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  1. The impact of cocaine and heroin on the placental transfer of methadone

    PubMed Central

    Malek, Antoine; Obrist, Cristina; Wenzinger, Silvana; von Mandach, Ursula

    2009-01-01

    Background Methadone is the therapeutic agent of choice for the treatment of opiate addiction in pregnancy. The co-consumption (heroin, cocaine) which may influence the effects of methadone is frequent. Therefore, the impact of cocaine and heroin on the placental transfer of methadone and the placental tissue was investigated under in vitro conditions. Methods Placentae (n = 24) were ex-vivo perfused with medium (m) (control, n = 6), m plus methadone (n = 6), m plus methadone and cocaine (n = 6) or m plus methadone and heroin (n = 6). Placental functionality parameters like antipyrine permeability, glucose consumption, lactate production, hormone production (hCG and leptin), microparticles release and the expression of P-glycoprotein were analysed. Results Methadone accumulated in placental tissue. Methadone alone decreased the transfer of antipyrine from 0.60 +/- 0.07 to 0.50 +/- 0.06 (fetal/maternal ratio, mean +/- SD, P < 0.01), whereas the combination with cocaine or heroin increased it (0.56 +/- 0.08 to 0.68 +/- 0.13, P = 0.03 and 0.58 +/- 0.21 to 0.71 +/- 0.24; P = 0.18). Microparticles (MPs) released from syncytiotrophoblast into maternal circuit increased by 30% after cocaine or heroin (P < 0.05) and the expression of P-glycoprotein in the tissue increased by ≥ 49% after any drug (P < 0.05). All other measured parameters did not show any significant effect when methadone was combined with cocaine or heroine. Conclusion The combination of cocaine or heroin with methadone increase antipyrine permeability. Changes of MPs resemble findings seen in oxidative stress of syncytiotrophoblast. PMID:19519880

  2. Is slow-onset long-acting monoamine transport blockade to cocaine as methadone is to heroin? Implication for anti-addiction medications.

    PubMed

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

    2010-12-01

    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.

  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

    Brunet, Bertrand R; Barnes, Allan J; Scheidweiler, Karl B; Mura, Patrick; Huestis, Marilyn A

    2008-09-01

    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.

  4. The quantitative analysis of heroin, methadone and their metabolites and the simultaneous detection of cocaine, acetylcodeine and their metabolites in human plasma by high-performance liquid chromatography coupled with tandem mass spectrometry.

    PubMed

    Rook, Elisabeth J; Hillebrand, Michel J X; Rosing, Hilde; van Ree, Jan M; Beijnen, Jos H

    2005-09-25

    For a pharmacokinetic-pharmacodynamic study in opioid tolerant patients, who were treated with heroin in combination with methadone, a liquid chromatographic assay with tandem mass spectrometry detection (LC-MS/MS) was developed for the simultaneous determination of heroin, methadone, heroin metabolites 6-monoacetylmorphine, morphine, and morphine-6 and 3-glucuronide and methadone metabolite EMDP. To detect any abuse of substances besides the prescribed opioids the assay was extended with the detection of cocaine, its metabolites benzoylecgonine and norcocaine and illicit heroin adulterants acetylcodeine and codeine. Heroin-d6, morphine-d3, morphine-3-glucuronide-d3 and methadone-d9 were used as internal standards. The sample pre-treatment consisted of solid phase extraction using mixed mode sorbent columns (MCX Oasis). Chromatographic separation was performed at 25 degrees C on a reversed phase Zorbax column with a gradient mobile phase consisting of ammonium formate (pH 4.0) and acetonitrile. The run time was 15 min. MS with relatively mild electrospray ionisation under atmospheric pressure was applied. The triple quadrupole MS was operating in the positive ion mode and multiple reaction monitoring (MRM) was used for drug quantification. The method was validated over a concentration range of 5-500 ng/mL for all analytes. The total recovery of heroin varied between 86 and 96% and of the heroin metabolites between 76 and 101%. Intra-assay and inter-assay accuracy and precision of all analytes were always within the designated limits (< or =20% at lower limit of quantification (LLQ) and < or =15% for other samples). This specific and sensitive assay was successfully applied in pharmacokinetic studies with medically prescribed heroin and toxicological cases.

  5. Methadone Anonymous: A 12-Step Program for Methadone Maintained Heroin Addicts.

    PubMed

    Gilman, Stephen M.; Galanter, Marc; Dermatis, Helen

    2001-12-01

    Methadone Anonymous (MA) is a new 12-step fellowship developed for methadone maintained heroin addicts. A total of 53 MA members completed a survey assessing factors related to methadone maintenance treatment program (MMTP) entry, drug use, MA participation, beliefs concerning effectiveness of MMTP and MA, and level of social cohesiveness. Length of time in MA was associated with a decreased use of alcohol, cocaine, and marijuana. Clients rated components of MA to be significantly more helpful to recovery than MMTP treatment components. Affiliation to five MA members known best by the respondents was significantly greater than affiliation to non-MA members. Length of time in MA was positively associated with MA affiliation. Social affiliation and endorsement of 12-step principles were positively correlated. These findings suggest that MA participation has benefits not available in professionally driven MMTP, and should be further studied.

  6. Effects of high-dose methadone maintenance on cocaine place conditioning, cocaine self-administration, and mu-opioid receptor mRNA expression in the rat brain.

    PubMed

    Leri, Francesco; Zhou, Yan; Goddard, Benjamin; Cummins, Erin; Kreek, Mary Jeanne

    2006-07-01

    Methadone maintenance at appropriate doses can effectively reduce cocaine abuse in heroin-dependent individuals. In the present studies, we investigated the effect of high-dose methadone maintenance cocaine conditioned place preference (CPP) and cocaine intravenous self-administration. Rats implanted with methadone-filled osmotic mini-pumps (20 and 55 mg/kg/day, SC) and conditioned with cocaine (1, 5, and 20 mg/kg, i.p.) did not express cocaine CPP. Similarly, rats implanted with methadone pumps (55 mg/kg/day) after cocaine conditioning (20 mg/kg) displayed neither spontaneous nor cocaine-precipitated (20 mg/kg, i.p.) CPP. In contrast, methadone maintenance (30 and 55 mg/kg/day, SC) did not alter the intravenous self-administration (continuous schedule of reinforcement) of various doses of cocaine (0.1, 0.5, and 2.0 mg/kg/inf). To explore neuropharmacological interactions between methadone maintenance and cocaine conditioning, we quantitatively measured mRNA levels of mu-opioid receptor (MOR) and proopiomelanocortin genes 10 days after methadone maintenance. MOR mRNA levels in both the nucleus accumbens core and frontal cortex were significantly elevated in rats exposed to cocaine during CPP conditioning. However, upregulation of MOR mRNA levels in the nucleus accumbens core were reduced by methadone maintenance in a dose-dependent manner. In conclusion, our results suggest that high-dose methadone maintenance does not alter the direct reinforcing effect of cocaine, but blocks spontaneous and cocaine-precipitated cocaine-seeking, possibly by preventing MOR alterations in the nucleus accumbens core induced by cocaine conditioning.

  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. Implosive Therapy Treatment of Heroin Addicts during Methadone Detoxification.

    ERIC Educational Resources Information Center

    Hirt, Michael; Greenfield, Heywood

    1979-01-01

    Examined effectiveness of implosive therapy with heroin addicts during detoxification from methadone. Treatment groups received 12 sessions of implosive therapy or eclectic counseling and were followed for a six-week period. The implosive therapy group were the only ones to significantly reduce their methadone level during treatment and follow-up.…

  9. Comparison of urine results concerning co-consumption of illicit heroin and other drugs in heroin and methadone maintenance programs.

    PubMed

    Musshoff, Frank; Trafkowski, Jens; Lichtermann, Dirk; Madea, Burkhard

    2010-09-01

    Urine samples of patients from a heroin maintenance program (HMP) and a methadone maintenance program (MMP) were chromatographically analyzed 1 month before and 6 and 12 months into treatment for the presence of classical markers of heroin use as well as for the presence of markers for illicit heroin abuse. Furthermore, the samples were immunochemically tested for cannabinoids, cocaine metabolites, amphetamine, methylendioxyamphetamines and benzodiazepines. A co-consumption of illicit heroin (HER) in the HMP was determined to be 50% but was significantly lower compared to the MMP with a co-use of 71%. The incidence was high because not only acetylcodeine (AC) as a very specific marker was considered but also other marker substances for illicit HER use. Amphetamines played only a minor part in both collectives, and the proportion of HER and methadone patients using cocaine was similar and decreased during treatment. Also, the benzodiazepine use decreased, and cannabis use was high in both collectives during treatment. Considering only the AC in the present study, a co-use of illicit HER in the HMP was similar to previous reports concerning HER-assisted treatment programs. If additional marker substances were examined, the suspicion of a co-use of illicit HER is markedly enhanced.

  10. Inflammatory response in heroin addicts undergoing methadone maintenance treatment.

    PubMed

    Chan, Yuan-Yu; Yang, Szu-Nian; Lin, Jyh-Chyang; Chang, Junn-Liang; Lin, Jaung-Geng; Lo, Wan-Yu

    2015-03-30

    Opioid addiction influences many physiological functions including reactions of the immune system. The objective of this study was to investigate the immune system function in heroin addicted patients undergoing methadone maintenance treatment (MMT) compared to healthy controls. We tested the cytokine production of IL-1β, IL-6, IL-8, IL-10 and tumor necrosis factor (TNF)-α from a group of heroin addicts (n=34) and healthy controls (n=20). The results show that production of IL-1β, IL-6 and IL-8 was significantly higher in the group of methadone-maintained patients than in the healthy control group. Plasma TNF-α and IL-6 levels were significantly correlated with the dairy methadone dosage administered, and the IL-1β level was significantly correlated with the duration of methadone maintenance treatment. These findings suggest that methadone maintenance treatment influences the immune system functions of opioid-dependent patients and may also induce long-term systemic inflammation.

  11. Protecting against cocaine, heroin, and sarin gas.

    PubMed

    McRee, Duncan

    2003-04-01

    The first X-ray structure of human carboxylesterase 1 (hCE1) and the structures of hCE1 with drug analogs bound reveal important molecular details of how the drugs cocaine, heroin, and tacrine are metabolized and cleared.

  12. Satisfaction With Methadone Among Heroin-Dependent Patients With Current Substance Use Disorders During Methadone Maintenance Treatment.

    PubMed

    Perez de Los Cobos, Jose; Trujols, Joan; Siñol, Núria; Duran-Sindreu, Santiago; Batlle, Francesca

    2016-04-01

    Methadone maintenance treatment (MMT) has long been used to treat heroin-dependent patients. However, satisfaction with methadone in this patient population is unknown. The aim of this cross-sectional case-control study was to evaluate satisfaction with methadone in heroin-dependent patients with current substance use disorders (SUDs). Cases included 152 methadone-maintained patients with current SUD, requiring inpatient detoxification treatment, and controls included 33 methadone-maintained patients in sustained full remission for SUD. Satisfaction with methadone as a medication to treat heroin addiction was measured by using the Scale to Assess Satisfaction with Medications for Addiction Treatment-methadone for heroin addiction (SASMAT-METHER). The SASMAT-METHER subscales assess the following domains: personal functioning and well-being, antiaddictive effect on heroin, and antiaddictive effect on other substances. Compared with patients with remitted SUD, patients with current SUD scored lower on all SASMAT-METHER assessments. In such patients, overall SASMAT-METHER scores were independently and negatively associated with downward desired adjustment of methadone dose and days of heroin use during last month; although various sets of factors were independently associated with each of the SASMAT-METHER subscales, the only determinant of dissatisfaction on all subscales was the desire for downward adjustment of methadone dose. In summary, MMT patients with current SUD are less satisfied with methadone than MMT patients with remitted SUD. In patients with current SUD, downward desired adjustment of methadone dose and days of heroin use during last month are independently associated with overall dissatisfaction with methadone.

