergency preparedness plans could have mitigated this impact. PMID:26470646

  11. Heroin shortage in Coastal Kenya: A rapid assessment and qualitative analysis of heroin users' experiences.

    PubMed

    Mital, Sasha; Miles, Gillian; McLellan-Lemal, Eleanor; Muthui, Mercy; Needle, Richard

    2016-04-01

    While relatively rare events, abrupt disruptions in heroin availability have a significant impact on morbidity and mortality risk among those who are heroin dependent. A heroin shortage occurred in Coast Province, Kenya from December 2010 to March 2011. This qualitative analysis describes the shortage events and consequences from the perspective of heroin users, along with implications for health and other public sectors. As part of a rapid assessment, 66 key informant interviews and 15 focus groups among heroin users in Coast Province, Kenya were conducted. A qualitative thematic analysis was undertaken in Atlas.ti. to identify salient themes related to the shortage. Overall, participant accounts were rooted in a theme of desperation and uncertainty, with emphasis on six sub-themes: (1) withdrawal and strategies for alleviating withdrawal, including use of medical intervention and other detoxification attempts; (2) challenges of dealing with unpredictable drug availability, cost, and purity; (3) changes in drug use patterns, and actions taken to procure heroin and other drugs; (4) modifications in drug user relationship dynamics and networks, including introduction of risky group-level injection practices; (5) family and community response; and (6) new challenges with the heroin market resurgence. The heroin shortage led to a series of consequences for drug users, including increased risk of morbidity, mortality and disenfranchisement at social and structural levels. Availability of evidence-based services for drug users and emergency preparedness plans could have mitigated this impact. Published by Elsevier B.V.

  12. Heroin overdose.

    PubMed

    Darke, Shane

    2016-11-01

    This narrative review aims to provide a brief history of the development of the heroin overdose field by discussing a selection of major 'classics' from the latter part of the 20th century. Papers considered landmarks were selected from 1972, 1977, 1983, 1984 and 1999. Findings of earlier works suggest much of what later research was to demonstrate. These include arguing that overdoses occurred primarily among tolerant older users, that most 'overdose' deaths involved low morphine concentrations, that most overdoses involve polypharmacy, that drug purity has only a moderate influence on overdose rates and that instant death following heroin administration is rare. Landmark studies of heroin overdose from the 1970s, 1980s and 1990s laid the foundations for subsequent overdose research, mainly by identifying the major demographic characteristics of overdose cases, risk factors, survival times and behaviours at overdose events. © 2016 Society for the Study of Addiction.

  13. Selective Effects of a Morphine Conjugate Vaccine on Heroin and Metabolite Distribution and Heroin-Induced Behaviors in Rats

    PubMed Central

    Pravetoni, M.; Harris, A.C.; Birnbaum, A.K.; Pentel, P.R.

    2013-01-01

    Morphine conjugate vaccines have effectively reduced behavioral effects of heroin in rodents and primates. To better understand how these effects are mediated, heroin and metabolite distribution studies were performed in rats in the presence and absence of vaccination. In non-vaccinated rats 6-monoacetylmorphine (6-MAM) was the predominant opioid in plasma and brain as early as 1 minute after i.v. administration of heroin and for up to 14 minutes. Vaccination with morphine conjugated to keyhole limpet hemocyanin (M-KLH) elicited high titers and concentrations of antibodies with high affinity for heroin, 6-MAM, and morphine. Four minutes after heroin administration vaccinated rats showed substantial retention of all three opioids in plasma compared to controls and reduced 6-MAM and morphine, but not heroin, distribution to brain. Administration of 6-MAM rather than heroin in M-KLH vaccinated rats showed a similar drug distribution pattern. Vaccination reduced heroin-induced analgesia and blocked heroin-induced locomotor activity throughout 2 weeks of repeated testing. Higher serum opioid-specific antibody concentrations were associated with higher plasma opioid concentrations, lower brain 6-MAM and morphine concentrations, and lower heroin-induced locomotor activity. Serum antibody concentrations over 0.2 mg/ml were associated with substantial effects on these measures. These data support a critical role for 6-MAM in mediating the early effects of i.v. heroin and suggest that reducing 6-MAM concentration in brain is essential to the efficacy of morphine conjugate vaccines. PMID:23220743

  14. Survey of methadone-drug interactions among patients of methadone maintenance treatment program in Taiwan

    PubMed Central

    2012-01-01

    Background Although methadone has been used for the maintenance treatment of opioid dependence for decades, it was not introduced in China or Taiwan until 2000s. Methadone-drug interactions (MDIs) have been shown to cause many adverse effects. However, such effects have not been scrutinized in the ethnic Chinese community. Methods The study was performed in two major hospitals in southern Taiwan. A total of 178 non-HIV patients aged ≥ 20 years who had participated in the Methadone Maintenance Treatment Program (MMTP) ≥ 1 month were recruited. An MDI is defined as concurrent use of drug(s) with methadone that may result in an increase or decrease of effectiveness and/or adverse effect of methadone. To determine the prevalence and clinical characteristics of MDIs, credible data sources, including the National Health Insurance (NHI) database, face-to-face interviews, medical records, and methadone computer databases, were linked for analysis. Socio-demographic and clinical factors associated with MDIs and co-medications were also examined. Results 128 (72%) MMTP patients took at least one medication. Clinically significant MDIs included withdrawal symptoms, which were found among MMTP patients co-administered with buprenorphine or tramadol; severe QTc prolongation effect, which might be associated with use of haloperidol or droperidol; and additive CNS and respiratory depression, which could result from use of methadone in combination with chlorpromazine or thioridazine. Past amphetamine use, co-infection with hepatitis C, and a longer retention in the MMTP were associated with increased odds of co-medication. Among patients with co-medication use, significant correlates of MDIs included the male gender and length of co-medication in the MMTP. Conclusions The results demonstrate clinical evidence of significant MDIs among MMTP patients. Clinicians should check the past medical history of MMTP clients carefully before prescribing medicines. Because combinations of

  15. African-specific variability in the acetylcholine muscarinic receptor M4: association with cocaine and heroin addiction.

    PubMed

    Levran, Orna; Randesi, Matthew; Peles, Einat; Correa da Rosa, Joel; Ott, Jurg; Rotrosen, John; Adelson, Miriam; Kreek, Mary Jeanne

    2016-06-01

    This study was designed to determine whether polymorphisms in acetylcholine receptors contribute to opioid dependence and/or cocaine dependence. The sample (n = 1860) was divided by drug and ancestry, and 55 polymorphisms (nine genes) were analyzed. Of the 20 SNPs that showed nominally significant associations, the association of the African-specific CHRM4 SNP rs2229163 (Asn417=) with cocaine dependence survived correction for multiple testing (Pcorrected = 0.047). CHRM4 is located in a region of strong linkage disequilibrium on chromosome 11 that includes genes associated with schizophrenia. CHRM4 SNP rs2229163 is in strong linkage disequilibrium with several African-specific SNPs in DGKZ and AMBRA1. Cholinergic receptors' variants may contribute to drug addiction and have a potential role as pharmacogenetic markers.

  16. rsfMRI effects of KB220Z™ on Neural Pathways in Reward Circuitry of Abstinent Genotyped Heroin Addicts

    PubMed Central

    Blum, Kenneth; Liu, Yijun; Wang, Wei; Wang, Yarong; Zhang, Yi; Oscar-Berman, Marlene; Smolen, Andrew; Febo, Marcelo; Han, David; Simpatico, Thomas; Cronjé, Frans J; Demetrovics, Zsolt; Gold, Mark S.

    2016-01-01

    Recently Willuhn et al. reported that cocaine use and even non-substance related addictive behavior, increases, as dopaminergic function is reduced. Chronic cocaine exposure has been associated with decreases in D2/D3 receptors, also associated with lower activation to cues in occipital cortex and cerebellum in a recent PET study from Volkow’s group. Therefore, treatment strategies, like dopamine agonist therapy, that might conserve dopamine function may be an interesting approach to relapse prevention in psychoactive drug and behavioral addictions. To this aim, we evaluated the effect of KB220Z™ on reward circuitry of ten heroin addicts undergoing protracted abstinence, an average 16.9 months. In a randomized placebo-controlled crossover study of KB220Z™ five subjects completed a triple blinded–experiment in which the subject, the person administering the treatment and the person evaluating the response to treatment were blinded as to which treatment any particular subject was receiving. In addition, nine subjects total were genotyped utilizing the GARSRX™ test. We preliminarily report that KB220Z ™ induced an increase in BOLD activation in caudate-accumbens-dopaminergic pathways compared to placebo following one-hour acute administration. Furthermore, KB220Z™ also reduced resting state activity in the putamen of abstinent heroin addicts. In the second phase of this pilot study of all ten abstinent heroin-dependent subjects, three brain regions of interest (ROIs) we observed to be significantly activated from resting state by KB220Z compared to placebo (P < 0.05). Increased functional connectivity was observed in a putative network that included the dorsal anterior cingulate, medial frontal gyrus, nucleus accumbens, posterior cingulate, occipital cortical areas and cerebellum. These results and other qEEG study results suggest a putative anti-craving/anti-relapse role for KB220Z in addiction by direct or indirect dopaminergic interaction. Due to

  17. Opioid Addiction and Abuse in Primary Care Practice: A Comparison of Methadone and Buprenorphine as Treatment Options

    PubMed Central

    Bonhomme, Jean; Shim, Ruth S.; Gooden, Richard; Tyus, Dawn; Rust, George

    2014-01-01

    Opioid abuse and addiction have increased in frequency in the United States over the past 20 years. In 2009, an estimated 5.3 million persons used opioid medications nonmedically within the past month, 200 000 used heroin, and approximately 9.6% of African Americans used an illicit drug. Racial and ethnic minorities experience disparities in availability and access to mental health care, including substance use disorders. Primary care practitioners are often called upon to differentiate between appropriate, medically indicated opioid use in pain management vs inappropriate abuse or addiction. Racial and ethnic minority populations tend to favor primary care treatment settings over specialty mental health settings. Recent therapeutic advances allow patients requiring specialized treatment for opioid abuse and addiction to be managed in primary care settings. The Drug Addiction Treatment Act of 2000 enables qualified physicians with readily available short-term training to treat opioid-dependent patients with buprenorphine in an office-based setting, potentially making primary care physicians active partners in the diagnosis and treatment of opioid use disorders. Methadone and buprenorphine are effective opioid replacement agents for maintenance and/or detoxification of opioid-addicted individuals. However, restrictive federal regulations and stigmatization of opioid addiction and treatment have limited the availability of methadone. The opioid partial agonist-antagonist buprenorphine/naloxone combination has proven an effective alternative. This article reviews the literature on differences between buprenorphine and methadone regarding availability, efficacy, safety, side-effects, and dosing, identifying resources for enhancing the effectiveness of medication-assisted recovery through coordination with behavioral/psychological counseling, embedded in the context of recovery-oriented systems of care. PMID:23092049

  18. Methadone enhances human influenza A virus replication.

    PubMed

    Chen, Yun-Hsiang; Wu, Kuang-Lun; Tsai, Ming-Ta; Chien, Wei-Hsien; Chen, Mao-Liang; Wang, Yun

    2017-01-01

    Growing evidence has indicated that opioids enhance replication of human immunodeficiency virus and hepatitis C virus in target cells. However, it is unknown whether opioids can enhance replication of other clinically important viral pathogens. In this study, the interaction of opioid agonists and human influenza A/WSN/33 (H1N1) virus was examined in human lung epithelial A549 cells. Cells were exposed to morphine, methadone or buprenorphine followed by human H1N1 viral infection. Exposure to methadone differentially enhanced viral propagation, consistent with an increase in virus adsorption, susceptibility to virus infection and viral protein synthesis. In contrast, morphine or buprenorphine did not alter H1N1 replication. Because A549 cells do not express opioid receptors, methadone-enhanced H1N1 replication in human lung cells may not be mediated through these receptors. The interaction of methadone and H1N1 virus was also examined in adult mice. Treatment with methadone significantly increased H1N1 viral replication in lungs. Our data suggest that use of methadone facilitates influenza A viral infection in lungs and might raise concerns regarding the possible consequence of an increased risk of serious influenza A virus infection in people who receive treatment in methadone maintenance programs. © 2015 Society for the Study of Addiction.

  19. Surveillance of emerging drugs of abuse in Hong Kong: validation of an analytical tool.

    PubMed

    Tang, Magdalene H Y; Ching, C K; Tse, M L; Ng, Carol; Lee, Caroline; Chong, Y K; Wong, Watson; Mak, Tony W L

    2015-04-01

    To validate a locally developed chromatography-based method to monitor emerging drugs of abuse whilst performing regular drug testing in abusers. Cross-sectional study. Eleven regional hospitals, seven social service units, and a tertiary level clinical toxicology laboratory in Hong Kong. A total of 972 drug abusers and high-risk individuals were recruited from acute, rehabilitation, and high-risk settings between 1 November 2011 and 31 July 2013. A subset of the participants was of South Asian ethnicity. In total, 2000 urine or hair specimens were collected. Proof of concept that surveillance of emerging drugs of abuse can be performed whilst conducting routine drug of abuse testing in patients. The method was successfully applied to 2000 samples with three emerging drugs of abuse detected in five samples: PMMA (paramethoxymethamphetamine), TFMPP [1-(3-trifluoromethylphenyl)piperazine], and methcathinone. The method also detected conventional drugs of abuse, with codeine, methadone, heroin, methamphetamine, and ketamine being the most frequently detected drugs. Other findings included the observation that South Asians had significantly higher rates of using opiates such as heroin, methadone, and codeine; and that ketamine and cocaine had significantly higher detection rates in acute subjects compared with the rehabilitation population. This locally developed analytical method is a valid tool for simultaneous surveillance of emerging drugs of abuse and routine drug monitoring of patients at minimal additional cost and effort. Continued, proactive surveillance and early identification of emerging drugs will facilitate prompt clinical, social, and legislative management.

  20. Pavlovian conditioned approach, extinction, and spontaneous recovery to an audiovisual cue paired with an intravenous heroin infusion.

    PubMed

    Peters, Jamie; De Vries, Taco J

    2014-01-01

    Novel stimuli paired with exposure to addictive drugs can elicit approach through Pavlovian learning. While such approach behavior, or sign tracking, has been documented for cocaine and alcohol, it has not been shown to occur with opiate drugs like heroin. Most Pavlovian conditioned approach paradigms use an operandum as the sign, so that sign tracking can be easily automated. We were interested in assessing whether approach behavior occurs to an audiovisual cue paired with an intravenous heroin infusion. If so, would this behavior exhibit characteristics of other Pavlovian conditioned behaviors, such as extinction and spontaneous recovery? Rats were repeatedly exposed to an audiovisual cue, similar to that used in standard self-administration models, along with an intravenous heroin infusion. Sign tracking was measured in an automated fashion by analyzing motion pixels within the cue zone during each cue presentation. We were able to observe significant sign tracking after only five pairings of the conditioned stimulus (CS) with the unconditioned stimulus (US). This behavior rapidly extinguished over 2 days, but exhibited pronounced spontaneous recovery 3 weeks later. We conclude that sign tracking measured by these methods exhibits all the characteristics of a classically conditioned behavior. This model can be used to examine the Pavlovian component of drug memories, alone, or in combination with self-administration methods.

  1. Dosing and Monitoring of Methadone in Pregnancy: Literature Review

    PubMed Central

    Shiu, Jennifer R; Ensom, Mary H H

    2012-01-01

    Background: The pharmacokinetics of methadone is altered during pregnancy, but the most appropriate dosing and monitoring regimen has yet to be identified. Objective: To review dosing and monitoring of methadone therapy in pregnancy. Methods: A literature search was performed in several databases (PubMed, MEDLINE, Embase, International Pharmaceutical Abstracts, and the Cochrane Database of Systematic Reviews) from inception to May 2012. The search terms were “methadone”, “pregnancy”, “pharmacokinetic”, “clearance”, “metabolism”, “therapeutic drug monitoring”, and “methadone dosing”. Additional papers were identified by searching the bibliographies of primary and review articles. All English-language primary articles related to methadone pharmacokinetics in pregnancy were included. Articles not related to maternal outcomes were excluded. Results: The literature search yielded 1 case report and 10 studies discussing use of methadone by pregnant women. Methadone pharmacokinetics in pregnancy has been studied in 3 pharmacokinetic trials, and split dosing of methadone in pregnant women has been described in 1 case report and 3 dosing trials. Only 4 trials evaluated monitoring of methadone concentration in pregnancy. The studies included in this review confirm that methadone pharmacokinetics is altered in pregnancy and is potentially correlated with increases in maternal withdrawal symptoms. Insufficient evidence is available to warrant routine monitoring of serum methadone concentrations in pregnant women with opioid dependence. Conclusions: Few studies of methadone pharmacokinetics and therapeutic drug monitoring are available for pregnant women with opioid dependence. Although it is known that methadone pharmacokinetics is altered in pregnancy, there is insufficient evidence to guide dosage adjustments and serum concentration monitoring. Until further studies are available, regular follow-up of maternal withdrawal symptoms and empiric

  2. The nature of methadone diversion in England: a Merseyside case study

    PubMed Central

    2012-01-01

    Background Methadone maintenance treatment (MMT) is a key element in treatment for opiate addiction; however concerns about the diversion of methadone remain. More current empirical data on methadone diversion are required. This research investigated the market for diverted methadone in Merseyside, UK, in order to provide a case study which can be transferred to other areas undertaking methadone maintenance treatment on a large scale. Methods Questionnaires were completed (in interview format) with 886 past year users of methadone recruited both in and out of prescribing agencies. Topic areas covered included current prescribing, obtaining and providing methadone, reasons for using illicit methadone and other drug use. Results Large proportions of participants had obtained illicit methadone for use in the past year with smaller proportions doing so in the past month. Proportions of participants buying and being given methadone were similar. Exchange of methadone primarily took place between friends and associates, with 'dealers' rarely involved. Gender, age, whether participant's methadone consumption was supervised and whether the aims of their treatment had been explained to them fully, influenced the extent to which participants were involved in diverting or using diverted methadone. Conclusion Methadone diversion is widespread although drug users generally do not make use of illicit methadone regularly (every month). The degree of altruism involved in the exchange of methadone does not negate the potential role of this action in overdose or the possibility of criminal justice action against individuals. Treatment agencies need to emphasise these risks whilst ensuring that treatment aims are effectively shared with clients to ensure adherence to treatment. PMID:22243982

  3. Pathways between Ecstasy Initiation and Other Drug Use

    PubMed Central

    Martins, Silvia S.; Ghandour, Lilian A.; Chilcoat, Howard D.

    2007-01-01

    This study aims to shed light on drug use pathways associated with ecstasy use initiation. Data from 54,573 respondents aged 12-21 years old from the 2002-2003 National Survey on Drug Use and Health (NSDUH) public use data files were analyzed via Cox proportional hazards models with time-dependent covariates. Our findings showed that marijuana, cocaine, and heroin were significant independent predictors of subsequent ecstasy use. Earlier ecstasy initiation was significantly associated with subsequent other illegal drug initiation (marijuana, cocaine and heroin). The strength of the association was greater for the pathway from earlier marijuana initiation to subsequent ecstasy initiation as compared to the pathway in the opposite direction. The pathway from earlier ecstasy initiation to subsequent cocaine and heroin initiation was also stronger as compared to pathways in the opposite directions. Pathways between ecstasy initiation and marijuana, cocaine and heroin initiation seem to be independent of the association between drug use and psychiatric symptoms/deviant behaviors. Ecstasy initiation seems to play a role in the subsequent initiation of cocaine and heroin. PMID:17174036

  4. Better retention of Malaysian opiate dependents treated with high dose methadone in methadone maintenance therapy

    PubMed Central

    2010-01-01

    Background Methadone is a synthetic opiate mu receptor agonist that is widely used to substitute for illicit opiates in the management of opiate dependence. It helps prevent opiate users from injecting and sharing needles which are vehicles for the spread of HIV and other blood borne viruses. This study has the objective of determining the utility of daily methadone dose to predict retention rates and re-injecting behaviour among opiate dependents. Methods Subjects comprised opiate dependent individuals who met study criteria. They took methadone based on the Malaysian guidelines and were monitored according to the study protocols. At six months, data was collected for analyses. The sensitivity and specificity daily methadone doses to predict retention rates and re-injecting behaviour were evaluated. Results Sixty-four patients volunteered to participate but only 35 (54.69%) remained active and 29 (45.31%) were inactive at 6 months of treatment. Higher doses were significantly correlated with retention rate (p < 0.0001) and re-injecting behaviour (p < 0.001). Of those retained, 80.0% were on 80 mg or more methadone per day doses with 20.0% on receiving 40 mg -79 mg. Conclusions We concluded that a daily dose of at least 40 mg was required to retain patients in treatment and to prevent re-injecting behaviour. A dose of at least 80 mg per day was associated with best results. PMID:21167035

  5. Cocaine

    MedlinePlus

    ... confidencial Press Room » Multi-Media Library » Image Gallery » Cocaine COCAINE To Save Images: First click on the thumbnail ... your Save in directory and then click Save. Cocaine Crack Cocaine RESOURCE CENTER Controlled Substances Act DEA ...

  6. Cyclosporine-inhibitable Cerebral Drug Transport Does not Influence Clinical Methadone Pharmacodynamics

    PubMed Central

    Meissner, Konrad; Blood, Jane; Francis, Amber M.; Yermolenka, Viktar; Kharasch, Evan D.

    2015-01-01

    Background Interindividual variability and drug interaction studies suggest that blood-brain barrier drug transporters mediate human methadone brain biodistribution. In vitro and animal studies suggest that methadone is a substrate for the efflux transporter P-glycoprotein, and that P-glycoprotein-mediated transport influences brain access and pharmacologic effect. This investigation tested whether methadone is a transporter substrate in humans. Methods Healthy volunteers received oral (N=16) or IV (N=12) methadone in different crossover protocols after nothing (control) or the validated P-glycoprotein inhibitor cyclosporine (4.5 mg/kg orally twice daily for 4 days, or 5 mg/kg IV over 2 hr). Plasma and urine methadone and metabolite concentrations were measured by mass spectrometry. Methadone effects were measured by miosis and thermal analgesia (maximally tolerated temperature and verbal analog scale rating of discreet temperatures). Results Cyclosporine marginally but significantly decreased methadone plasma concentrations and apparent oral clearance, but had no effect on methadone renal clearance or on hepatic N-demethylation. Cyclosporine had no effect on miosis, or on R-methadone concentration-miosis relationships after either oral or IV methadone. Peak miosis was similar in controls and cyclosporine-treated subjects after oral methadone (1.4 ± 0.4 and 1.3 ± 0.5 mm/mg, respectively) and IV methadone (3.1 ± 1.0 and 3.2 ± 0.8 mm respectively). Methadone increased maximally tolerated temperature, but analgesia testing was confounded by cyclosporine-related pain. Conclusions Cyclosporine did not affect methadone pharmacodynamics. This result does not support a role for cyclosporine-inhibitable transporters mediating methadone brain access and biodistribution. PMID:25072223

  7. Heroin and saccharin demand and preference in rats.

    PubMed

    Schwartz, Lindsay P; Kim, Jung S; Silberberg, Alan; Kearns, David N

    2017-09-01

    Several recent studies have investigated the choice between heroin and a non-drug alternative reinforcer in rats. A common finding in these studies is that there are large individual differences in preference, with some rats preferring heroin and some preferring the non-drug alternative. The primary goal of the present study was to determine whether individual differences in how heroin or saccharin is valued, based on demand analysis, predicts choice. Rats lever-pressed for heroin infusions and saccharin reinforcers on fixed-ratio schedules. The essential value of each reinforcer was obtained from resulting demand curves. Rats were then trained on a mutually exclusive choice procedure where pressing one lever resulted in heroin and pressing another resulted in saccharin. After seven sessions of increased access to heroin or saccharin, rats were reexposed to the demand and choice procedures. Demand for heroin was more elastic than demand for saccharin (i.e., heroin had lower essential value than saccharin). When allowed to choose, most rats preferred saccharin. The essential value of heroin, but not saccharin, predicted preference. The essential value of both heroin and saccharin increased following a week of increased access to heroin, but similar saccharin exposure had no effect on essential value. Preference was unchanged after increased access to either reinforcer. Heroin-preferring rats differed from saccharin-preferring rats in how they valued heroin, but not saccharin. To the extent that choice models addiction-related behavior, these results suggest that overvaluation of opioids specifically, rather than undervaluation of non-drug alternatives, could identify susceptible individuals. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Cognitive consequences of cannabis use: comparison with abuse of stimulants and heroin with regard to attention, memory and executive functions.

    PubMed

    Lundqvist, Thomas

    2005-06-01

    This review aims to compare cognitive consequence between cannabis, and stimulants and heroin with regards to attention, memory and executive functions. The available studies using brain imaging techniques and neuropsychological tests show that acutely, all drugs create a disharmony in the neuropsychological network, causing a decrease of activity in areas responsible for short-term memory and attention, with the possible exception of heroin. Cannabis induces loss of internal control and cognitive impairment, especially of attention and memory, for the duration of intoxication. Heavy cannabis use is associated with reduced function of the attentional/executive system, as exhibited by decreased mental flexibility, increased perserveration, and reduced learning, to shift and/or sustain attention. Recent investigations on amphetamine/methamphetamine have documented deficits in learning, delayed recall, processing speed, and working memory. MDMA users exhibit difficulties in coding information into long-term memory, display impaired verbal learning, are more easily distracted, and are less efficient at focusing attention on complex tasks. The degree of executive impairment increases with the severity of use, and the impairments are relatively lasting over time. Chronic cocaine users display impaired attention, learning, memory, reaction time and cognitive flexibility. Heroin addiction may have a negative effect on impulse control, and selective processing.

  9. Painkiller (Oxy, Vike) Facts

    MedlinePlus

    ... That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana ( ... these pills just like they sell heroin or cocaine. Some people borrow or steal these pills from ...

  10. Results of hair analyses for drugs of abuse and comparison with self-reports and urine tests.

    PubMed

    Musshoff, F; Driever, F; Lachenmeier, K; Lachenmeier, D W; Banger, M; Madea, B

    2006-01-27

    Urine as well as head and pubic hair samples from drug abusers were analysed for opiates, cocaine and its metabolites, amphetamines, methadone and cannabinoids. Urine immunoassay results and the results of hair tests by means of gas chromatography-mass spectrometry were compared to the self-reported data of the patients in an interview protocol. With regard to the study group, opiate abuse was claimed from the majority in self-reports (89%), followed by cannabinoids (55%), cocaine (38%), and methadone (32%). Except for opiates the comparison between self-reported drug use and urinalysis at admission showed a low correlation. In contrast to urinalysis, hair tests revealed consumption in more cases. There was also a good agreement between self-reports of patients taking part in an official methadone maintenance program and urine test results concerning methadone. However, hair test results demonstrated that methadone abuse in general was under-reported by people who did not participate in a substitution program. Comparing self-reports and the results of hair analyses drug use was dramatically under-reported, especially cocaine. Cocaine hair tests appeared to be highly sensitive and specific in identifying past cocaine use even in settings of negative urine tests. In contrast to cocaine, hair lacks sensitivity as a detection agent for cannabinoids and a proof of cannabis use by means of hair analysis should include the sensitive detection of the metabolite THC carboxylic acid in the lower picogram range.

  11. Infrequent Illicit Methadone Use Among Stimulant-Using Patients in Methadone Maintenance Treatment Programs: A National Drug Abuse Treatment Clinical Trials Network Study

    PubMed Central

    Wu, Li-Tzy; Blazer, Dan G.; Stitzer, Maxine L.; Patkar, Ashwin A.; Blaine, Jack D.

    2009-01-01

    We sought to determine the prevalence, patterns, and correlates of past-month illicit methadone use and history of regular illicit use among stimulant-using methadone maintenance treatment patients. We obtained self-reported information on illicit methadone use from 383 participants recruited from six community-based methadone maintenance programs. Overall, 1.6% of participants reported illicit use in the past month, and 4.7% reported a history of regular use. Younger age and history of outpatient psychological treatment were associated with increased odds of past-month illicit use. Illicit methadone use among patients in maintenance programs is infrequent; however, a number of factors may increase risk of illicit use. PMID:18612886

  12. Neonatal abstinence syndrome

    MedlinePlus

    ... takes drugs such as heroin, codeine, oxycodone (Oxycontin), methadone or buprenorphine. These and other substances pass through ... babies with severe symptoms need medicines such as methadone and morphine to treat withdrawal symptoms. These babies ...

  13. Bioavailabilities of rectal and oral methadone in healthy subjects

    PubMed Central

    Dale, Ola; Sheffels, Pamela; Kharasch, Evan D

    2004-01-01

    Aims Rectal administration of methadone may be an alternative to intravenous and oral dosing in cancer pain, but the bioavailability of the rectal route is not known. The aim of this study was to compare the absolute rectal bioavailability of methadone with its oral bioavailability in healthy humans. Methods Seven healthy subjects (six males, one female, aged 20–39 years) received 10 mg d5-methadone-HCl rectally (5 ml in 20% glycofurol) together with either d0-methadone intravenously (5 mg) or orally (10 mg) on two separate occasions. Blood samples for the LC-MS analyses of methadone and it's metabolite EDDP were drawn for up to 96 h. Noninvasive infrared pupillometry was peformed at the same time as blood sampling. Results The mean absolute rectal bioavalability of methadone was 0.76 (0.7, 0.81), compared to 0.86 (0.75, 0.97) for oral administration (mean (95% CI)). Rectal absorption of methadone was more rapid than after oral dosing with Tmax values of 1.4 (0.9, 1.8) vs. 2.8 (1.6, 4.0) h. The extent of formation of the metabolite EDDP did not differ between routes of administration. Single doses of methadone had a duration of action of at least 10 h and were well tolerated. Conclusions Rectal administration of methadone results in rapid absorption, a high bioavailability and long duration of action. No evidence of presystemic elimination was seen. Rectal methadone has characteristics that make it a potential alternative to intravenous and oral administration, particularly in cancer pain and palliative care. PMID:15255797

  14. Cocaine abuse versus cocaine dependence: cocaine self-administration and pharmacodynamic response in the human laboratory.