  13. Adolescent and young adult heroin patients: drug use and success in methadone maintenance treatment.

    PubMed

    Kellogg, Scott; Melia, Dorothy; Khuri, Elizabeth; Lin, Amy; Ho, Ann; Kreek, Mary Jeanne

    2006-01-01

    This study examined the impact of methadone maintenance treatment on an inclusive group of adolescent and young adult opiate-dependent patients, ages 15-23, admitted over a 6-year period, during their first year in the program. Retention in treatment was the primary outcome variable, and at 12 months, 48% were still in treatment. The findings were: (a) a stepwise discriminant function analysis revealed that patients who consistently used heroin were at a greater risk of leaving treatment within the first 12 months; (b) the use of cocaine was an indicator of higher levels of heroin use in those who reached the one-year mark; (c) among patients who stayed in treatment for one year, there was a significant reduction in heroin use, a trend toward a reduction in cocaine use, and no significant impact on benzodiazepine use; and (d) the group that stayed in treatment was slightly younger than the group that left before the first year ended. There were no gender or ethnic differences between the two groups. Suggestions for interventions that might improve treatment outcome are presented.

  14. Incarcerated intravenous heroin users: predictors of post-release utilization of methadone maintenance treatment.

    PubMed

    Lin, Huang-Chi; Wang, Peng-Wei; Yang, Yi-Hsin; Tsai, Jih-Jin; Yen, Cheng-Fang

    2016-01-01

    Incarcerated intravenous heroin users have more problematic patterns of heroin use, but are less likely to access methadone maintenance treatment by their own initiative than heroin users in the community. The present study examined predictors for receiving methadone maintenance treatment post-release among incarcerated intravenous heroin users within a 24-month period. This cohort study recruited 315 incarcerated intravenous heroin users detained in 4 prisons in southern Taiwan and followed up within the 24-month period post-release. Cox proportional hazards regression analysis was applied to determine the predictive effects of sociodemographic and drug-use characteristics, attitude toward methadone maintenance treatment, human immunodeficiency virus serostatus, perceived family support, and depression for access to methadone maintenance treatment after release. There were 295 (93.7%) incarcerated intravenous heroin users released that entered the follow-up phase of the study. During the 24-month follow-up period, 50.8% of them received methadone maintenance treatment. After controlling for the effects of the detainment period before and after recruitment by Cox proportional hazards regression analysis, incarcerated intravenous heroin users who had positive human immunodeficiency virus serostatus (HR = 2.85, 95% CI = 1.80-4.52, p < .001) and had ever received methadone maintenance treatment before committal (HR = 1.94, 95% CI = 1.23-3.05, p < .01) were more likely to enter methadone maintenance treatment within the 24-month follow-up period. Positive human immunodeficiency virus serostatus with fully subsidized treatment and previous methadone maintenance treatment experiences predicted access of methadone maintenance treatment post-release. Strategies for getting familiar with methadone maintenance treatment during detainment, including providing methadone maintenance treatment prior to release and lowering the economic burden of receiving treatment, may

  15. 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.

  16. Effect of reinforcement probability and prize size on cocaine and heroin abstinence in prize-based contingency management.

    PubMed

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

    2008-01-01

    Although treatment outcome in prize-based contingency management has been shown to depend on reinforcement schedule, the optimal schedule is still unknown. Therefore, we conducted a retrospective analysis of data from a randomized clinical trial (Ghitza et al., 2007) to determine the effects of the probability of winning a prize (low vs. high) and the size of the prize won (small, large, or jumbo) on likelihood of abstinence until the next urine-collection day for heroin and cocaine users (N=116) in methadone maintenance. Higher probability of winning, but not the size of individual prizes, was associated with a greater percentage of cocaine-negative, but not opiate-negative, urines.

  17. Psychiatric morbidity among cocaine and heroin users in the community.

    PubMed

    Tortajada, Silvia; Herrero, Ma Jesús; Domingo-Salvany, Antònia; Molist, Gemma; Barrio, Gregorio; de la Fuente, Luís; Brugal, Ma Teresa

    2012-01-01

    Drug abuse is a serious public health problem. Moreover, co-occurring mental health and substance abuse disorders are common among drug users. This paper examines psychiatric disorders of young cocaine and heroin users using the World Mental Health Composite International Diagnostic Interview (WMH-CIDI). A cohort of 1266 young (18-30 years) current regular cocaine (705) and heroin (561) users were recruited outside the health services in Barcelona, Madrid and Seville, Spain. The WMH-CIDI was used to evaluate mental disorders; the Severity of Dependence Scale (SDS) measured the degree of dependence; and the Duke-UNC Functional Social Support Questionnaire (FSSQ) assessed social support, in a crosssectional study design. About 43% was diagnosed with a lifetime mental disorder. The most common diagnoses were depression (37.5%) and specific phobia (6.8%). During the last 12 months, prevalence rates were also slightly higher in heroin group (26.4%) than in cocaine cohort (21.7%). Every day cocaine consumption, having unstable living conditions and low social support were variables highly associated with psychiatric morbidity in cocaine cohort. In heroin cohort, earning money through illegal activities was associated with psychiatric morbidity, while the moderate use of alcohol acted as a protective factor for mental pathology. Morbidity was associated to having received psychiatric/psychological treatment during the last 12 months in both cohorts. This study has shown a relatively high prevalence of psychiatric morbidity in cocaine and heroin users recruited in non-clinical settings. Future studies examining differences between cocaine and heroin patterns of consumption associated with mental diseases are necessary.

  18. Analysis of Cocaine, Heroin, and their Metabolites in Saliva

    DTIC Science & Technology

    1990-07-10

    from a study of the metabolism of radiolabeled cocaine.6 Later, cocaine was found in the saliva of impaired drivers.7 Most studies show similar...reported.9,10 The latter was a controlled study examined the metabolism of heroin in plasma and saliva. This study followed the metabolism of heroin by...in Table 1. Table 1 - HPLC Conditions Column: Alltech/Applied Science Econosphere C8, 250 x 4.6 mm Solvent A: 0.1M Ammonium Acetate Solvent B: 10:90

  19. Methadone

    PubMed Central

    Sim, S. K.

    1973-01-01

    Methadone and acetylmethadol, although possessing almost all of morphine's pharmacological properties, differ from other morphine-like drugs in their longer action, more gradual and less intense withdrawal syndrome, and blockade of euphoric effect of other opiates in addicts. A high percentage of patients maintained on methadone are better able to hold employment or to be otherwise socially productive than when dependent on heroin or morphine. A review of published results and procedures used in methadone maintenance treatment programs for heroin dependence is presented. Former heroin addicts are usually maintained on 80 to 120 mg. (high dose) or 20 to 60 mg. (low dose) oral methadone daily. Some programs are reported to have produced 80% success (patients employed or otherwise socially productive). Selection of patients, availability of allied therapeutic and rehabilitative facilities, strict control of supply, record keeping and periodic evaluation are considered essential. Different criteria (“drug-free” vs. “socially productive”) for judging “success” of treatment of heroin-dependent persons by methadone maintenance and administrative problems in large-scale treatment programs constitute the principal aspects of controversy. PMID:4599599

  20. Nutritional effects of marijuana, heroin, cocaine, and nicotine.

    PubMed

    Mohs, M E; Watson, R R; Leonard-Green, T

    1990-09-01

    Use of addictive drugs, such as cocaine, marijuana, and nicotine, affects food and liquid intake behavior, taste preference, and body weight. Changes in specific nutrient status and metabolism can also develop; heroin addiction can cause hyperkalemia and morphine use can result in calcium inhibition. Nutrition-related physiological aspects, such as impaired gastrin release, hypercholesterolemia, hypothermia, and hyperthermia, are also seen with morphine use. Nutrition-related conditions can affect sensitivity to and dependence on drugs and their effects. Diabetes decreases sensitivity to and dependence on morphine, protein deprivation produces preferential fat utilization with low cocaine use, and vitamin D deficiency decelerates morphine dependency. During use and/or withdrawal from nicotine, heroin, marijuana, and cocaine, major changes in food selection and intake occur, which result in weight gain or loss. Detailed human studies are needed to investigate the effects of drug use on the broad spectrum of nutrients and to determine the role of nutrition during drug withdrawal.

  1. Epigenetically modified nucleotides in chronic heroin and cocaine treated mice.

    PubMed

    Chao, Mu-Rong; Fragou, Domniki; Zanos, Panos; Hu, Chiung-Wen; Bailey, Alexis; Kouidou, Sofia; Kovatsi, Leda

    2014-09-17

    Epigenetic changes include the addition of a methyl group to the 5' carbon of the cytosine ring, known as DNA methylation, which results in the generation of the fifth DNA base, namely 5-methylcytosine. During active or passive demethylation, an intermediate modified base is formed, 5-hydroxymethylcytosine. We have currently quantified 5-methylcytosine and 5-hydroxymethylcytosine in the liver and brain of mice treated with cocaine or heroin, using liquid chromatography/tandem mass spectrometry (LC-MS/MS). Our results show that global 5-methylcytosine levels are not affected by heroin or cocaine administration, neither in the liver nor in the brain. However, 5-hydroxymethylcytosine levels are reduced in the liver following cocaine administration, while they are not affected by cocaine in the brain or by heroin administration in the liver and the brain. Elucidation of the epigenetic phenomena that takes place with respect to drug abuse and addiction, via quantitative analysis of different modified bases, may enable a better understanding of the underlying mechanisms and may lead to more personalized and effective treatment options.

  2. Sex effects in cocaine using methadone patients randomized to contingency management interventions

    PubMed Central

    Burch, Ashley E.; Rash, Carla J.; Petry, Nancy M.

    2015-01-01

    Contingency management (CM) is an effective treatment for promoting cocaine abstinence in patients receiving methadone maintenance. However, few studies have examined the effect of sex on treatment outcomes in this population. This study evaluated the impact of sex on longest duration of abstinence (LDA) and percent negative urine samples in 323 cocaine-using methadone patients from four randomized clinical trials comparing CM to standard methadone care. Overall, women had better treatment outcomes compared to men, demonstrated by an increase in both LDA and percentages of negative samples. Patients receiving CM also had significantly higher LDA and percentages of negative samples compared to patients receiving standard care, but sex by treatment condition effects were not significant. These data suggest that cocaine using methadone patients who are women have better substance use outcomes than men in interventions that regularly monitor cocaine use, and CM is equally efficacious regardless of sex. PMID:26237326

  3. Aggressive responding of male heroin addicts under methadone treatment: psychometric and neuroendocrine correlates.

    PubMed

    Gerra, G; Zaimovic, A; Raggi, M A; Giusti, F; Delsignore, R; Bertacca, S; Brambilla, F

    2001-12-01

    Objective measures of experimentally-induced aggressiveness were evaluated in 20 methadone-treated heroin addicts, in comparison to 20 normal healthy male subjects. All the subjects were submitted to preliminary DSM IV interviews, Buss Durkee Hostility Inventory (BDHI) and Minnesota Multiphasic Personality Inventory (MMPI II). During a laboratory task, the point subtraction aggression paradigm (PSAP), subjects earned monetary reinforcers with repeated button presses, and were provoked by the subtraction of money, which was attributed to a fictitious other participants. Subjects could respond by ostensibly subtracting money from the fictitious subject (the aggressive response), or protecting their counter (escape response). Money-earning responses were significantly lower (t=4.38, P<0.001) and aggressive responses significantly higher (t=5.45; P<0.001) in methadone patients in comparison to controls. During the experimentally-induced aggressiveness, plasma adrenocorticotropic hormone (ACTH), cortisol (CORT) and growth hormone (GH) concentrations increased significantly less and norepinephrine (NE) and epinephrine (EPI) levels, together with heart rate (HR), significantly more in methadone subjects than in healthy subjects. PSAP aggressive responses positively correlated with catecholamines changes, BDHI 'direct' and 'irritability' scores, MMPI 'psychopathic deviate' scores both in methadone subjects and controls, and with CORT responses only in healthy subjects. No correlation was found between methadone doses, or exposure extent, and aggressiveness levels. Our findings suggest that heroin dependent patients have higher outward-directed aggressiveness than healthy subjects, in relationship with monoamines hyper-reactivity, also under methadone medication. Aggressiveness in methadone patients seems to be related more to the personality traits than to drug effects. Hypothalamus-pituitary-adrenal (HPA) axis responses, unexpectedly dissociated from catecholamines rise

  4. METODO, a prospective observational study to assess the efficacy and tolerability of methadone in heroin-addicted patients undergoing a methadone maintenance treatment: preliminary results at baseline evaluation.

    PubMed

    D'Egidio, Pietro Fausto; Bignamini, Emanuele; De Vivo, Enrico; Leonardi, Claudio; Pieri, Maria Chiara; González-Saiz, Francisco; Lucchini, Alfio

    2013-12-01

    METODO (methadone efficacy therapy optimization dosage on-going) is a prospective observational study to assess the efficacy and tolerability of methadone in 500 heroin-addicted patients taking a methadone maintenance treatment, enrolled through 2010 to 2011 in five Italian sites, observed over 2 years. The Opiate Dosage Adequacy Scale has been used for the evaluation of the "adequacy" of the methadone dosage and to stratify patients in adequate and not adequate groups. The treatment efficacy has been evaluated in correlation to the dosage adequacy during the visits. Moreover, patients have been evaluated according to the retention rate and duration of retention in treatment and a series of questionnaires.

  5. The comparative toxicology and major organ pathology of fatal methadone and heroin toxicity cases.

    PubMed

    Darke, Shane; Duflou, Johan; Torok, Michelle

    2010-01-01

    In order to determine the comparative toxicology and systemic disease of cases of death due to methadone and heroin toxicity, 1193 coronial cases of opioid overdose that occurred in New South Wales, Australia between 1 January 1998 and 31 December 2007 were inspected. These comprised 193 cases in which cause of death involved methadone toxicity (METH) and 1000 cases in which cause of death involved heroin toxicity in the absence of methadone (HER). METH cases were significantly more likely to have benzodiazepines (63.7% vs. 32.2%), and less likely to have alcohol (23.6% vs. 42.7%) detected. METH cases were significantly more likely to be diagnosed with pre-existing systemic pathology (94.3% vs. 79.9%), and multiple organ system pathology (68.8% vs. 41.4%). Specifically, METH cases were more likely to have cardiac (58.9% vs. 34.5%), pulmonary (53.6% vs. 30.9%), hepatic (80.7% vs. 62.8%) and renal (25.0% vs. 9.5%) disease. Given the notable differences in toxicology and disease patterns, great caution appears warranted in prescribing benzodiazepines to methadone users, and regular physical examinations of methadone treatment patients would appear clinically warranted.

  6. 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

  7. Prize Reinforcement Contingency Management for Cocaine Dependence: Integration with Group Therapy in a Methadone Clinic

    ERIC Educational Resources Information Center

    Petry, Nancy M.; Martin, Bonnie; Simcic, Francis

    2005-01-01

    In this study, the authors evaluated a low-cost contingency management (CM) procedure for reducing cocaine use and enhancing group therapy attendance in 77 cocaine-dependent methadone patients. Patients were randomly assigned to 12 weeks of standard treatment or standard treatment with CM, in which patients earned the opportunity to win prizes…

  8. Effect of chronic heroin and cocaine administration on global DNA methylation in brain and liver.

    PubMed

    Fragou, Domniki; Zanos, Panos; Kouidou, Sofia; Njau, Samuel; Kitchen, Ian; Bailey, Alexis; Kovatsi, Leda

    2013-04-26

    Drug abuse is associated with epigenetic changes, such as histone modifications and DNA methylation. The purpose of the present study was to examine the effect of chronic cocaine and heroin administration on global DNA methylation in brain and liver. Male, 8 week old, C57BL/6J mice received heroin in a chronic 'intermittent' escalating dose paradigm, or cocaine in a chronic escalating dose 'binge' paradigm, which mimic the human pattern of opioid or cocaine abuse respectively. Following sacrifice, livers and brains were removed and DNA was extracted from them. The extracted DNA was hydrolyzed and 2'-deoxycytidine and 5-methyl-2'-deoxycytidine were determined by HPLC-UV. The % 5-methyl-2'-deoxycytidine content of DNA was significantly higher in the brain compared to the liver. There were no differences between the control animals and the cocaine or heroin treated animals in neither of the tissues examined, which is surprising since cocaine administration induced gross morphological changes in the liver. Moreover, there was no difference in the % 5-methyl-2'-deoxycytidine content of DNA between the cocaine and the heroin treated animals. The global DNA methylation status in the brain and liver of mice chronically treated with cocaine or heroin remains unaffected, but this finding cannot exclude the existence of anatomical region or gene-specific methylation differences. This is the first time that global DNA methylation in the liver and whole brain has been studied following chronic cocaine or heroin treatment.

  9. 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

  10. Adipocyte-derived hormones in heroin addicts: the influence of methadone maintenance treatment.

    PubMed

    Housová, J; Wilczek, H; Haluzík, M M; Kremen, J; Krízová, J; Haluzík, M

    2005-01-01

    Heroin addiction markedly affects the nutritional and metabolic status and frequently leads to malnutrition. The aim of our study was to compare circulating concentration of adipose tissue-derived hormones leptin, adiponectin and resistin in 12 patients with heroin addiction before and after one-year methadone maintenance treatment with the group of 20 age- and body mass index-matched healthy subjects. Basal serum leptin and adiponectin levels in heroin addicts were significantly decreased (3.4+/-0.4 vs. 4.5+/-0.6 ng/ml and 18.9+/-3.3 vs. 33.9+/-3.1 ng/microl, respectively; p 0.05) while serum resistin concentrations were increased compared to healthy subjects (10.1+/-1.2 vs. 4.6+/-0.3 ng/ml; p 0.05). Moreover, positive correlation of serum leptin levels with body mass index was lost in the addicts in contrast to control group. One year of methadone maintenance treatment normalized serum leptin, but not serum adiponectin and resistin concentrations. In conclusion, circulating concentrations of leptin, adiponectin and resistin are markedly altered in patients with chronic heroin addiction. These alterations appear to be relatively independent of nutritional status and insulin sensitivity.

  11. Concurrent Alcohol Dependence Among Methadone-Maintained Cocaine Abusers Is Associated with Greater Abstinence

    PubMed Central

    Byrne, Shannon A.; Petry, Nancy M.

    2011-01-01

    Concurrent alcohol dependence (AD) among polysubstance abusers has been associated with negative consequences, although it may not necessarily lead to poor treatment outcomes. One of the most efficacious treatments for cocaine abuse is contingency management (CM), but little research has explored the impact of AD on abstinence outcomes, particularly among patients in methadone maintenance. Using data from three trials of CM for cocaine use, we compared baseline characteristics and post-treatment and follow-up cocaine outcomes between methadone maintained, cocaine dependent patients (N=193) with and without concurrent AD, randomized to standard care (SC) with or without CM. Patients with and without concurrent AD had similar baseline characteristics, with the exception that AD patients reported more alcohol use. AD patients achieved longer durations of cocaine abstinence and were more likely to submit a cocaine negative sample at follow-up than non-AD patients. Patients randomized to CM achieved better outcomes than those randomized to SC, but there was no interaction between treatment condition and AD status. These findings suggest that cocaine using methadone patients with AD achieve greater cocaine abstinence than their non-AD counterparts and should not be necessarily viewed as more difficult to treat. PMID:21463068

  12. Cocaine

    MedlinePlus

    ... The Brain & the Actions of Cocaine, Opiates, and Marijuana The first in a 5-part series, offers ... when a person uses cocaine, opiates (heroine), or marijuana. Download PDF 4.13 MB Chat Day Transcripts ...

  13. Active heroin injectors' perceptions and use of methadone maintenance treatment: cynical performance or self-prescribed risk reduction?

    PubMed

    Koester, S; Anderson, K; Hoffer, L

    1999-12-01

    In addition to the numerous heroin users who voluntarily enter methadone treatment as a way to free themselves from illicit drug addiction and those ordered to do so by the courts, there are a large number of opioid users who enter methadone treatment with other objectives in mind. These include shorter-term goals that users do not necessarily equate with complete heroin abstinence. In this paper we report the results of a qualitative study designed to identify and describe the motivations active heroin users have for entering methadone treatment, and to suggest that many of these short-term methadone episodes may operate as self-prescribed attempts at risk reduction, and act as pilot tests for users considering or anticipating entering treatment to quit the use of illicit drugs. We argue that heroin users' motivations, perceptions about methadone, and the strategies they devise for adapting methadone treatment for their own needs should be recognized for their value in reducing the multiple risks associated with drug use.

  14. Anxiety disorders are associated with early onset of heroin use and rapid transition to dependence in methadone maintained patients.

    PubMed

    Karsinti, Emily; Fortias, Maeva; Dupuy, Gaël; Ksouda, Kamilia; Laqueille, Xavier; Simonpoli, Anne-Marie; Touzeau, Didier; Avril, Elisabeth; Orizet, Cyrille; Belforte, Beatriz; Coeuru, Philippe; Polomeni, Pierre; Icick, Romain; Jarroir, Marine; Bloch, Vanessa; Scott, Jan; Lépine, Jean-Pierre; Bellivier, Frank; Vorspan, Florence

    2016-11-30

    Early onset of heroin use is a severity marker of heroin use disorder. We studied the interaction between early onset and rapid transition to heroin dependence recorded with retrospective interviews in 213 patients with severe heroin dependence and history of methadone maintenance treatment. General linear models were used to identify independent factors associated with early onset, factors associated with rapid transition to dependence, and a multivariate model was used to study the interaction of those two dimensions. Lifetime history of anxiety disorders and age at onset of cannabis use are shared common risk factors and are associated with the interaction.

  15. Neurotoxicity of heroin-cocaine combinations in rat cortical neurons.

    PubMed

    Cunha-Oliveira, Teresa; Rego, A Cristina; Garrido, Jorge; Borges, Fernanda; Macedo, Tice; Oliveira, Catarina R

    2010-09-30

    Cocaine and heroin are frequently co-abused by humans, in a combination known as speedball. Recently, chemical interactions between heroin (Her) or its metabolite morphine (Mor) and cocaine (Coc) were described, resulting in the formation of strong adducts. In this work, we evaluated whether combinations of Coc and Her affect the neurotoxicity of these drugs, using rat cortical neurons incubated with Coc, Her, Her followed by Coc (Her+Coc) and Her plus Coc (Her:Coc, 1:1). Neurons exposed to Her, Her+Coc and Her:Coc exhibited a decrease in cell viability, which was more pronounced in neurons exposed to Her and Her+Coc, in comparison with neurons exposed to the mixture (Her:Coc). Cells exposed to the mixture showed increased intracellular calcium and mitochondrial dysfunction, as determined by a decrease in intracellular ATP levels and in mitochondrial membrane potential, displaying both apoptotic and necrotic characteristics. Conversely, a major increase in cytochrome c release, caspase 3-dependent apoptosis, and decreased metabolic neuronal viability were observed upon sequential exposure to Her and Coc. The data show that drug combinations potentiate cortical neurotoxicity and that the mode of co-exposure changes cellular death pathways activated by the drugs, strongly suggesting that chemical interactions occurring in Her:Coc, such as adduct formation, shift cell death mechanisms towards necrosis. Since impairment of the prefrontal cortex is involved in the loss of impulse control observed in drug addicts, the data presented here may contribute to explain the increase in treatment failure observed in speedball abusers.

  16. 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…

  17. Analysis of illicit cocaine and heroin samples seized in Luxembourg from 2005-2010.

    PubMed

    Schneider, Serge; Meys, François

    2011-10-10

    This article discusses drug purity, frequency of appearance and concentration ranges of adulterants of 471 illicit cocaine and 962 illicit heroin samples seized in Luxembourg from January 2005 to December 2010. For cocaine samples the mean concentration was lowest in 2009 (43.2%) and highest in 2005 (54.7%) but no clear trend could be observed during the last 6 years. 14 different adulterants have been detected in cocaine samples, from which phenacetin has been the most abundant in terms of frequency of appearance and concentration until 2009. In 2010 the veterinary antihelminthic drug levamisole has become the most abundant adulterant detected in cocaine samples, its concentrations however remained low (1.5-4.1%). The mean heroin concentration was 26.6% in 2005, a decline has been observed in 2006 and the concentrations have been relatively stable since then (15.8-17.4%). Paracetamol and caffeine were by far the most abundant adulterants detected in heroin samples.

  18. 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

  19. Changes in dopamine transporter binding in nucleus accumbens following chronic self-administration cocaine: heroin combinations.