    PubMed

    Walsh, Sharon L; Donny, Eric C; Nuzzo, Paul A; Umbricht, Annie; Bigelow, George E

    2010-01-01

    Cocaine has high abuse liability but only a subset of individuals who experiment with it develop dependence. The DSM-IV (APA. Diagnostic and Statistical Manual of Mental Disorders DSM-IV-R. American Psychiatric Association, Washington, DC, 2000) provides criteria for diagnosing cocaine abuse and cocaine dependence as distinct disorders- the latter characterized by additional symptoms related to loss of control over drug use. In this study, two groups of cocaine users (n=8/group), matched on demographic factors and length of cocaine use history and meeting criteria for either cocaine abuse (CocAb) or cocaine dependence (CocDep), were compared on (1) measures related to impulsivity and sensation seeking, (2) response to experimenter-administered cocaine (0, 12.5, 25 and 50mg/70 kg, i.v.), and (3) cocaine self-administration using a Relapse Choice and a Progressive Ratio Procedure (0, 12.5 and 25mg/70 kg, i.v.). Groups did not differ on impulsivity or sensation seeking scores. After experimenter-administered cocaine, the CocAb group reported feeling more suspicious and observers rated them significantly higher on unpleasant effects (e.g., irritability, difficulty concentrating). In contrast, the CocDep group reported significantly greater desire for cocaine, which was sustained over the course of the study, and gave higher street value estimates for cocaine (p<0.05). While cocaine self-administration was dose-related and generally comparable across the two procedures, the CocDep users chose to take significantly more cocaine than the CocAb users. These data suggest that, while regular long-term users of cocaine with cocaine abuse or dependence diagnoses cannot be distinguished by trait measures related to impulsivity, they do exhibit significant differences with regard to cocaine-directed behavior and response to cocaine administration. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

  15. Conformation switching of an aptamer based on cocaine enhancement on a surface of modified GCE.

    PubMed

    Shahdost-Fard, Faezeh; Roushani, Mahmoud

    2016-07-01

    An ultrasensitive aptasensor was fabricated as an electrochemical nanotool based on the conformation switching of an aptamer (Apt). The Apt which was covalently attached on the surface of a glassy carbon electrode (GCE) covered with cadmium telluride (CdTe) quantum dots (QDs) works as a unique modifier for assaying cocaine. The Apt was combined with cocaine to form a three-way junction complex; this complex increased the steric hindrance of the modified GCE surface and resulted in a variation of the corresponding current of a redox probe. In the present study, DPV technique for cocaine detection was applied and resulted in an unprecedented detection limit (LOD) of 5.0±0.1pmolL(-1), which is more sensitive than previously reported methods. One of the greatest advantages of this aptasensor is the elimination of enzymes or antibodies. It is also relatively a highly sensitive, simple, reproducible, and controllable nanotool. Likewise, it can be easily miniaturized, which is a necessary condition for the high-throughput system and on-site applications. The offered nanotool has a great promise for the routine analysis of the ultra-trace amounts of cocaine, which is important for law enforcement and clinical medicine. It is notable to say that further attempts are under way in our laboratory for the construction of other aptasensors with higher performance for specific targets such as the detection of methadone (MTD) and ibuprofen (IBP). Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Cocaine withdrawal

    MedlinePlus

    ... Substance use - cocaine withdrawal; Substance abuse - cocaine withdrawal; Drug abuse - cocaine withdrawal; Detox - cocaine ... Elsevier Saunders; 2016:chap 50. National Institute on Drug Abuse. What is cocaine? Updated May 2016. www.drugabuse. ...

  17. Ion-Selective Electrodes for Basic Drugs.

    DTIC Science & Technology

    1981-01-01

    coated wire ion selective electrodes for methadone , methylamphetamine, J cocaine, protriptyline i 20. ABSTRACT (Continue on reverse side If neeeeary...end Identify by block number) Coated-wire ion-selective electrodes based on dinonylnaphthalene u-i sulfonic acid (DNNS) are prepared for methadone ...range from 10- 5.5M for cocaine and methylamphetamine electrodes to 10Ś.0M for methadone , and 10-6.5M for DD I 󈨍 1473 EDITION OF I NOV 5 IS OBSOLETE

  18. The disposition and behavioral effects of methadone in Greyhounds.

    PubMed

    KuKanich, Butch; Borum, Stacy L

    2008-05-01

    To determine the behavioral effects and pharmacokinetics of methadone in healthy Greyhounds. Prospective experimental study. Three male and three female healthy Greyhounds. Methadone hydrochloride, 0.5 mg kg(-1) IV (equivalent to 0.45 mg kg(-1) methadone base), was administered as an IV bolus. Trained observers subjectively assessed the behavioral effects of methadone. Blood samples were obtained at predetermined time points and plasma methadone concentrations were measured by liquid chromatography with tandem mass spectrometry. Pharmacokinetic variables were estimated with computer software. Methadone was well tolerated by the dogs with panting and defecation observed as adverse effects. Mild sedation was present, but no vomiting, excitement, or dysphoria was observed. The elimination half-life, volume of distribution, and plasma clearance were 1.53 +/- 0.18 hours, 7.79 +/- 1.87 L kg(-1), and 56.04 +/- 9.36 mL minute(-1) kg(-1), respectively. Methadone was well tolerated by Greyhounds. The volume of distribution was larger than expected, with resultant lower plasma concentrations than expected. Higher doses may need to be administered to Greyhounds in comparison with non-Greyhound dogs in order to achieve similar plasma drug concentrations. A dosage of 1-1.5 mg kg(-1) every 3-4 hours is suggested for future studies of analgesic efficacy of methadone in Greyhounds.

  19. Environmental enrichment as a potential intervention for heroin seeking.

    PubMed

    Galaj, E; Manuszak, M; Ranaldi, R

    2016-06-01

    Heroin-related cues can trigger craving and relapse in addicts or heroin seeking in rats. In the present study we investigated whether environmental enrichment (EE) implemented after heroin exposure can reduce cue-induced reinstatement of heroin seeking and expression of heroin conditioned place preference. In Experiment 1, male Long Evans rats that already acquired a heroin self-administration habit, were housed in enriched or non-enriched environments, underwent extinction training and later were tested for cue-induced reinstatement of heroin seeking. In Experiment 2, rats were conditioned with heroin in one compartment of a CPP apparatus and saline in the other, exposed to 30days of enrichment or no enrichment and were later tested for heroin CPP. The results showed that exposure to EE significantly reduced responding during the reinstatement test (Experiment 1) and prevented the expression of heroin CPP (Experiment 2). Our findings suggest that EE can be an effective behavioral approach to diminish the effects of conditioned cues on heroin seeking. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  20. Experience-Seeking Characteristics of Methadone Clients.

    ERIC Educational Resources Information Center

    Kohn, Paul M.; And Others

    1979-01-01

    Methadone clients scored higher than controls on measures reflecting boredom, desire for change and attraction to physically thrilling activities. Correlations of these measures with length of most recent dependency before treatment, time on program, and time since initial dependency suggest peculiarities of methadone clients antedated involvement…

  1. Nonmedical prescription opioids and pathways of drug involvement in the US: Generational differences.

    PubMed

    Wall, Melanie; Cheslack-Postava, Keely; Hu, Mei-Chen; Feng, Tianshu; Griesler, Pamela; Kandel, Denise B

    2018-01-01

    This study sought to specify (1) the position of nonmedical prescription opioids (NMPO) in drug initiation sequences among Millennials (1979-96), Generation X (1964-79), and Baby Boomers (1949-64) and (2) gender and racial/ethnic differences in sequences among Millennials. Data are from the 2013-2014 National Surveys on Drug Use and Health (n = 73,026). We identified statistically significant drug initiation sequences involving alcohol/cigarettes, marijuana, NMPO, cocaine, and heroin using a novel method distinguishing significant sequences from patterns expected only due to correlations induced by common liability among drugs. Alcohol/cigarettes followed by marijuana was the most common sequence. NMPO or cocaine use after marijuana, and heroin use after NMPO or cocaine, differed by generation. Among successively younger generations, NMPO after marijuana and heroin after NMPO increased. Millennials were more likely to initiate NMPO than cocaine after marijuana; Generation X and Baby Boomers were less likely (odds ratios = 1.4;0.3;0.2). Millennials were more likely than Generation X and Baby Boomers to use heroin after NMPO (hazards ratios = 7.1;3.4;2.5). In each generation, heroin users were far more likely to start heroin after both NMPO and cocaine than either alone. Sequences were similar by gender. Fewer paths were significant among African-Americans. NMPOs play a more prominent role in drug initiation sequences among Millennials than prior generations. Among Millennials, NMPO use is more likely than cocaine to follow marijuana use. In all generations, transition to heroin from NMPO significantly occurs only when both NMPO and cocaine have been used. Delineation of drug sequences suggests optimal points in development for prevention and treatment efforts. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Acute eosinophilic pneumonia secondary to heroin inhalation.

    PubMed

    Eyüpoğlu, Damla; Ortaç Ersoy, Ebru; Rollas, Kazım; Topeli, Arzu

    2017-06-01

    Smoking heroin (chasing the dragon), is a method of inhaling heroin via heating the drug on a tin-foil above a flame. It also has been associated both with the indirect effects of heroin overdose and with direct pulmonary toxicity. We describe a case of acute eosinophilic pneumonia secondary to heroin inhalation in our medical intensive care unit. She presented with fever, cough, dyspnea and pleuritic chest pain. Chest radiograph showed bilateral infiltrations. Examination of bronchoalveolar lavage fluid revealed significant eosinophilia. She was diagnosed with acute eosinophilic pneumonia. After heroin abstinence and corticosteroid therapy, remission was achieved rapidly and the patient was discharge on the fourth day of her hospital stay.

  3. Attitudes towards drug legalization among drug users.

    PubMed

    Trevino, Roberto A; Richard, Alan J

    2002-01-01

    Research shows that support for legalization of drugs varies significantly among different sociodemographic and political groups. Yet there is little research examining the degree of support for legalization of drugs among drug users. This paper examines how frequency and type of drug use affect the support for legalization of drugs after adjusting for the effects of political affiliation and sociodemographic characteristics. A sample of 188 drug users and non-drug users were asked whether they would support the legalization of marijuana, cocaine, and heroin. Respondents reported their use of marijuana, crack, cocaine, heroin, speedball, and/or methamphetamines during the previous 30 days. Support for legalization of drugs was analyzed by estimating three separate logistic regressions. The results showed that the support for the legalization of drugs depended on the definition of "drug user" and the type of drug. In general, however, the results showed that marijuana users were more likely to support legalizing marijuana, but they were less likely to support the legalization of cocaine and heroin. On the other hand, users of crack, cocaine, heroin, speedball, and/or methamphetamines were more likely to support legalizing all drugs including cocaine and heroin.

  4. The Source of Methadone in Overdose Deaths in Western Virginia in 2004

    PubMed Central

    Weimer, Melissa B.; Korthuis, P. Todd; Behonick, George S.; Wunsch, Martha J.

    2011-01-01

    Objectives Methadone-related overdose deaths increased in the United States by 468% from 1999 to 2005. Current studies associate the nonmedical use of methadone with methadone-related deaths. This study describes medical examiner cases in rural Virginia in 2004 with methadone identified by toxicology and compares cases according to source of methadone. Methods In 2004, all intentional and unintentional poisoning deaths from the Office of The Chief Medical Examiner, Western District of Virginia, were reviewed to identify cases in which methadone was a direct or contributing cause of death. The Virginia Prescription Monitoring Program was reviewed for prescription opioids in the name of these identified decedents. Decedent participation in local opioid treatment programs (OTP) was also assessed. Results The source of methadone in the 61 methadone-related overdose deaths was mostly nonprescribed (67%), although 28% of decedents were prescribed methadone for analgesia. Only 5% of decedents were actively enrolled in an OTP. The majority of deaths were attributed to polysubstance overdose. Conclusions The majority of methadone overdose deaths in this study were related to illicit methadone use, rather than prescribed or OTP uses. Interventions to decrease methadone-related deaths should focus on reduction of nonprescription use of methadone. PMID:21844834

  5. Combined Cocaine Hydrolase Gene Transfer and Anti-Cocaine Vaccine Synergistically Block Cocaine-Induced Locomotion

    PubMed Central

    Carroll, Marilyn E.; Zlebnik, Natalie E.; Anker, Justin J.; Kosten, Thomas R.; Orson, Frank M.; Shen, Xiaoyun; Kinsey, Berma; Parks, Robin J.; Gao, Yang; Brimijoin, Stephen

    2012-01-01

    Mice and rats were tested for reduced sensitivity to cocaine-induced hyper-locomotion after pretreatment with anti-cocaine antibody or cocaine hydrolase (CocH) derived from human butyrylcholinesterase (BChE). In Balb/c mice, direct i.p. injection of CocH protein (1 mg/kg) had no effect on spontaneous locomotion, but it suppressed responses to i.p. cocaine up to 80 mg/kg. When CocH was injected i.p. along with a murine cocaine antiserum that also did not affect spontaneous locomotion, there was no response to any cocaine dose. This suppression of locomotor activity required active enzyme, as it was lost after pretreatment with iso-OMPA, a selective BChE inhibitor. Comparable results were obtained in rats that developed high levels of CocH by gene transfer with helper-dependent adenoviral vector, and/or high levels of anti-cocaine antibody by vaccination with norcocaine hapten conjugated to keyhole limpet hemocyanin (KLH). After these treatments, rats were subjected to a locomotor sensitization paradigm involving a “training phase" with an initial i.p. saline injection on day 1 followed by 8 days of repeated cocaine injections (10 mg/kg, i.p.). A 15-day rest period then ensued, followed by a final “challenge" cocaine injection. As in mice, the individual treatment interventions reduced cocaine-stimulated hyperactivity to a modest extent, while combined treatment produced a greater reduction during all phases of testing compared to control rats (with only saline pretreatment). Overall, the present results strongly support the view that anti-cocaine vaccine and cocaine hydrolase vector treatments together provide enhanced protection against the stimulatory actions of cocaine in rodents. A similar combination therapy in human cocaine users might provide a robust therapy to help maintain abstinence. PMID:22912888

  6. Suppression of hypothalamic-pituitary-adrenal axis by acute heroin challenge in rats during acute and chronic withdrawal from chronic heroin administration

    PubMed Central

    Zhou, Yan; Leri, Francesco; Ho, Ann; Kreek, Mary Jeanne

    2013-01-01

    It is known that heroin dependence and withdrawal are associated with changes in the hypothalamic-pituitary-adrenal (HPA) axis. The objective of these studies in rats was to systematically investigate the level of HPA activity and response to a heroin challenge at two time points during heroin withdrawal, and to characterize the expression of associated stress-related genes 30 minutes after each heroin challenge. Rats received chronic (10-day) intermittent escalating-dose heroin administration (3×2.5 mg/kg/day on day 1; 3×20 mg/kg/day by day 10). Hormonal and neurochemical assessments were performed in acute (12 hours after last heroin injection) and chronic (10 days after the last injection) withdrawal. Both plasma ACTH and corticosterone levels were elevated during acute withdrawal, and heroin challenge at 20 mg/kg (the last dose of chronic escalation) at this time point attenuated this HPA hyperactivity. During chronic withdrawal, HPA hormonal levels returned to baseline, but heroin challenge at 5 mg/kg decreased ACTH levels. In contrast, this dose of heroin challenge stimulated the HPA axis in heroin naïve rats. In the anterior pituitary, pro-opiomelanocortin (POMC) mRNA levels were increased during acute withdrawal and retuned to control levels after chronic withdrawal. In the medial hypothalamus, however, the POMC mRNA levels were decreased during acute withdrawal, and increased after chronic withdrawal. Our results suggest a long-lasting change in HPA abnormal responsivity during chronic heroin withdrawal. PMID:23771528

  7. Cardiovascular manifestations of substance abuse: part 2: alcohol, amphetamines, heroin, cannabis, and caffeine.

    PubMed

    Frishman, William H; Del Vecchio, Alexander; Sanal, Shirin; Ismail, Anjum

    2003-01-01

    The abuse of alcohol is associated with chronic cardiomyopathy, hypertension, and arrhythmia. Abstinence or using alcohol in moderation can reverse these cardiovascular problems. Alcohol is also distinguished among the substances of abuse by having possible protective effects against coronary artery disease and stroke when used in moderate amounts. Amphetamines (eg, speed, ice, ecstasy) have many of the cardiovascular toxicities seen with cocaine, including acute and chronic cardiovascular diseases. Heroin and other opiates can cause arrhythmias and noncardiac pulmonary edema, and may reduce cardiac output. Cardiovascular problems are less common with cannabis (marijuana) than with opiates, but major cognitive disorders may be seen with its chronic use. It is still controversial whether caffeine can cause hypertension and coronary artery disease, and questions have been raised about its safety in patients with heart failure and arrhythmia.

  8. The Mechanism of Autoinduction of Methadone N-demethylation in Human Hepatocytes

    PubMed Central

    Campbell, Scott D.; Crafford, Amanda; Williamson, Brian L.; Kharasch, Evan D.

    2013-01-01

    Background There is considerable inter-and intraindividual variability in methadone metabolism and clearance. Methadone dosing is particularly challenging during initiation of therapy, due to time-dependent increases in hepatic clearance (autoinduction). Although methadone N-demethylation is catalyzed in vitro by cytochrome P4502B6 (CYP2B6) and CYP3A4, and clearance in vivo depends on CYP2B6, mechanism(s) of autoinduction are incompletely understood. In this investigation we determined mechanism(s) of methadone autoinduction using human hepatocytes. Methods Fresh human hepatocytes were exposed to 0.1-10 μM methadone for 72 hr. Cells were washed and methadone N-demethylation assessed. CYP2B6, CYP3A4, and CYP3A5 mRNA, protein expression (by gel-free high performance liquid chromatography-mass spectrometry) and catalytic activity (bupropion hydroxylation and alfentanil dealkylation for CYP2B6 and CYP3A4/5, respectively) were measured. Mechanisms of CYP induction were characterized using pregnane X receptor and constitutive androstane receptor reporter gene assays. Results Methadone (10 μM) increased methadone N-demethylation 2-fold, CYP2B6 and CYP3A4 mRNA 3-fold, and protein expression 2-fold. CYP3A5 mRNA was unchanged. CYP2B6 and CYP3A4/5 activities increased 2-fold. Induction by methadone enantiomers (R- vs S-methadone) did not differ. Induction was relatively weak compared with maximum induction by phenobarbital and rifampin. Lower methadone concentrations had smaller effects. Methadone was an agonist for the pregnane X receptor but not the constitutive androstane receptor. Conclusions Methadone caused concentration-dependent autoinduction of methadone N-demethylation in human hepatocytes, related to induction of CYP2B6 and CYP3A4 mRNA expression, protein expression, and catalytic activity. Induction was related to pregnane X receptor but not constitutive androstane receptor activation. These in vitro findings provide mechanistic insights into clinical

  9. Cocaine.

    ERIC Educational Resources Information Center

    Piazza, Nick J.; Yeager, Rebecca D.

    Cocaine was first used by Europeans in the nineteenth century when extract from the coca leaf was combined with various beverages. Cocaine comes as a white crystalline powder. However, a product called crack cocaine may come as an opaque crystal similar in size and shape to rock salt. A third form of cocaine is known as coca paste, which is an…

  10. User’s Guide for the Longitudinal Scalogram Analysis Program

    DTIC Science & Technology

    1991-01-01

    cannabis, pills, psychedelics , cocaine, and heroin. The LSA analysis was restricted to these respondents (n = 791), because complete information about...Total n = 791. 0 = not passed, I = passed. Items am legal drugs, cannabis, pills, psychedelics , cocaine, and heroin. Asterisks denote longitudinal

  11. Attitudes toward buprenorphine and methadone among opioid-dependent individuals

    PubMed Central

    Schwartz, Robert P.; Kelly, Sharon M.; O'Grady, Kevin E.; Mitchell, Shannon Gwin; Peterson, James A.; Reisinger, Heather Schacht; Agar, Michael H.; Brown, Barry S.

    2009-01-01

    Attitudes and beliefs about drug abuse treatment have long been known to shape response to that treatment. Two major pharmacological alternatives are available for opioid dependence: methadone, which has been available for the past 40 years, and buprenorphine, a recently-introduced medication. This mixed methods study examined the attitudes of opioid-dependent individuals toward methadone and buprenorphine. A total of 195 participants (n = 140 who were enrolling in one of 6 Baltimore area methadone programs and n = 55 who were out-of-treatment) were administered the Attitudes toward Methadone and toward Buprenorphine Scales and a subset (n = 46) received an ethnographic interview. In-treatment group had significantly more positive attitudes toward methadone than did the out-of-treatment group (p < .001), while they did not differ in their attitudes toward buprenorphine. Both groups had significantly more positive attitudes toward buprenorphine than methadone. Addressing these attitudes may increase treatment entry and retention. PMID:18770082

  12. The becoming of methadone in Kenya: How an intervention's implementation constitutes recovery potential.

    PubMed

    Rhodes, Tim

    2018-03-01

    This analysis treats the recent introduction of methadone treatment in Kenya as a case of 'evidence-making intervention'. Using 30 qualitative interviews with people in receipt of methadone treatment in Nairobi, Kenya, methadone's becoming is treated as an effect of its narrative and material implementations. The interviews are shown to enact a narrative of methadone recovery potential towards normalcy beyond addiction. Such recovery potential is materialised in practice through social interactions wherein methadone's embodied effects are seen to be believed. Here, the recovering body affects others' recovery potential. In a context of competing claims about methadone's effects, including the circulation of doubt about experimenting with methadone treatment, embodied methadone effect helps moderate the multiverse of methadone knowledge. The material dynamics of methadone treatment delivery also affect its recovery potential, with the methadone queue enacting a rationing of recovery hope. Here, the experience of methadone's implementation loops back to a life with drugs. I conclude that there is a coexistence of potentiality and actuality, a 'methadone multiple', produced through its narrative and material implementations. Copyright © 2018 Elsevier Ltd. All rights reserved.

  13. Early development of infants exposed to drugs prenatally.

    PubMed

    Eyler, F D; Behnke, M

    1999-03-01

    This article includes a summary and critique of methodological limitations of the peer-reviewed studies of developmental outcome during the first 2 years in children prenatally exposed to the most commonly used drugs of abuse: tobacco, alcohol, marijuana, heroin/methadone, and cocaine. Reported effects vary by specific drug or drug combinations and amount and timing of exposure; however, few thresholds have been established. Drug effects also appear to be exacerbated in children with multiple risks, including poverty, and nonoptimal caregiving environments. Although prenatal exposure to any one drug cannot reliably predict the outcome of an individual child, it may be a marker for an array of variables that can impact development. Appropriate intervention strategies require future research that determines which factors place exposed children at risk and which are protective for optimal development.

  14. Within- and between- subject variability in methadone pharmacokinetics and pharmacodynamics in methadone maintenance subjects

    PubMed Central

    Hanna, Julia; Foster, David JR; Salter, Amy; Somogyi, Andrew A; White, Jason M; Bochner, Felix

    2005-01-01

    Aims To investigate within- and between-subject variability of the pharmacodynamics and pharmacokinetics of (R)- and (S)-methadone in methadone maintenance subjects at steady-state. Methods Six non-holder subjects were studied on three occasions at 7–16 day intervals; doses (20–170 mg/day) remained unchanged. Blood samples and pharmacodynamic data were collected 10–12 times over a 24-h inter-dosing interval. All pharmacodynamic data were expressed as the area under the end-point versus time curve. Using analyses of variance with mixed effects, best estimates were made of the ratio of between- to within-subject variation, with corresponding 95% confidence intervals (CI) for within-subject variation at the average value. Results Subjects were relatively consistent between occasions, whereas there was much greater between-subject variability (P < 0.02) for all measures. Estimates of the ratio of between- to within-subject variation ranged from 2.2–12.8 for pharmacodynamic measures, and 1.3–7.9 for pharmacokinetic parameters. For pain, total mood disturbance, withdrawal, pupil size and respiration rate, 95% CI for within-subject measures ranged ≤2-fold, while this was greater for subjective direct opioid effects (4.2-fold). For CL/F of the active (R)-methadone, the variance ratio was 4.9 (P < 0.0003), with 95% CI for within-subject measures ranging ≤2-fold. (S)-methadone CL/F demonstrated greater within-subject variability (3.4-fold), possibly contributing to a smaller (2.7; P < 0.0003) ratio of between- to within-subject variance. Conclusions Non-holder methadone maintenance treatment participants appear to respond consistently with respect to pharmacokinetics and pharmacodynamics over a 1–2 month period. Such knowledge may help prescribers to determine whether alternative dosing regimens or treatments might be more appropriate in this population. PMID:16187972

  15. Perinatal methadone exposure produces physical dependence and altered behavioral development in the rat.

    PubMed

    Kunko, P M; Smith, J A; Wallace, M J; Maher, J R; Saady, J J; Robinson, S E

    1996-06-01

    Pregnant rats were implanted with osmotic minipumps containing either methadone hydrochloride (9 mg/kg/day) or sterile water. Their offspring were cross-fostered so that the following prenatal/postnatal exposure groups were obtained: water/water, methadone/water, water/methadone and methadone/methadone. Methadone slightly reduced litter size, particularly the number of male offspring, and reduced litter birth weight. The induction or maintenance of physical dependence in the postnatal methadone exposure groups was confirmed by an experiment in which PD19 pups were challenged with naloxone (1 mg/kg, s.c.). Methadone concentrations were assayed in pup brain on postnatal days 4, 10 and 22. Postnatal exposure to methadone via maternal milk produced measurable levels of methadone which decreased with age. Neuromuscular and physical development were assessed. Exposure to methadone accelerated acquisition of the righting reflex, but tended to delay the acquisition of the negative geotaxic response. Postnatal exposure to methadone was associated with decreased somatic growth as measured through postnatal day 21. The older pups (postnatal day 21) exposed to methadone exhibited variations in activity levels: pups exposed to methadone both prenatally and postnatally exhibited the least amount of spontaneous locomotor activity and pups exposed only postnatally exhibited the most activity. Therefore, it is possible to induce and/or maintain physical dependence via lactation in rat pups fostered to methadone-treated dams. Perinatal exposure to methadone by this route produces several subtle disruptions of pup development in the absence of gross maternal or fetal toxicity.

  16. Acupuncture inhibits cue-induced heroin craving and brain activation★

    PubMed Central

    Cai, Xinghui; Song, Xiaoge; Li, Chuanfu; Xu, Chunsheng; Li, Xiliang; Lu, Qi

    2012-01-01

    Previous research using functional MRI has shown that specific brain regions associated with drug dependence and cue-elicited heroin craving are activated by environmental cues. Craving is an important trigger of heroin relapse, and acupuncture may inhibit craving. In this study, we performed functional MRI in heroin addicts and control subjects. We compared differences in brain activation between the two groups during heroin cue exposure, heroin cue exposure plus acupuncture at the Zusanli point (ST36) without twirling of the needle, and heroin cue exposure plus acupuncture at the Zusanli point with twirling of the needle. Heroin cue exposure elicited significant activation in craving-related brain regions mainly in the frontal lobes and callosal gyri. Acupuncture without twirling did not significantly affect the range of brain activation induced by heroin cue exposure, but significantly changed the extent of the activation in the heroin addicts group. Acupuncture at the Zusanli point with twirling of the needle significantly decreased both the range and extent of activation induced by heroin cue exposure compared with heroin cue exposure plus acupuncture without twirling of the needle. These experimental findings indicate that presentation of heroin cues can induce activation in craving-related brain regions, which are involved in reward, learning and memory, cognition and emotion. Acupuncture at the Zusanli point can rapidly suppress the activation of specific brain regions related to craving, supporting its potential as an intervention for drug craving. PMID:25368637

  17. Acupuncture inhibits cue-induced heroin craving and brain activation.

    PubMed

    Cai, Xinghui; Song, Xiaoge; Li, Chuanfu; Xu, Chunsheng; Li, Xiliang; Lu, Qi

    2012-11-25

    Previous research using functional MRI has shown that specific brain regions associated with drug dependence and cue-elicited heroin craving are activated by environmental cues. Craving is an important trigger of heroin relapse, and acupuncture may inhibit craving. In this study, we performed functional MRI in heroin addicts and control subjects. We compared differences in brain activation between the two groups during heroin cue exposure, heroin cue exposure plus acupuncture at the Zusanli point (ST36) without twirling of the needle, and heroin cue exposure plus acupuncture at the Zusanli point with twirling of the needle. Heroin cue exposure elicited significant activation in craving-related brain regions mainly in the frontal lobes and callosal gyri. Acupuncture without twirling did not significantly affect the range of brain activation induced by heroin cue exposure, but significantly changed the extent of the activation in the heroin addicts group. Acupuncture at the Zusanli point with twirling of the needle significantly decreased both the range and extent of activation induced by heroin cue exposure compared with heroin cue exposure plus acupuncture without twirling of the needle. These experimental findings indicate that presentation of heroin cues can induce activation in craving-related brain regions, which are involved in reward, learning and memory, cognition and emotion. Acupuncture at the Zusanli point can rapidly suppress the activation of specific brain regions related to craving, supporting its potential as an intervention for drug craving.

  18. Elevated Norepinephrine may be a Unifying Etiological Factor in the Abuse of a Broad Range of Substances: Alcohol, Nicotine, Marijuana, Heroin, Cocaine, and Caffeine

    PubMed Central

    Fitzgerald, Paul J.