    PubMed

    Pattison, Lindsey P; McIntosh, Scot; Sexton, Tammy; Childers, Steven R; Hemby, Scott E

    2014-10-01

    Concurrent use of cocaine and heroin (speedball) has been shown to exert synergistic effects on dopamine neurotransmission in the nucleus accumbens (NAc), as observed by significant increases in extracellular dopamine levels and compensatory elevations in the maximal reuptake rate of dopamine. The present studies were undertaken to determine whether chronic self-administration of cocaine, heroin or a combination of cocaine:heroin led to compensatory changes in the abundance and/or affinity of high- and low-affinity DAT binding sites. Saturation binding of the cocaine analog [(125) I] 3β-(4-iodophenyl)tropan-2β-carboxylic acid methyl ester ([(125) I]RTI-55) in rat NAc membranes resulted in binding curves that were best fit to two-site binding models, allowing calculation of dissociation constant (Kd ) and binding density (Bmax ) values corresponding to high- and low-affinity DAT binding sites. Scatchard analysis of the saturation binding curves clearly demonstrate the presence of high- and low- affinity binding sites in the NAc, with low-affinity sites comprising 85 to 94% of the binding sites. DAT binding analyses revealed that self-administration of cocaine and a cocaine:heroin combination increased the affinity of the low-affinity site for the cocaine congener RTI-55 compared to saline. These results indicate that the alterations observed following chronic speedball self-administration are likely due to the cocaine component alone; thus further studies are necessary to elaborate upon the synergistic effect of cocaine:heroin combinations on the dopamine system in the NAc.

  20. Elevated Hair Cortisol Levels among Heroin Addicts on Current Methadone Maintenance Compared to Controls

    PubMed Central

    Yang, Jin; Li, Jifeng; Xu, Guanyi; Zhang, Jing; Chen, Zheng; Lu, Zuhong; Deng, Huihua

    2016-01-01

    Whether methadone maintenance treatment (MMT) can improve the basal function of the hypothalamic–pituitary–adrenal (HPA) axis, which is suppressed by long-term heroin consumption, is a matter of debate. The stress state and depression and anxiety symptoms may affect the basal activity of the HPA axis in MMT patients. However, the effect of psychological factors on HPA activity was not simultaneously controlled in previous studies. This study investigated differences in HPA basal activity between MMT patients and controls using psychological variables as covariates. The participants included 52 MMT patients and 41 age-matched, non-heroin-dependent controls. Psychological states were self-reported with the Perceived Stress Scale, Self-Rating Depression Scale and Self-Rating Anxiety Scale. The hair cortisol level was adopted as a biomarker of HPA basal activity and was determined with liquid chromatography tandem mass spectrometry. The results revealed that MMT patients had significantly higher hair cortisol levels than the controls (p<0.05), but the difference was not significant (p>0.05) when the perceived stress, depression and anxiety scores were used as covariates. We concluded that patients with long-term MMT showed higher basal activity of the HPA axis. The high chronic stress state and increase in depression and anxiety symptoms may mask the suppression effect of methadone on the HPA activity. PMID:27010803

  1. Elevated Hair Cortisol Levels among Heroin Addicts on Current Methadone Maintenance Compared to Controls.

    PubMed

    Yang, Jin; Li, Jifeng; Xu, Guanyi; Zhang, Jing; Chen, Zheng; Lu, Zuhong; Deng, Huihua

    2016-01-01

    Whether methadone maintenance treatment (MMT) can improve the basal function of the hypothalamic-pituitary-adrenal (HPA) axis, which is suppressed by long-term heroin consumption, is a matter of debate. The stress state and depression and anxiety symptoms may affect the basal activity of the HPA axis in MMT patients. However, the effect of psychological factors on HPA activity was not simultaneously controlled in previous studies. This study investigated differences in HPA basal activity between MMT patients and controls using psychological variables as covariates. The participants included 52 MMT patients and 41 age-matched, non-heroin-dependent controls. Psychological states were self-reported with the Perceived Stress Scale, Self-Rating Depression Scale and Self-Rating Anxiety Scale. The hair cortisol level was adopted as a biomarker of HPA basal activity and was determined with liquid chromatography tandem mass spectrometry. The results revealed that MMT patients had significantly higher hair cortisol levels than the controls (p<0.05), but the difference was not significant (p>0.05) when the perceived stress, depression and anxiety scores were used as covariates. We concluded that patients with long-term MMT showed higher basal activity of the HPA axis. The high chronic stress state and increase in depression and anxiety symptoms may mask the suppression effect of methadone on the HPA activity.

  2. Simultaneous analysis of buprenorphine, methadone, cocaine, opiates and nicotine metabolites in sweat by liquid chromatography tandem mass spectrometry

    PubMed Central

    Concheiro, Marta; Shakleya, Diaa M.

    2013-01-01

    A liquid chromatography tandem mass spectrometry method for buprenorphine (BUP), norbuprenorphine (NBUP), methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), cocaine, benzoylecgonine, ecgonine methyl ester (EME), morphine, codeine, 6-acetylmorphine, heroin, 6-acetylcodeine, cotinine, and trans-3′-hydroxycotinine quantification in sweat was developed and comprehensively validated. Sweat patches were mixed with 6 mL acetate buffer at pH 4.5, and supernatant extracted with Strata-XC-cartridges. Reverse-phase separation was achieved with a gradient mobile phase of 0.1% formic acid and acetonitrile in 15 min. Quantification was achieved by multiple reaction monitoring of two transitions per compound. The assay was a linear 1–1,000 ng/patch, except EME 5–1,000 ng/patch. Intra-, inter-day and total imprecision were <10.1%CV, analytical recovery 87.2–107.7%, extraction efficiency 35.3– 160.9%, and process efficiency 25.5–91.7%. Ion suppression was detected for EME (−63.3%) and EDDP (−60.4%), and enhancement for NBUP (42.6%). Deuterated internal standards compensated for these effects. No carryover was detected, and all analytes were stable for 24 h at 22 °C, 72 h at 4 °C, and after three freeze/thaw cycles. The method was applied to weekly sweat patches from an opioid-dependent BUP-maintained pregnant woman; 75.0% of sweat patches were positive for BUP, 93.8% for cocaine, 37.5% for opiates, 6.3% for methadone and all for tobacco biomarkers. This method permits a fast and simultaneous quantification of 14 drugs and metabolites in sweat patches, with good selectivity and sensitivity. PMID:21125263

  3. Performance assessment of heroin and cocaine vapor particle detection systems

    NASA Astrophysics Data System (ADS)

    Hoglund, David E.; Lucero, Daniel P.

    1994-03-01

    This paper discusses the preparation to assess the performance of heroin and cocaine vapor/particle detection systems. Equipment available commercially and field prototype system equipment will be assessed. Breadboard or brassboard devices or prototype modules will not be assessed. The assessment comprises a performance specifications verification and target response and a controlled field test for equipment available commercially only. Special purpose test procedures, tools, and detection targets were developed to ensure the reproducibility and control of all assessment tests. The sampling equipment parameters and their relative importance and the test procedures and objectives were defined and designed to maximize the information obtained within the test constraints. Test results will be obtained for standardized fundamental representative targets, independent of detection strategy, which can be correlated to a wide range of applications by the potential users. United States Customs Service will not form conclusions regarding the equipment performance for specific applications. It is anticipated the utility of the assessment program will be in availing equipment standardized test results to law enforcement agencies to examine the compatibility of the equipment performance with their requirements, applications, and detection strategy.

  4. Methadone-related opioid agonist pharmacotherapy for heroin addiction. History, recent molecular and neurochemical research and future in mainstream medicine.

    PubMed

    Kreek, M J

    2000-01-01

    In 1963, Professor Vincent P. Dole at the Rockefeller University formed a small team to develop a pharmacotherapy for the management of heroin addiction. They hypothesized that heroin addiction is a disease of the brain with behavioral manifestations, and not merely a personality disorder or criminal behavior and began to address the specific question of whether a long-acting opioid agonist could be used in the long-term maintenance treatment of heroin addiction. Over the next 35 years, many studies documented the safety, efficacy and effectiveness of methadone pharmacotherapy for heroin addiction, but Federal regulations and stigmatization of heroin addiction prevented implementation of treatment. Finally, in 1999, NIH published a report unequivocally supporting methadone maintenance pharmacotherapy for heroin addiction. Two other effective opioid agonist treatments have been developed: the even longer acting opioid agonist l-alpha-acetylmethadol (LAAM) has been approved for pharmacotherapy for heroin addiction, and still under study is the opioid partial agonist-antagonist buprenorphine-naloxone combination. A variety of studies, both laboratory based and clinical, have revealed the mechanisms of action of long-acting opioid agonists in treatment, including prevention of disruption of molecular, cellular and physiologic events and, in fact, allowing normalization of those functions disrupted by chronic heroin use. Recent molecular biological studies have revealed single nucleotide polymorphisms of the human mu opioid receptor gene; the mu opioid receptor is the site of action of heroin, the major opiate drug of abuse, analgesic agents such as morphine, and the major treatment agents for heroin addiction. These findings support the early hypotheses of our laboratory that addiction may be due to a combination of genetic, drug-induced and environmental (including behavioral) factors and also, that atypical stress responsivity may contribute to the acquisition and

  5. Sexual Dysfunction in Heroin Dependents: A Comparison between Methadone and Buprenorphine Maintenance Treatment

    PubMed Central

    Yee, Anne; Danaee, Mahmoud; Loh, Huai Seng; Sulaiman, Ahmad Hatim; Ng, Chong Guan

    2016-01-01

    Introduction Methadone has long been regarded as an effective treatment for opioid dependence. However, many patients discontinue maintenance therapy because of its side effects, with one of the most common being sexual dysfunction. Buprenorphine is a proven alternative to methadone. This study aimed to investigate sexual dysfunction in opioid-dependent men on buprenorphine maintenance treatment (BMT) and methadone maintenance treatment (MMT). The secondary aim was to investigate the correlation between sexual dysfunction and the quality of life in these patients. Methods Two hundred thirty-eight men participated in this cross-sectional study. Four questionnaires were used, the Mini International Neuropsychiatric Interview, Opiate Treatment Index, Malay version of the International Index of Erectile Function 15 (Mal-IIEF-15), and World Health Organization Quality of Life-BREF Scale. Multivariate analysis of covariance was used to examine the relationship between MMT and BMT and the Mal-IIEF 15 scores while controlling for all the possible confounders. Results The study population consisted of 171 patients (71.8%) on MMT and 67 (28.2%) on BMT. Patients in the MMT group who had a sexual partner scored significantly lower in the sexual desire domain (p < 0.012) and overall satisfaction (p = 0.043) domain compared with their counterparts in the BMT group. Similarly, patients in the MMT group without a sexual partner scored significantly lower in the orgasmic function domain (p = 0.008) compared with those in the BMT group without a partner. Intercourse satisfaction (p = 0.026) and overall satisfaction (p = 0.039) were significantly associated with the social relationships domain after adjusting for significantly correlated sociodemographic variables. Conclusions Sexual functioning is critical for improving the quality of life in patients in an opioid rehabilitation program. Our study showed that buprenorphine causes less sexual dysfunction than methadone. Thus

  6. The effects of cocaine and heroin price on drug-related emergency department visits.

    PubMed

    Dave, Dhaval

    2006-03-01

    This paper estimates the empirical relationship between cocaine and heroin prices and drug-related hospital ED admissions for 21 U.S. cities. These outcomes bypass some of the problems with self-reports and directly measure a component of healthcare costs associated with heavy drug usage. The price elasticity of the probability of a cocaine and heroin episode is estimated at -0.27 and -0.10, respectively. A 10% increase in prices can prevent 10,723 cocaine and heroin-related ED visits, with cost savings between 21 million dollars and 47 million dollars. These low magnitudes of the drug outcome-price response have implications for the cost-effectiveness of enforcement-driven price increases.

  7. Structural basis of heroin and cocaine metabolism by a promiscuous human drug-processing enzyme.

    PubMed

    Bencharit, Sompop; Morton, Christopher L; Xue, Yu; Potter, Philip M; Redinbo, Matthew R

    2003-05-01

    We present the first crystal structures of a human protein bound to analogs of cocaine and heroin. Human carboxylesterase 1 (hCE1) is a broad-spectrum bioscavenger that catalyzes the hydrolysis of heroin and cocaine, and the detoxification of organophosphate chemical weapons, such as sarin, soman and tabun. Crystal structures of the hCE1 glycoprotein in complex with the cocaine analog homatropine and the heroin analog naloxone provide explicit details about narcotic metabolism in humans. The hCE1 active site contains both specific and promiscuous compartments, which enable the enzyme to act on structurally distinct chemicals. A selective surface ligand-binding site regulates the trimer-hexamer equilibrium of hCE1 and allows each hCE1 monomer to bind two narcotic molecules simultaneously. The bioscavenger properties of hCE1 can likely be used to treat both narcotic overdose and chemical weapon exposure.

  8. Induction of depressive-like effects by subchronic exposure to cocaine or heroin in laboratory rats.

    PubMed

    Zilkha, Noga; Feigin, Eugene; Barnea-Ygael, Noam; Zangen, Abraham

    2014-08-01

    The effect of psychoactive drugs on depression has usually been studied in cases of prolonged drug addiction and/or withdrawal, without much emphasis on the effects of subchronic or recreational drug use. To address this issue, we exposed laboratory rats to subchronic regimens of heroin or cocaine and tested long-term effects on (i) depressive-like behaviors, (ii) brain-derived neurotrophic factor (BDNF) levels in reward-related brain regions, and (iii) depressive-like behavior following an additional chronic mild stress procedure. The long-term effect of subchronic cocaine exposure was a general reduction in locomotor activity whereas heroin exposure induced a more specific increase in immobility during the forced swim test. Both cocaine and heroin exposure induced alterations in BDNF levels that are similar to those observed in several animal models of depression. Finally, both cocaine and heroin exposure significantly enhanced the anhedonic effect of chronic mild stress. These results suggest that subchronic drug exposure induces depressive-like behavior which is accompanied by modifications in BDNF expression and increases the vulnerability to develop depressive-like behavior following chronic stress. Implications for recreational and small-scale drug users are discussed. In the present study, we examined the long-term effects of limited subchronic drug exposure on depressive-like symptoms. Our results demonstrate that short-term, subchronic administration of either cocaine or heroin promotes some depressive-like behaviors, while inducing alterations in BDNF protein levels similar to alterations observed in several animal models of depression. In addition, subchronic cocaine or heroin enhanced the anhedonic effect of chronic stress.

  9. Voucher-based reinforcement of cocaine abstinence in treatment-resistant methadone patients: effects of reinforcement magnitude.

    PubMed

    Silverman, K; Chutuape, M A; Bigelow, G E; Stitzer, M L

    1999-09-01

    Voucher-based reinforcement of cocaine abstinence has been one of the most effective means of treating cocaine abuse in methadone patients, but it has not been effective in all patients. This study was designed to determine if we could promote cocaine abstinence in a population of treatment-resistant cocaine abusing methadone patients by increasing the magnitude of voucher-based abstinence reinforcement. Participants were 29 methadone patients who previously failed to achieve sustained cocaine abstinence when exposed to an intervention in which they could earn up to $1155 in vouchers (exchangeable for goods/services) for providing cocaine-free urines. Each patient was exposed in counterbalanced order to three 9-week voucher conditions that varied in magnitude of voucher reinforcement. Patients were exposed to a zero, low and high magnitude condition in which they could earn up to $0, $382, or $3480 in vouchers for providing cocaine-free urines. Analyses for 22 patients exposed to all three conditions showed that increasing voucher magnitude significantly increased patients' longest duration of sustained cocaine abstinence (P<0.001) and percent of cocaine-free urines (P<0.001), and significantly decreased patients' reports of cocaine injections (P=0.024). Almost half (45%) of the patients in the high magnitude condition achieved >/=4 weeks of sustained cocaine abstinence, whereas only one patient in the low and none in the zero magnitude condition achieved more than 2 weeks. Reinforcement magnitude was a critical determinant of the effectiveness of this abstinence reinforcement intervention.

  10. Prize reinforcement contingency management for cocaine dependence: integration with group therapy in a methadone clinic.

    PubMed

    Petry, Nancy M; Martin, Bonnie; Simcic, Francis

    2005-04-01

    In this study, the authors evaluated a low-cost contingency management (CM) procedure for reducing cocaine use and enhancing group therapy attendance in 77 cocaine-dependent methadone patients. Patients were randomly assigned to 12 weeks of standard treatment or standard treatment with CM, in which patients earned the opportunity to win prizes ranging from $1 to $100 for submitting cocainenegative samples and attending therapy. Patients in the CM condition submitted more cocaine-negative samples and attended more groups than patients in standard treatment. The best predictor of cocaine abstinence at follow-up was duration of abstinence during treatment. On average, patients in the CM condition earned $117 in prizes. Data from this study suggest that some aspects of reinforcement can be implemented in group therapy in community-based clinics.

  11. 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…

  12. 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…

  13. B vitamins status: effect of prolonged heroin addiction and methadone treatment.

    PubMed

    Prayurahong, B; Migasena, P; Pongpaew, P; Vudhivai, N; Busapathumrong, P

    1991-03-01

    Vitamin B1, B2 and B6 status were determined in 90 male heroin addicts admitted to Pramongkutklao Army Hospital. Their age (Mean +/- S.D.) was 25.5 +/- 7.8 years. Their activation coefficients of the enzyme transketolase, glutathione oxidoreductase and aspartate aminotransferase (ETK AC, EGR AC and EAST AC respectively) were significantly increased for addicts who were on drugs for a long time which indicated a biochemical deficiency. In addition, 26 follow-up cases treated with methadone for a period of one and two weeks were compared before and after treatment and it was found that ETK AC, EGR AC, and EAST AC were significantly decreased. This means that improvement in the vitamin B1, B2 and B6 status was obtained during admission.

  14. The impact of recent cocaine use on plasma levels of methadone and buprenorphine in patients with and without HIV-infection.

    PubMed

    Tetrault, Jeanette M; McCance-Katz, Elinore F; Moody, David E; Fiellin, David A; Lruie, Bonnie S; DInh, An T; Fiellin, Lynn E

    2015-04-01

    Cocaine decreases methadone and buprenorphine plasma concentrations. HIV infection and/or antiretroviral medication use may impact these relationships. We sought to determine the association between recent cocaine use and methadone and buprenorphine concentrations in HIV-infected and uninfected subjects in clinical care. R- and S-methadone or buprenorphine and norbuprenorphine concentrations were assessed at 0.5, 1, 2, and 24 hours after dosing in subjects with confirmed cocaine use and abstinence. We compared methadone and buprenorphine concentrations for cocaine use vs. abstinence, by HIV status in 16 subjects receiving methadone (6 HIV-infected) and 17 receiving buprenorphine (8 HIV-infected). With recent cocaine use, peak R-methadone (244 vs. 297 ng/mL, p = 0.03) and peak S-methadone (285 vs. 339 ng/mL); p = 0.03 concentrations were lower in HIV-uninfected subjects only. Peak buprenorphine and norbuprenorphine concentrations were unchanged regardless of cocaine use or HIV status. Cocaine may decrease methadone concentrations in HIV-uninfected subjects. HIV infection or its treatment may attenuate cocaine's effect on methadone.

  15. Drug specificity in extended access cocaine and heroin self-administration.

    PubMed

    Lenoir, Magalie; Guillem, Karyn; Koob, George F; Ahmed, Serge H

    2012-11-01

    Increased drug availability can precipitate a rapid escalation of drug consumption in both vulnerable humans and laboratory animals. Drug intake escalation is observed across a broad spectrum of drugs of abuse, including stimulants, opiates, ethanol and phencyclidine. Whether and to what extent the processes underlying escalated levels of drug intake vary across different substances is poorly understood. The present study sought to address this question in rats self-administering both cocaine and heroin-two addictive drugs with both common and different neurobiological effects. In experiment 1, we determined how cocaine intake is initially related to heroin intake in non-escalated rats with a limited access to both drugs. In experiment 2, two groups of rats were initially allowed to self-administer either cocaine or heroin for 1 hour per day and then after behavioral stabilization, for 6 hours per day to precipitate drug intake escalation. In each group, dose-injection functions for cocaine and heroin self-administration were generated. In experiment 1, regardless of the dose, rats with a high intake of one drug did not necessarily have a high intake of the alternate drug. In experiment 2, escalated levels of heroin or cocaine self-administration did not generalize to the other drug. This outcome was confirmed in a third drug substitution experiment following different access lengths to cocaine self-administration (i.e. 1, 4 and 8 hours). The processes underlying spontaneous and escalated drug overconsumption appear thus to vary across different drugs of abuse. More research should be devoted in the future to these differences.

  16. 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.

  17. Behavioral factors predicting response to employment-based reinforcement of cocaine abstinence in methadone patients.

    PubMed

    Holtyn, August F; Washington, Wendy Donlin; Knealing, Todd W; Wong, Conrad J; Kolodner, Ken; Silverman, Kenneth

    2016-06-01

    We sought to identify behavioral factors associated with response to an employment-based intervention, in which participants had to provide drug-free urine samples to gain access to paid employment. The present secondary analysis included data from a randomized clinical trial. The trial evaluated whether employment-based reinforcement could decrease cocaine use in community methadone patients. Participants (N=56) in the trial worked in a model workplace for 4 hr every weekday and earned about $10 per hr. After a 4-week baseline, participants were randomly assigned to an Abstinence & Work (n = 28) or Work Only (n = 28) condition and could work for an additional 26 weeks. Abstinence & Work participants had to provide cocaine-negative urine samples to work and maintain maximum pay. Work Only participants only had to work to earn pay. For Work Only participants, cocaine abstinence during baseline and the intervention period were significantly (rs = .72, p <.001) correlated. For Abstinence & Work participants, baseline opiate abstinence was significantly correlated (rs = .59, p <.001) and workplace attendance was marginally correlated (rs = .32, p = .098) with cocaine abstinence during the intervention period. Furthermore, participants who provided over 60% cocaine-negative urine samples during the intervention period (i.e., responders) had significantly higher baseline rates of opiate abstinence (p <.0001) and workplace attendance (p = .042) than non-responders. Employment-based reinforcement of cocaine abstinence may be improved by increasing opiate abstinence and workplace attendance prior to initiating the cocaine-abstinence intervention.

  18. Synergistic elevations in nucleus accumbens extracellular dopamine concentrations during self-administration of cocaine/heroin combinations (Speedball) in rats.

    PubMed

    Hemby, S E; Co, C; Dworkin, S I; Smith, J E

    1999-01-01

    The abuse of cocaine/opiate combinations (speedball) represents a growing trend in illicit drug use. Delineation of neurobiological substrates mediating the reinforcing effects of the combination may increase our knowledge of reinforcement mechanisms and provide useful new information for the development of pharmacotherapies. Several studies suggest dopaminergic innervations of the nucleus accumbens (NAc) have a central role in the brain processes underlying drug reinforcement. The present study was undertaken to determine the relationship between the self-administration of cocaine/heroin combinations and NAc extracellular dopamine concentrations ([DA]e) using in vivo microdialysis and microbore high-pressure liquid chromatography. Rats were assigned randomly to one of three groups to self-administer i.v. cocaine (125, 250, and 500 micrograms/infusion; n = 5), heroin (4.5, 9, and 18 micrograms/infusion; n = 5), or cocaine/heroin combinations (125/4.5; 250/9, and 500/18 micrograms/infusion; n = 4) under a fixed ratio (FR) 10: 20-s time-out schedule of reinforcement/multicomponent dosing session. After stable rates of responding were engendered and maintained, microdialysis samples were collected in 10-min intervals during the self-administration session. Self-administration of cocaine/heroin combinations produced synergisitic elevations in NAc [DA]e (1000% baseline) compared with cocaine (400% baseline) and heroin (not significantly different from baseline levels). Neither the number of infusions nor the interinfusion intervals was significantly different between the groups across the self-administration session. Moreover, cocaine concentrations were not significantly different between the cocaine and cocaine/heroin groups. These results demonstrate that heroin interacts with cocaine to produce synergistic elevations in [DA]e, providing a neurochemical basis for understanding the abuse liability of cocaine/opiate combinations.