    2013-01-01

    A wide range of commonly abused drugs have effects on the noradrenergic neurotransmitter system, including alterations during acute intoxication and chronic use of these drugs. It is not established, however, that individual differences in noradrenergic signaling, which may be present prior to use of drugs, predispose certain persons to substance abuse. This paper puts forth the novel hypothesis that elevated noradrenergic signaling, which may be raised largely due to genetics but also due to environmental factors, is an etiological factor in the abuse of a wide range of substances, including alcohol, nicotine, marijuana, heroin, cocaine, and caffeine. Data are reviewed for each of these drugs comprising their interaction with norepinephrine during acute intoxication, long-term use, subsequent withdrawal, and stress-induced relapse. In general, the data suggest that these drugs acutely boost noradrenergic signaling, whereas long-term use also affects this neurotransmitter system, possibly suppressing it. During acute withdrawal after chronic drug use, noradrenergic signaling tends to be elevated, consistent with the observation that norepinephrine lowering drugs such as clonidine reduce withdrawal symptoms. Since psychological stress can promote relapse of drug seeking in susceptible individuals and stress produces elevated norepinephrine release, this suggests that these drugs may be suppressing noradrenergic signaling during chronic use or instead elevating it only in reward circuits of the brain. If elevated noradrenergic signaling is an etiological factor in the abuse of a broad range of substances, then chronic use of pharmacological agents that reduce noradrenergic signaling, such as clonidine, guanfacine, lofexidine, propranolol, or prazosin, may help prevent or treat drug abuse in general. PMID:24151426

  19. Cocaine adulteration.

    PubMed

    Kudlacek, Oliver; Hofmaier, Tina; Luf, Anton; Mayer, Felix P; Stockner, Thomas; Nagy, Constanze; Holy, Marion; Freissmuth, Michael; Schmid, Rainer; Sitte, Harald H

    2017-10-01

    Cocaine is a naturally occurring and illicitly used psychostimulant drug. Cocaine acts at monoaminergic neurotransmitter transporters to block uptake of the monoamines, dopamine, serotonin and norepinephrine. The resulting increase of monoamines in the extracellular space underlies the positively reinforcing effects that cocaine users seek. In turn, this increase in monoamines underlies the development of addiction, and can also result in a number of severe side effects. Currently, cocaine is one of the most common illicit drugs available on the European market. However, cocaine is increasingly sold in impure forms. This trend is driven by cocaine dealers seeking to increase their profit margin by mixing ("cutting") cocaine with numerous other compounds ("adulterants"). Importantly, these undeclared compounds put cocaine consumers at risk, because consumers are not aware of the additional potential threats to their health. This review describes adulterants that have been identified in cocaine sold on the street market. Their typical pharmacological profile and possible reasons why these compounds can be used as cutting agents will be discussed. Since a subset of these adulterants has been found to exert effects similar to cocaine itself, we will discuss levamisole, the most frequently used cocaine cutting agent today, and its metabolite aminorex. Copyright © 2017. Published by Elsevier B.V.

  20. Disrupted white matter structural connectivity in heroin abusers.

    PubMed

    Sun, Yan; Wang, Gui-Bin; Lin, Qi-Xiang; Lu, Lin; Shu, Ni; Meng, Shi-Qiu; Wang, Jun; Han, Hong-Bin; He, Yong; Shi, Jie

    2017-01-01

    Neurocognitive impairment is one of the factors that put heroin abusers at greater risk for relapse, and deficits in related functional brain connections have been found. However, the alterations in structural brain connections that may underlie these functional and neurocognitive impairments remain largely unknown. In the present study, we investigated topological organization alterations in the structural network of white matter in heroin abusers and examined the relationships between the network changes and clinical measures. We acquired diffusion tensor imaging datasets from 76 heroin abusers and 78 healthy controls. Network-based statistic was applied to identify alterations in interregional white matter connectivity, and graph theory methods were used to analyze the properties of global networks. The participants also completed a battery of neurocognitive measures. One increased subnetwork characterizing widespread abnormalities in structural connectivity was present in heroin users, which mainly composed of default-mode, attentional and visual systems. The connection strength was positively correlated with increases in fractional anisotropy in heroin abusers. Intriguingly, the changes in within-frontal and within-temporal connections in heroin abusers were significantly correlated with daily heroin dosage and impulsivity scores, respectively. These findings suggest that heroin abusers have extensive abnormal white matter connectivity, which may mediate the relationship between heroin dependence and clinical measures. The increase in white matter connectivity may be attributable to the inefficient microstructure integrity of white matter. The present findings extend our understanding of cerebral structural disruptions that underlie neurocognitive and functional deficits in heroin addiction and provide circuit-level markers for this chronic disorder. © 2015 Society for the Study of Addiction.

  1. The Dynamics of a Heroin Addiction Epidemic

    ERIC Educational Resources Information Center

    DuPont, Robert L.; Greene, Mark H.

    1973-01-01

    Discusses recent trends in heroin addiction in Washington, D.C. In 1969 a comprehensive, multimodal treatment program for addicts was introduced and a major law enforcement commitment was made to reduce the heroin supply. These factors, together with changing community attitudes, may be responsible for a remarkable decline in heroin addiction. (JR)

  2. Disposition of nasal, intravenous, and oral methadone in healthy volunteers.

    PubMed

    Dale, Ola; Hoffer, Christine; Sheffels, Pamela; Kharasch, Evan D

    2002-11-01

    Nasal administration of many opioids demonstrates rapid uptake and fast onset of action. Nasal administration may be an alternative to intravenous and oral administration of methadone and was therefore studied in human volunteers. The study was approved by the Institutional Review Board of the University of Washington, Seattle. Eight healthy volunteers (6 men and 2 women) aged 19 to 33 years were enrolled after informed written consent was obtained. Subjects received 10 mg methadone hydrochloride nasally, orally, or intravenously on 3 separate occasions in a crossover design. Nasal methadone (50 mg/mL in aqueous solution) was given as a 100-microL spray in each nostril (Pfeiffer BiDose sprayer). Blood samples for liquid chromatography-mass spectrometry analyses of methadone and the metabolite 2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolinium were drawn for up to 96 hours. The methadone effect was measured by noninvasive infrared pupilometry coincident with blood sampling. Nasal uptake of methadone was rapid, with maximum plasma concentrations occurring within 7 minutes. The maximum effects of intravenous, nasal, and oral methadone, on the basis of dark-adapted pupil diameter, were reached in about 15 minutes, 30 minutes, and 2 hours, respectively. The respective durations were 24, 10, and 8 hours. Both nasal and oral bioavailabilities were 0.85. Subjects reported that nasal methadone caused a burning sensation. Nasal administration of methadone results in rapid absorption and onset of effect and high bioavailability, which was greater than that reported for other nasal opioids, with a similar duration of effect. Nasal administration may be an alternative route of methadone administration; however, improved formulations are desirable to reduce nasal irritation.

  3. Drug specificity in drug versus food choice in male rats.

    PubMed

    Tunstall, Brendan J; Riley, Anthony L; Kearns, David N

    2014-08-01

    Although different classes of drug differ in their mechanisms of reinforcement and effects on behavior, little research has focused on differences in self-administration behaviors maintained by users of these drugs. Persistent drug choice despite available reinforcement alternatives has been proposed to model behavior relevant to addiction. The present study used a within-subjects procedure, where male rats (Long-Evans, N = 16) were given a choice between cocaine (1.0 mg/kg/infusion) and food (a single 45-mg grain pellet) or between heroin (0.02 mg/kg/infusion) and food in separate phases (drug order counterbalanced). All rats were initially trained to self-administer each drug, and the doses used were based on previous studies showing that small subsets of rats tend to prefer drug over food reinforcement. The goal of the present study was to determine whether rats that prefer cocaine would also prefer heroin. Choice sessions consisted of 2 forced-choice trials with each reinforcer, followed by 14 free-choice trials (all trials separated by 10-min intertrial interval). Replicating previous results, small subsets of rats preferred either cocaine (5 of the 16 rats) or heroin (2 of the 16 rats) to the food alternative. Although 1 of the 16 rats demonstrated a preference for both cocaine and heroin to the food alternative, there was no relationship between degree of cocaine and heroin preference in individual rats. The substance-specific pattern of drug preference observed suggests that at least in this animal model, the tendencies to prefer cocaine or heroin in preference to a nondrug alternative are distinct behavioral phenomena.

  4. Dynamic vaccine blocks relapse to compulsive intake of heroin

    PubMed Central

    Schlosburg, Joel E.; Vendruscolo, Leandro F.; Bremer, Paul T.; Lockner, Jonathan W.; Wade, Carrie L.; Nunes, Ashlee A. K.; Stowe, G. Neil; Edwards, Scott; Janda, Kim D.; Koob, George F.

    2013-01-01

    Heroin addiction, a chronic relapsing disorder characterized by excessive drug taking and seeking, requires constant psychotherapeutic and pharmacotherapeutic interventions to minimize the potential for further abuse. Vaccine strategies against many drugs of abuse are being developed that generate antibodies that bind drug in the bloodstream, preventing entry into the brain and nullifying psychoactivity. However, this strategy is complicated by heroin’s rapid metabolism to 6-acetylmorphine and morphine. We recently developed a “dynamic” vaccine that creates antibodies against heroin and its psychoactive metabolites by presenting multihaptenic structures to the immune system that match heroin’s metabolism. The current study presents evidence of effective and continuous sequestration of brain-permeable constituents of heroin in the bloodstream following vaccination. The result is efficient blockade of heroin activity in treated rats, preventing various features of drugs of abuse: heroin reward, drug-induced reinstatement of drug seeking, and reescalation of compulsive heroin self-administration following abstinence in dependent rats. The dynamic vaccine shows the capability to significantly devalue the reinforcing and motivating properties of heroin, even in subjects with a history of dependence. In addition, targeting a less brain-permeable downstream metabolite, morphine, is insufficient to prevent heroin-induced activity in these models, suggesting that heroin and 6-acetylmorphine are critical players in heroin’s psychoactivity. Because the heroin vaccine does not target opioid receptors or common opioid pharmacotherapeutics, it can be used in conjunction with available treatment options. Thus, our vaccine represents a promising adjunct therapy for heroin addiction, providing continuous heroin antagonism, requiring minimal medical monitoring and patient compliance. PMID:23650354

  5. Buprenorphine from detox and beyond: preliminary evaluation of a pilot program to increase heroin dependent individuals' engagement in a full continuum of care.

    PubMed

    Donovan, Dennis M; Knox, Patricia C; Skytta, Jenny A F; Blayney, Jessica A; DiCenzo, Jessica

    2013-04-01

    Absence of successful transition to post-detoxification treatment leads to high rates of relapse among detoxified heroin users. The present study evaluated a pilot buprenorphine treatment program (BTP). Heroin dependent individuals were inducted onto buprenorphine/naloxone in detox, maintained while transitioning through an intensive inpatient program (IIP), and gradually tapered off medication over 5 months of outpatient (OP) treatment. Compared to programmatic indicators of treatment engagement in the year prior to BTP implementation, referrals from detox to IIP, entry into and completion of IIP and subsequent OP, and days in OP treatment increased substantially. BTP completers, compared to non-completers, viewed abstinence as more difficult and as requiring more assistance to achieve, were less likely to be current cocaine and alcohol users or to have relapsed during the course of treatment. Although preliminary and in need of replication, initial adjunctive use of buprenorphine in an abstinence-based continuum of care may improve post-detoxification treatment entry, engagement, and completion. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Facial recognition of heroin vaccine opiates: type 1 cross-reactivities of antibodies induced by hydrolytically stable haptenic surrogates of heroin, 6-acetylmorphine, and morphine.

    PubMed

    Matyas, Gary R; Rice, Kenner C; Cheng, Kejun; Li, Fuying; Antoline, Joshua F G; Iyer, Malliga R; Jacobson, Arthur E; Mayorov, Alexander V; Beck, Zoltan; Torres, Oscar B; Alving, Carl R

    2014-03-14

    Novel synthetic compounds similar to heroin and its major active metabolites, 6-acetylmorphine and morphine, were examined as potential surrogate haptens for the ability to interface with the immune system for a heroin vaccine. Recent studies have suggested that heroin-like haptens must degrade hydrolytically to induce independent immune responses both to heroin and to the metabolites, resulting in antisera containing mixtures of antibodies (type 2 cross-reactivity). To test this concept, two unique hydrolytically stable haptens were created based on presumed structural facial similarities to heroin or to its active metabolites. After conjugation of a heroin-like hapten (DiAmHap) to tetanus toxoid and mixing with liposomes containing monophosphoryl lipid A, high titers of antibodies after two injections in mice had complementary binding sites that exhibited strong type 1 ("true") specific cross-reactivity with heroin and with both of its physiologically active metabolites. Mice immunized with each surrogate hapten exhibited reduced antinociceptive effects caused by injection of heroin. This approach obviates the need to create hydrolytically unstable synthetic heroin-like compounds to induce independent immune responses to heroin and its active metabolites for vaccine development. Facial recognition of hydrolytically stable surrogate haptens by antibodies together with type 1 cross-reactivities with heroin and its metabolites can help to guide synthetic chemical strategies for efficient development of a heroin vaccine. Copyright © 2014. Published by Elsevier Ltd.

  7. Facial recognition of heroin vaccine opiates: Type 1 cross-reactivities of antibodies induced by hydrolytically stable haptenic surrogates of heroin, 6-acetylmorphine, and morphine

    PubMed Central

    Matyas, Gary R.; Rice, Kenner C.; Cheng, Kejun; Li, Fuying; Antoline, Joshua F. G.; Iyer, Malliga R.; Jacobson, Arthur E.; Mayorov, Alexander V.; Beck, Zoltan; Torres, Oscar; Alving, Carl R.

    2014-01-01

    Novel synthetic compounds similar to heroin and its major active metabolites, 6-acetylmorphine and morphine, were examined as potential surrogate haptens for the ability to interface with the immune system for a heroin vaccine. Recent studies have suggested that heroin-like haptens must degrade hydrolytically to induce independent immune responses both to heroin and to the metabolites, resulting in antisera containing mixtures of antibodies (type 2 cross-reactivity). To test this concept, two unique hydrolytically stable haptens were created based on presumed structural facial similarities to heroin or to its active metabolites. After conjugation of a heroin-like hapten (DiAmHap) to tetanus toxoid and mixing with liposomes containing monophosphoryl lipid A, high titers of antibodies after two injections in mice had complementary binding sites that exhibited strong type 1 (“true”) specific cross-reactivity with heroin and with both of its physiologically active metabolites. Mice immunized with each surrogate hapten exhibited reduced antinociceptive effects caused by injection of heroin. This approach obviates the need to create hydrolytically unstable synthetic heroin-like compounds to induce independent immune responses to heroin and its active metabolites for vaccine development. Facial recognition of hydrolytically stable surrogate haptens by antibodies together with type 1 cross-reactivities with heroin and its metabolites can help to guide synthetic chemical strategies for efficient development of a heroin vaccine. PMID:24486371

  8. Characteristics of primary amphetamine users in Sweden: a criminal justice population examined with the Addiction Severity Index.

    PubMed

    Hakansson, A; Schlyter, F; Berglund, M

    2009-01-01

    Characteristics of primary amphetamine, heroin and cocaine users were compared in a criminal justice population. 7,085 clients with suspected or reported substance use were studied using the Addiction Severity Index. Variables separating amphetamine, heroin and cocaine users were analyzed in stepwise logistic regression. There were considerably more primary amphetamine users (n = 1,396) than heroin (n = 392) and cocaine (n = 119) users. Amphetamine users were older, a more rural population, and less likely to be non-Nordic immigrants. Compared with heroin, amphetamine use was associated with older age, Nordic origin, nonurban residence, memory/concentration problems, parental alcohol problems, and less history of other opioid use, overdose and detoxification. Compared with cocaine, amphetamine use was associated with older age, Nordic origin, nonurban residence, injecting, tobacco and institution treatment. Overlap of drug use between groups was relatively uncommon. This pattern of amphetamine use, common among Swedish criminals, has relatively distinct boundaries from heroin and cocaine use, commonly involves injecting, and differs from other countries. Psychiatric problems and alcohol heredity were common, and evidence-based treatment for amphetamine users is needed. The connection between amphetamine use and criminal behavior is insufficiently understood and should be further addressed. Copyright 2008 S. Karger AG, Basel.

  9. A bacterial cocaine esterase protects against cocaine-induced epileptogenic activity and lethality.

    PubMed

    Jutkiewicz, Emily M; Baladi, Michelle G; Cooper, Ziva D; Narasimhan, Diwahar; Sunahara, Roger K; Woods, James H

    2009-09-01

    Cocaine toxicity results in cardiovascular complications, seizures, and death and accounts for approximately 20% of drug-related emergency department visits every year. Presently, there are no treatments to eliminate the toxic effects of cocaine. The present study hypothesizes that a bacterial cocaine esterase with high catalytic efficiency would provide rapid and robust protection from cocaine-induced convulsions, epileptogenic activity, and lethality. Cocaine-induced paroxysmal activity and convulsions were evaluated in rats surgically implanted with radiotelemetry devices (N=6 per treatment group). Cocaine esterase was administered 1 minute after a lethal dose of cocaine or after cocaine-induced convulsions to determine the ability of the enzyme to prevent or reverse, respectively, the effects of cocaine. The cocaine esterase prevented all cocaine-induced electroencephalographic changes and lethality. This effect was specific for cocaine because the esterase did not prevent convulsions and death induced by a cocaine analog, (-)-2beta-carbomethoxy-3beta-phenyltropane. The esterase prevented lethality even after cocaine-induced convulsions occurred. In contrast, the short-acting benzodiazepine, midazolam, prevented cocaine-induced convulsions but not the lethal effects of cocaine. The data showed that cocaine esterase successfully degraded circulating cocaine to prevent lethality and that cocaine-induced convulsions alone are not responsible for the lethal effects of cocaine in this model. Therefore, further investigation into the use of cocaine esterase for treating cocaine overdose and its toxic effects is warranted.

  10. Detection of drugs in the urine of body-packers.

    PubMed

    Gherardi, R K; Baud, F J; Leporc, P; Marc, B; Dupeyron, J P; Diamant-Berger, O

    1988-05-14

    The presence of opiates and benzoylecgonine, the major metabolite of cocaine, in the urine was detected by means of enzyme immunoassay in a series of 120 smugglers who had either ingested or inserted into their rectum cocaine or heroin packaged for transportation. There was a striking relation between the presence of drugs in the urine and swallowing of drug-filled bundles (cocaine 49 of 50 cases, heroin 9 of 10). The proportion of positive results was also high in cases of rectal insertion (cocaine 2 of 2, heroin 35 of 58). In 30 cases of cocaine-packet ingestion, serial measurements showed that the accuracy of the test progressively decreased with respect to the detection of residual packets in the body. Drug detection in the urine of suspected body-packers seems to be a useful test, positive results justifying subsequent radiological investigations.

  11. Cocaine

    MedlinePlus

    Cocaine is a white powder. It can be snorted up the nose or mixed with water and injected with a needle. Cocaine can also be made into small white rocks, ... Crack is smoked in a small glass pipe. Cocaine speeds up your whole body. You may feel ...

  12. 'Miracle cure' or 'liquid handcuffs': reporting on naltrexone and methadone in the Australian print media.

    PubMed

    Matthew-Simmons, Francis; Ritter, Alison

    2014-09-01

    The news media is an important source of information regarding new developments in medicine and public health interventions. Previous research has indicated that in many cases, reporting on new treatments can be inaccurate or sensationalist. This paper presents analysis of Australian print media reporting on two treatment options for heroin dependence (naltrexone and methadone). The aim of this study was to quantitatively compare the volume and content of Australian print media reporting on these two treatments, one of which had a long history of use in Australia, and the other which was comparatively newer. The study constituted a quantitative content analysis of a sample of 859 Australian newspaper articles, published over a 10-year period (1997-2007). Each article paragraph was coded for positive outcomes/benefits of treatment, as well as negative outcomes associated with treatment. The analysis revealed that during this period, the Australian print media was significantly more likely to report the potential positive outcomes of naltrexone treatment, compared with the negative outcomes. In contrast, reporting on methadone focused more on the negative outcomes and side effects. The relative frequency by which the benefits of naltrexone were mentioned in this sample of news content is somewhat at odds with the extant efficacy and effectiveness research evidence. The findings suggest that reporting on these treatments in the Australian print media has not been balanced. This type of reporting has potential implications for public attitudes, as well as policy decisions. © 2014 Australasian Professional Society on Alcohol and other Drugs.

  13. Do drug seizures predict drug-related emergency department presentations or arrests for drug use and possession?

    PubMed

    Wan, Wai-Yin; Weatherburn, Don; Wardlaw, Grant; Sarafidis, Vasilis; Sara, Grant

    2016-01-01

    Direct evidence of the effect of drug seizures on drug use and drug-related harm is fairly sparse. The aim of this study was to see whether seizures of heroin, cocaine and ATS predict the number of people arrested for use and possession of these drugs and the number overdosing on them. We examined the effect of seizure frequency and seizure weight on arrests for drug use and possession and on the frequency of drug overdose with autoregressive distributed lag (ARDL) models. Granger causality tests were used to test for simultaneity. Over the short term (i.e. up to 4 months), increases in the intensity of high-level drug law enforcement (as measured by seizure weight and frequency) directed at ATS, cocaine and heroin did not appear to have any suppression effect on emergency department (ED) presentations relating to ATS, cocaine and heroin, or on arrests for use and/or possession of these drugs. A significant negative contemporaneous relationship was found between the heroin seizure weight and arrests for use and/or possession of heroin. However no evidence emerged of a contemporaneous or lagged relationship between heroin seizures and heroin ED presentations. The balance of evidence suggests that, in the Australian context, increases in the monthly seizure frequency and quantity of ATS, cocaine and heroin are signals of increased rather than reduced supply. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Chloramphenicol significantly affects the pharmacokinetics of oral methadone in Greyhound dogs.

    PubMed

    KuKanich, Butch; KuKanich, Kate

    2015-11-01

    To assess the effects of cytochrome P450 (CYP) inhibitors (ketoconazole, chloramphenicol, trimethoprim, fluoxetine, cimetidine and medetomidine) in various combinations on the pharmacokinetics of oral methadone in Greyhound dogs to determine the specific effects of the different inhibitors and if a clinically relevant interaction occurs. Non-randomized, sequential design. Six healthy Greyhound dogs (three male, three female). Canine CYP inhibitors (ketoconazole, chloramphenicol, trimethoprim, fluoxetine, cimetidine and medetomidine) were administered in varying combinations prior to the administration of oral methadone. Plasma was obtained from each dog to enable the determination of methadone and CYP inhibitor drug concentrations using liquid chromatography with either mass spectrometry or ultraviolet detection. Significant increases in the area under the curve (AUC) and maximum plasma concentrations (CMAX ) of methadone occurred in all groups administered chloramphenicol. The AUC (6 hours ng mL(-1)) and CMAX (6 ng mL(-1)) of methadone significantly increased to 541 hours ng mL(-1) and 47.8 ng mL(-1), respectively, when methadone was administered with chloramphenicol as a sole inhibitor. There were no significant effects of CYP inhibitors other than chloramphenicol on methadone pharmacokinetics, which suggests that chloramphenicol was primarily responsible for the pharmacokinetic interaction. This study demonstrated significant effects of chloramphenicol on the pharmacokinetics of oral methadone. Further studies should investigate the effects of chloramphenicol on methadone pharmacokinetics in multiple dog breeds and examine whether oral methadone would be an effective analgesic in dogs. In addition, the safety of chloramphenicol and its effects on the pharmacokinetics of parenteral methadone warrant assessment. © 2015 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

  15. A Bacterial Cocaine Esterase Protects Against Cocaine-Induced Epileptogenic Activity and Lethality

    PubMed Central

    Jutkiewicz, Emily M.; Baladi, Michelle G.; Cooper, Ziva D.; Narasimhan, Diwahar; Sunahara, Roger K.; Woods, James H.

    2012-01-01

    Study objective Cocaine toxicity results in cardiovascular complications, seizures, and death and accounts for approximately 20% of drug-related emergency department visits every year. Presently, there are no treatments to eliminate the toxic effects of cocaine. The present study hypothesizes that a bacterial cocaine esterase with high catalytic efficiency would provide rapid and robust protection from cocaine-induced convulsions, epileptogenic activity, and lethality. Methods Cocaine-induced paroxysmal activity and convulsions were evaluated in rats surgically implanted with radiotelemetry devices (N=6 per treatment group). Cocaine esterase was administered 1 minute after a lethal dose of cocaine or after cocaine-induced convulsions to determine the ability of the enzyme to prevent or reverse, respectively, the effects of cocaine. Results The cocaine esterase prevented all cocaine-induced electroencephalographic changes and lethality. This effect was specific for cocaine because the esterase did not prevent convulsions and death induced by a cocaine analog, (−)-2β-carbomethoxy-3β-phenyltropane. The esterase prevented lethality even after cocaine-induced convulsions occurred. In contrast, the short-acting benzodiazepine, midazolam, prevented cocaine-induced convulsions but not the lethal effects of cocaine. Conclusion The data showed that cocaine esterase successfully degraded circulating cocaine to prevent lethality and that cocaine-induced convulsions alone are not responsible for the lethal effects of cocaine in this model. Therefore, further investigation into the use of cocaine esterase for treating cocaine overdose and its toxic effects is warranted. PMID:19013687

  16. Preparation of longitudinal sections of hair samples for the analysis of cocaine by MALDI-MS/MS and TOF-SIMS imaging.

    PubMed

    Flinders, Bryn; Cuypers, Eva; Zeijlemaker, Hans; Tytgat, Jan; Heeren, Ron M A

    2015-10-01

    Matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) for the analysis of intact hair is a powerful tool for the detection of drugs of abuse in toxicology and forensic applications. Here we present a quick, easy, and reproducible method of preparing longitudinal sections of single hairs. This method improves the accessibility of chemicals embedded in the hair matrix for molecular imaging with mass spectrometry. The images obtained from a single, sectioned hair sample show molecular distributions in the exposed medulla, cortex, and a portion of the cuticle observed as a narrow layer surrounding the cortex. Using MALDI-MS/MS imaging, the distribution of cocaine was observed throughout five longitudinally sectioned drug-user hair samples. The images showed the distribution of the product ion at m/z 182, derived from the precursor ion of cocaine at m/z 304. MetA-SIMS images of longitudinally sectioned hair samples showed a more detailed distribution of cocaine at m/z 304, benzoylecgonine the major metabolite of cocaine at m/z 290 and other drugs such as methadone which was observed at m/z 310. Chronological information of drug intake can be obtained more sensitively. The chronological detail is in hours rather than months, which is of great interest in clinical as well as forensic applications. Copyright © 2015 John Wiley & Sons, Ltd.

  17. Employment-based abstinence reinforcement as a maintenance intervention for the treatment of cocaine dependence: a randomized controlled trial.

    PubMed

    DeFulio, Anthony; Donlin, Wendy D; Wong, Conrad J; Silverman, Kenneth

    2009-09-01

    Due to the chronic nature of cocaine dependence, long-term maintenance treatments may be required to sustain abstinence. Abstinence reinforcement is among the most effective means of initiating cocaine abstinence. Practical and effective means of maintaining abstinence reinforcement programs over time are needed. To determine whether employment-based abstinence reinforcement can be an effective long-term maintenance intervention for cocaine dependence. Participants (n = 128) were enrolled in a 6-month job skills training and abstinence initiation program. Participants who initiated abstinence, attended regularly and developed needed job skills during the first 6 months were hired as operators in a data entry business and assigned randomly to an employment-only (control, n = 24) or abstinence-contingent employment (n = 27) group. A non-profit data entry business. Participants Unemployed welfare recipients who used cocaine persistently while enrolled in methadone treatment in Baltimore. Abstinence-contingent employment participants received 1 year of employment-based contingency management, in which access to employment was contingent upon provision of drug-free urine samples under routine and then random drug testing. If a participant provided drug-positive urine or failed to provide a mandatory sample, then that participant received a temporary reduction in pay and could not work until urinalysis confirmed recent abstinence. Cocaine-negative urine samples at monthly assessments across 1 year of employment. During the 1 year of employment, abstinence-contingent employment participants provided significantly more cocaine-negative urine samples than employment-only participants [79.3% and 50.7%, respectively; P = 0.004, odds ratio (OR) = 3.73, 95% confidence interval (CI) = 1.60-8.69]. Conclusions Employment-based abstinence reinforcement that includes random drug testing is effective as a long-term maintenance intervention, and is among the most promising treatments

  18. Levels of heroin and its metabolites in blood and brain extracellular fluid after i.v. heroin administration to freely moving rats

    PubMed Central

    Gottås, A; Øiestad, E L; Boix, F; Vindenes, V; Ripel, Å; Thaulow, C H; Mørland, J

    2013-01-01

    BACKGROUND AND PURPOSE Heroin, with low affinity for μ-opioid receptors, has been considered to act as a prodrug. In order to study the pharmacokinetics of heroin and its active metabolites after i.v. administration, we gave a bolus injection of heroin to rats and measured the concentration of heroin and its metabolites in blood and brain extracellular fluid (ECF). EXPERIMENTAL APPROACH After an i.v. bolus injection of heroin to freely moving Sprague–Dawley rats, the concentrations of heroin and metabolites in blood samples from the vena jugularis and in microdialysis samples from striatal brain ECF were measured by ultraperformance LC-MS/MS. KEY RESULTS Heroin levels decreased very fast, both in blood and brain ECF, and could not be detected after 18 and 10 min respectively. 6-Monoacetylmorphine (6-MAM) increased very rapidly, reaching its maximal concentrations after 2.0 and 4.3 min, respectively, and falling thereafter. Morphine increased very slowly, reaching its maximal levels, which were six times lower than the highest 6-MAM concentrations, after 12.6 and 21.3 min, with a very slow decline during the rest of the experiment and only surpassing 6-MAM levels at least 30 min after injection. CONCLUSIONS AND IMPLICATIONS After an i.v. heroin injection, 6-MAM was the predominant opioid present shortly after injection and during the first 30 min, not only in the blood but also in rat brain ECF. 6-MAM might therefore mediate most of the effects observed shortly after heroin intake, and this finding questions the general assumption that morphine is the main and most important metabolite of heroin. PMID:23865556

  19. A System Description of the Heroin Trade

    DTIC Science & Technology

    1994-01-01

    19 3.3. Estimated Distribution of Heroin Smuggling by U.S. Entry Region ............................................. 20 4.1...14. Distribution of Incoming Heroin Among U.S. Entry Regions (Cells A351 to R418) .................................... 84 C-15. Distribution of...Transportation Modes into U.S. Entry Regions (Cells A419 to P472) .................................... 86 C.16. Seizures of Heroin (Cells A473 to P498

  20. Perinatal exposure to methadone affects central cholinergic activity in the weanling rat.

    PubMed

    Robinson, S E; Mo, Q; Maher, J R; Wallace, M J; Kunko, P M

    1996-06-01

    Pregnant rats were implanted with osmotic minipumps containing either methadone hydrochloride (initial dose, 9 mg/kg/day) or sterile water. Their offspring were cross-fostered so that they were exposed to methadone prenatally and/or postnatally. Perinatal methadone exposure disrupted cholinergic activity on postnatal day 21 as measured by the turnover rate of acetylcholine (TRACh) in both female and male rats, although there were some sexually-dimorphic responses. The most profoundly affected brain region was the striatum, where prenatal exposure to methadone increased ACh turnover, whether or not the rats continued to be exposed to methadone postnatally. It appears unlikely that neonatal withdrawal contributes to brain regional changes in ACh turnover, as continued postnatal exposure to methadone did not prevent the prenatal methadone induced changes.