  19. Distinctive Profiles of Gene Expression in the Human Nucleus Accumbens Associated with Cocaine and Heroin Abuse

    PubMed Central

    Albertson, Dawn N; Schmidt, Carl J; Kapatos, Gregory; Bannon, Michael J

    2008-01-01

    Drug abuse is thought to induce long-term cellular and behavioral adaptations as a result of alterations in gene expression. Understanding the molecular consequences of addiction may contribute to the development of better treatment strategies. This study utilized highthroughput Affymetrix microarrays to identify gene expression changes in the post-mortem nucleus accumbens of chronic heroin abusers. These data were analyzed independently and in relation to our previously reported data involving human cocaine abusers, in order to determine which expression changes were drug specific and which may be common to the phenomenon of addiction. A significant decrease in the expression of numerous genes encoding proteins involved in presynaptic release of neurotransmitter was seen in heroin abusers, a finding not seen in the cocaine-abusing cohort. Conversely, the striking decrease in myelin-related genes observed in cocaine abusers was not evident in our cohort of heroin subjects. Overall, little overlap in gene expression profiles was seen between the two drug-abusing cohorts: out of the approximately 39 000 transcripts investigated, the abundance of only 25 was significantly changed in both cocaine and heroin abusers, with nearly one-half of these being altered in opposite directions. These data suggest that the profiles of nucleus accumbens gene expression associated with chronic heroin or cocaine abuse are largely unique, despite what are thought to be common effects of these drugs on dopamine neurotransmission in this brain region. A re-examination of our current assumptions about the commonality of molecular mechanisms associated with substance abuse seems warranted. PMID:16710320

  20. Topiramate impairs cognitive function in methadone-maintained individuals with concurrent cocaine dependence

    PubMed Central

    Rass, Olga; Umbricht, Annie; Bigelow, George E.; Strain, Eric C.; Johnson, Matthew W.; Mintzer, Miriam Z.

    2014-01-01

    Topiramate is being investigated as a potential pharmacotherapy for the treatment of addictive disorders. However, its cognitive side effects raise concerns about its use, especially in populations with cognitive impairment, such as persons with chronic substance use disorders. This study investigated the topiramate's cognitive effects in individuals dually dependent on cocaine and opioids as part of a double-blind, randomized, controlled trial of topiramate for the cocaine dependence treatment. Following five weeks of stabilization on daily oral methadone (M=96 mg), participants were randomized to topiramate (n=18) or placebo (n=22). Cognitive testing took place at two time points: study weeks 4-5 to assess baseline performance and 10-13 weeks later to assess performance during stable dosing (300 mg topiramate or placebo). All participants were maintained on methadone at both testing times, and testing occurred two hours after the daily methadone plus topiramate/placebo administration. The topiramate and placebo groups did not differ on sex, level of education, premorbid intelligence, methadone dose, or illicit drug use. Topiramate slowed psychomotor and information processing speed, worsened divided attention, reduced n-back working memory accuracy, and increased the false alarm rate in recognition memory. Topiramate had no effects on visual processing, other measures of psychomotor function, risk-taking, self-control, Sternberg working memory, free recall, and metamemory. These findings indicate that topiramate may cause cognitive impairment in this population. This effect may limit its acceptability and use as a treatment in individuals with chronic opiate and cocaine use disorders, among whom pre-existing cognitive impairments are common. PMID:25365653

  1. Heroin

    MedlinePlus

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Heroin KidsHealth > For Teens > Heroin A A A What's ... How Can Someone Quit? Avoiding Heroin What Is Heroin? Heroin is a highly addictive drug made from ...

  2. Methadone dose in heroin-dependent patients: role of clinical factors, comedications, genetic polymorphisms and enzyme activity

    PubMed Central

    Mouly, Stéphane; Bloch, Vanessa; Peoc'h, Katell; Houze, Pascal; Labat, Laurence; Ksouda, Kamilia; Simoneau, Guy; Declèves, Xavier; Bergmann, Jean Francois; Scherrmann, Jean-Michel; Laplanche, Jean-Louis; Lepine, Jean-Pierre; Vorspan, Florence

    2015-01-01

    Aims Methadone is characterized by wide intersubject variability regarding the dose needed to obtain full therapeutic response. We assessed the influence of sociodemographic, ethnic, clinical, metabolic and genotypic variables on methadone maintenance dose requirement in opioid-dependent responder patients. Methods Eighty-one stable patients (60 men and 21 women, 43.7 ± 8.1 years old, 63.1 ± 50.9 mg day−1 methadone), divided into quartiles with respect to the median daily dose, were enrolled and underwent clinical examination, treatment history and determination of liver/intestinal cytochrome P450 (CYP) 3A4 activity measured by the midazolam test, R,S-methadone trough concentration and clinically significant polymorphisms of the OPRM1, DRD2, COMT, ABCB1, CYP2B6, CYP3A5, CYP2C19 and CYP2D6 genes. Results Methadone maintenance dose was correlated to the highest dose ever used (r2 = 0.57, P < 0.0001). Fractioned methadone intake (odds ratio 4.87, 95% confidence interval 1.27–18.6, P = 0.02), bodyweight (odds ratio 1.57, 95% confidence interval 1.01–2.44, P = 0.04), history of cocaine dependence (80 vs. 44 mg day−1 in never-addict patients, P = 0.005) and ethnicity (Asian > Caucasian > African, P = 0.04) were independently associated with high-dose methadone in multiple regression analysis. A modest correlation was observed between liver/intestinal CYP3A4 activity and methadone dose at steady state (Spearman rank correlation coefficient [rs] = 0.21, P = 0.06) but not with highest dose ever used (rs = 0.15, P = 0.18) or dose-normalized R,S-methadone trough concentrations (rs = −0.05, P = 0.64). Concomitant CYP3A4 inhibitors only affected the relationship between methadone dose and R,S-methadone trough concentration. None of the genetic polymorphisms explored was predictive of the methadone maintenance dose. Conclusions Methadone maintenance dose was predicted by sociodemographic and clinical variables rather than genetic polymorphisms or liver/intestinal CYP

  3. Treatment-like steady-state methadone in rats interferes with incubation of cocaine sensitization and associated alterations in gene expression☆

    PubMed Central

    Leri, Francesco; Zhou, Yan; Carmichael, Brendan; Cummins, Erin; Kreek, Mary Jeanne

    2013-01-01

    In a previous study, steady-state methadone treatment was found to prevent associative cocaine learning, as well as related decreases in mRNA expression of preprohypocretin/preproorexin (ppHcrt) in the lateral hypothalamus (LH) and dopamine D2 receptor (DR2) in the caudate-putamen (CP), and increases in mu-opioid receptor in the ventral striatum of rats. To investigate whether the same regimen of methadone exposure could prevent the incubation of cocaine sensitization and related alterations in gene expression, male Sprague–Dawley rats received 45 mg/kg/day steadydose “binge” cocaine administration (IP) for 14 days followed by mini-pumps releasing 30 mg/kg/day methadone (SC). After 14 days of methadone, and a subsequent 10-day drug-free period, all rats were tested for sensitization (cocaine test dose: 15 mg/kg) and brain tissue was collected to quantify mRNA expression. Rats exposed to cocaine displayed cocaine-induced stereotypy at test, as well as enhanced ppHcrt mRNA in the LH and reduced DR2 mRNA in the CP. Importantly, these alterations were significantly reduced in rats treated with methadone following cocaine. These results suggest that steady-state methadone can interfere with the incubation of neuroadaptations underlying changes in behavioral responses to cocaine and cocaine-associated stimuli, and that these effects can be observed even after withdrawal from methadone. PMID:21745729

  4. Treatment-like steady-state methadone in rats interferes with incubation of cocaine sensitization and associated alterations in gene expression.

    PubMed

    Leri, Francesco; Zhou, Yan; Carmichael, Brendan; Cummins, Erin; Kreek, Mary Jeanne

    2012-02-01

    In a previous study, steady-state methadone treatment was found to prevent associative cocaine learning, as well as related decreases in mRNA expression of preprohypocretin/preproorexin (ppHcrt) in the lateral hypothalamus (LH) and dopamine D2 receptor (DR2) in the caudate-putamen (CP), and increases in mu-opioid receptor in the ventral striatum of rats. To investigate whether the same regimen of methadone exposure could prevent the incubation of cocaine sensitization and related alterations in gene expression, male Sprague-Dawley rats received 45 mg/kg/day steady-dose "binge" cocaine administration (IP) for 14 days followed by mini-pumps releasing 30 mg/kg/day methadone (SC). After 14 days of methadone, and a subsequent 10-day drug-free period, all rats were tested for sensitization (cocaine test dose: 15 mg/kg) and brain tissue was collected to quantify mRNA expression. Rats exposed to cocaine displayed cocaine-induced stereotypy at test, as well as enhanced ppHcrt mRNA in the LH and reduced DR2 mRNA in the CP. Importantly, these alterations were significantly reduced in rats treated with methadone following cocaine. These results suggest that steady-state methadone can interfere with the incubation of neuroadaptations underlying changes in behavioral responses to cocaine and cocaine-associated stimuli, and that these effects can be observed even after withdrawal from methadone.

  5. Standard magnitude prize reinforcers can be as efficacious as larger magnitude reinforcers in cocaine-dependent methadone patients

    PubMed Central

    Petry, Nancy M.; Alessi, Sheila M.; Barry, Danielle; Carroll, Kathleen M.

    2014-01-01

    Objective Contingency management (CM) reduces cocaine use in methadone patients, but only about 50% of patients respond to CM interventions. This study evaluated whether increasing magnitudes of reinforcement will improve outcomes. Methods Cocaine-dependent methadone patients (N = 240) were randomized to one of four 12-week treatment conditions: usual care (UC), UC plus “standard” prize CM in which average expected prize earnings were about $300, UC plus high magnitude prize CM in which average expected prize earnings were about $900, or UC plus voucher CM with an expected maximum of about $900 in vouchers. Results All three CM conditions yielded significant reductions in cocaine use relative to UC, with effect sizes (d) ranging from 0.38 to 0.59. No differences were noted between CM conditions, with at least 55% of patients in each CM condition achieving one week or more of cocaine abstinence versus 35% in UC. During the 12 weeks after the intervention ended, CM increased time until relapse relative to UC, but the effects of CM were no longer significant at a 12-month follow-up. Conclusions Providing the standard magnitude of $300 in prizes was as effective as larger magnitude CM in cocaine-dependent methadone patients in this study. Given its strong evidence base and relatively low costs, standard magnitude prize CM should be considered for adoption in methadone clinics to encourage cocaine abstinence, but new methods need to be developed to sustain abstinence. PMID:25198284

  6. Plasma level monitoring of the major metabolites of diacetylmorphine (heroin) by the "chasing the dragon" route in severe heroin addicts.

    PubMed

    Dubois, N; Demaret, I; Ansseau, M; Rozet, E; Hubert, Ph; Charlier, C

    2013-01-01

    The objective of the present study was to verify if severe physical health problems frequently encountered in heroin addicts and the concomitant use of alcohol and legal or illegal drugs other than heroin influenced the pharmacokinetics of the major metabolites of heroin. We conducted a 90 minutes follow-up of the plasma concentrations of the pharmaceutical heroin, named diacetylmorphine (DAM), in patients recruited in a DAM assisted treatment centre. TADAM (Traitement Assisté par DiAcétylMorphine) aimed to compare the efficacy of heroin-assisted treatment (HAT) compared with methadone maintenance treatment (MMT) for heroin users considered as treatment resistant patients and who have severe physical and mental health problems. Eleven patients were recruited. Blood samples were collected at baseline and 15, 45 and 90 minutes after DAM administration. All patients received DAM by the "chasing the dragon" route. Plasma samples were analyzed by a previously described ultra-high pressure liquid chromatography coupled to tandem mass spectrometry (UHPLC/MS-MS) method. A principal component analysis (PCA) was performed and 8 metabolite concentrations ratios were calculated to evaluate the influence of various factors (DAM dose, patient pathologies, concomitant use of medications, methadone, street heroin, alcohol and cocaine) on heroin metabolite pharmacokinetics. It seemed to be not affected by the DAM dose, patient pathologies and the concomitant use of medications, methadone, street heroin and alcohol. Cocaine use was the only parameter which showed differences in heroin pharmacokinetics.

  7. Cocaine use among heroin users in Spain: the diffusion of crack and cocaine smoking. Spanish Group for the Study on the Route of Administration of Drugs

    PubMed Central

    Barrio, G.; De la Fuente, L.; Royuela, L.; Diaz, A.; Rodriguez-Artalej..., F.

    1998-01-01

    STUDY OBJECTIVE: To describe the prevalence and patterns of use of crack and cocaine hydrochloride among heroin users in Spain. To explore if the expansion of heroin smoking is accompanied by a similar phenomenon for cocaine. DESIGN: Cross sectional study in 1995. Face to face interviews using a structured questionnaire. SETTING: Three cities with different prevalences of heroin use by smoking: high (Seville), intermediate (Madrid), and low (Barcelona). PARTICIPANTS: 909 heroin users, 452 in treatment and 457 out of treatment. MAIN RESULTS: Last month prevalence of crack use was 62.3% in Seville, 19.4% in Madrid, and 7.7% in Barcelona. Most users in Madrid (86.5%) and Barcelona (100%) generally prepared their own crack, usually with ammonia as alkali; in Seville most users (69.7%) bought preprocessed crack. The proportion of users who began taking cocaine (crack or cocaine hydrochloride) by smoking has increased progressively since the seventies, rising to 74.1% in Seville, 61.5% in Madrid, and 28% in Barcelona in 1992-1995, with the earliest increase in Seville. The factors associated with crack use were: residence in Seville (odds ratio (OR) = 16.3), cocaine hydrochloride use mainly by smoking (OR = 5.0), by sniffing (OR = 2.7) or by injecting (OR = 2.5), heroin use mainly by smoking (OR = 2.8) and weekly use of cannabis (OR = 1.9). CONCLUSIONS: In Spain smoking cocaine may be progressively diffusing from the south west to the north east, similar to what has happened with smoking heroin, but beginning later in time. The factors associated with smoking cocaine are basically ecological or cultural in nature (characteristics of the available drugs and the main route of heroin administration in each city).   PMID:9616422

  8. Screening for illicit heroin use in patients in a heroin-assisted treatment program.

    PubMed

    Rook, Elisabeth J; Huitema, Alwin D R; van den Brink, Wim; Hillebrand, Michel J X; van Ree, Jan M; Beijnen, Jos H

    2006-01-01

    The aim of this study was to investigate the use of illicit heroin among patients in a heroin-assisted treatment program. In this program, pharmaceutical-grade heroin was administered to heroin-addicted patients. Monitoring of illicit heroin use was considered important for the evaluation of this treatment program. Acetylcodeine and codeine, common adulterants of "street" heroin, were used as markers for illicit heroin. A liquid chromatography method with tandem mass spectrometric detection (LC-MS-MS) was developed, for quantitative analysis of heroin and methadone, their metabolites, and the simultaneous detection of acetylcodeine. One-hundred patients in a heroin-assisted treatment program were screened for acetylcodeine in plasma. Furthermore, patients were interviewed about illicit heroin use, and they were tested for alcohol and cocaine use. In plasma samples of 16% of the patients, acetylcodeine was detected. Overall agreement between self-report and plasma samples was 95% (kappa: 0.81). Patients who tested positive for acetylcodeine had visited the outpatients' clinics significantly less frequently than the patients who tested negative. Alcohol and cocaine use was more common in patients who tested positive for acetylcodeine. Illicit heroin use was observed in a limited percentage of patients. Overall agreement between self-report and markers of illicit heroin use was good.

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

    PubMed

    Concheiro, Marta; Gray, Teresa R; Shakleya, Diaa M; Huestis, Marilyn A

    2010-09-01

    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

  10. 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

  11. Rats maintained chronically on buprenorphine show reduced heroin and cocaine seeking in tests of extinction and drug-induced reinstatement.

    PubMed

    Sorge, Robert E; Rajabi, Heshmat; Stewart, Jane

    2005-09-01

    Buprenorphine is being introduced as a maintenance therapy in opioid addiction, but it is not clear how buprenorphine will affect co-use of cocaine in opioid users. We examined the effects of chronic buprenorphine (BUP0: 0.0 mg/kg/day; BUP1.5: 1.5 mg/kg/day; BUP3: 3.0 mg/kg/day) on the locomotor activity effects of acute heroin (0.25 mg/kg, subcutaneously (s.c.)) and cocaine (20 mg/kg, intraperitoneally (i.p.)). Buprenorphine had no effect on the stimulatory effect of heroin, but potentiated the locomotor response to cocaine. To investigate further the interactions between buprenorphine (BUP1.5 and BUP3), heroin (0.125, 0.25 and 0.375 mg/kg, s.c.), and cocaine (10, 20 and 30 mg/kg, i.p.), we used in vivo microdialysis and high-performance liquid chromatography to analyze extracellular levels of dopamine (DA) in the nucleus accumbens (NAc). Buprenorphine attenuated the heroin-induced rise in NAc DA, but greatly potentiated the cocaine-induced rise. Finally, we examined the potential of the highest dose of buprenorphine (BUP3) to reduce heroin and cocaine seeking in the presence of drug-associated cues under extinction conditions and in tests for reinstatement induced by heroin (0.25 mg/kg, s.c.), cocaine (20 mg/kg, i.p.), and 15-min footshock stress (0.8 mA, 0.5 s/shock, 40 s mean OFF time) in rats trained to self-administer both drugs. Buprenorphine reduced heroin and cocaine seeking during extinction and following acute heroin and cocaine priming injections, but had no effect on stress-induced reinstatement. These results indicate that the suppression of responding following priming injections of drugs did not result from reduced motor activity, but possibly from a reduction in the salience of drug-associated cues induced by chronic buprenorphine treatment.

  12. Use of methylene blue as a simulant for the physical properties of cocaine HCl and heroin HCl

    NASA Astrophysics Data System (ADS)

    Patrick, Julie C.; Orzechowska, Grazyna E.; Poziomek, Edward J.

    1997-02-01

    Technological challenges in the development and testing of illicit narcotics include assuring safety of researchers and operations personnel from drug exposure, assessing the efficiency of sampling and sample handling, checking for artifacts introduced by field procedures, and maintaining quality control/quality assurance. The dye methylene blue was chosen as a simulant for cocaine HCl and heroin HCl. The similarities include the presence of fused ring systems, molecular weights over 300 g/mol, and melting points between 200 and 300 degrees C. A significant difference is that methylene blue has a much lower solubility in water than cocaine HCl and heroin HCl. Experiments have been conducted to successfully increase the solubility of the simulant to match those of cocaine HCl and heroin HCl by adding solidum methyl sulfate.

  13. Cocaine and heroin in waste water plants: a 1-year study in the city of Florence, Italy.

    PubMed

    Mari, Francesco; Politi, Lucia; Biggeri, Annibale; Accetta, Gabriele; Trignano, Claudia; Di Padua, Marianna; Bertol, Elisabetta

    2009-08-10

    The diffusion and trends in use of each substance is a basic information in policy planning of strategies aiming at deterrence of drug abuse or in the organization of the fight against drug trafficking. The actual diffusion of illicit drugs in a population is hardly measurable, but, among the various measures available, the analysis of waste water plants represents one of the most reliable source of data. We analyzed waste water in order to monitor illicit drug use by local population. We investigated the use of cocaine and heroin in the city of Florence, Italy, over a 1-year (July 2006-June 2007) period using state-of-the-art measuring techniques from waste water samples. Cocaine, benzoylecgonine, and morphine were determined in water samples by gas chromatography-mass spectrometer, and the amount of illicit substance was estimated. Data indicate for cocaine a bimodal distribution (December and March), while heroin showed a main peak in April. The heroin-to-cocaine use ratio in terms of estimated doses per month ranged from 0.11 to 0.76, representing new evidence of wider distribution of cocaine than heroin in Florence. Waste water analysis can become a valuable tool in monitoring use of illicit drugs over time. In particular, it can highlight changes in the magnitude and relative use of illicit drug at a population level thereby becoming useful to develop strategies against drug trafficking and abuse. If routinely performed, it can be part of Epidemiologic Surveillance Programmes on drug abuse.

  14. Genetic association analyses of PDYN polymorphisms with heroin and cocaine addiction.

    PubMed

    Clarke, T-K; Ambrose-Lanci, L; Ferraro, T N; Berrettini, W H; Kampman, K M; Dackis, C A; Pettinati, H M; O'Brien, C P; Oslin, D W; Lohoff, F W

    2012-06-01

    Genetic factors are believed to account for 30-50% of the risk for cocaine and heroin addiction. Dynorphin peptides, derived from the prodynorphin (PDYN) precursor, bind to opioid receptors, preferentially the kappa-opioid receptor, and may mediate the aversive effects of drugs of abuse. Dynorphin peptides produce place aversion in animals and produce dysphoria in humans. Cocaine and heroin have both been shown to increase expression of PDYN in brain regions relevant for drug reward and use. Polymorphisms in PDYN are therefore hypothesized to increase risk for addiction to drugs of abuse. In this study, 3 polymorphisms in PDYN (rs1022563, rs910080 and rs1997794) were genotyped in opioid-addicted [248 African Americans (AAs) and 1040 European Americans (EAs)], cocaine-addicted (1248 AAs and 336 EAs) and control individuals (674 AAs and 656 EAs). Sex-specific analyses were also performed as a previous study identified PDYN polymorphisms to be more significantly associated with female opioid addicts. We found rs1022563 to be significantly associated with opioid addiction in EAs [P = 0.03, odds ratio (OR) = 1.31; false discovery rate (FDR) corrected q-value]; however, when we performed female-specific association analyses, the OR increased from 1.31 to 1.51. Increased ORs were observed for rs910080 and rs199774 in female opioid addicts also in EAs. No statistically significant associations were observed with cocaine or opioid addiction in AAs. These data show that polymorphisms in PDYN are associated with opioid addiction in EAs and provide further evidence that these risk variants may be more relevant in females.

  15. 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.

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

    PubMed Central

    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. PMID:19192855

  17. [Heroin].

    PubMed

    Demaret, I; Lemaître, A; Ansseau, M

    2013-01-01

    Heroin (or diacetylmorphine), a depressant nervous central system, is a semi-synthetic opiate. Its main adverse effect, respiratory depression, can lead to death, especially after an intravenous injection. By loss of tolerance, an overdose can be lethal following heroin use after a period of abstinence (voluntary or not). Mortality rate among heroin users is between 1 and 3%. Addiction, following a regular and continuous use, occurs in less than a quarter of persons who ever tried heroine. Heroin addicts often present with different problems (for instance, a criminal behaviour), without any obvious link with addiction. For a fraction of the addicts, addiction becomes a chronic relapsing disease, requiring a long term maintenance substitution therapy. However, relapses and sometimes continuous heroin use are frequent, For treatment resistant and severe heroin addicts, heroin-assisted treatment can be a solution. Despite the numerous available therapies, heroin is considered to be the drug with the most negative effects on the user.

  18. Heroin

    MedlinePlus

    ... 19-23, 2016 DEA Museum and Visitors' Center Heroin Last Updated: Monday, April 3, 2017 What is ... from morphine and extracted from certain poppy plants. Heroin comes in a white or brownish powder, or ...

  19. 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…

  20. Precise simultaneous quantification of methadone and cocaine in rat serum and brain tissue samples following their successive i.p. administration.

    PubMed

    Nakhla, David S; Hussein, Lobna A; Magdy, N; Abdallah, Inas A; Hassan, Hazem E

    2017-03-24

    A sensitive high-performance liquid chromatography (HPLC) assay with dual UV detection has been developed and validated for the simultaneous quantification of methadone and cocaine in rat serum and brain tissue samples. Liquid-liquid extraction using hexanes was applied for samples extraction with Levo-Tetrahydropalmatine (L-THP) as the internal standard. Chromatographic separation of the analytes was achieved on a reversed-phase Waters Symmetry(®) C18 column (150mm×4.6mm, 5μm). A gradient elution was employed with a mobile phase consisting of 5mM potassium phosphate containing 0.1% triethylamine (pH=6.5) (A) and acetonitrile (B) with a flow rate of 1mL/min. UV detection was employed at 215nm and 235nm for the determination of methadone and cocaine, respectively. The calibration curves were linear over the range of 0.05-10μg/mL for both methadone and cocaine. The assay was validated according to FDA guidelines for bioanalytical method validation and results were satisfactory and met FDA criteria. Inter-day accuracy values of serum and brain samples ranged from 96.97 to 105.59% while intra-day accuracy values ranged from 91.49 to 111.92%. Stability assays showed that both methadone and cocaine were stable during sample storage, preparation, and analytical procedures. The method was successfully used to analyze biological samples obtained from a drug- drug interaction pharmacokinetics (PK) study conducted in rats to investigate the effect of methadone on cocaine PK. Our method not only can be used for bioanalysis of samples obtained from rats but also can potentially be applied to human biological serum samples to monitor compliance to methadone maintenance therapy (MMT) and to detect possible cocaine-methadone co-abuse.