  1. Enhanced Choice for Viewing Cocaine Pictures in Cocaine Addiction

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Moeller, S.J.; Goldstein, R.; Moeller, S.J.

    Individuals with cocaine use disorder (CUD) chose cocaine over nondrug rewards. In two newly designed laboratory tasks with pictures, we document this modified choice outside of a cocaine administration paradigm. Choice for viewing cocaine, pleasant, unpleasant, or neutral pictures-under explicit contingencies (choice made between two fully visible side-by-side images) and under more implicit contingencies (selections made between pictures hidden under flipped-over cards)-was examined in 20 CUD and 20 matched healthy control subjects. Subjects also provided self-reported ratings of each picture's pleasantness and arousal. Under both contingencies, CUD subjects chose to view more cocaine pictures than control subjects, group differences thatmore » were not fully explained by the self-reported picture ratings. Furthermore, whereas CUD subjects choice for viewing cocaine pictures exceeded choice for viewing unpleasant pictures (but did not exceed choice for viewing pleasant pictures, in contrast to their self-reported ratings), healthy control subjects avoided viewing cocaine pictures as frequently as, or even more than, unpleasant pictures. Finally, CUD subjects with the most cocaine viewing selections, even when directly compared with selections of the pleasant pictures, also reported the most frequent recent cocaine use. Enhanced drug-related choice in cocaine addiction can be demonstrated even for nonpharmacologic (pictorial) stimuli. This choice, which is modulated by alternative stimuli, partly transcends self-reports (possibly indicative of a disconnect in cocaine addiction between self-reports and objective behavior) to provide an objective marker of addiction severity. Neuroimaging studies are needed to establish the neural underpinnings of such enhanced cocaine-related choice.« less

  2. Novel C-1 Substituted Cocaine Analogs Unlike Cocaine or Benztropine

    PubMed Central

    Ali, Solav; Hashim, Audrey; Sheikh, Imran S.; Theddu, Naresh; Gaddiraju, Narendra V.; Mehrotra, Suneet; Schmitt, Kyle C.; Murray, Thomas F.; Sershen, Henry; Unterwald, Ellen M.; Davis, Franklin A.

    2012-01-01

    Despite a wealth of information on cocaine-like compounds, there is no information on cocaine analogs with substitutions at C-1. Here, we report on (R)-(−)-cocaine analogs with various C-1 substituents: methyl (2), ethyl (3), n-propyl (4), n-pentyl (5), and phenyl (6). Analog 2 was equipotent to cocaine as an inhibitor of the dopamine transporter (DAT), whereas 3 and 6 were 3- and 10-fold more potent, respectively. None of the analogs, however, stimulated mouse locomotor activity, in contrast to cocaine. Pharmacokinetic assays showed compound 2 occupied mouse brain rapidly, as cocaine itself; moreover, 2 and 6 were behaviorally active in mice in the forced-swim test model of depression and the conditioned place preference test. Analog 2 was a weaker inhibitor of voltage-dependent Na+ channels than cocaine, although 6 was more potent than cocaine, highlighting the need to assay future C-1 analogs for this activity. Receptorome screening indicated few significant binding targets other than the monoamine transporters. Benztropine-like “atypical” DAT inhibitors are known to display reduced cocaine-like locomotor stimulation, presumably by their propensity to interact with an inward-facing transporter conformation. However, 2 and 6, like cocaine, but unlike benztropine, exhibited preferential interaction with an outward-facing conformation upon docking in our DAT homology model. In summary, C-1 cocaine analogs are not cocaine-like in that they are not stimulatory in vivo. However, they are not benztropine-like in binding mechanism and seem to interact with the DAT similarly to cocaine. The present data warrant further consideration of these novel cocaine analogs for antidepressant or cocaine substitution potential. PMID:22895898

  3. Monkey motor stimulation and altered social behavior during chronic methadone administration.

    PubMed

    Crowley, T J; Hydinger, M; Stynes, A J; Feiger, A

    1975-08-21

    To assess the effects of chronic methadone administration on locomotor, social, and eating behavior od drug-native individuals under circumstances approximating those of methadone "maintenance" clinics, we gave single, daily oral doses of methadone to 5 Macaca radiata monkeys living in a social group. We obtained motor activity counts automatically during 6 weeks of baseline, 10 weeks of drug administration, and 3 weeks of post-drug abstinence. Social behaviors of association, dominance, submission, and sexuality were counted 5 days per week, and animal weights, food eaten and food-reinforced work were recorded. Plasma methadone levels were near those achieved in mechadone clincs. Methadone produced mixed stimulation and sedation in the daytime, with stimulation predominating for 4 hrs following administration. At night the subjects moved less while taking the drug. Associative behaviors were reduced by methadone, but dominance, submission, and sexual behaviors were not altered. The monkeys ate less while taking the drug, losing weight and working less for food. In these primates methadone had significant stimulant properties, impaired important social behaviors, and reduced the potency of food as a reinforcer of work. The results are compared with methadone's effects upon humans.

  4. Methadone pharmacogenetics: CYP2B6 polymorphisms determine plasma concentrations, clearance and metabolism

    PubMed Central

    Kharasch, Evan D.; Regina, Karen J.; Blood, Jane; Friedel, Christina

    2015-01-01

    Background Interindividual variability in methadone disposition remains unexplained, and methadone accidental overdose in pain therapy is a significant public health problem. Cytochrome P4502B6 (CYP2B6) is the principle determinant of clinical methadone elimination. The CYP2B6 gene is highly polymorphic, with several variant alleles. CYP2B6.6, the protein encoded by the CYP2B6*6 polymorphism, deficiently catalyzes methadone metabolism in vitro. This investigation determined the influence of CYP2B6*6, and other allelic variants encountered, on methadone concentrations, clearance, and metabolism. Methods Healthy volunteers in genotype cohorts CYP2B6*1/*1 (n=21), CYP2B6*1/*6 (n=20), and CYP2B6*6/*6 (n=17), and also CYP2B6*1/*4 (n=1), CYP2B6*4/*6 (n=3), CYP2B6*5/*5 (n=2) subjects received single doses of intravenous and oral methadone. Plasma and urine methadone and metabolite concentrations were determined by tandem mass spectrometry. Results Average S-methadone apparent oral clearance was 35 and 45% lower in CYP2B6*1/*6 and CYP2B6*6/*6 genotypes, respectively, compared with CYP2B6*1/*1, and R-methadone apparent oral clearance was 25 and 30% lower. R- and S-methadone apparent oral clearance was 3- and 4-fold greater in CYP2B6*4 carriers. Intravenous and oral R- and S-methadone metabolism was significantly lower in CYP2B6*6 carriers compared with CYP2B6*1 homozygotes, and greater in CYP2B6*4 carriers. Methadone metabolism and clearance were lower in African-Americans due to the CYP2B6*6 genetic polymorphism. Conclusions CYP2B6 polymorphisms influence methadone plasma concentrations, due to altered methadone metabolism and thus clearance. Genetic influence is greater for oral than intravenous, and S- than R-methadone. CYP2B6 pharmacogenetics explains, in part, interindividual variability in methadone elimination. CYP2B6 genetic effects on methadone metabolism and clearance may identify subjects at risk for methadone toxicity and drug interactions. PMID:26389554

  5. Acute progressive paraplegia in heroin-associated myelopathy.

    PubMed

    Mahoney, Kyle W; Romba, Meghan; Gailloud, Philippe; Izbudak, Izlem; Saylor, Deanna

    2018-05-01

    As the opioid epidemic continues, understanding manifestations of abuse, including heroin-associated myelopathy remains essential. Here we describe a young man with a past medical history significant for polysubstance abuse who developed acute-onset, rapidly progressive myelopathy after resumption of intravenous heroin use. He had significant spinal cord involvement with findings suggestive of heroin-associated myelopathy. The salient features of this case include diffusion imaging of the spine and spinal angiography supporting a possible vasculopathy as the pathophysiologic mechanism underlying heroin-associated myelopathy. Additionally, CSF studies showed the transition from a neutrophilic pleocytosis to a lymphocytic pleocytosis suggesting an inflammatory component. Copyright © 2018 Elsevier Ltd. All rights reserved.

  6. Methadone: A Substrate and Mechanism-Based Inhibitor of CYP19 (Aromatase)

    PubMed Central

    Bies, Robert; Kamden, Landry K.; Desta, Zeruesenay; Flockhart, David A.

    2010-01-01

    The peripheral conversion of testosterone to estradiol by aromatase is the primary source of endogenous estrogen in postmenopausal women. Studies indicating that placental aromatase is able to metabolize methadone to its primary metabolite, 2-ethylidene-1, 5-dimethyl-3, 3-diphenylpyrrolidin (EDDP), led us to test the hypothesis that methadone is able to act as an inhibitor of aromatase. Using recombinant human CYP19, we examined the ability of methadone to bring about either reversible or mechanism-based inhibition of the conversion of testosterone to estradiol. To test for reversible inhibition, racemic methadone or its metabolite EDDP or 2-ethyl-5-methyl-3, 3-diphenylpyrroline (EMDP) was incubated for 30 min with testosterone at the Km (4 μM). To test for mechanism-based inhibition, microsomal preincubations were performed for up to 30 min using racemic methadone (1–1000 μM), R- or S-methadone (0.5–500 μM), or EDDP or EMDP (10 and 100 μM) followed by incubation with testosterone at a Vmax concentration (50 μM). Racemic methadone, EDDP, and EMDP did not act as competitive inhibitors of CYP19. Preincubation of methadone, EDDP, or EMDP with CYP19 resulted in time- and concentration-dependent inhibition, indicating a mechanism-based reaction that destroys CYP19 activity. The KI and kinact values for racemic methadone were calculated to be 40.6 ± 2.8 μM and 0.061 ± 0.001 min−1, respectively. No stereoselectivity was observed. Methadone is metabolized by CYP19 and may act as a potent inhibitor of CYP19 in vivo. These findings may contribute to variability in methadone clearance, to drug-drug interactions, and to side effects observed in individual patients. PMID:20410453

  7. Methadone prolongs cardiac conduction in young patients with cancer-related pain

    PubMed Central

    Anghelescu, Doralina L.; Patel, Rakesh M.; Mahoney, Daniel P.; Trujillo, Luis; Faughnan, Lane G.; Steen, Brenda D.; Baker, Justin N.; Pei, Deqing

    2016-01-01

    Objective Methadone prolongs cardiac conduction, from mild corrected QT (QTc) prolongation to torsades de pointes and ventricular fibrillation, in adults. However, methadone use for pain and its effects on cardiac conduction have not been investigated in pediatric populations. Methods A retrospective review of QTc intervals in patients receiving methadone analgesia was conducted. Medical records from a 4-year period (September 2006 to October 2010) at a pediatric oncology institution were reviewed, and correlations were tested between cardiac conduction and methadone dosage and duration of therapy, electrolyte levels, renal and hepatic dysfunction, and concurrent medications. Results Of the 61 patients who received methadone, 37 met our inclusion criteria and underwent 137 electrocardiograms (ECGs). During methadone treatment, the mean QTc was longer than that at baseline (446.5 vs 437.55 ms). The mean methadone dose was 27.0 ± 24.3 mg/d (range, 5–125 mg/d; median, 20 mg/d) or 0.47 ± 0.45 mg/kg per day (range, 0.05–2.25 mg/kg per day; median, 0.37 mg/kg per day), and the mean duration of therapy was 49 days. The authors identified a correlation between automated and manual ECG readings by two cardiologists (Pearson r = 0.649; p < 0.0001), but the authors found no correlations between methadone dose or duration and concurrent QTc-prolonging medications, sex, age, electrolyte abnormalities, or renal or hepatic dysfunction. Conclusion At a clinically effective analgesic dose, methadone dosage and duration were not correlated with QTc prolongation, even in the presence of other risk factors, suggesting that methadone use may be safe in pediatric populations. The correlation between automated and manual ECG readings suggests that automated ECG readings are reliable for monitoring cardiac conductivity during the reported methadone-dosage regimens. PMID:27194198

  8. Characterization of methadone as a β-arrestin-biased μ-opioid receptor agonist

    PubMed Central

    Doi, Seira; Mori, Tomohisa; Uzawa, Naoki; Arima, Takamichi; Takahashi, Tomoyuki; Uchida, Masashi; Yawata, Ayaka; Narita, Michiko; Uezono, Yasuhito; Suzuki, Tsutomu

    2016-01-01

    Background Methadone is a unique µ-opioid receptor agonist. Although several researchers have insisted that the pharmacological effects of methadone are mediated through the blockade of NMDA receptor, the underlying mechanism by which methadone exerts its distinct pharmacological effects compared to those of other µ-opioid receptor agonists is still controversial. In the present study, we further investigated the pharmacological profile of methadone compared to those of fentanyl and morphine as measured mainly by the discriminative stimulus effect and in vitro assays for NMDA receptor binding, µ-opioid receptor-internalization, and µ-opioid receptor-mediated β-arrestin recruitment. Results We found that fentanyl substituted for the discriminative stimulus effects of methadone, whereas a relatively high dose of morphine was required to substitute for the discriminative stimulus effects of methadone in rats. Under these conditions, the non-competitive NMDA receptor antagonist MK-801 did not substitute for the discriminative stimulus effects of methadone. In association with its discriminative stimulus effect, methadone failed to displace the receptor binding of MK801 using mouse brain membrane. Methadone and fentanyl, but not morphine, induced potent µ-opioid receptor internalization accompanied by the strong recruitment of β-arrestin-2 in µ-opioid receptor-overexpressing cells. Conclusions These results suggest that methadone may, at least partly, produce its pharmacological effect as a β-arrestin-biased µ-opioid receptor agonist, similar to fentanyl, and NMDA receptor blockade is not the main contributor to the pharmacological profile of methadone. PMID:27317580

  9. Differential effect of opioid and cannabinoid receptor blockade on heroin-seeking reinstatement and cannabinoid substitution in heroin-abstinent rats

    PubMed Central

    Fattore, L; Spano, MS; Melis, V; Fadda, P; Fratta, W

    2011-01-01

    BACKGROUND AND PURPOSE Opioids and cannabinoids interact in drug addiction and relapse. We investigated the effect of the opioid receptor antagonist naloxone and/or the cannabinoid CB1 receptor antagonist rimonabant on cannabinoid-induced reinstatement of heroin seeking and on cannabinoid substitution in heroin-abstinent rats. EXPERIMENTAL APPROACH Rats were trained to self-administer heroin (30 µg·kg−1 per infusion) under a fixed-ratio 1 reinforcement schedule. After extinction of self-administration (SA) behaviour, we confirmed the effect of naloxone (0.1–1 mg·kg−1) and rimonabant (0.3–3 mg·kg−1) on the reinstatement of heroin seeking induced by priming with the CB1 receptor agonist WIN55,212-2 (WIN, 0.15–0.3 mg·kg−1). Then, in a parallel set of heroin-trained rats, we evaluated whether WIN (12.5 µg·kg−1 per infusion) SA substituted for heroin SA after different periods of extinction. In groups of rats in which substitution occurred, we studied the effect of both antagonists on cannabinoid intake. KEY RESULTS Cannabinoid-induced reinstatement of heroin seeking was significantly attenuated by naloxone (1 mg·kg−1) and rimonabant (3 mg·kg−1) and fully blocked by co-administration of sub-threshold doses of the two antagonists. Moreover, contrary to immediate (1 day) or delayed (90 days) drug substitution, rats readily self-administered WIN when access was given after 7, 14 or 21 days of extinction from heroin, and showed a response rate that was positively correlated with the extinction period. In these animals, cannabinoid intake was increased by naloxone (1 mg·kg−1) and decreased by rimonabant (3 mg·kg−1). CONCLUSIONS AND IMPLICATIONS Our findings extend previous research on the crosstalk between cannabinoid and opioid receptors in relapse mechanisms, which suggests a differential role in heroin-seeking reinstatement and cannabinoid substitution in heroin-abstinent rats. LINKED ARTICLES This article is part of a themed issue on

  10. Emergence of cocaine and methamphetamine injection among HIV-positive injection drug users in Northern and Western India

    PubMed Central

    Mehta, Shruti H.; Srikrishnan, Aylur K; Noble, Eva; Vasudevan, Canjeevaram K; Solomon, Suniti; Kumar, M Suresh; Solomon, Sunil S

    2014-01-01

    Background Little is known regarding the epidemiology of drug injection and risk behaviors among injection drug users (IDUs) across India. In particular, there is limited data on the prevalence of stimulant injection. Methods We sampled 801 HIV positive IDUs from 14 locations throughout India to represent the geography of India as well as the diversity in IDU epidemic stage (established epidemics, emerging epidemics and large cities). All participants underwent a behavioral survey and blood draw. Given prior associations with stimulant injection and HIV risk, we compared stimulant injectors (cocaine and/or methamphetamine) to those who injected opiates and/or pharmaceuticals only. Results The median age was 33; 86% were male. The primary drugs injected were heroin, buprenorphine and other pharmaceuticals. In all but four sites, >50% of those actively injecting reported needle sharing. Stimulant injection was most common in emerging epidemics. Compared to exclusive opiate injectors, stimulant injectors were significantly younger, more likely to be educated and employed, more likely to report non-injection use of heroin, crack/cocaine and amphetamines, heavy alcohol use, recent needle sharing (71% vs. 57%), sex with a casual partner (57% vs. 31%) and men having sex with other men (33% vs. 9%; p<0.01 for all). Conclusions Emerging IDU epidemics have a drug/sexual risk profile not previously been observed in India. Given the high prevalence of stimulant injection in these populations, HIV prevention/treatment programs may need to be redesigned to maximize effectiveness. The high levels of injection sharing overall reinforce the need to ensure access to harm-reduction services for all. PMID:24382362

  11. Excess mortality among people who report lifetime use of illegal drugs in the United States: A 20-year follow-up of a nationally representative survey.

    PubMed

    Walker, Elizabeth Reisinger; Pratt, Laura A; Schoenborn, Charlotte A; Druss, Benjamin G

    2017-02-01

    The purpose of this study was to determine the mortality risks, over 20 years of follow-up in a nationally representative sample, associated with illegal drug use and to describe risk factors for mortality. We analyzed data from the 1991 National Health Interview Survey, which is a nationally representative household survey in the United States, linked to the National Death Index through 2011. This study included 20,498 adults, aged 18-44 years in 1991, with 1047 subsequent deaths. A composite variable of self-reported lifetime illegal drug use was created (hierarchical categories of heroin, cocaine, hallucinogens/inhalants, and marijuana use). Mortality risk was significantly elevated among individuals who reported lifetime use of heroin (HR=2.40, 95% CI: 1.65-3.48) and cocaine (HR=1.27, 95% CI: 1.04-1.55), but not for those who used hallucinogens/inhalants or marijuana, when adjusting for demographic characteristics. Baseline health risk factors (smoking, alcohol use, physical activity, and BMI) explained the greatest amount of this mortality risk. After adjusting for all baseline covariates, the association between heroin or cocaine use and mortality approached significance. In models adjusted for demographics, people who reported lifetime use of heroin or cocaine had an elevated mortality risk due to external causes (poisoning, suicide, homicide, and unintentional injury). People who had used heroin, cocaine, or hallucinogens/inhalants had an elevated mortality risk due to infectious diseases. Heroin and cocaine are associated with considerable excess mortality, particularly due to external causes and infectious diseases. This association can be explained mainly by health risk behaviors. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. Plasma levels and symptom complaints in patients maintained on daily dosage of methadone hydrochloride.

    PubMed

    Horns, W H; Rado, M; Goldstein, A

    1975-06-01

    Plasma methadone levels, symptom complaints, and urine tests for illicit opiate use were followed weekly in 17 patients on a methadone maintenance program. There were very large differences between patients in the plasma level established at a given dosage, implying large differences in the rate of methadone metabolism. Despite virtually constant daily dosage, the plasma methadone levels fluctuated greatly from week to week and from day to day in individual patients. With rate exceptions there was no relationship between plasma methadone level and symptom complaints or between weekly chamges in plasma methadone level and changes in symptom complaints. Except possible to identify the ocassional patient with unusually low plasam methadone levels, the determination of methadone levels is not likely to be or practical value in methadone programs.

  13. Trends and characteristics of heroin overdoses in Wisconsin, 2003-2012.

    PubMed

    Meiman, Jon; Tomasallo, Carrie; Paulozzi, Leonard

    2015-07-01

    Heroin abuse has increased substantially during the past decade in the United States. This study describes trends and demographic shifts of heroin overdoses and heroin-related fatalities in Wisconsin and contrasts these with prescription opioid overdoses. This study was cross-sectional using databases of emergency department (ED) visits, hospital admissions, and death certificates in Wisconsin, United States, during 2003-2012. Cases were Wisconsin residents treated for heroin or prescription opioid overdose, and residents who died of heroin-related drug poisoning. Primary measurements were rates over time and by geographic region, and rates and rate ratios for selected demographic characteristics. During 2003-2012, age-adjusted rates of heroin overdoses treated in EDs increased from 1.0 to 7.9/100,000 persons; hospitalized heroin overdoses increased from 0.7 to 3.5/100,000. Whites accounted for 68% of hospitalized heroin overdoses during 2003-2007 but 80% during 2008-2012. Heroin-related deaths were predominantly among urban residents; however, rural fatalities accounted for zero deaths in 2003 but 31 (17%) deaths in 2012. Among patients aged 18-34 years, those hospitalized with heroin overdose were more often men (73.0% versus 54.9%), uninsured (44.2% versus 29.9%), and urban (84.3% versus 73.2%) than those with prescription opioid overdose. Rates of ED visits for heroin overdose in this age group exceeded rates for prescription opioid overdose in 2012 (26.1/100,000 versus 12.6/100,000 persons, respectively). An epidemic of heroin abuse is characterized by demographic shifts toward whites and rural residents. Rates of heroin overdose in younger persons now exceed rates of prescription opioid overdose. Published by Elsevier Ireland Ltd.

  14. Pharmacokinetics and pharmacodynamics of the injectable formulation of methadone hydrochloride and methadone in lipid nanocarriers administered orally to horses.

    PubMed

    Crosignani, N; Luna, S P; Dalla Costa, T; Pimenta, E L; Detoni, C B; Guterres, S S; Puoli Filho, J N; Pantoja, J C; Pigatto, M C

    2017-08-01

    We investigated the thermal, electrical and mechanical antinociceptive and physiological effects (heart rate, respiratory rate, arterial blood pressure, head height and abdominal auscultation score), and pharmacokinetics, of 0.5 mg/kg of the injectable formulation (ORAL) or nanoparticulated methadone (NANO) given orally, in six adult mares, using a crossover, blind and prospective design. Repeated-measure models were used to compare parametric data between and within treatments, followed by Tukey's test. Nonparametric data were analysed with Wilcoxon signed-rank, adjusted by Bonferroni tests. Blood samples were also collected up to 6 h after dosing for plasma drug quantification by LC-MS/MS. Methadone pharmacokinetic parameters were determined by noncompartmental and compartmental approaches. There were no differences in pharmacodynamic parameters. No statistical differences were observed in the pharmacokinetic parameters from noncompartmental analysis for both groups, except a significant decrease in peak plasma concentration, increase in apparent volume of distribution per fraction absorbed (Vd ss /F) and increased mean residence time (MRT) for NANO. One-compartment open model with first order elimination best described the pharmacokinetic profiles for both groups. Neither ORAL nor NANO administered orally to horses produced antinociception. The nanoencapsulated formulation of methadone given orally to horses did not improve methadone pharmacokinetic parameters or increased systemic body exposure to methadone. © 2017 John Wiley & Sons Ltd.

  15. Hapten Optimization for Cocaine Vaccine with Improved Cocaine Recognition

    PubMed Central

    Ramakrishnan, Muthu; Kinsey, Berma M.; Singh, Rana A.; Kosten, Thomas R.; Orson, Frank M.

    2014-01-01

    In the absence of any effective pharmacotherapy for cocaine addiction, immunotherapy is being actively pursued as a therapeutic intervention. While several different cocaine haptens have been explored to develop anti-cocaine antibodies, none of the hapten was successfully designed which had a protonated tropane nitrogen as is found in native cocaine under physiological conditions, including the succinyl norcocaine (SNC) hapten that has been tested in phase II clinical trials. Herein, we discuss three different cocaine haptens: hexyl-norcocaine (HNC), bromoacetamido butyl- norcocaine (BNC), and succinyl-butyl- norcocaine (SBNC), each with a tertiary nitrogen structure mimicking that of native cocaine which could optimize the specificity of anti-cocaine antibodies for better cocaine recognition. Mice immunized with these haptens conjugated to immunogenic proteins produced high titer anti-cocaine antibodies. However, during chemical conjugation of HNC and BNC haptens to carrier proteins, the 2β methyl ester group is hydrolyzed and immunizing mice with these conjugate vaccines in mice produced antibodies that bound both cocaine and the inactive benzoylecgonine metabolite. While in the case of the SBNC conjugate vaccine hydrolysis of the methyl ester did not appear to occur, leading to antibodies with high specificity to cocaine over BE. Though we observed similar specificity with a SNC hapten, the striking difference is that SBNC carries a positive charge on the tropane nitrogen atom, and therefore it is expected to have better binding of cocaine. The 50% cocaine inhibitory concentration (IC50) value for SBNC antibodies (2.8 μM) was significantly better than the SNC antibodies (9.4 μM) when respective hapten-BSA was used as a substrate. In addition, antibodies from both sera had no inhibitory effect from BE. In contrast to BNC and HNC, the SBNC conjugate was also found to be highly stable without any noticeable hydrolysis for several months at 4°C and 2-3 days in p

  16. Prenatal and postnatal cocaine exposure predict teen cocaine use

    PubMed Central

    Delaney-Black, Virginia; Chiodo, Lisa M.; Hannigan, John H.; Greenwald, Mark K.; Janisse, James; Patterson, Grace; Huestis, Marilyn A.; Partridge, Robert T.; Ager, Joel; Sokol, Robert J.

    2015-01-01

    Preclinical studies have identified alterations in cocaine and alcohol self-administration and behavioral responses to pharmacological challenges in adolescent offspring following prenatal exposure. To date, no published human studies have evaluated the relation between prenatal cocaine exposure and postnatal adolescent cocaine use. Human studies of prenatal cocaine-exposed children have also noted an increase in behaviors previously associated with substance use/abuse in teens and young adults, specifically childhood and teen externalizing behaviors, impulsivity, and attention problems. Despite these findings, human research has not addressed prior prenatal exposure as a potential predictor of teen drug use behavior. The purpose of this study was to evaluate the relations between prenatal cocaine exposure and teen cocaine use in a prospective longitudinal cohort (n = 316) that permitted extensive control for child, parent and community risk factors. Logistic regression analyses and Structural Equation Modeling revealed that both prenatal exposure and postnatal parent/caregiver cocaine use were uniquely related to teen use of cocaine at age 14 years. Teen cocaine use was also directly predicted by teen community violence exposure and caregiver negativity, and was indirectly related to teen community drug exposure. These data provide further evidence of the importance of prenatal exposure, family and community factors in the intergenerational transmission of teen/young adult substance abuse/use. PMID:20609384

  17. Temporal correlation between opiate seizures in East/Southeast Asia and B.C. heroin deaths: a transoceanic model of heroin death risk.

    PubMed

    McLean, Mark E

    2003-01-01

    Because heroin supply changes cannot be measured directly, their impact on populations is poorly understood. British Columbia has experienced an injection drug use epidemic since the 1980s that resulted in 2,590 illicit drug deaths from 1990-1999. Since previous work indicates heroin seizures can correlate with supply and B.C. receives heroin only from Southeast Asia, this study examined B.C. heroin deaths against opiate seizures in East/Southeast Asia. Opiate seizures in East/Southeast Asia and data from two B.C. mortality datasets containing heroin deaths were examined. The Pearson correlation coefficient for seizures against each mortality dataset was determined. Opiate seizures, all illicit drug deaths and all opiate deaths concurrently increased twice and decreased twice from 1989-1999, and all reached new peak values in 1993. Three B.C. sub-regions exhibited illicit drug deaths rate trends concurrent with the three principal datasets studied. The Pearson correlation coefficient for opiate-induced deaths against opiate seizures from 1980-1999 was R=0.915 (p<0.0001), and for illicit drug deaths against opiate seizures from 1987-1999 was R=0.896 (p<0.0001). From 1980-1999, opiate seizures in East/Southeast Asia were very strongly correlated with B.C. opiate and illicit drug deaths. The number of B.C. heroin-related deaths may be strongly linked to heroin supply. Enforcement services are not effective in preventing harm caused by heroin in B.C.; therefore, Canada should examine other methods to prevent harm. The case for harm reduction is strengthened by the ineffectiveness of enforcement and the unlikelihood of imminent eradication of heroin production in Southeast Asia.

  18. Stereoselective quantification of methadone and a d(6)-labeled isotopomer using high performance liquid chromatography-atmospheric pressure chemical ionization mass-spectrometry: application to a pharmacokinetic study in a methadone maintained subject.

    PubMed

    Foster, David J R; Morton, Erin B; Heinkele, Georg; Mürdter, Thomas E; Somogyi, Andrew A

    2006-08-01

    There is evidence that the apparent oral clearance of rac-methadone is induced during the early phase of methadone maintenance treatment. However, it is not known if this is due to changes in bioavailability or if this phenomenon is stereoselective. This knowledge can be obtained by administering a dose of stable-labeled methadone at selected times during ongoing treatment. Therefore, the authors developed a stereoselective high performance liquid chromatography-atmospheric pressure chemical ionization mass-spectrometry assay for the quantification of the enantiomers of methadone and a d(6)-labeled isotopomer. The compounds were quantified in a single assay after liquid-liquid extraction and stereoselective high performance liquid chromatograph with atmospheric pressure chemical ionization-mass spectrometry detection. The following ions were monitored: m/z 310.15 for unlabeled methadone; m/z 316.15 for methadone-d(6); and m/z 313.15 for the methadone-d(3) (internal standard). Calibration curves ranged from 0.5 to 75 ng/mL for each compound. Extraction recovery was approximately 80% for all analytes, without evidence of differences between the unlabeled and stable-labeled compounds or concentration dependency. Minor ion promotion was observed (<15%) but this was identical for all analytes including the d(3)-labeled internal standard, with peak area ratios in extracted samples identical to control injections. The isotopomers did not alter each others' ionisation, even at 10:1 concentration ratios, and 10-fold diluted samples were within 10% of the nominal concentration. Assay performance was acceptable, with interassay and intra-assay bias and precision <10% for all compounds, including the upper and lower limits of quantitation. In conclusion, the assay was successfully applied to quantify the concentration of the methadone enantiomers of both orally administered unlabeled methadone and an intravenous 5 mg dose of methadone-d(6) in a patient receiving chronic oral

  19. What caused the recent reduction in heroin supply in Australia?

    PubMed

    Wodak, Alex

    2008-08-01

    Heroin availability and purity decreased and prices increased in Australia suddenly in early 2001. The heroin market in Australia has still not returned to the status quo ante after more than six years. Benefits of the heroin shortage, including a substantial reduction in drug overdose deaths and property crime, are generally considered to have outweighed adverse effects which included increased use of other drugs, especially stimulants, with a subsequent increase in aggression, violence and mental illness. Some commentators attributed the heroin shortage to a combination of factors, while an influential study highlighted the importance of supply control asserting that increased funding and improved effectiveness of domestic drug law enforcement produced critical heroin seizures which disrupted major syndicates, thereby producing the heroin shortage. Evidence to support a critical role for drug law enforcement in the heroin shortage is weak with some recent evidence contradicting key assertions used to support the supply control hypothesis. Although the most likely interpretation is still a combination of multiple factors, the most important factors appear to have been a substantial recent reduction in source opium cultivation and heroin production in Burma, but probably also increased heroin consumption en route through China and a switch from heroin to amphetamine production in Burma. This interpretation is consistent with the international experience of several recent decades in numerous countries where national heroin shortages have occurred rarely and generally only briefly, notwithstanding vigorous and very well resourced supply control efforts. The recent reduction in heroin supply in Australia, the most severe, longest lasting and best-documented heroin shortage in the world, cannot be confidently attributed, solely or largely, to improved domestic drug law enforcement. At best, domestic law enforcement may have made a small contribution compared to several

  20. Perinatal methadone exposure affects dopamine, norepinephrine, and serotonin in the weanling rat.

    PubMed

    Robinson, S E; Maher, J R; Wallace, M J; Kunko, P M

    1997-01-01

    On gestational day 7 pregnant rats were implanted with osmotic minipumps containing either methadone hydrochloride (initial dose, 9 mg/kg/day) or sterile water. Their offspring were cross-fostered so that they were exposed to methadone prenatally and/or postnatally. On postnatal day 21, dopamine (DA), norepinephrine (NE), serotonin (5-HT), and their metabolites were analyzed. Perinatal methadone exposure disrupted dopaminergic, noradrenergic, and serotonergic activity in a brain region- and gender-specific fashion. The ratio of the DA metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) to DA was reduced in the frontal cortex of males exposed to methadone postnatally. No effects of perinatal methadone exposure were observed on DA and DOPAC in the striatum. The ratio of 3-methoxy-4-hydroxyphenylglycol (MOPEG) to NE in the hippocampus was increased significantly in males exposed to methadone prenatally. Striatal and parietal cortical 5-hydroxyindoleacetic acid (5-HIAA), but not its ratio to 5-HT, was increased slightly in rats exposed to methadone postnatally. Although parietal cortical 5-HT, 5-HIAA, and 5-hydroxytryptophan were all affected by perinatal methadone exposure, the ratios of metabolite and precursor to 5-HT were not affected. Effects of methadone exposure appeared to depend upon the developmental stage at which exposure occurred and did not appear to result from the phenomenon of neonatal withdrawal. Changes in activity of these three neurotransmitter systems may contribute to the effect of perinatal methadone on the activity of other neurons, such as cholinergic neurons.

  1. Cocaine Self-Administration Produces Long-Lasting Alterations in Dopamine Transporter Responses to Cocaine

    PubMed Central

    Siciliano, Cody A.; Fordahl, Steve C.

    2016-01-01

    Cocaine addiction is a debilitating neuropsychiatric disorder characterized by uncontrolled cocaine intake, which is thought to be driven, at least in part, by cocaine-induced deficits in dopamine system function. A decreased ability of cocaine to elevate dopamine levels has been repeatedly observed as a consequence of cocaine use in humans, and preclinical work has highlighted tolerance to cocaine's effects as a primary determinant in the development of aberrant cocaine taking behaviors. Here we determined that cocaine self-administration in rats produced tolerance to the dopamine transporter-inhibiting effects of cocaine in the nucleus accumbens core, which was normalized following a 14 or 60 d abstinence period; however, although these rats appeared to be similar to controls, a single self-administered infusion of cocaine at the end of abstinence, even after 60 d, fully reinstated tolerance to cocaine's effects. A single cocaine infusion in a naive rat had no effect on cocaine potency, demonstrating that cocaine self-administration leaves the dopamine transporter in a “primed” state, which allows for cocaine-induced plasticity to be reinstated by a subthreshold cocaine exposure. Further, reinstatement of cocaine tolerance was accompanied by decreased cocaine-induced locomotion and escalated cocaine intake despite extended abstinence from cocaine. These data demonstrate that cocaine leaves a long-lasting imprint on the dopamine system that is activated by re-exposure to cocaine. Further, these results provide a potential mechanism for severe cocaine binge episodes, which occur even after sustained abstinence from cocaine, and suggest that treatments aimed at transporter sites may be efficacious in promoting binge termination following relapse. SIGNIFICANCE STATEMENT Tolerance is a DSM-V criterion for substance abuse disorders. Abusers consistently show reduced subjective effects of cocaine concomitant with reduced effects of cocaine at its main site of action

  2. Pharmacokinetics and Analgesic Effects of Methadone in Children and Adults with Sickle Cell Disease

    PubMed Central

    Horst, Jennifer; Frei-Jones, Melissa; Deych, Elena; Shannon, William; Kharasch, Evan D.

    2017-01-01

    Background Vaso-occlusive episodes (VOE) are a significant source of morbidity among children and adults with sickle cell disease (SCD). There is little information on methadone use for SCD pain. This investigation evaluated methadone pharmacokinetics in children and adults with SCD, with a secondary aim to assess pain relief and opioid consumption. Procedure Participants included children (<18 yr) and adults with a VOE requiring hospitalization. Patients were randomly assigned to receive standard care (opioid patient controlled analgesia; control group) or one dose of intravenous methadone (0.1–0.125 mg/kg) in addition to standard care (methadone group). Venous methadone and metabolite concentrations were measured. Pain scores, pain relief scores, and opioid consumption were recorded. Results Twenty-four children (12 methadone, 12 controls) and twenty-three adults (11 methadone, 12 controls) were studied. In children, the half-life of R-and S-methadone enantiomers was 34±16 and 24±9 hr, respectively. In adults, R- and S-methadone half-lives were 52±17 and 38±12 hr. Pain scores were lower (p=0.002) and pain relief scores were higher (p=0.0396) in children receiving methadone vs controls. There was no difference in pain scores and pain relief in adults receiving methadone vs controls. There was no difference in opioid consumption between methadone and control groups, in both adults and children. Conclusions Intravenous methadone disposition in children and adults with SCD was comparable to subjects without SCD from prior studies. Methadone produced more pain relief than standard care in children with SCD. Higher methadone doses may be more effective and should be evaluated in both children and adults with SCD. PMID:27572136

  3. There is no age limit for methadone: a retrospective cohort study

    PubMed Central

    2011-01-01

    Background Data from the US indicates that methadone-maintained populations are aging, with an increase of patients aged 50 or older. Data from European methadone populations is sparse. This retrospective cohort study sought to evaluate the age trends and related developments in the methadone population of Basel-City, Switzerland. Methods The study included methadone patients between April 1, 1995 and March 31, 2003. Anonymized data was taken from the methadone register of Basel-City. For analysis of age distributions, patient samples were split into four age categories from '20-29 years' to '50 years and over'. Cross-sectional comparisons were performed using patient samples of 1996 and 2003. Results Analysis showed a significant increase in older patients between 1996 and 2003 (p < 0.001). During that period, the percentage of patients aged 50 and over rose almost tenfold, while the proportion of patients aged under 30 dropped significantly from 52.8% to 12.3%. The average methadone dose (p < 0.001) and the 1-year retention rate (p < 0.001) also increased significantly. Conclusions Findings point to clear trends in aging of methadone patients in Basel-City which are comparable, although less pronounced, to developments among US methadone populations. Many unanswered questions on medical, psychosocial and health economic consequences remain as the needs of older patients have not yet been evaluated extensively. However, older methadone patients, just as any other patients, should be accorded treatment appropriate to their medical condition and needs. Particular attention should be paid to adequate solutions for persons in need of care. PMID:21592331

  4. Community-based opioid overdose prevention programs providing naloxone - United States, 2010.

    PubMed

    2012-02-17

    Drug overdose death rates have increased steadily in the United States since 1979. In 2008, a total of 36,450 drug overdose deaths (i.e., unintentional, intentional [suicide or homicide], or undetermined intent) were reported, with prescription opioid analgesics (e.g., oxycodone, hydrocodone, and methadone), cocaine, and heroin the drugs most commonly involved . Since the mid-1990s, community-based programs have offered opioid overdose prevention services to persons who use drugs, their families and friends, and service providers. Since 1996, an increasing number of these programs have provided the opioid antagonist naloxone hydrochloride, the treatment of choice to reverse the potentially fatal respiratory depression caused by overdose of heroin and other opioids. Naloxone has no effect on non-opioid overdoses (e.g., cocaine, benzodiazepines, or alcohol) . In October 2010, the Harm Reduction Coalition, a national advocacy and capacity-building organization, surveyed 50 programs known to distribute naloxone in the United States, to collect data on local program locations, naloxone distribution, and overdose reversals. This report summarizes the findings for the 48 programs that completed the survey and the 188 local programs represented by the responses. Since the first opioid overdose prevention program began distributing naloxone in 1996, the respondent programs reported training and distributing naloxone to 53,032 persons and receiving reports of 10,171 overdose reversals. Providing opioid overdose education and naloxone to persons who use drugs and to persons who might be present at an opioid overdose can help reduce opioid overdose mortality, a rapidly growing public health concern.

  5. Leucoencephalopathy following abuse of sniffed heroin.

    PubMed

    Lefaucheur, Romain; Lebas, Axel; Gérardin, Emmanuel; Grangeon, Lou; Ozkul-Wermester, Ozlem; Aubier-Girard, Carole; Martinaud, Olivier; Maltête, David

    2017-01-01

    A 29-year-old man was admitted for acute cognitive impairment. Three weeks earlier, he had been admitted for coma due to sniffed heroin abuse responsive to naloxone infusion. At admission, the patient presented with apraxia, severe memory impairment and anosognosia. Brain MRI revealed symmetric hyperintensities of supratentorial white matter, sparing brainstem and cerebellum, on FLAIR and B1000 sequences. Four months later, repeated neuropsychological assessment revealed dramatic improvement of global cognitive functions. Toxic leucoencephalopathy excluding the cerebellum and brainstem is a rare complication of heroin abuse, and seems to concern especially patients that use heroin by sniff or injection. In these patients, cognitive troubles are predominant, prognosis seems better and infratentorial brain structures can be spared. In conclusion, our observation emphasizes that heroin-induced encephalopathy can have a favourable outcome and that imaging and clinical patterns can indicate the mode of drug administration. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Prenatal and postnatal cocaine exposure predict teen cocaine use.

    PubMed

    Delaney-Black, Virginia; Chiodo, Lisa M; Hannigan, John H; Greenwald, Mark K; Janisse, James; Patterson, Grace; Huestis, Marilyn A; Partridge, Robert T; Ager, Joel; Sokol, Robert J

    2011-01-01

    Preclinical studies have identified alterations in cocaine and alcohol self-administration and behavioral responses to pharmacological challenges in adolescent offspring following prenatal exposure. To date, no published human studies have evaluated the relation between prenatal cocaine exposure and postnatal adolescent cocaine use. Human studies of prenatal cocaine-exposed children have also noted an increase in behaviors previously associated with substance use/abuse in teens and young adults, specifically childhood and teen externalizing behaviors, impulsivity, and attention problems. Despite these findings, human research has not addressed prior prenatal exposure as a potential predictor of teen drug use behavior. The purpose of this study was to evaluate the relations between prenatal cocaine exposure and teen cocaine use in a prospective longitudinal cohort (n=316) that permitted extensive control for child, parent and community risk factors. Logistic regression analyses and Structural Equation Modeling revealed that both prenatal exposure and postnatal parent/caregiver cocaine use were uniquely related to teen use of cocaine at age 14 years. Teen cocaine use was also directly predicted by teen community violence exposure and caregiver negativity, and was indirectly related to teen community drug exposure. These data provide further evidence of the importance of prenatal exposure, family and community factors in the intergenerational transmission of teen/young adult substance abuse/use. Copyright © 2010 Elsevier Inc. All rights reserved.

  7. Dealing with aggressive methadone patients in community pharmacy: a critical incident study.

    PubMed

    Irwin, Amy; Laing, Christianne; Mearns, Kathryn

    2012-01-01

    Community pharmacists are an important link between methadone patients and the health service in the United Kingdom. However, many pharmacists feel ill prepared to deal with methadone patients, with aggressive behavior a particular concern. To assess the perceived impact of methadone patient aggression on pharmacy practice. Sixteen registered pharmacists with a minimum of 3 years' work experience were recruited from within 3 Scottish health boards. Critical incident interviews were conducted to assess pharmacist behavior during an interaction with an aggressive methadone patient. Factors considered by pharmacists to have a negative impact on an interaction with an aggressive methadone patient included intoxication of the patient, the presence of a new or an inexperienced pharmacist, and a restricted time frame for dispensing methadone. Positive factors when dealing with aggressive patients were authoritative behavior by the pharmacist, a separate dispensing area for methadone patients, or a solid counter and a positive relationship between pharmacist and patient. Aggression from methadone patients is a risk when dispensing methadone. However, action can be taken by the pharmacist to minimize the impact of that aggression on pharmacy practice. The provision of further training and support, particularly to inexperienced pharmacists, could further reduce the negative impact of patient aggression. The present study indicates that such training could be based on nontechnical skills to strengthen current leadership and teamwork behaviors. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. Attitudes and beliefs towards methadone maintenance treatment among Australian prison health staff.

    PubMed

    Gjersing, Linn R; Butler, Tony; Caplehorn, John R M; Belcher, Josephine M; Matthews, Richard

    2007-09-01

    Justice Health NSW has one of the most extensive prison-based methadone programmes in the world. We examine prison health staff attitudes towards methadone treatment and compare these with community methadone staff. A cross-sectional survey of 202 staff employed by Justice Health New South Wales was undertaken in 2003. Results. The mean scores on the various sub-scales were: abstinence-orientation (AO) 2.9 (95% CI 2.8 - 3.0); disapproval of drug use (DDU) 3.3 (95% CI 3.2 - 3.4); knowledge (Know) 2.7 (95% CI 2.4 - 2.9); and toxicity 4.6 (95% CI 4.2 - 5.0). Both the AO and DDU score were correlated negatively with the Know score (r = -0.37 and r = -0.13, respectively). Prison health staff had higher AO (2.9 vs. 2.6, p < 0.001) and DDU (3.3 vs. 2.6, p < 0.001) scores, and lower Know (2.7 vs. 7.0, p < 0.001) scores than methadone staff working in the Australian community. They were more knowledgeable than US community methadone staff about the toxicity of methadone (4.6 vs. 0.0, p < 0.001). This is the first survey to examine prison health staff attitudes to methadone treatment. Correctional health staff tend to be more abstinence-orientated, more likely to disapprove of drug use, and less knowledgeable about the risks and benefits of methadone than Australian community methadone staff. The findings have important implications for training health staff working in the prison environment with regard to client retention on methadone treatment.

  9. Substance use -- cocaine

    MedlinePlus

    ... Charlie, coca, coke, flake, rock, snow, speedball, toot. Cocaine's Effects on Your Brain Cocaine is a strong stimulant. ... injecting, and last 15 to 30 minutes. Harmful Effects of Cocaine Cocaine can harm the body in many ways ...

  10. Factors associated with HCV risk practices in methadone-maintained patients: the importance of considering the couple in prevention interventions.

    PubMed

    Roux, Perrine; Lions, Caroline; Michel, Laurent; Mora, Marion; Daulouède, Jean-Pierre; Marcellin, Fabienne; Spire, Bruno; Morel, Alain; Carrieri, Patrizia M

    2014-09-10

    One important public health issue associated with opioid use today is the risk of hepatitis C (HCV) infection. Although methadone maintenance may help to decrease HCV-related risk practices, HCV risk behaviors persist and are strongly associated with specific substance use patterns, mental status and social context. The ANRS-Methaville study gave us the opportunity to better disentangle the different relationships between these various factors and HCV risk practices. The ANRS-Methaville multisite randomized trial was designed to assess the feasibility of initiating methadone in primary care by comparing it with methadone initiation in specialized centers. This study recruited 195 participants initiating methadone maintenance and followed up for 12 months. Longitudinal data from this trial was used to acquire a greater understanding of HCV risk practices and their pattern of correlates in this population. We selected 176 patients who had data on HCV risk practices at M0 and M12, accounting for 312 visits. HCV risk practices were defined as follows: sharing needles or syringes, sharing drug paraphernalia, getting a tattoo or having a piercing in a non-professional context, sharing toiletry items. To identify factors associated with HCV risk practices, we performed a mixed logistic regression analysis. HCV risk practices were reported by 19% and 15% of participants at baseline and M12, respectively. After adjustment for age, cocaine use and alcohol dependence as well as suicidal risk, living in a couple with a non-drug user and in a couple with a drug user were both independent predictors of HCV risk practices (OR[CI95%] = 4.16 [1.42-12.12]; OR[CI95%] = 9.85 [3.13-31.06], respectively). Identifying individuals at risk of HCV transmission during methadone treatment such as stimulant users, alcohol dependent individuals, and those at suicidal risk is necessary to optimize response to treatment. Innovative prevention approaches tailored to couples are also

  11. Factors associated with HCV risk practices in methadone-maintained patients: the importance of considering the couple in prevention interventions

    PubMed Central

    2014-01-01

    Background One important public health issue associated with opioid use today is the risk of hepatitis C (HCV) infection. Although methadone maintenance may help to decrease HCV-related risk practices, HCV risk behaviors persist and are strongly associated with specific substance use patterns, mental status and social context. The ANRS-Methaville study gave us the opportunity to better disentangle the different relationships between these various factors and HCV risk practices. Methods The ANRS-Methaville multisite randomized trial was designed to assess the feasibility of initiating methadone in primary care by comparing it with methadone initiation in specialized centers. This study recruited 195 participants initiating methadone maintenance and followed up for 12 months. Longitudinal data from this trial was used to acquire a greater understanding of HCV risk practices and their pattern of correlates in this population. We selected 176 patients who had data on HCV risk practices at M0 and M12, accounting for 312 visits. HCV risk practices were defined as follows: sharing needles or syringes, sharing drug paraphernalia, getting a tattoo or having a piercing in a non-professional context, sharing toiletry items. To identify factors associated with HCV risk practices, we performed a mixed logistic regression analysis. Results HCV risk practices were reported by 19% and 15% of participants at baseline and M12, respectively. After adjustment for age, cocaine use and alcohol dependence as well as suicidal risk, living in a couple with a non-drug user and in a couple with a drug user were both independent predictors of HCV risk practices (OR[CI95%] = 4.16 [1.42-12.12]; OR[CI95%] = 9.85 [3.13-31.06], respectively). Conclusions Identifying individuals at risk of HCV transmission during methadone treatment such as stimulant users, alcohol dependent individuals, and those at suicidal risk is necessary to optimize response to treatment. Innovative prevention

  12. Methadone, monoamine oxidase, and depression: opioid distribution and acute effects on enzyme activity

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kaufmann, C.A.; Kreek, M.J.; Raghunath, J.

    1983-09-01

    Narcotic withdrawal is often accompanied by an atypical depression which responds to resumption of narcotics. It was hypothesized that methadone might exert its antidepressant effects through monoamine oxidase (MAO) inhibition. The current study examined /sub 3/H-methadone distribution in rat brain and effects on regional MAO activity with acute doses (2.5 mg/kg) which approximate those found during chronic methadone maintenance in man. Limbic areas (amygdala, basomedial hypothalamus, caudate-putamen, hippocampus, preoptic nucleus), as well as pituitary and liver were assayed for MAO activity and methadone concentration. MAO activities did not differ significantly in acute methadone or saline-treated cage-mates at 1 or 24more » hr. The concentrations of methadone at 1 hr ranged between 17 and 223 ng/100 mg wet wt tissue in the preoptic nucleus and pituitary, respectively. No significant correlation was found between change in MAO activity (MAO methadone/MAO saline) and methadone concentration in any region at 1 or 24 hr. This study does not support the hypothesis that methadone acts as an antidepressant through MAO inhibition, at least not following acute administration of this exogenous opioid.« less

  13. Polysubstance Use and Heroin Relapse among Adolescents following Residential Treatment

    ERIC Educational Resources Information Center

    Branson, Christopher E.; Clemmey, Philip; Harrell, Paul; Subramaniam, Geetha; Fishman, Marc

    2012-01-01

    This study examined posttreatment patterns of polysubstance use and heroin relapse in a sample of 43 adolescents (ages 14-20) entering short-term residential treatment for primary heroin use. At 12-month follow-up, youths that achieved heroin abstinence (N = 19) were significantly less likely than youths that relapsed to heroin (N = 24) to endorse…

  14. [Forensic Analysis of 20 Dead Cases Related to Heroin Abuse].

    PubMed

    Huang, W Q; Li, L H; Li, Z; Hong, S J

    2016-08-01

    To perform retrospective analysis on 20 dead cases related to heroin abuse, and to provide references for the forensic assessment of correlative cases. Among 20 dead cases related to heroin abuse, general situation, using method of drug, cause of death and result of forensic examination were analyzed by statistical analysis for summarizing the cause of death and pathologic changes. The dead were mostly young adults, with more male than female. The results of histopathological examinations showed non-specific pathological changes. There were four leading causes of death, including acute poisoning of heroin abuse or leakage (13 cases, 65%), concurrent diseases caused by heroin abuse (3 cases, 15%), inspiratory asphyxia caused by taking heroin (2 cases, 10%), and heroin withdrawal syndrome (2 cases, 10%). The forensic identification on dead related to heroin abuse must base on the comprehensive autopsy, and combine with the qualitative and quantitative analysis of heroin and its metabolites in death and the case information, as well as the scene investigation. Copyright© by the Editorial Department of Journal of Forensic Medicine

  15. ZNF804A variants confer risk for heroin addiction and affect decision making and gray matter volume in heroin abusers.

    PubMed

    Sun, Yan; Zhao, Li-Yan; Wang, Gui-Bin; Yue, Wei-Hua; He, Yong; Shu, Ni; Lin, Qi-Xiang; Wang, Fan; Li, Jia-Li; Chen, Na; Wang, Hui-Min; Kosten, Thomas R; Feng, Jia-Jia; Wang, Jun; Tang, Yu-De; Liu, Shu-Xue; Deng, Gui-Fa; Diao, Gan-Huan; Tan, Yun-Long; Han, Hong-Bin; Lin, Lu; Shi, Jie

    2016-05-01

    Drug addiction shares common neurobiological pathways and risk genes with other psychiatric diseases, including psychosis. One of the commonly identified risk genes associated with broad psychosis has been ZNF804A. We sought to test whether psychosis risk variants in ZNF804A increase the risk of heroin addiction by modulating neurocognitive performance and gray matter volume (GMV) in heroin addiction. Using case-control genetic analysis, we compared the distribution of ZNF804A variants (genotype and haplotype) in 1035 heroin abusers and 2887 healthy subjects. We also compared neurocognitive performance (impulsivity, global cognitive ability and decision-making ability) in 224 subjects and GMV in 154 subjects based on the ZNF804A variants. We found significant differences in the distribution of ZNF804A intronic variants (rs1344706 and rs7597593) allele and haplotype frequencies between the heroin and control groups. Decision-making impairment was worse in heroin abusers who carried the ZNF804A risk allele and haplotype. Subjects who carried more risk alleles and haplotypes of ZNF804A had greater GMV in the bilateral insular cortex, right temporal cortex and superior parietal cortex. The interaction between heroin addiction and ZNF804A variants affected GMV in the left sensorimotor cortex. Our findings revealed several ZNF804A variants that were significantly associated with the risk of heroin addiction, and these variants affected decision making and GMV in heroin abusers compared with controls. The precise neural mechanisms that underlie these associations are unknown, which requires future investigations of the effects of ZNF804A on both dopamine neurotransmission and the relative increases in the volume of various brain areas. © 2015 Society for the Study of Addiction.

  16. [CNS metabolism in high-risk drug abuse, German version : Insights gained from 1H- and 31P MRS and PET].

    PubMed

    Bodea, S V

    2017-06-01

    High-risk drug consumption is a considerable problem for public health actors in industrialised countries. The latest trends show a market tendency towards diversification and increasing demand for high-purity synthetic drugs. Whilst most consumers seek medical help after cannabis use, it is high-risk drugs like cocaine, heroin and amphetamines that account for most of the 1000 drug-related deaths that occur in Germany every year. This article presents the most prominent in vivo cerebral metabolic information in cocaine, heroin and methamphetamine users provided by MRI spectroscopy and PET imaging. We reviewed the literature reporting neuroimaging studies of in vivo metabolic data for methamphetamine, cocaine and heroin consumption published up to March 2017. The search was conducted using PubMed with the following key words: methamphetamine, cocaine, heroin, MR spectroscopy, PET. MRI and PET are indispensable tools in gauging brain metabolic response to illegal drug abuse. Future breakthroughs in this field will most likely come from the investigation of novel neurotransmitter systems in PET and imaging phosphorus and carbon metabolites in MRI.

  17. Intermittent subcutaneous methadone administration in the management of cancer pain.

    PubMed

    Centeno, Carlos; Vara, Francisco

    2005-01-01

    Methadone is a strong opioid analgesic that has been used successfully in cancer pain management. The oral route of administration is generally preferred for opioid analgesics. However that route sometimes cannot be used. Experience with continuous subcutaneous methadone infusions has produced local intolerance. The aim of this study was to analyze the use of intermittent subcutaneous methadone injections. Ten patients whose pain was well-controlled with oral methadone (average dose 30 mg, range 10 to 120 mg) participated in the study. A subcutaneous small vein needle (butterfly) was used exclusively for administration of methadone. Over a period of seven days the local discomfort of each injection was evaluated by means of a Verbal Numerical Rating Scale (NRS) and the site of infusion was observed. When any degree of erythema or inflammation was seen, the infusion site was changed. The initial subcutaneous dose was the same as the previously administered oral dose. A daily record was kept of the dose used, level of pain, and toxicity symptoms. This close vigilance was aimed at avoiding dosage errors due to variations among individuals in acceptance to previous oral medication. Changes in dosage were allowed according to standard medical criteria. Two patients were withdrawn from the study due to non-painful irritation at the infusion point. Another eight patients tolerated repeated administration of subcutaneous methadone over seven days. Any local irritation from subcutaneous methadone that occurred was managed satisfactorily by changing the infusion site and limiting doses to 30 mg. In seven of 182 repeat administration, injection site changes were necessitated by local irritation. The NRS for local discomfort was 2/10. The two patients who were intolerant of the subcutaneous injections were receiving injected doses which were significantly higher than the others (42 mg as compared to 25 mg). Dose adjustments needed when changing from the oral to the

  18. Differential effects of the metabotropic glutamate 2/3 receptor agonist LY379268 on nicotine versus cocaine self-administration and relapse in squirrel monkeys.

    PubMed

    Justinova, Zuzana; Le Foll, Bernard; Redhi, Godfrey H; Markou, Athina; Goldberg, Steven R

    2016-05-01

    Group II metabotropic glutamate receptors (mGluR2 and mGluR3) have been suggested to play an important role in mediation of drug-reinforced behaviors, as well as in the mechanisms underlying relapse in abstinent subjects. The prototypical mGluR2/3 agonist, LY379268, has been shown to attenuate nicotine reinforcement and cue-induced reinstatement of drug seeking in rats, as well as reinstatement induced by drug-associated stimuli and contexts across different drugs of abuse (i.e., cocaine, heroin, and methamphetamine). However, in primates, LY379268 has been shown to produce conflicting results on abuse-related effects of cocaine, and there are no data available for nicotine. To explore the therapeutic potential of mGluR2/3 agonists, we compared the effects of LY379268 (0.03-1.0 mg/kg) on nicotine, cocaine, and food self-administration under a fixed-ratio (FR10) schedule in three separate groups of squirrel monkeys. Moreover, we studied the effects of LY379268 on nicotine/cocaine priming-induced and cue-induced reinstatement of drug-seeking behavior in nicotine- and cocaine-experienced groups of animals. LY379268 blocked nicotine, but not cocaine, self-administration in monkeys. There was a partial overlap between doses that affected nicotine and food self-administration. In abstinent monkeys, LY379268 dose-dependently blocked nicotine, but not cocaine, priming-induced reinstatement of drug seeking. In both cocaine-experienced and nicotine-experienced groups of animals, LY379268 potently reduced cue-induced reinstatement of drug-seeking behavior. The present findings provide strong support for the potential utility of mGlu2/3 receptor agonists for the treatment of nicotine dependence and suggest their utility for prevention of relapse induced by environmental cues associated with drug taking.

  19. Diversion of methadone and buprenorphine by patients in opioid substitution treatment in Sweden: prevalence estimates and risk factors.

    PubMed

    Johnson, Björn; Richert, Torkel

    2015-02-01

    Diversion--patients who sell or share their medication--is a hotly debated but relatively unresearched phenomenon. We have investigated the prevalence of self-reported diversion of methadone and buprenorphine at OST programs in Sweden. We have also examined if demographic, treatment, and social factors can be associated with an increased risk of diversion. Structured interviews were conducted with 411 patients from eleven OST programs. A standardized questionnaire with 106 close- and five open-ended questions were used. 280 interviews were done on site, by the researchers, while 131 interviews were conducted by specially trained patients through privileged access interviewing. The data were analyzed through frequency- and averages-calculations, cross-tabulations, and logistic regression analysis. In total, 24.1% (n=99) of the patients reported diversion in the past month. 67.6% (n=277) stated that they had diverted at some point. The peer interviews showed significantly higher levels of diversion (37.4% past month) compared with the researcher interviews (17.2%). Neither demographic factors, dosages, nor collection routines were associated with diversion. The likelihood of diversion was higher for patients on mono-buprenorphine (OR=5.64) and buprenorphine-naloxone (OR=2.10), than among methadone patients. Other factors which increased the likelihood of diversion were current illicit drug use (OR=5.60), having had patients as a primary source of illicit methadone or buprenorphine prior to treatment (OR=3.39), and mainly socializing with active drug users (OR=2.12). Self-reported diversion was considerably higher than in previous studies. This is most likely due to the new methodological strategy we used, but may also partly be explained by low availability of OST in Sweden, leading to a high demand for the substances by heroin users outside treatment. Efforts to decrease diversion should primarily focus on psychosocial and lifestyle-changing interventions, and

  20. Cigarette Cue Attentional Bias in Cocaine-Smoking and Non-Cocaine-Using Cigarette Smokers.

    PubMed

    Marks, Katherine R; Alcorn, Joseph L; Stoops, William W; Rush, Craig R

    2016-09-01

    Cigarette smoking in cocaine users is nearly four times higher than the national prevalence and cocaine use increases cigarette smoking. The mechanisms underlying cigarette smoking in cocaine-using individuals need to be identified to promote cigarette and cocaine abstinence. Previous studies have examined the salience of cigarette and cocaine cues separately. The present aim was to determine whether cigarette attentional bias (AB) is higher in cigarettes smokers who smoke cocaine relative to individuals who only smoke cigarettes. Twenty cigarette smokers who smoke cocaine and 20 non-cocaine-using cigarette smokers completed a visual probe task with eye-tracking technology. During this task, the magnitude of cigarette and cocaine AB was assessed through orienting bias, fixation time, and response time. Cocaine users displayed an orienting bias towards cigarette cues. Cocaine users also endorsed a more urgent desire to smoke to relieve negative affect associated with cigarette craving than non-cocaine users (g = 0.6). Neither group displayed a cigarette AB, as measured by fixation time. Cocaine users, but not non-cocaine users, displayed a cocaine AB as measured by orienting bias (g = 2.0) and fixation time (g = 1.2). There were no significant effects for response time data. Cocaine-smoking cigarettes smokers display an initial orienting bias toward cigarette cues, but not sustained cigarette AB. The incentive motivation underlying cigarette smoking also differs. Cocaine smokers report more urgent desire to smoke to relieve negative affect. Identifying differences in motivation to smoke cigarettes may provide new treatment targets for cigarette and cocaine use disorders. These results suggest that cocaine-smoking cigarette smokers display an initial orienting bias towards cigarette cues, but not sustained attention towards cigarette cues, relative to non-cocaine-using smokers. Smoked cocaine users also report a more urgent desire to smoke to relieve negative affect

  1. Trends in Reporting Methadone-Associated Cardiac Arrhythmia, 1997–2011

    PubMed Central

    Kao, David; Bartelson, Becki Bucher; Khatri, Vaishali; Dart, Richard; Mehler, Philip S.; Katz, David; Krantz, Mori J.

    2013-01-01

    Background: Long-acting opioids are a leading cause of accidental death in the United States, and methadone is associated with greater mortality rates. Whether this increase is related to the proarrhythmic properties of methadone is unclear. Objective: To describe methadone-associated arrhythmia events reported in the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS). Design: Description of national adverse event registry data before and after publication of a 2002 report describing an association between methadone and arrhythmia. Setting: FAERS, November 1997 and June 2011. Patients: Adults with QTc prolongation or torsade de pointes and ventricular arrhythmia or cardiac arrest. Measurements: FAERS reports before and after the 2002 report. Results: 1646 cases of ventricular arrhythmia or cardiac arrest and 379 cases of QTc prolongation or torsade de pointes were associated with methadone. Monthly reports of QTc prolongation or torsade de pointes increased from a mean of 0.3 (95% CI, 0.1 to 0.5) before the 2002 publication to a mean of 3.5 (CI, 2.5 to 4.8) after it. After 2000, methadone was the second-most common primary suspect in cases of QTc prolongation or torsade de pointes after dofetilide (a known proarrhythmic drug) and was associated with disproportionate reporting similar to that of antiarrhythmic agents known to promote torsade de pointes. Antiretroviral drugs for HIV were the most common coadministered drugs. Limitation: Reports to FAERs are voluntary and selective, and incidence rates cannot be determined from spontaneously reported data. Conclusion: Since 2002, reports to FAERS of methadone-associated arrhythmia have increased substantially and are disproportionately represented relative to other events with the drug. Coadministration of methadone with antiretrovirals in patients with HIV may pose particular risk. Primary Funding Source: Colorado Clinical and Translational Sciences Institute, National Institutes of Health, and

  2. Resistance exercise decreases heroin self-administration and alters gene expression in the nucleus accumbens of heroin-exposed rats.

    PubMed

    Smith, Mark A; Fronk, Gaylen E; Abel, Jean M; Lacy, Ryan T; Bills, Sarah E; Lynch, Wendy J

    2018-04-01

    Preclinical studies consistently report that aerobic exercise decreases drug self-administration and other forms of drug-seeking behavior; however, relatively few studies have examined other types of physical activity. The purpose of the present study was to examine the effects of resistance exercise (i.e., strength training) on heroin self-administration and mRNA expression of genes known to mediate opioid reinforcement and addictive behavior in the nucleus accumbens (NAc) of heroin-exposed rats. Female rats were obtained during late adolescence and divided into two groups. Resistance exercise rats were trained to climb a vertical ladder wearing a weighted vest; sedentary control rats were placed repeatedly on the ladder oriented horizontally on its side. All rats were implanted with intravenous catheters and trained to self-administer heroin on a fixed ratio (FR1) schedule of reinforcement. mRNA expression in the NAc core and shell was examined following behavioral testing. Resistance exercise significantly decreased heroin self-administration, resulting in a downward shift in the dose-effect curve. Resistance exercise also reduced mRNA expression for mu opioid receptors and dopamine D1, D2, and D3 receptors in the NAc core. Resistance exercise increased mRNA expression of dopamine D5 receptors in the NAc shell and increased mRNA expression of brain-derived neurotrophic factor (exons I, IIB, IIC, IV, VI, IX) in the NAc core. These data indicate that resistance exercise decreases the positive reinforcing effects of heroin and produces changes in opioid and dopamine systems in the NAc of heroin-exposed rats.

  3. Oxytocin decreases cocaine taking, cocaine seeking, and locomotor activity in female rats

    PubMed Central

    Leong, Kah-Chung; Zhou, Luyi; Ghee, Shannon M.; See, Ronald E.; Reichel, Carmela M.

    2015-01-01

    Oxytocin has been shown to decrease cocaine taking and seeking in male rats, suggesting potential treatment efficacy for drug addiction. In the present study, we extended these findings to the assessment of cocaine seeking and taking in female rats. Further, we made direct comparisons of oxytocin’s impact on cocaine induced locomotor activity in both males and females. In females, systemic oxytocin (0.3, 1.0, 3.0 mg/kg) attenuated lever pressing for cocaine during self-administration and oxytocin (1.0 mg/kg) attenuated cue-induced cocaine seeking following extinction. Cocaine increased baseline locomotor activity to a greater degree in females relative to males. Oxytocin (0.1, 0.3, 1.0, and 3.0 mg/kg) reduced cocaine-induced locomotor activity in females, but not significantly in males. These data illustrate sex similarities in oxytocin’s attenuation of cocaine seeking, but sex differences in cocaine-induced locomotor effects. While reductions in cocaine seeking cannot be attributed to a reduction in locomotor activity in males, attenuation of locomotor function cannot be entirely ruled out as an explanation for a decrease in cocaine seeking in females suggesting that oxytocin’s effect on cocaine seeking may be mediated by different mechanisms in male and females. PMID:26523890

  4. Post-marketing surveillance of methadone and buprenorphine in the United States.

    PubMed

    Dasgupta, Nabarun; Bailey, Elise J; Cicero, Theodore; Inciardi, James; Parrino, Mark; Rosenblum, Andrew; Dart, Richard C

    2010-07-01

    There have been recent increases in the use of methadone and buprenorphine in the United States. Methadone is increasingly being used for pain management, and buprenorphine use has expanded to include treatment for opioid addiction, leading to exposures of these drugs in new populations. There is a debate about the relative safety of these two drugs in routine outpatient medical use. Data from the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS) System Programs were used to analyze rates of abuse, misuse, and diversion using the Drug Diversion, Key Informant, Poison Center and Opioid Treatment Programs, 2003-2007. National rate and rate ratios were calculated using population and person-time exposed denominators. Detailed data are presented on severity of medical outcome and drug formulations. Between 2003 and 2007, there were steady increases in the rates of abuse, misuse, and diversion of both methadone and buprenorphine. Rate ratios (per 100,000 population per quarter) of abuse, misuse, and diversion were consistently higher for methadone than buprenorphine. RADARS System poison centers received 7,476 calls for methadone and 1,117 calls for buprenorphine. After accounting for availability, there were higher rates of calls for methadone misuse, abuse, and diversion than buprenorphine in three of the four programs. The numbers of exposures requiring medical attention correspond to 46.8% and 25.8% of all calls, for methadone and buprenorphine, respectively. The most commonly diverted form of methadone was solid oral tablets (which are typically dispensed at pharmacies, not at opioid treatment programs), comprising 73% of cases. Buprenorphine appears to have a better safety profile than methadone during routine outpatient medical use. However, both medications have roles in the treatment of pain and opioid addiction, and further research into their respective benefits and risks should be conducted.

  5. A Primer on Heroin and Fentanyl.

    PubMed

    Worley, Julie

    2017-06-01

    Heroin and fentanyl use have reached epidemic proportions in the United States and are now blamed for the majority of drug-related overdose deaths. Both drugs are produced primarily in South America and Asia and enter the United States illegally. One result of smoking or injecting heroin or fentanyl is the development of a substance use disorder (SUD), which causes changes in brain chemistry and function. These changes result in negative behaviors and an inability to stop use. Yet, treatments are available and recovery is possible. Nurses have the potential to impact the heroin and fentanyl epidemic through developing therapeutic relationships with patients who are at risk or already have a SUD. Strategies for effective communication include maintaining a supportive, nonjudgmental attitude and incorporating motivational interviewing. All patients should be screened for opioid use and referred for treatment if indicated. It is important for nurses to be knowledgeable about heroin and fentanyl and available treatments. [Journal of Psychosocial Nursing and Mental Health Services, 55(6), 16-20.]. Copyright 2017, SLACK Incorporated.

  6. The price elasticity of demand for heroin: Matched longitudinal and experimental evidence.

    PubMed

    Olmstead, Todd A; Alessi, Sheila M; Kline, Brendan; Pacula, Rosalie Liccardo; Petry, Nancy M

    2015-05-01

    This paper reports estimates of the price elasticity of demand for heroin based on a newly constructed dataset. The dataset has two matched components concerning the same sample of regular heroin users: longitudinal information about real-world heroin demand (actual price and actual quantity at daily intervals for each heroin user in the sample) and experimental information about laboratory heroin demand (elicited by presenting the same heroin users with scenarios in a laboratory setting). Two empirical strategies are used to estimate the price elasticity of demand for heroin. The first strategy exploits the idiosyncratic variation in the price experienced by a heroin user over time that occurs in markets for illegal drugs. The second strategy exploits the experimentally induced variation in price experienced by a heroin user across experimental scenarios. Both empirical strategies result in the estimate that the conditional price elasticity of demand for heroin is approximately -0.80. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. The price elasticity of demand for heroin: matched longitudinal and experimental evidence#

    PubMed Central

    Olmstead, Todd A.; Alessi, Sheila M.; Kline, Brendan; Pacula, Rosalie Liccardo; Petry, Nancy M.

    2015-01-01

    This paper reports estimates of the price elasticity of demand for heroin based on a newly constructed dataset. The dataset has two matched components concerning the same sample of regular heroin users: longitudinal information about real-world heroin demand (actual price and actual quantity at daily intervals for each heroin user in the sample) and experimental information about laboratory heroin demand (elicited by presenting the same heroin users with scenarios in a laboratory setting). Two empirical strategies are used to estimate the price elasticity of demand for heroin. The first strategy exploits the idiosyncratic variation in the price experienced by a heroin user over time that occurs in markets for illegal drugs. The second strategy exploits the experimentally-induced variation in price experienced by a heroin user across experimental scenarios. Both empirical strategies result in the estimate that the conditional price elasticity of demand for heroin is approximately −0.80. PMID:25702687

  8. Criminal outcomes and costs of treatment services for injecting and non-injecting heroin users: evidence from a national prospective cohort survey.

    PubMed

    Healey, Andrew; Knapp, Martin; Marsden, John; Gossop, Michael; Stewart, Duncan

    2003-07-01

    To assess the incremental cost-effectiveness of drug addiction treatment programmes provided in the UK by the National Health Service and not-for-profit agencies in terms of crime-related outcomes. All costs and crime-related outcomes were implicitly evaluated relative to a 'no treatment' alternative. Longitudinal observational data on a national sample of heroin addicts referred to addiction treatment services throughout England were re-analysed. Predictions from a Poisson random-effects model were used to estimate the incremental effectiveness and cost-effectiveness of treatment programmes. Interaction variables were used to assess whether the injecting of heroin on entry to treatment had an impact on cost-effectiveness. The findings rejected the null hypothesis that increasing time in treatment (and therefore treatment cost) has no mean crime prevention effect on clients referred for community-based methadone treatment, treatment delivered within specialist drug dependency units and residential rehabilitation programmes (P < 0.05). However, the size of the cost per unit of effect based on model predictions was sensitive to the exclusion of a small group of outlying observations. The interaction between client injecting status and time in treatment was found to be statistically significant (P < 0.05), with an estimated reduction in treatment cost-effectiveness across all treatment programmes for clients who reported injecting drugs at treatment intake. Whilst the analyses did not include an evaluation of the effect of treatment programmes on client health and quality of life and stopped short of providing a social weighting for the predicted reduction in crimes, they do offer a useful starting point for establishing the cost-effectiveness of treating heroin addiction. The onus is on public decision-makers to decide whether the predicted reductions in crime are worth the opportunity costs of investing extra resources in a major expansion of treatment services.

  9. The cocaine cutting agent levamisole is frequently detected in cocaine users.

    PubMed

    Pope, Jeffrey D; Drummer, Olaf H; Schneider, Hans G

    2018-06-21

    Cocaine use in Australia is increasing, with approximately 2.5% of the surveyed population having used cocaine. In the USA, levamisole, a widely used anti-helminthic veterinary drug has been increasingly detected as a cutting agent in cocaine seizures. Levamisole is known to cause agranulocytosis in humans. We ascertained the prevalence of levamisole-adulterated cocaine, detectable in the urine from patients that had undergone a pathology request for a urine drug screen. We assayed routinely requested urines that were positive for cocaine on immunoassay with liquid chromatography high resolution quadrupole time of flight mass spectrometry (LC-QToF). We investigated available urine samples from a period of 2 years that had a positive result for cocaine. In addition, we examined samples that were below the cut-off for cocaine on immunoassay. Specimens were analysed for the presence of levamisole and other 'unknown' drugs. In the period under investigation the laboratory examined 3665 urine samples for cocaine: 1.4% (n = 51) of the samples were positive for cocaine by immunoassay and half of these (n = 26, 51%) were further examined by LC-QToF. In addition, we examined 10 samples that were negative by immunoassay (as defined by AS/NZS 4308:2008). Levamisole was detected in the urine of cocaine users in approximately 75% of cases. Other illicit drugs were also frequently found in this cohort. The most common illicit drugs detected were methamphetamine, ecstasy and cannabis. Australian cocaine is widely adulterated with levamisole. Cocaine users are at risk of levamisole related health problems in addition to the problems related to cocaine. Copyright © 2018 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.

  10. The NK1 Receptor Antagonist L822429 Reduces Heroin Reinforcement

    PubMed Central

    Barbier, Estelle; Vendruscolo, Leandro F; Schlosburg, Joel E; Edwards, Scott; Juergens, Nathan; Park, Paula E; Misra, Kaushik K; Cheng, Kejun; Rice, Kenner C; Schank, Jesse; Schulteis, Gery; Koob, George F; Heilig, Markus

    2013-01-01

    Genetic deletion of the neurokinin 1 receptor (NK1R) has been shown to decrease the reinforcing properties of opioids, but it is unknown whether pharmacological NK1R blockade has the same effect. Here, we examined the effect of L822429, a rat-specific NK1R antagonist, on the reinforcing properties of heroin in rats on short (1 h: ShA) or long (12 h: LgA) access to intravenous heroin self-administration. ShA produces heroin self-administration rates that are stable over time, whereas LgA leads to an escalation of heroin intake thought to model important dependence-related aspects of addiction. L822429 reduced heroin self-administration and the motivation to consume heroin, measured using a progressive-ratio schedule, in both ShA and LgA rats. L822429 also decreased anxiety-like behavior in both groups, measured on the elevated plus maze, but did not affect mechanical hypersensitivity observed in LgA rats. Expression of TacR1 (the gene encoding NK1R) was decreased in reward- and stress-related brain areas both in ShA and LgA rats compared with heroin-naïve rats, but did not differ between the two heroin-experienced groups. In contrast, passive exposure to heroin produced increases in TacR1 expression in the prefrontal cortex and nucleus accumbens. Taken together, these results show that pharmacological NK1R blockade attenuates heroin reinforcement. The observation that animals with ShA and LgA to heroin were similarly affected by L822429 indicates that the SP/NK1R system is not specifically involved in neuroadaptations that underlie escalation resulting from LgA self-administration. Instead, the NK1R antagonist appears to attenuate acute, positively reinforcing properties of heroin and may be useful as an adjunct to relapse prevention in detoxified opioid-dependent subjects. PMID:23303056

  11. Fatal methadone intoxication in an infant listed as a homicide.

    PubMed

    Bonsignore, Alessandro; Groppi, Angelo; Ventura, Francesco; De Stefano, Francesco; Palmiere, Cristian

    2016-09-01

    Voluntary methadone administration for the purpose of sedation eventually resulting in the infant's death is extremely infrequent, though it has been observed. In this report, we describe an autopsy case pertaining to a 32-month-old infant who was repeatedly exposed to methadone by his parents. Autopsy revealed a coarctation of the aorta with a focal stenosis located at the junction of the distal aortic arch and the descending aorta. Left ventricular hypertrophy was also observed. Both these findings were considered to not have played a role in the child's death. Methadone was detected in the femoral blood (0.633 mg/l), urine (5.25 mg/l), bile (2.64 mg/l), and gastric contents (1.08 mg). A segmental hair analysis showed the presence of methadone and morphine in both the proximal and distal portion of the lock. Methadone was also detected in nail samples. A segmental hair analysis performed on the younger brother of the deceased revealed the presence of methadone and morphine in both the proximal and distal segments, as well as the presence of 6-monoacetylmorphine exclusively in the distal portion. Though the parents denied any involvement in methadone administration or exposure for the purpose of sedation, the manner of death was listed as homicide. The case emphasizes the usefulness of hair analysis to identify threatening situations for the children of drug-dependent parents and possibly support measures by the authorities to recognize and intervene in these potentially fatal situations.

  12. Anti-Cocaine Vaccine Based on Coupling a Cocaine Analog to a Disrupted Adenovirus

    PubMed Central

    Koob, George; Hicks, Martin J.; Wee, Sunmee; Rosenberg, Jonathan B.; De, Bishnu P.; Kaminksy, Stephen M.; Moreno, Amira; Janda, Kim D.; Crystal, Ronald G.

    2012-01-01

    The challenge in developing an anti-cocaine vaccine is that cocaine is a small molecule, invisible to the immune system. Leveraging the knowledge that adenovirus (Ad) capsid proteins are highly immunogenic in humans, we hypothesized that linking a cocaine hapten to Ad capsid proteins would elicit high-affinity, high-titer antibodies against cocaine, sufficient to sequester systemically administered cocaine and prevent access to the brain, thus suppressing cocaine-induced behaviors. Based on these concepts, we developed dAd5GNE, a disrupted E1−E3− serotype 5 Ad with GNE, a stable cocaine analog, covalently linked to the Ad capsid proteins. In pre-clinical studies, dAd5GNE evoked persistent, high titer, high affinity IgG anti-cocaine antibodies, and was highly effective in blocking cocaine-induced hyperactivity and cocaine self-administration behavior in rats. Future studies will be designed to expand the efficacy studies, carry out relevant toxicology studies, and test dAd5GNE in human cocaine addicts. PMID:22229312

  13. Electroencephalographic activity and mood in cocaine-dependent outpatients: effects of cocaine cue exposure.

    PubMed

    Bauer, L O; Kranzler, H R

    1994-08-01

    Electroencephalographic (EEG) and subjective reactions to cocaine cues were evaluated in 18 cocaine-dependent outpatients, after 14 or fewer days of abstinence, and 16 noncocaine-dependent controls. EEG activity and desire for cocaine were recorded while subjects viewed three 5-min films that featured either cocaine-associated, erotic, or neutral stimuli. Other measures of mood state and cocaine craving, derived from the Mood Adjective Checklist and the Cocaine Craving Questionnaire, respectively, were recorded immediately after each film. Analyses of absolute EEG power within six frequency bands (delta, theta, slow and fast alpha, slow and fast beta) revealed no EEG abnormalities in the cocaine-dependent group under any condition. In both subject groups, the cocaine-associated and erotic films produced a similar reduction in total EEG power. The cocaine-associated and erotic films also produced a similar increase in the self-rated desire for cocaine, but this change only occurred in the cocaine-dependent group.

  14. Selective attention and drug related attention bias in methadone maintenance patients.

    PubMed

    Nejati, Majid; Nejati, Vahid; Mohammadi, Mohammad Reza

    2011-01-01

    One of the main problems of the drug abusers is drug related attention bias, which causes craving, and as a result drive the drug abusers to take narcotics. Methadone is used as a maintenance treatment for drug abusers. The purpose of this study is evaluation of the effect of Methadone maintenance therapy (MMT) on selective attention and drug related attention bias. This study investigated drug cue-related attention bias and selective attention in 16 methadone-maintained patients before and 45 days after methadone therapy period. Stroop color-word test and addiction Stroop test were used as measurement methods. Results show less reaction time and higher accuracy in Color-Word Stroop Test after MMT and less delay for addict related word in addiction Stroop test. It is concluded that methadone can improve selective attention capability and reduce drug related attention bias.

  15. Fatal Methadone Toxicity: Potential Role of CYP3A4 Genetic Polymorphism

    PubMed Central

    Richards-Waugh, Lauren L.; Primerano, Donald A.; Dementieva, Yulia; Kraner, James C.; Rankin, Gary O.

    2014-01-01

    Methadone is difficult to administer as a therapeutic agent because of a wide range of interindividual pharmacokinetics, likely due to genetic variability of the CYP450 enzymes responsible for metabolism to its principal metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP). CYP3A4 is one of the primary CYP450 isoforms responsible for the metabolism of methadone to EDDP in humans. The purpose of this study was to evaluate the role of CYP3A4 genetic polymorphisms in accidental methadone fatalities. A study cohort consisting of 136 methadone-only and 92 combined methadone/benzodiazepine fatalities was selected from cases investigated at the West Virginia and Kentucky Offices of the Chief Medical Examiner. Seven single nucleotide polymorphisms (SNPs) were genotyped within the CYP3A4 gene. Observed allelic and genotypic frequencies were compared with expected frequencies obtained from The National Center for Biotechnology Information dbSNP database. SNPs rs2242480 and rs2740574 demonstrated an apparent enrichment within the methadone-only overdose fatalities compared with the control group and the general population. This enrichment was not apparent in the methadone/benzodiazepine cases for these two SNPs. Our findings indicate that there may be two or more SNPs on the CYP3A4 gene that cause or contribute to the methadone poor metabolizer phenotype. PMID:25217544

  16. Children's Heroes and Heroines: Developing Values Manifested through Artwork.

    ERIC Educational Resources Information Center

    McCrary, Judy H.

    This study assessed the personal values of a group of 17 kindergarten-age children. Children participated in a classroom discussion of heroes and heroines, then drew a picture of their heroes or heroines. The researcher analyzed each child's artwork and determined the outstanding values represented by the hero or heroine. A parallel was drawn…

  17. Synthesis and positron emission tomographic (PET) baboon studies of [{sup 11}C]methadone and R-(-)-[{sup 11}C]methandone

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ding, Y.S.; Fowler, J.S.; Volkow, N.D.

    1996-05-01

    Methadone (MET) maintenance has been used successfully for many years in the rehabilitation of heroin addicts. MET, a typical m{mu}-opioid receptor agonist, exists as two enantiomers and is used clinically as the racemic mixture. However, R-(-)-MET has a 10-fold higher affinity for m{mu} receptors than S-(+)-MET (IC{sub 50}: 3.0 nM and 26.4 nM, respectively) and R-(-)-MET is almost entirely responsible for the therapeutic actions of the racemate. In order to examine the pharmacokinetics and stereoselectivity of the drug, we have synthesized both [{sup 11}C]MET and R-(-)-[{sup 11}C]MET. Preparing the precursor by one-step approach to the N-demethylated methadone was precluded asmore » other investigators cited problems with intramolecular cyclization. Therefore, a four-step synthesis using MET (or R-(-)-MET) as starting material was required to obtain the precursor, followed by a two-step radiolabeling synthesis (N-methylation followed by oxidation) to obtain [{sup 11}C]MET (or R-(-)-[{sup 11}C]MET). Comparative PET studies in the same baboon showed peak striatal uptake was 0.022%/cc at 5 minutes with a half time of clearance from peak of 100 minutes for R-(-)-[{sup 11}C]MET and a peak uptake of 0.013%/cc with a half time of 90 min for [{sup 11}C]MET. R-(-)-[{sup 11}C]MET also showed a slower disappearance in plasma. Both tracers showed higher C-11 in basal ganglia (BG), thalamus and midbrain relative to the cerebellum (CB) and occipital cortex (OC) but the BG/OC ratio was higher for R-(-)-[{sup 11}C]MET (1.3 vs 1.1). Pretreatment with naloxone (1 mg/kg, iv) increased R-(-)-[{sup 11}C]MET uptake in all brain regions whereas unlabeled MET slightly increased C-11 clearance in BG, OC and CB. These initial results show higher brain concentration and specificity of the pharmacologically active enantiomer of methadone along with significant non-specific binding.« less

  18. The heroin addict! A personal view.

    PubMed

    Cyngler, Charles

    2002-04-01

    Heroin beckons like the sweet seductive calls of Ulysses' sirens. The alluring nectar of the poppy seed, once experienced is not easy to escape. The greed for pleasure is endless. Gratification begets gratification. This paper explores issues and complications of treatment intervention in heroin addiction. The author is a general practitioner with 25 years experience and special interest in substance abuse medicine.

  19. Impact of Cannabis Use During Stabilization on Methadone Maintenance Treatment

    PubMed Central

    Scavone, Jillian L.; Sterling, Robert C.; Weinstein, Stephen P.; Van Bockstaele, Elisabeth J.

    2016-01-01

    Background and Objectives Illicit drug use, particularly of cannabis, is common among opiate-dependent individuals, and has the potential to impact treatment in a negative manner. Methods To examine this, patterns of cannabis use prior to and during methadone maintenance treatment (MMT) were examined to assess possible cannabis-related effects on MMT, particularly during methadone stabilization. Retrospective chart analysis was used to examine outpatient records of patients undergoing MMT (n=91), focusing specifically on past and present cannabis use and its association with opiate abstinence, methadone dose stabilization, and treatment compliance. Results Objective rates of cannabis use were high during methadone induction, dropping significantly following dose stabilization. History of cannabis use correlated with cannabis use during MMT, but did not negatively impact the methadone induction process. Pilot data also suggested that objective ratings of opiate withdrawal decrease in MMT patients using cannabis during stabilization. Conclusions and Scientific Significance The present findings may point to novel interventions to be employed during treatment for opiate dependence that specifically target cannabinoid-opioid system interactions. PMID:23795873

  20. Hapten optimization for cocaine vaccine with improved cocaine recognition.

    PubMed

    Ramakrishnan, Muthu; Kinsey, Berma M; Singh, Rana A; Kosten, Thomas R; Orson, Frank M

    2014-09-01

    In the absence of any effective pharmacotherapy for cocaine addiction, immunotherapy is being actively pursued as a therapeutic intervention. While several different cocaine haptens have been explored to develop anticocaine antibodies, none of the hapten was successfully designed, which had a protonated tropane nitrogen as is found in native cocaine under physiological conditions, including the succinyl norcocaine (SNC) hapten that has been tested in phase II clinical trials. Herein, we discuss three different cocaine haptens: hexyl norcocaine (HNC), bromoacetamido butyl norcocaine (BNC), and succinyl butyl norcocaine (SBNC), each with a tertiary nitrogen structure mimicking that of native cocaine which could optimize the specificity of anticocaine antibodies for better cocaine recognition. Mice immunized with these haptens conjugated to immunogenic proteins produced high titre anticocaine antibodies. However, during chemical conjugation of HNC and BNC haptens to carrier proteins, the 2β methyl ester group is hydrolyzed, and immunizing mice with these conjugate vaccines in mice produced antibodies that bound both cocaine and the inactive benzoylecgonine metabolite. While in the case of the SBNC conjugate, vaccine hydrolysis of the methyl ester did not appear to occur, leading to antibodies with high specificity to cocaine over BE. Although we observed similar specificity with a SNC hapten, the striking difference is that SBNC carries a positive charge on the tropane nitrogen atom, and therefore, it is expected to have better binding of cocaine. The 50% cocaine inhibitory concentration (IC50 ) value for SBNC antibodies (2.8 μm) was significantly better than the SNC antibodies (9.4 μm) when respective hapten-BSA was used as a substrate. In addition, antibodies from both sera had no inhibitory effect from BE. In contrast to BNC and HNC, the SBNC conjugate was also found to be highly stable without any noticeable hydrolysis for several months at 4 °C and 2-3

  1. Cold Preparation of Heroin in a Black Tar Market.

    PubMed

    Roth, Alexis M; Armenta, Richard F; Wagner, Karla D; Strathdee, Steffanie A; Goldshear, Jesse L; Cuevas-Mota, Jazmine; Garfein, Richard S

    2017-07-29

    Black tar heroin is typically prepared for injection with heat which decreases the risk of HIV transmission by inactivating the virus. We received reports that persons who inject drugs (PWID) in Tijuana, Baja California, Mexico, a black tar heroin market, were using only water to dissolve heroin. Because Tijuana abuts San Diego County, CA, United States, we undertook the present analyses to determine the prevalence of this practice among PWID in San Diego, California. PWID completed quarterly behavioral assessments and serological testing for blood-borne viruses. Bivariate and multivariable logistic regression models were constructed to assess for individual, social, and structural correlates of preparing heroin without heat within the preceding 6 months. Nearly half of black tar heroin users (149/305) reported they had prepared heroin without heat within 6 months. In multivariable analysis, cold preparation was independently associated with younger age (10 year decrease; AOR = 1.25; 95% CI 1.03, 1.53), more drug injecting acquaintances (per 5 acquaintance increase; AOR = 1.05; 95% CI 1.01, 1.09) and prefilled syringe use (injecting drugs from syringes that are already filled with drugs before purchase; AOR = 1.86; 95% CI 1.14, 3.02). Conclusions/Importance: To our knowledge, this is the first paper to report that PWID living in a black tar heroin market are preparing heroin without heat. Additional research is needed to determine whether this is an endemic practice or PWID are engaging in new forms of drug preparation in response to changes in the environment.

  2. Oral Fluid Cocaine and Benzoylecgonine Concentrations Following Controlled Intravenous Cocaine Administration

    PubMed Central

    Ellefsen, Kayla N.; Concheiro, Marta; Pirard, Sandrine; Gorelick, David A.; Huestis, Marilyn A.

    2016-01-01

    Limited oral fluid (OF) pharmacokinetic data collected with commercially available collection devices after controlled cocaine administration hinder OF result interpretations. Ten cocaine-using adults provided OF, collected with Oral-Eze® (OE) and StatSure Saliva Sampler™ (SS) devices, an hour prior to and up to 69 h after 25 mg intravenous (IV) cocaine administration. Cocaine and benzoylecgonine (BE) were quantified by a validated 2D-GC-MS method. Large inter-subject variability was observed. Cocaine was detected in OF in the first 0.17 h sample after IV administration, with much more rapid elimination than BE. OE median observed Cmax (range) was 932 (394–1,574) μg/L for cocaine and 248 (96.9–953) μg/L for BE. SS median (range) observed cocaine and BE Cmax trended lower at 732 (83.3–1,892) μg/L and 360 (77.2–836) μg/L, respectively. OE and SS cocaine OF detection times were 12.5 and 6.5 h and for BE 30.5 and 28.0 h, respectively at 1 μg/L. There were no significant pharmacokinetic differences between OE and SS OF collection devices, except cocaine half-life was significantly shorter in SS OF specimens. This difference could be attributed to differences in stabilizing buffers present in OF collection devices, which may affect cocaine stability in OF specimens, or decreased recovery from collection pads. Both OE and SS OF collection devices were effective in monitoring cocaine and metabolite concentrations with similar detection windows. Furthermore, we demonstrated that different confirmatory OF cutoffs can be selected to produce shorter or longer cocaine and metabolite detection windows to address specific needs of clinical and forensic drug testing programs. PMID:26851651

  3. Metabotropic Glutamate 7 (mGlu7) Receptor: A Target for Medication Development for the Treatment of Cocaine Dependence

    PubMed Central

    Li, Xia; Xi, Zheng-Xiong; Markou, Athina

    2013-01-01

    Brain glutamate has been shown to play an important role in reinstatement to drug seeking, a behavior considered to be of relevance to relapse to drug taking in humans. Therefore, glutamate receptors, in particular metabotropic glutamate (mGlu) receptors, have become important targets for medication development for the treatment of drug dependence. In this review article, we focus on the mGlu7 receptor subtype, and discuss recent findings with AMN082, a selective mGlu7 receptor allosteric agonist, in animal models with relevance to drug dependence. Systemic or local administration of AMN082 into the nucleus accumbens (NAc), a critical brain region involved in reward and drug dependence processes, inhibited the reinforcing and motivational effects of cocaine, heroin and ethanol, as assessed by the intravenous drug self-administration procedure. In addition, AMN082 inhibited the reward-enhancing effects induced by cocaine, as assessed in the intracranial self-stimulation procedure, and cocaine- or cue-induced reinstatement of drug-seeking behavior. In vivo microdialysis studies indicated that systemic or intra-NAc administration of AMN082 significantly decreased extracellular γ-aminobutyric acid (GABA) and elevated extracellular glutamate, but had no effect on extracellular dopamine in the NAc, suggesting that a non-dopaminergic mechanism underlies the effects of AMN082 on the actions of cocaine. Further, data indicated that AMN082-induced changes in glutamate were the net effect of two actions: one is the direct inhibition of glutamate release by activation of mGlu7 receptors on glutamatergic neurons; another is the indirect increases of glutamate release mediated by decreases in GABA transmission. These increases in extracellular glutamate functionally antagonized cocaine-induced inhibition of NAc-ventral pallidum GABAergic neurotransmission, and therefore, the rewarding effects of cocaine. In addition, elevated extracellular glutamate activated presynaptic mGlu2

  4. Normalizing effect of heroin maintenance treatment on stress-induced brain connectivity

    PubMed Central

    Walter, Marc; Gerber, Hana; Seifritz, Erich; Brenneisen, Rudolf; Wiesbeck, Gerhard A.; Riecher-Rössler, Anita; Lang, Undine E.; Borgwardt, Stefan

    2015-01-01

    Recent evidence has shown that a single maintenance dose of heroin attenuates psychophysiological stress responses in heroin-dependent patients, probably reflecting the effectiveness of heroin-assisted therapies for the treatment of severe heroin addiction. However, the underlying neural circuitry of these effects has not yet been investigated. Using a cross-over, double-blind, vehicle-controlled design, 22 heroin-dependent and heroin-maintained outpatients from the Centre of Substance Use Disorders at the University Hospital of Psychiatry in Basel were studied after heroin and placebo administration, while 17 healthy controls from the general population were included for placebo administration only. Functional magnetic resonance imaging was used to detect brain responses to fearful faces and dynamic causal modelling was applied to compute fear-induced modulation of connectivity within the emotional face network. Stress responses were assessed by hormone releases and subjective ratings. Relative to placebo, heroin acutely reduced the fear-induced modulation of connectivity from the left fusiform gyrus to the left amygdala and from the right amygdala to the right orbitofrontal cortex in dependent patients. Both of these amygdala-related connectivity strengths were significantly increased in patients after placebo treatment (acute withdrawal) compared to healthy controls, whose connectivity estimates did not differ from those of patients after heroin injection. Moreover, we found positive correlations between the left fusiform gyrus to amygdala connectivity and different stress responses, as well as between the right amygdala to orbitofrontal cortex connectivity and levels of craving. Our findings indicate that the increased amygdala-related connectivity during fearful face processing after the placebo treatment in heroin-dependent patients transiently normalizes after acute heroin maintenance treatment. Furthermore, this study suggests that the assessment of

  5. Monitoring cocaine use and abstinence among cocaine users for contingency management interventions.

    PubMed

    Holtyn, August F; Knealing, Todd W; Jarvis, Brantley P; Subramaniam, Shrinidhi; Silverman, Kenneth

    2017-06-01

    During contingency management interventions, reinforcement of cocaine abstinence is arranged by delivering an incentive when a urine sample tests cocaine-negative. The use of qualitative versus quantitative urinalysis testing may have important implications for effects on cocaine abstinence. Qualitative testing (i.e., testing that solely identifies whether a particular substance is present or absent) may not detect short-term cocaine abstinence because a single instance of cocaine use can result in cocaine-positive urine over many days. Quantitative testing (i.e., testing that identifies how much of a substance is present) may be more sensitive to short-term cocaine abstinence; however, the selection of a criterion for distinguishing new use versus carryover from previous use is an important consideration. The present study examined benzoylecgonine concentrations, the primary metabolite of cocaine, in urine samples collected three times per week for 30 weeks from 28 cocaine users who were exposed to a cocaine abstinence contingency. Of the positive urine samples (benzoylecgonine concentration >300 ng/ml), 29%, 21%, 14%, and 5% of the samples decreased in benzoylecgonine concentration by more than 20%, 40%, 60%, and 80% per day, respectively. As the size of the decrease increased, the likelihood of that sample occurring during a period leading to a cocaine-negative urine sample (benzoylecgonine concentration ≤300 ng/ml) also increased. The number of days required to produce a cocaine-negative sample following a positive sample ranged from 1 to 10 days and was significantly correlated with the starting benzoylecgonine level ( r = 0.43, p < 0.001). The present analyses may aid in the development of procedures that allow for the precise reinforcement of recent cocaine abstinence during contingency management interventions.

  6. Hopelessness in Alcohol- and Heroin-Dependent Women.

    ERIC Educational Resources Information Center

    Beck, Aaron T.; And Others

    1984-01-01

    Administered the Beck Hopelessness Scale to alcoholic (N=20) and heroin-addicted (N=20) women. Results indicated that although both groups expressed comparable levels of overall hopelessness, alcoholic women anticipated more success and better lives in the next 10 years than did the heroin-dependent women. (LLL)

  7. Cocaine-specific Antibodies Blunt the Subjective Effects of Smoked Cocaine in Humans

    PubMed Central

    Haney, Margaret; Gunderson, Erik W.; Jiang, Huiping; Collins, Eric D.; Foltin, Richard W.

    2012-01-01

    Background Rates of relapse among cocaine-dependent patients are high, and new treatment approaches are needed. Clinical data demonstrate that a cocaine vaccine (TA-CD: Celtic Pharmaceutical) produces selective anti-cocaine antibodies, yet the impact of these antibodies on cocaine’s direct effects is unknown. The objective of this human laboratory study was to measure the relationship between antibody titers and the effects of smoked cocaine on ratings of intoxication, craving and cardiovascular effects. Methods Ten cocaine-dependent men not seeking drug treatment spent 2 nights per week for 13 weeks inpatient where the effects of cocaine (0, 25, 50 mg) were determined prior to vaccination and at weekly intervals thereafter. Two doses of TA-CD (82 µg, n=4; 360 µg, n=6) were administered at weeks 1, 3, 5 and 9. Results Peak plasma antibody levels, which were highly variable, significantly predicted cocaine’s effects. Those individuals in the upper half of antibody production had an immediate (within 4 minutes of cocaine smoking) and robust (55–81%) reduction in ratings of Good Drug Effect and Cocaine Quality, while those in the lower half showed only a nonsignificant attenuation (6–26%). Self-reported cocaine use while participants were outpatient tended to decrease as a function of antibody titer (p < 0.12). By contrast, higher antibody levels predicted significantly greater cocaine-induced tachycardia. Conclusions The TA-CD vaccine substantially decreased smoked cocaine’s intoxicating effects in those generating sufficient antibody. These data support further testing of cocaine immunotherapy as a treatment for cocaine dependence. PMID:19846066

  8. Metabolomic profiling of brain tissues of mice chronically exposed to heroin.

    PubMed

    Li, Ren-Shi; Takeda, Tomoki; Ohshima, Takashi; Yamada, Hideyuki; Ishii, Yuji

    2017-02-01

    The chronic neurotoxicity of heroin on the nervous system is poorly understood. To address this issue, we comprehensively assessed the alteration of brain metabolomics caused by chronic heroin exposure and the withdrawal of heroin. Male C57BL/6J mice (n = 10) were given heroin (15 μmol/kg, i.p., twice a day) for 12 days while the withdrawal group received saline-treatment instead of heroin for the last two days. The control group received saline. We developed an UPLC-TOF/MS-based metabolomic approach to analyze the metabolites and carry out a metabolic pathway analysis in the brain. The major metabolites contributing to the discrimination were identified as amino acids, tricarboxylic-acid cycle intermediates, neurotransmitters, nucleotides and other compounds. A marked reduction in histidine and a slight but significant increase in phenylalanine and tryptophan were observed after heroin was withdrawn while the increased level of catecholamines was restored to baseline. Interestingly, N-acetylserotonin - a precursor of melatonin - was increased with the withdrawal of heroin while melatonin was markedly reduced along with the sub-chronic exposure to heroin. This shows that heroin disrupts not only the energy metabolism but also the biosynthesis of both catecholamines and melatonin in the mouse brain. Therefore, these substances are candidate biomarkers for chronic heroin-abuse. Copyright © 2016 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

  9. Levamisole and cocaine synergism: a prevalent adulterant enhances cocaine's action in vivo.

    PubMed

    Tallarida, Christopher S; Egan, Erin; Alejo, Gissel D; Raffa, Robert; Tallarida, Ronald J; Rawls, Scott M

    2014-04-01

    Levamisole is estimated by the Drug Enforcement Agency (DEA) to be present in about 80% of cocaine seized in the United States and linked to debilitating, and sometimes fatal, immunologic effects in cocaine abusers. One explanation for the addition of levamisole to cocaine is that it increases the amount of product and enhances profits. An alternative possibility, and one investigated here, is that levamisole alters cocaine's action in vivo. We specifically investigated effects of levamisole on cocaine's stereotypical and place-conditioning effects in an established invertebrate (planarian) assay. Acute exposure to levamisole or cocaine produced concentration-dependent increases in stereotyped movements. For combined administration of the two agents, isobolographic analysis revealed that the observed stereotypical response was enhanced relative to the predicted effect, indicating synergism for the interaction. In conditioned place preference (CPP) experiments, cocaine produced a significant preference shift; in contrast, levamisole was ineffective at all concentrations tested. For combination experiments, a submaximal concentration of cocaine produced CPP that was enhanced by inactive concentrations of levamisole, indicating synergism. The present results provide the first experimental evidence that levamisole enhances cocaine's action in vivo. Most important is the identification of synergism for the levamisole/cocaine interaction, which now requires further study in mammals. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. The effects of heroin administration and drug cues on impulsivity.

    PubMed

    Jones, Jermaine D; Vadhan, Nehal P; Luba, Rachel R; Comer, Sandra D

    2016-08-01

    Drug addiction is a chronic relapsing disorder characterized by compulsive drug seeking and continued use despite negative consequences. Behavioral impulsivity is a strong predictor of the initiation and maintenance of drug addiction. Preclinical data suggest that heroin may exacerbate impulsive characteristics in an individual but this has yet to be assessed in clinical samples. The current secondary data analysis sought to investigate the effects of heroin on impulsivity along with the effects of exposure to drug cues. Using the current data set, we also tentatively assessed the etiological relationship between impulsivity and heroin abuse. Sixteen heroin-dependent participants were recruited to complete Immediate Memory Task/Delayed Memory Task (IMT/DMT) and GoStop tasks following repeated heroin administration, following acute heroin administration, and following a drug cue exposure session. Four preceding days of active heroin availability, compared to four preceding days of placebo drug availability, increased impulsivity assessed using the IMT and DMT. Presentation of drug cues similarly acted to increase impulsivity assessments on all three tasks. It also appears that heavier users were more susceptible to the influence of drug cues on impulsivity. The present study represents a step toward a more comprehensive understanding of the interaction between opioid abuse and impulsivity. A better understanding of these factors could provide critical insight into the maintenance of heroin use and relapse.

  11. QT-interval effects of methadone, levomethadyl, and buprenorphine in a randomized trial.

    PubMed

    Wedam, Erich F; Bigelow, George E; Johnson, Rolley E; Nuzzo, Paul A; Haigney, Mark C P

    2007-12-10

    Levomethadyl acetate, methadone hydrochloride, and buprenorphine hydrochloride are equally effective treatments for opioid dependence. Each blocks the human ether-a-go-go-related gene (hERG)-associated channel in vitro and represents a risk for QT prolongation. To compare the effects of 3 known hERG-associated channel blockers on the corrected QT (QTc), we conducted a randomized, controlled trial of opioid-addicted subjects. We analyzed 12-lead electrocardiograms collected at baseline and every 4 weeks from 165 opioid-addicted participants in a 17-week randomized double-blind clinical trial of equally effective doses of levomethadyl, methadone, and buprenorphine at a major referral center. Analyses were limited to the 154 patients with a normal baseline QTc = (QT/ radical R-R) who had at least 1 subsequent in-treatment electrocardiogram. Patients were randomized to receive treatment with levomethadyl, methadone, or buprenorphine (hereinafter, levomethadyl, methadone, and buprenorphine groups, respectively). The prespecified end points were a QTc greater than 470 milliseconds in men (or >490 milliseconds in women), or an increase from baseline in QTc greater than 60 milliseconds. Baseline QTc was similar in the 3 groups. The levomethadyl and methadone groups were significantly more likely to manifest a QTc greater than 470 or 490 milliseconds (28% for the levomethadyl group vs 23% for the methadone group vs 0% for the buprenorphine group; P < .001) or an increase from baseline in QTc greater than 60 milliseconds (21% of the levomethadyl group [odds ratio, 15.8; 95% confidence interval, 3.7-67.1] and 12% of the methadone group [odds ratio, 8.4; 95% confidence interval, 1.9-36.4]) compared with the buprenorphine group (2% of subjects; P < .001). In subjects whose dosage of levomethadyl or methadone remained fixed over at least 8 weeks, the QTc continued to increase progressively over time (P = .08 for the levomethadyl group, P = .01 for the methadone group

  12. The effects of cocaine, alcohol and cocaine/alcohol combinations in conditioned taste aversion learning.

    PubMed

    Busse, Gregory D; Verendeev, Andrey; Jones, Jermaine; Riley, Anthony L

    2005-09-01

    We have recently reported that alcohol attenuates cocaine place preferences. Although the basis for this effect is unknown, alcohol may attenuate cocaine reward by potentiating its aversive effects. To examine this possibility, these experiments assessed the effects of alcohol on cocaine-induced taste aversions under conditions similar to those that resulted in attenuated place preferences. Specifically, Experiments 1 and 2 assessed the effects of alcohol (0.5 g/kg) on taste aversions induced by 20, 30 and 40 mg/kg cocaine. Experiment 3 examined the role of intertrial interval in the effects of alcohol (0.5 g/kg) on cocaine (30 mg/kg) taste aversions. In Experiments 1 and 2, cocaine was effective at conditioning aversions. Alcohol produced no measurable effect. Combining cocaine and alcohol produced no greater aversion than cocaine alone (and, in fact, weakened aversions at the lowest dose of cocaine). In Experiment 3, varying the intertrial interval from 3 days (as in the case of Experiments 1 and 2) to 1 day (a procedure identical to that in which alcohol attenuated cocaine place preferences) resulted in significant alcohol- and cocaine-induced taste aversions. Nonetheless, alcohol remained ineffective in potentiating cocaine aversions. Thus, under these conditions alcohol does not potentiate cocaine's aversiveness. These results were discussed in terms of their implication for the effects of alcohol on cocaine-induced place preferences. Further, the effects of alcohol on place preferences conditioned by cocaine were discussed in relation to other assessments of the effects of alcohol on the affective properties of cocaine and the implications of these interactions for alcohol and cocaine co-use.

  13. Human Methadone Self-Administration and the Generalized Matching Law

    ERIC Educational Resources Information Center

    Spiga, Ralph; Maxwell, R. Stockton; Meisch, Richard A.; Grabowski, John

    2005-01-01

    The present study examined whether in humans the generalized matching law described the relation between relative responding and relative drug intake by humans under concurrent variable interval variable interval (conc VI VI) schedules of drug reinforcement. Methadone-maintained patients, stabilized on 80 mg per day of methadone, were recruited…

  14. Quinine-induced thrombocytopenia following intravenous use of heroin

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Christie, D.J.; Walker, R.H.; Kolins, M.D.

    1983-06-01

    Profound thrombocytopenia developed in a 22-year-old man after intravenous use of heroin. A high-titer, quinine-dependent, platelet-specific antibody was detected in his serum using lysis of normal platelets labeled with chromium 51 and an electroimmunoassay for measurement of platelet-associated IgG. The antibody was specific for quinine and failed to react with platelets in the presence of quinidine hydrochloride or two structural analogues of heroin. Quinine, a common adulterant found in heroin, was detected in the patient's blood and urine. On the basis of these observations, the patient was judged to have quinine-induced immunologic thrombocytopenia. To our knowledge, this report is themore » first to confirm that quinine used as an adulterant can induce immunologic thrombocytopenia following an injection of heroin.« less

  15. Morphine tolerance as a function of ratio schedule: response requirement or unit price?

    PubMed

    Hughes, Christine E; Sigmon, Stacey C; Pitts, Raymond C; Dykstra, Linda A

    2005-05-01

    Key pecking by 3 pigeons was maintained by a multiple fixed-ratio 10, fixed-ratio 30, fixed-ratio 90 schedule of food presentation. Components differed with respect to amount of reinforcement, such that the unit price was 10 responses per 1-s access to food. Acute administration of morphine, l-methadone, and cocaine dose-dependently decreased overall response rates in each of the components. When a rate decreasing dose of morphine was administered daily, tolerance, as measured by an increase in the dose that reduced response rates to 50% of control (i.e., the ED50 value), developed in each of the components; however, the degree of tolerance was smallest in the fixed-ratio 90 component (i.e., the ED50 value increased the least). When the l-methadone dose-effect curve was redetermined during the chronic morphine phase, the degree of cross-tolerance conferred to l-methadone was similar across components, suggesting that behavioral variables may not influence the degree of cross-tolerance between opioids. During the chronic phase, the cocaine dose-effect curve shifted to the right for 2 pigeons and to the left for 1 pigeon, which is consistent with predictions based on the lack of pharmacological similarity between morphine and cocaine. When the morphine, l-methadone, and cocaine dose-effect curves were redetermined after chronic morphine administration ended, the morphine and l-methadone ED50s replicated those obtained prior to chronic morphine administration. The morphine data suggest that the fixed-ratio value (i.e., the absolute output) determines the degree of tolerance and not the unit price.

  16. Cocaine (Coke, Crack) Facts

    MedlinePlus

    ... That People Abuse » Cocaine (Coke, Crack) Facts Cocaine (Coke, Crack) Facts Listen Cocaine is a white ... 69 KB) "My life was built around getting cocaine and getting high." ©istock.com/ Marjot Stacey is ...

  17. Crack Cocaine Injection Practices and HIV Risk: Findings From New York and Bridgeport

    PubMed Central

    Lankenau, Stephen E.; Clatts, Michael C.; Goldsamt, Lloyd A.; Welle, Dorinda L.

    2007-01-01

    This article examines the behavioral practices and health risks associated with preparing crack cocaine for injection. Using an ethno-epidemiological approach, injection drug users (n=38) were recruited between 1999 and 2000 from public settings in New York City and Bridgeport, Connecticut and responded to a semistructured interview focusing on crack injection initiation and their most recent crack injection. Study findings indicate that methods of preparing crack for injection were impacted by a transforming agent, heat applied to the “cooker,” heroin use, age of the injector, and geographic location of the injector. The findings suggest that crack injectors use a variety of methods to prepare crack, which may carry different risks for the transmission of bloodborne pathogens. In particular, crack injection may be an important factor in the current HIV epidemic. PMID:18079990

  18. Interaction of different antidepressants with acute and chronic methadone in mice, and possible clinical implications.

    PubMed

    Schreiber, Shaul; Barak, Yonatan; Hostovsky, Avner; Baratz-Goldstein, Renana; Volis, Ina; Rubovitch, Vardit; Pick, Chaim G

    2014-04-01

    We studied the interaction of a single dose of different antidepressant medications with a single (acute) dose or implanted mini-pump (chronic) methadone administration in mice, using the hotplate assay. For the acute experiment, subthreshold doses of six antidepressant drugs were administered separately with a single dose of methadone. The addition of a subthreshold dose of desipramine or clomipramine to methadone produced significant augmentation of the methadone effect with each drug (p < 0.05). Fluvoxamine given at a fixed subthreshold dose induced a synergistic effect only with a low methadone dose. Escitalopram, reboxetine and venlafaxine given separately, each at a fixed subthreshold dose, induced no interaction. Possible clinical implications of these findings are that while escitalopram, reboxetine and venlafaxine do not affect methadone's antinociception in mice and are safe to be given together with methadone when indicated, fluvoxamine, clomipramine and desipramine considerably augment methadone-induced effects and should be avoided in this population due to the risk of inducing opiate overdose. For the chromic experiment, when a subthreshold dose of either escitalopram, desipramine or clomipramine was injected to mice following 2 weeks of methadone administration with the mini-pump, none of the antidepressant drugs strengthened methadone's analgesic effect. Further studies are needed before possible clinical implications can be drawn.

  19. The 5-HT(2C) receptor agonist lorcaserin reduces cocaine self-administration, reinstatement of cocaine-seeking and cocaine induced locomotor activity.

    PubMed

    Harvey-Lewis, Colin; Li, Zhaoxia; Higgins, Guy A; Fletcher, Paul J

    2016-02-01

    Lorcaserin (Lorqess, Belviq(®)) is a selective 5-HT(2C) receptor agonist that has received FDA approval for the treatment of obesity. 5-HT(2C) receptor agonists are also efficacious in decreasing multiple aspects of cocaine motivation and reward in preclinical models. This would suggest that lorcaserin is a clinically available therapeutic with the potential to treat cocaine addiction. Here we report the effects of lorcaserin (0.1 mg/kg-1.0 mg/kg) on multiple aspects of cocaine-related behaviours in rats. We find that lorcaserin dose-dependently decreases cocaine self-administration on progressive and fixed ratio schedules of reinforcement. Lorcaserin also reduces reinstatement of cocaine-seeking behaviour in response to priming injections of cocaine and/or reintroduction of cocaine-associated cues. Finally, lorcaserin dose-dependently decreases cocaine-induced hyperlocomotion. Our results, when considered in concert with similar emergent findings in non-human primates, strongly support continued research into the potential of lorcaserin as a clinical treatment for cocaine addiction. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Gender differences in pharmacokinetics and pharmacodynamics of methadone substitution therapy.

    PubMed

    Graziani, Manuela; Nisticò, Robert

    2015-01-01

    Gender-related differences in the pharmacological effects of drug are an emerging topic. This review examines gender differences in both pharmacokinetic and pharmacodynamic aspects of methadone, a long-acting opioid agonist that is prescribed as a treatment for opioid dependence and the management of chronic pain. We performed a search in the Medline database from 1990 to 2014 in order to find published literature related to gender differences in pharmacokinetics (PK) and pharmacodynamics (PD) of methadone. None of the studies were carried out with the primary or secondary aim to identify any gender differences in the pharmacokinetic profile of methadone. Importantly; high inter-subjects variability in PK parameters was found also intra female population. The reported differences in volume of distribution could be ascribed to the physiological differences between men and women in body weight and composition, taking into account that the dose of methadone was established irrespective of body weight of patients (Peles and Adelson, 2006). On the other hand, the few studies present in literature found no gender difference in some direct pharmacodynamic parameters. Some reports have suggested that female gender is associated with an increased risk for long-QT-related cardiac arrhythmias in methadone maintenance subjects. Even though it may be too simplistic to expect variability only in one parameter to explain inter-individual variation in methadone response, we believe that a better knowledge of gender-related differences might have significant implications for better outcomes in opioid dependence substitution therapy in women.

  1. An in vitro approach to potential methadone metabolic-inhibition interactions.

    PubMed

    Bomsien, Stephanie; Skopp, Gisela

    2007-09-01

    The aim of this study was to assess the drug interaction potential of psychotropic medication on methadone N-demethylation using cDNA-expressed cytochrome P450 CYP enzymes. Methadone was incubated with various drugs (n = 10) and cDNA-expressed CYP3A4, CYP2D6, CYP2B6, CYP2C19 and CYP1A2 enzymes to screen for their inhibition potency. The nature of enzyme selective activity for inhibition was further investigated for potent inhibitors. To test for a mechanism-based component in inhibition, all substances were tested with preincubation and without. 2-Ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) concentration was determined by liquid chromatography/tandem mass spectrometry following liquid/liquid extraction. Formation of EDDP was catalysed by CYP3A4, CYP2D6 and CYP2C19. The N-demethylation of methadone was preferentially inhibited by amitriptyline, buprenorphine, methylenedioxymethamphetamine (MDMA) and zolpidem. Both amitriptyline and buprenorphine were strong, reversible inhibitors of CYP3A4. Similarly, amitriptyline and MDMA were identified as inhibitors of CYP2D6. Zolpidem revealed a mechanism-based inhibition of CYP3A4. Amitriptyline, MDMA and zolpidem are likely to slow down conversion of methadone and to increase its area under the curve (AUC). A consideration of the in vitro evidence of drug-methadone interactions should help to improve patient care during methadone maintenance treatment.

  2. Choosing Under the Influence: A Drug-Specific Mechanism by Which the Setting Controls Drug Choices in Rats

    PubMed Central

    Vandaele, Youna; Cantin, Lauriane; Serre, Fuschia; Vouillac-Mendoza, Caroline; Ahmed, Serge H

    2016-01-01

    Ample evidence shows that the setting can control drug choices in both humans and animals. Here we reveal in rats that a major mechanism of this control involves a regulation of the drug influence on other competing options at the time of choice. Briefly, rats were offered a choice between a drug dose (cocaine or heroin) and a brief access to water sweetened with saccharin in two different settings. In one setting, choosing under the influence was not possible and rats largely preferred saccharin over either cocaine or heroin. In contrast, when the same rats were shifted to a setting where choosing under the influence was possible, they chose the drug either nonexclusively or exclusively depending on whether the drug enhanced or suppressed sweet reward, respectively. Thus, when rats were under the orexigenic influence of heroin at the time of choice, they more frequently chose saccharin in alternation with heroin. In contrast, when rats were under the anorexic influence of cocaine, they stopped choosing saccharin and continued taking cocaine exclusively. These setting- and drug-specific changes in preference were rapid and reversible, and could be induced by passively administering cocaine or heroin before choice. Finally, rats behaved as if they were oblivious to the drug influence on their choices. This behavior could explain why rats are vulnerable to harm themselves, sometimes to the point of death, in settings where choices are made under the drug influence, notably if this influence excludes other important options or, conversely, enhances harmful ones. PMID:26129679

  3. Choosing Under the Influence: A Drug-Specific Mechanism by Which the Setting Controls Drug Choices in Rats.

    PubMed

    Vandaele, Youna; Cantin, Lauriane; Serre, Fuschia; Vouillac-Mendoza, Caroline; Ahmed, Serge H

    2016-01-01

    Ample evidence shows that the setting can control drug choices in both humans and animals. Here we reveal in rats that a major mechanism of this control involves a regulation of the drug influence on other competing options at the time of choice. Briefly, rats were offered a choice between a drug dose (cocaine or heroin) and a brief access to water sweetened with saccharin in two different settings. In one setting, choosing under the influence was not possible and rats largely preferred saccharin over either cocaine or heroin. In contrast, when the same rats were shifted to a setting where choosing under the influence was possible, they chose the drug either nonexclusively or exclusively depending on whether the drug enhanced or suppressed sweet reward, respectively. Thus, when rats were under the orexigenic influence of heroin at the time of choice, they more frequently chose saccharin in alternation with heroin. In contrast, when rats were under the anorexic influence of cocaine, they stopped choosing saccharin and continued taking cocaine exclusively. These setting- and drug-specific changes in preference were rapid and reversible, and could be induced by passively administering cocaine or heroin before choice. Finally, rats behaved as if they were oblivious to the drug influence on their choices. This behavior could explain why rats are vulnerable to harm themselves, sometimes to the point of death, in settings where choices are made under the drug influence, notably if this influence excludes other important options or, conversely, enhances harmful ones.

  4. Implementing methadone maintenance treatment in prisons in Malaysia.

    PubMed

    Wickersham, Jeffrey A; Marcus, Ruthanne; Kamarulzaman, Adeeba; Zahari, Muhammad Muhsin; Altice, Frederick L

    2013-02-01

    In Malaysia, human immunodeficiency virus (HIV) infection is highly concentrated among people who inject opioids. For this reason, the country undertook a three-phase roll-out of a methadone maintenance treatment (MMT) programme. In Phase 3, described in this paper, MMT was implemented within prisons and retention in care was assessed. After developing standard operating procedures and agreement between its Prisons Department and Ministry of Health, Malaysia established pilot MMT programmes in two prisons in the states of Kelantan (2008) and Selangor (2009) - those with the highest proportions of HIV-infected prisoners. Community-based MMT programmes were also established in Malaysia to integrate treatment activities after prisoners' release. Having failed to reduce the incidence of HIV infection, in 2005 Malaysia embarked on a harm reduction strategy. STANDARD OPERATING PROCEDURES WERE MODIFIED TO: (i) escalate the dose of methadone more slowly; (ii) provide ongoing education and training for medical and correctional staff and inmates; (iii) increase the duration of methadone treatment before releasing prisoners; (iv) reinforce linkages with community MMT programmes after prisoners' release; (v) screen for and treat tuberculosis; (vi) escalate the dose of methadone during treatment for HIV infection and tuberculosis; and (vii) optimize the daily oral dose of methadone (> 80 mg) before releasing prisoners. Prison-based MMT programmes can be effectively implemented but require adequate dosing and measures are needed to improve communication between prison and police authorities, prevent police harassment of MMT clients after their release, and improve systems for tracking release dates.

  5. Heroin and Methamphetamine Injection: An Emerging Drug Use Pattern.

    PubMed

    Al-Tayyib, Alia; Koester, Stephen; Langegger, Sig; Raville, Lisa

    2017-07-03

    We sought to describe an emerging drug use pattern characterized by injection of both methamphetamine and heroin. We examined differences in drug injection patterns by demographics, injection behaviors, HIV and HCV status, and overdose. Persons who inject drugs (PWID) were recruited as part of the National HIV Behavioral Surveillance (NHBS) system in Denver, Colorado. We used chi-square statistics to assess differences between those who reported only heroin injection, only methamphetamine injection, and combined heroin and methamphetamine injection. We used generalized linear models to estimate unadjusted and adjusted prevalence ratios to describe the association between drug injection pattern and reported nonfatal overdose in 2015. We also examined changes in the drug reported as most frequently injected across previous NHBS cycles from 2005, 2009, and 2012. Of 592 participants who completed the survey in 2015, 173 (29.2%) reported only injecting heroin, 123 (20.8%) reported only injecting methamphetamine, and 296 (50.0%) reported injecting both drugs during the past 12 months. Injecting both heroin and methamphetamine was associated with a 2.8 (95% confidence interval: 1.7, 4.5) fold increase in reported overdose in the past 12 months compared with only injecting heroin. The proportion of those reporting methamphetamine as the most frequently injected drug increased from 2.1% in 2005 to 29.6% in 2015 (p < 0.001). The rapid increase in methamphetamine injection, and the emergence of combining methamphetamine with heroin, may have serious public health implications.

  6. Reward and Toxicity of Cocaine Metabolites Generated by Cocaine Hydrolase.

    PubMed

    Murthy, Vishakantha; Geng, Liyi; Gao, Yang; Zhang, Bin; Miller, Jordan D; Reyes, Santiago; Brimijoin, Stephen

    2015-08-01

    Butyrylcholinesterase (BChE) gene therapy is emerging as a promising concept for treatment of cocaine addiction. BChE levels after gene transfer can rise 1000-fold above those in untreated mice, making this enzyme the second most abundant plasma protein. For months or years, gene transfer of a BChE mutated into a cocaine hydrolase (CocH) can maintain enzyme levels that destroy cocaine within seconds after appearance in the blood stream, allowing little to reach the brain. Rapid enzyme action causes a sharp rise in plasma levels of two cocaine metabolites, benzoic acid (BA) and ecgonine methyl ester (EME), a smooth muscle relaxant that is mildly hypotensive and, at best, only weakly rewarding. The present study, utilizing Balb/c mice, tested reward effects and cardiovascular effects of administering EME and BA together at molar levels equivalent to those generated by a given dose of cocaine. Reward was evaluated by conditioned place preference. In this paradigm, cocaine (20 mg/kg) induced a robust positive response but the equivalent combined dose of EME + BA failed to induce either place preference or aversion. Likewise, mice that had undergone gene transfer with mouse CocH (mCocH) showed no place preference or aversion after repeated treatments with a near-lethal 80 mg/kg cocaine dose. Furthermore, a single administration of that same high cocaine dose failed to affect blood pressure as measured using the noninvasive tail-cuff method. These observations confirm that the drug metabolites generated after CocH gene transfer therapy are safe even after a dose of cocaine that would ordinarily be lethal.

  7. Examining the Rise in Mexican Drug Cartel Related Violence

    DTIC Science & Technology

    2016-06-10

    funneling money and weapons south to be used by the cartels.5 3 Mexican DTOs supply American consumers with marijuana , methamphetamines and heroin...Tijuana and Juarez. The Sinaloa Cartel is highly diversified and able to smuggle the drugs heroine, marijuana , cocaine, and methamphetamines via all...counter the corruption throughout government, the Mexican Congress passed a law in August 2009 decriminalizing small amounts of cocaine, marijuana and

  8. In silico ordinary differential equation/partial differential equation hemodialysis model estimates methadone removal during dialysis.

    PubMed

    Linares, Oscar A; Schiesser, William E; Fudin, Jeffrey; Pham, Thien C; Bettinger, Jeffrey J; Mathew, Roy O; Daly, Annemarie L

    2015-01-01

    There is a need to have a model to study methadone's losses during hemodialysis to provide informed methadone dose recommendations for the practitioner. To build a one-dimensional (1-D), hollow-fiber geometry, ordinary differential equation (ODE) and partial differential equation (PDE) countercurrent hemodialyzer model (ODE/PDE model). We conducted a cross-sectional study in silico that evaluated eleven hemodialysis patients. Patients received a ceiling dose of methadone hydrochloride 30 mg/day. Outcome measures included: the total amount of methadone removed during dialysis; methadone's overall intradialytic mass transfer rate coefficient, km ; and, methadone's removal rate, j ME. Each metric was measured at dialysate flow rates of 250 mL/min and 800 mL/min. The ODE/PDE model revealed a significant increase in the change of methadone's mass transfer with increased dialysate flow rate, %Δkm =18.56, P=0.02, N=11. The total amount of methadone mass transferred across the dialyzer membrane with high dialysate flow rate significantly increased (0.042±0.016 versus 0.052±0.019 mg/kg, P=0.02, N=11). This was accompanied by a small significant increase in methadone's mass transfer rate (0.113±0.002 versus 0.014±0.002 mg/kg/h, P=0.02, N=11). The ODE/PDE model accurately predicted methadone's removal during dialysis. The absolute value of the prediction errors for methadone's extraction and throughput were less than 2%. ODE/PDE modeling of methadone's hemodialysis is a new approach to study methadone's removal, in particular, and opioid removal, in general, in patients with end-stage renal disease on hemodialysis. ODE/PDE modeling accurately quantified the fundamental phenomena of methadone's mass transfer during hemodialysis. This methodology may lead to development of optimally designed intradialytic opioid treatment protocols, and allow dynamic monitoring of outflow plasma opioid concentrations for model predictive control during dialysis in humans.

  9. Heroin and pharmaceutical opioid overdose events: Emergency medical response characteristics.

    PubMed

    Banta-Green, Caleb J; Coffin, Phillip O; Schoeppe, Jennie A; Merrill, Joseph O; Whiteside, Lauren K; Ebersol, Abigail K

    2017-09-01

    Emergency Medical Services (EMS) data may provide insight into opioid overdose incidence, clinical characteristics, and medical response. This analysis describes patient characteristics, clinical features, and EMS response to opioid overdoses, comparing heroin and pharmaceutical opioid (PO) overdoses, using a structured opioid overdose case criteria definition. A case series study was conducted. EMS medical staff screened cases for possible overdoses and study staff categorized the likelihood of opioid overdose. Medical form data were abstracted. Patient characteristics, clinical presentation, and medical response to heroin and PO-involved overdoses were compared with bi-variate test statistics. We identified 229 definite or probable opioid overdose cases over six months: heroin in 98 (43%) cases (10 also involved PO), PO without heroin in 85 (37%) cases, and 46 (20%) that could not be categorized and were excluded from analyses. Heroin overdose patients were younger than PO (median age 33 v 41 (p<0.05)), more often male (80% v 61% (p=<0.01)), intubated less (8% v 22%, p<0.01) and more likely to be administered naloxone (72% v 51%, p<0.01). No significant differences were found between heroin and PO overdoses for initial respiratory rate, Glasgow Coma Scale score, or co-ingestants, but heroin users were more likely to have miotic pupils (p<0.01). While heroin and PO events presented similarly, heroin-involved cases were more likely to receive naloxone and less likely to be intubated. Standardized case definitions and data documentation could aid opioid overdose surveillance as well as provide data for measuring the impact of professional and lay interventions. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Essential/precursor chemicals and drug consumption: impacts of US sodium permanganate and Mexico pseudoephedrine controls on the numbers of US cocaine and methamphetamine users.

    PubMed

    Cunningham, James K; Liu, Lon-Mu; Callaghan, Russell C

    2016-11-01

    In December 2006 the United States regulated sodium permanganate, a cocaine essential chemical. In March 2007 Mexico, the United States' primary source for methamphetamine, closed a chemical company accused of illicitly importing 60+ tons of pseudoephedrine, a methamphetamine precursor chemical. US cocaine availability and methamphetamine availability, respectively, decreased in association. This study tested whether the controls had impacts upon the numbers of US cocaine users and methamphetamine users. Auto-regressive integrated moving average (ARIMA) intervention time-series analysis. Comparison series-heroin and marijuana users-were used. United States, 2002-14. The National Survey on Drug Use and Health (n = 723 283), a complex sample survey of the US civilian, non-institutionalized population. Estimates of the numbers of (1) past-year users and (2) past-month users were constructed for each calendar quarter from 2002 to 2014, providing each series with 52 time-periods. Downward shifts in cocaine users started at the time of the cocaine regulation. Past-year and past-month cocaine users series levels decreased by approximately 1 946 271 (-32%) (P < 0.05) and 694 770 (-29%) (P < 0.01), respectively-no apparent recovery occurred through 2014. Downward shifts in methamphetamine users started at the time of the chemical company closure. Past-year and past-month methamphetamine series levels decreased by 494 440 (-35%) [P < 0.01; 95% confidence interval (CI) = -771 897, -216 982] and 277 380 (-45%) (P < 0.05; CI = -554 073, -686), respectively-partial recovery possibly occurred in 2013. The comparison series changed little at the intervention times. Essential/precursor chemical controls in the United States (2006) and Mexico (2007) were associated with large, extended (7+ years) reductions in cocaine users and methamphetamine users in the United States. © 2016 Society for the Study of Addiction.

  11. (-)-Stepholidine reduces cue-induced reinstatement of cocaine seeking and cocaine self-administration in rats.

    PubMed

    Manuszak, M; Harding, W; Gadhiya, S; Ranaldi, R

    2018-05-31

    Dopamine receptors are implicated in cocaine reward and seeking. We hypothesize that (-)-stepholidine, a dopamine D1/D2/D3 multi-receptor agent, would be effective in reducing cocaine reward and seeking in an animal model. We investigated the effects of (-)-stepholidine in cue-induced reinstatement of cocaine seeking and cocaine self-administration (reward). Cue-induced reinstatement experiment: Rats were trained to press a lever reinforced by cocaine (1 mg/kg/injection) for 15 consecutive daily sessions, after which the response was extinguished by withholding cocaine and cocaine-paired cues (light and pump activation). This was followed by a cue-induced reinstatement test where subjects were exposed to two cocaine cue presentations and presses on the active lever produced cues. Subjects were treated with one of four (-)-stepholidine doses prior to the reinstatement test. Cocaine self-administration (reward) experiment: Rats were trained to self-administer cocaine under a progressive ratio schedule of reinforcement. After stable breakpoints were established, rats were injected with four doses of (-)-stepholidine prior to testing; each dose was injected prior to a separate test session with no-treatment sessions intervening to re-establish break points. (-)-Stepholidine significantly reduced cue-induced reinstatement of cocaine seeking in a dose-related manner. Additionally, (-)-stepholidine significantly reduced break points for cocaine reward. (-)-Stepholidine did not significantly affect locomotor activity. (-)-Stepholidine reduces cue-induced reinstatement of cocaine seeking and cocaine reward, suggesting that it may be useful in treating relapse in cocaine addiction. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. Anhydroecgonine methyl ester, a cocaine pyrolysis product, may contribute to cocaine behavioral sensitization.

    PubMed

    Garcia, Raphael Caio Tamborelli; Torres, Larissa Helena; Balestrin, Natália Trigo; Andrioli, Tatiana Costa; Flório, Jorge Camilo; de Oliveira, Carolina Dizioli Rodrigues; da Costa, José Luiz; Yonamine, Mauricio; Sandoval, Maria Regina Lopes; Camarini, Rosana; Marcourakis, Tania

    2017-02-01

    Crack cocaine has a high potential to induce cocaine addiction and its smoke contains cocaine's pyrolysis product anhydroecgonine methyl ester (AEME), a partial agonist at M 1 - and M 3 -muscarinic acetylcholine receptor and an antagonist at the remaining subtypes. No reports have assessed AEME's role in addiction. Adult male Wistar rats were intraperitoneally administered with saline, 3mg/kg AEME, 15mg/kg cocaine, or a cocaine-AEME combination on every other day during a period of 9 days. After a 7-days withdrawal period, a challenge injection of the respective drugs was performed on the 17th day. The locomotor activity was evaluated on days 1, 3, 5, 7, 9 and 17, as well as dopamine levels (9th day) and dopaminergic receptors proteins (D 1 R and D 2 R on the 17th day) in the caudate-putamen (CPu) and nucleus accumbens (NAc). AEME was not able to induce the expression of behavioral sensitization, but it substantially potentiates cocaine-effects, with cocaine-AEME combination presenting higher expression than cocaine alone. An increase in the dopamine levels in the CPu in all non-saline groups was observed, with the highest levels in the cocaine-AEME group. There was a decrease in D 1 R protein level in this brain region only for cocaine and cocaine-AEME groups. In the NAc, an increase in the dopamine levels was only observed for cocaine and cocaine-AEME groups, with no changes in both D 1 R and D 2 R protein levels. These behavioral and neurochemical data indicate that AEME alone does not elicit behavioral sensitization but it significantly potentiates cocaine effects when co-administered, resulting in dopamine increase in CPu and NAc, brain regions where dopamine release is mediated by cholinergic activity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. Miss Heroin.

    ERIC Educational Resources Information Center

    Riley, Bernice

    This script, with music, lyrics and dialog, was written especially for youngsters to inform them of the potential dangers of various drugs. The author, who teaches in an elementary school in Harlem, New York, offers Miss Heroin as her answer to the expressed opinion that most drug and alcohol information available is either too simplified and…

  14. Children of Methadone-Maintained Mothers: Three-Year Follow-Up.

    ERIC Educational Resources Information Center

    Johnson, Helen L.; And Others

    The physical and neurobehavioral findings at 3 years of age for 39 children born to mothers on methadone- maintenance and 23 children born to drug-free comparison mothers are reported. The methadone children had a higher incidence of head circumferences less than the third percentile, nystagmus/strabismus, and otitis media. No differences were…

  15. Prevalence of heroin markers in urine for pain management patients.

    PubMed

    Knight, Julie; Puet, Brandi L; DePriest, Anne; Heltsley, Rebecca; Hild, Cheryl; Black, David L; Robert, Timothy; Caplan, Yale H; Cone, Edward J

    2014-10-01

    Surveys of current trends indicate heroin abuse is associated with nonmedical use of pain relievers. Consequently, there is an interest in evaluating the presence of heroin-specific markers in chronic pain patients who are prescribed controlled substances. A total of 926,084 urine specimens from chronic pain patients were tested for heroin/diacetylmorphine (DAM), 6-acetylmorphine (6AM), 6-acetylcodeine (6AC), codeine (COD), and morphine (MOR). Heroin and markers were analyzed using liquid chromatography tandem mass spectrometry (LC-MS-MS). Opiates were analyzed following hydrolysis using LC-MS-MS. The prevalence of heroin use was 0.31%, as 2871 were positive for one or more heroin-specific markers including DAM, 6AM, or 6AC (a known contaminant of illicit heroin). Of these, 1884 were additionally tested for the following markers of illicit drug use: 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA), methamphetamine (MAMP), 11-nor-9-carboxy-Δ(9)-tetracannabinol (THCCOOH), and benzoylecgonine (BZE); 654 (34.7%) had positive findings for one or more of these analytes. The overall prevalence of heroin markers were as follows: DAM 1203 (41.9%), 6AM 2570 (89.5%), 6AC 1082 (37.7%). MOR was present in 2194 (76.4%) and absent (heroin-positive specimens. COD was present in 1218 (42.4%) specimens. Prevalence of combinations for specimens containing MOR were as follows: DAM only 13 (0.59%), 6AM only 1140 (52.0%), 6AC only 24 (1.1%), DAM/6AM/6AC 710 (32.4%), 6AM/6AC 188 (8.6%), DAM/6AM 113 (5.2%), DAM/6AC 6 (0.27%). Importantly, the prevalence of combinations for specimens without MOR were as follows: DAM only 161 (23.8%), 6AM only 217 (32.1%), 6AC only 92 (13.6%), DAM/6AM/6AC 50 (7.4%), 6AM/6AC 7 (1.0%), DAM/6AM 145 (21.4%), DAM/6AC 5 (0.74%). Unexpected patterns of excretion were observed, such as the presence of DAM and 6AC in the absence of 6AM and MOR; therefore, multiple heroin markers may be useful to assess for

  16. A novel UCS memory retrieval-extinction procedure to inhibit relapse to drug seeking.

    PubMed

    Luo, Yi-xiao; Xue, Yan-xue; Liu, Jian-feng; Shi, Hai-shui; Jian, Min; Han, Ying; Zhu, Wei-li; Bao, Yan-ping; Wu, Ping; Ding, Zeng-bo; Shen, Hao-wei; Shi, Jie; Shaham, Yavin; Lu, Lin

    2015-07-14

    We recently reported that a conditioned stimulus (CS) memory retrieval-extinction procedure decreases reinstatement of cocaine and heroin seeking in rats and heroin craving in humans. Here we show that non-contingent cocaine or methylphenidate injections (UCS retrieval) 1 h before the extinction sessions decreases cocaine-priming-induced reinstatement, spontaneous recovery, and renewal of cocaine seeking in rats. Unlike the CS-based memory retrieval-extinction procedure, the UCS memory retrieval manipulation decreases renewal and reinstatement of cocaine seeking in the presence of cocaine cues that were not present during extinction training and also decreases cocaine seeking when the procedure commences after 28 days of abstinence. The inhibitory effect of the UCS retrieval manipulation on cocaine-priming-induced reinstatement is mediated by regulation of AMPA-receptor endocytosis in the basolateral amygdala. The UCS memory retrieval-extinction procedure has superior relapse prevention characteristics than the CS memory retrieval-extinction procedure and could be a promising method for decreasing relapse in human addicts.

  17. A novel UCS memory retrieval-extinction procedure to inhibit relapse to drug seeking

    PubMed Central

    Luo, Yi-xiao; Xue, Yan-xue; Liu, Jian-feng; Shi, Hai-shui; Jian, Min; Han, Ying; Zhu, Wei-li; Bao, Yan-ping; Wu, Ping; Ding, Zeng-bo; Shen, Hao-wei; Shi, Jie; Shaham, Yavin; Lu, Lin

    2015-01-01

    We recently reported that a conditioned stimulus (CS) memory retrieval-extinction procedure decreases reinstatement of cocaine and heroin seeking in rats and heroin craving in humans. Here we show that non-contingent cocaine or methylphenidate injections (UCS retrieval) 1 h before the extinction sessions decreases cocaine-priming-induced reinstatement, spontaneous recovery, and renewal of cocaine seeking in rats. Unlike the CS-based memory retrieval-extinction procedure, the UCS memory retrieval manipulation decreases renewal and reinstatement of cocaine seeking in the presence of cocaine cues that were not present during extinction training and also decreases cocaine seeking when the procedure commences after 28 days of abstinence. The inhibitory effect of the UCS retrieval manipulation on cocaine-priming-induced reinstatement is mediated by regulation of AMPA-receptor endocytosis in the basolateral amygdala. The UCS memory retrieval-extinction procedure has superior relapse prevention characteristics than the CS memory retrieval-extinction procedure and could be a promising method for decreasing relapse in human addicts. PMID:26169171

  18. [Nevirapine induces abstinence symptoms in patients on a methadone maintenance program with HIV infection].

    PubMed

    Baño Rodrigo, M D; Agujetas Rodríguez, M; López García, M L; Guillén Llera, J L

    2000-01-01

    The objective of this study was to investigate the potential inductive effect of nevirapine (NVP) with methadone. Eight patients on the methadone maintenance programme with anti-retroviral therapy because of their infection with HIV, well maintained with methadone and without symptoms of abstinence were studied. All were included in a study of measurement of plasma levels of methadone. Anti-retroviral medication was changed, including NVP, and patients began with symptoms of abstinence 5 to 10 days later. Our results indicate an inductive effect of NVP on the methadone metabolism which caused symptoms of abstinence in all patients, which prompted an increase in the dose and plasma concentration of methadone was lost; patients continued with significantly low plasma levels (p < 0.01) after a therapy mean duration of 6.5 months, with no full recovery.

  19. Stigma towards Marijuana Users and Heroin Users.

    PubMed

    Brown, Seth A

    2015-01-01

    Despite high levels of stigmatizing attitudes and behaviors toward individuals with substance use problems, there is surprisingly limited research on understanding the contributors to such high levels. College students with no history of marijuana or heroin use (N=250) completed self-report measures to examine the level of substance use stigma towards individuals using two illicit substances (marijuana and heroin) and the contribution of three perceiver characteristics (sex, previous contact with substance users, and five beliefs about substance use) to three dimensions of stigma (social distance, negative emotions, and forcing treatment). Greater levels of internalized stigma were noted towards individuals who use heroin (versus marijuana). For marijuana use, those who had less previous contact and higher endorsement of certain beliefs (rarity, severity, and less controllability) were associated with greater stigmatizing attitudes. For heroin use, the associations were weak or non-existent. The findings strengthen the argument that substance use stigma needs to be examined and perhaps addressed substance by substance, rather than as a group. Further, contact interventions may be a particularly effective strategy for altering substance use stigma.

  20. Out-of-hospital mortality among patients receiving methadone for noncancer pain.

    PubMed

    Ray, Wayne A; Chung, Cecilia P; Murray, Katherine T; Cooper, William O; Hall, Kathi; Stein, C Michael

    2015-03-01

    Growing methadone use in pain management has raised concerns regarding its safety relative to other long-acting opioids. Methadone hydrochloride may increase the risk for lethal respiratory depression related to accidental overdose and life-threatening ventricular arrhythmias. To compare the risk of out-of-hospital death in patients receiving methadone for noncancer pain with that in comparable patients receiving sustained-release (SR) morphine sulfate. A retrospective cohort study was conducted using Tennessee Medicaid records from 1997 through 2009. The cohort included patients receiving morphine SR or methadone who were aged 30 to 74 years, did not have cancer or another life-threatening illness, and were not in a hospital or nursing home. At cohort entry, 32 742 and 6014 patients had filled a prescription for morphine SR or methadone, respectively. The patients' median age was 48 years, 57.9% were female, and comparable proportions had received cardiovascular, psychotropic, and other musculoskeletal medications. Nearly 90% of the patients received the opioid for back pain or other musculoskeletal pain. The median doses prescribed for morphine SR and methadone were 90 mg/d and 40 mg/d, respectively. The primary study end point was out-of-hospital mortality, given that opioid-related deaths typically occur outside the hospital. There were 477 deaths during 28 699 person-years of follow-up (ie, 166 deaths per 10 000 person-years). After control for study covariates, patients receiving methadone had a 46% increased risk of death during the follow-up period, with an adjusted hazard ratio (HR) of 1.46 (95% CI, 1.17-1.83; P < .001), resulting in 72 (95% CI, 27-130) excess deaths per 10 000 person-years of follow-up. Methadone doses of 20 mg/d or less, the lowest dose quartile, were associated with an increased risk of death (HR, 1.59; 95% CI, 1.01-2.51, P = .046) relative to a comparable dose of morphine SR (<60 mg/d). The increased risk of death