  1. Benzodiazepine use among patients in heroin-assisted vs. methadone maintenance treatment: findings of the German randomized controlled trial.

    PubMed

    Eiroa-Orosa, Francisco José; Haasen, Christian; Verthein, Uwe; Dilg, Christoph; Schäfer, Ingo; Reimer, Jens

    2010-12-01

    Benzodiazepine (BZD) use has been found to be associated with poorer psychosocial adjustment, higher levels of polydrug use and more risk-taking behaviors among opioid dependent patients. The aim of this paper is to analyze the correlation between BZD use, BZD prescription and treatment outcome among participants in the German trial on heroin-assisted treatment. 1015 patients who participated in the study comparing heroin-assisted and methadone maintenance treatment (HAT & MMT) for 12 months were included in the analysis. Analyses were carried out to assess the association of treatment outcome with baseline BZD use, with ongoing BZD use and with different patterns of BZD prescription. Baseline BZD use correlated with lower retention rates but not with poorer outcome. Ongoing BZD use correlated with poorer outcomes. Significantly better outcomes were found in the course of phobic anxiety symptomatology for those with regular prescription of BZD. The percentage of BZD positive urine tests decreased more in HAT than in MMT. Poorer outcome for benzodiazepine users may be mediated by a higher severity of addiction. Cautious prescribing of benzodiazepines may be beneficial due to the reduction of overall illicit use.

  2. 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)

  3. Comparing injection and non-injection routes of administration for heroin, methamphetamine, and cocaine users in the United States.

    PubMed

    Novak, Scott P; Kral, Alex H

    2011-01-01

    Research examining the demographic and substance use characteristics of illicit drug use in the United States has typically failed to consider differences in routes of administration or has exclusively focused on a single route of administration?injection drug use. Data from National Survey on Drug Use and Health were used to compare past-year injection drug users and non-injection drug users' routes of administration of those who use the three drugs most commonly injected in the United States: heroin, methamphetamine, and cocaine. Injection drug users were more likely than those using drugs via other routes to be older (aged 35 and older), unemployed, possess less than a high school education, and reside in rural areas. IDUs also exhibited higher rates of abuse/dependence, perceived need for substance abuse treatment, and co-occurring physical and psychological problems. Fewer differences between IDUs and non-IDUs were observed for heroin users compared with methamphetamine or cocaine users.

  4. Experimentally induced aggressiveness in heroin-dependent patients treated with buprenorphine: comparison of patients receiving methadone and healthy subjects.

    PubMed

    Gerra, Gilberto; Zaimovic, Amir; Raggi, Maria Augusta; Moi, Gabriele; Branchi, Barbara; Moroni, Mirko; Brambilla, Francesca

    2007-01-15

    Objective measures of experimentally induced aggressiveness were evaluated in heroin-dependent patients (HDP), 15 receiving buprenorphine (BUP) and 15 receiving methadone (METH) treatment. HDP were randomly assigned to BUP and METH groups. Fifteen healthy subjects (CONT) were included in the study as controls. During a laboratory task, the Point Subtraction Aggression Paradigm, subjects earned monetary reinforcement and could respond by ostensibly subtracting money from a fictitious subject (the aggressive response). Money-earning (points maintained) responses did not differ in BUP patients and in controls. In contrast, point-maintained responses were significantly lower in the group of HDP treated with METH than in both the BUP and CONT groups. Aggressive responses were significantly higher in the HDP group than in the CONT group. No significant differences in aggressive responses were found between the BUP and METH groups. Baseline concentrations of plasma adrenocorticotropic hormone (ACTH) and cortisol (CORT) were higher in HDP than in CONT. During the experimental task, ACTH and CORT increased significantly less in METH patients than in BUP patients and CONT. Norepinephrine (NE) and epinephrine (EPI) levels increased significantly more in HDP than in CONT, without any difference between the METH and BUP patients. PSAP aggressive responses positively correlated with NE and EPI changes, as well as with Buss-Durkee Hostility Inventory (BDHI) scores in both METH and BUP patients and also in CONT subjects. No correlation was found between the extent of heroin exposure, drug doses and aggressiveness levels. BUP, similarly to METH, does not seem to affect outward-directed aggressiveness, as aggressive responses related more to monoamine levels and personality traits than to the action of opioid agonists. Money-earning responses seemed to be unimpaired in BUP patients.

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

    PubMed Central

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

    2013-01-01

    Objective: 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. Methods: 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. Results: 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. Conclusion: 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. PMID:24892317

  6. Heroin

    MedlinePlus

    ... Heroin is a highly addictive drug made from morphine, a psychoactive (mind-altering) substance that is extracted ... an opioid. It is related to chemically to morphine and other prescription opiates like vicodin, which are ...

  7. [Application of hair analysis of selected psychoactive substances for medico-legal purposes. Part II. Cases of complex fatal poisonings: interactions of heroine - cocaine - amphetamines].

    PubMed

    Rojek, Sebastian; Kłys, Małgorzata; Rzepecka-Woźniak, Ewa; Konopka, Tomasz

    2010-01-01

    The study represents an attempt at employing segmental hair analysis in complex poisonings with xenobiotic mixtures of heroine - cocaine - amphetamines in the context of the cause of death as a consequence of complex interaction mechanisms which occurred prior to death. Two cases of complex poisonings: heroine - cocaine and heroine - cocaine - amphetamines were analyzed and documented with macro- and microscopic examinations and complex toxicological examinations, including the analysis of classic biological material, i.e. samples of selective blood, and alternative material, i.e. hair samples. Determinations of opioids, cocaine and its metabolite and amphetamines in the hair biological matrix were performed using high performance liquid chromatography--atmospheric pressure chemical ionization--tandem mass spectrometry (HPLC-APCI-MS-MS). Segmental hair analysis of the investigated cases indicated a prolonged intake of similar psychoactive substances and a developed adaptation of the addicted to interaction mechanisms, which, however, led gradually to multiorgan anatomopathological changes, and in consequence to death.

  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. 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

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

    2009-10-01

    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 (1g) by solid phase extraction. Linearity was 2.5-500ng/g, except for methadone (10-2000ng/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.

  10. The effects of housing costs on polydrug abuse patterns: a comparison of heroin, cocaine, and alcohol abusers.

    PubMed

    Petry, N M

    2001-02-01

    This study evaluated how price of housing affects hypothetical purchasing decisions. Participants (26 heroin, 28 cocaine, and 15 alcohol abusers, and 25 controls) were exposed to 4 conditions in which they "purchased" drugs, food, housing, and entertainment. Whereas income remained constant, housing prices varied across conditions. Except for 23% of heroin abusers, participants purchased housing regardless of cost, so that income increased as housing cost decreased. Demand for food was income inelastic, whereas demand for entertainment was income elastic. Each group showed income elastic demand for their drug of choice. Hypothetical choices were reliable; drug choices were correlated with urinalysis results, and willingness to forgo housing in the simulation was correlated with time spent homeless in real life. This study shows that changes in housing prices may affect choices for drug and nondrug reinforcers.

  11. Chronic heroin and cocaine abuse is associated with decreased serum concentrations of the nerve growth factor and brain-derived neurotrophic factor.

    PubMed

    Angelucci, Francesco; Ricci, Valerio; Pomponi, Massimiliano; Conte, Gianluigi; Mathé, Aleksander A; Attilio Tonali, Pietro; Bria, Pietro

    2007-11-01

    Chronic cocaine and heroin users display a variety of central nervous system (CNS) dysfunctions including impaired attention, learning, memory, reaction time, cognitive flexibility, impulse control and selective processing. These findings suggest that these drugs may alter normal brain functions and possibly cause neurotoxicity. Neurotrophins are a class of proteins that serve as survival factors for CNS neurons. In particular, nerve growth factor (NGF) plays an important role in the survival and function of cholinergic neurons while brain-derived neurotrophic factor (BDNF) is involved in synaptic plasticity and in the maintenance of midbrain dopaminergic and cholinergic neurons. In the present study, we measured by enzyme-linked immunosorbent assay (ELISA) the NGF and BDNF levels in serum of three groups of subjects: heroin-dependent patients, cocaine-dependent patients and healthy volunteers. Our goal was to identify possible change in serum neurotrophins in heroin and cocaine users. BDNF was decreased in heroin users whereas NGF was decreased in both heroin and cocaine users. These findings indicate that NGF and BDNF may play a role in the neurotoxicity and addiction induced by these drugs. In view of the neurotrophin hypothesis of schizophrenia the data also suggest that reduced level of neurotrophins may increase the risk of developing psychosis in drug users.

  12. Drug Abuse: Methadone Becomes the Solution and the Problem

    ERIC Educational Resources Information Center

    Bazell, Robert J.

    1973-01-01

    Methadone is used to divert heroin addicts from using stronger drugs. Rate of crimes committed by drug addicts has fallen considerably after putting them on methadone. Despite criticisms, methadone use seems to be encouraging for the future. (PS)

  13. Changes in neurocognition and adherence over six months in HIV-infected individuals with cocaine or heroin dependence.

    PubMed

    Anderson, Albert M; Higgins, Melinda K; Ownby, Raymond L; Waldrop-Valverde, Drenna

    2015-01-01

    We sought to examine the course of adherence and cognition in HIV-infected individuals with either cocaine or heroin dependence and investigate independent predictors of cognition change. A prospective study over six months was undertaken in which adherence was measured by monthly electronic pill cap monitoring (Medication Event Monitoring System), while a comprehensive neuropsychological battery resulting in a composite score (NPZ8) was performed at baseline and six months. Multivariable regression models were performed in order to determine independent associations with change in cognition. There were 101 subjects at baseline, of whom 62% were male and 83% were non-Hispanic black. 46.6% of subjects at baseline had completed high school, 36.6% reported active cocaine use during the course of the study, and 0% reported active heroin use during the course of the study. 66 subjects completed the final cognitive assessment at six months. Subjects had markedly impaired cognitive function at baseline (NPZ8 -1.49) which persisted at six months (NPZ8 -1.47) in the group of study completers. There was an average monthly decrease in adherence of -2.91% overall (p = 0.008). In the multivariable model, each of the following variables: baseline cognition (R(2) change = 0.121, p = 0.006), cocaine use during the study (R(2) change = 0.059, p = 0.046), and monthly adherence change (R(2) change = 0.078, p = 0.018) independently contributed to NPZ8 change with an overall R(2) change = 0.219 (p = 0.001). This study shows an overall decrease in adherence over time in this population of subjects with a history of drug dependence. Active cocaine use, baseline cognition, and temporal adherence changes independently contributed to changes in cognition. Further study on enhancing adherence, cognition, and limiting drug abuse are warranted in this subgroup of HIV-infected individuals.

  14. Cocaine

    MedlinePlus

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Cocaine KidsHealth > For Teens > Cocaine A A A What's ... How Can Someone Quit? Avoiding Cocaine What Is Cocaine? Cocaine is a powerful and highly addictive drug ...

  15. The Methadone Illusion

    ERIC Educational Resources Information Center

    Lennard, Henry L.; And Others

    1972-01-01

    Methadone treatment for heroin addiction does not touch the roots of the drug problem" and to think that the use of another drug can solve the profound and complex task facing us is indeed an illusion." (Author/AL)

  16. Genome-Wide Pharmacogenomic Study on Methadone Maintenance Treatment Identifies SNP rs17180299 and Multiple Haplotypes on CYP2B6, SPON1, and GSG1L Associated with Plasma Concentrations of Methadone R- and S-enantiomers in Heroin-Dependent Patients.

    PubMed

    Yang, Hsin-Chou; Chu, Shih-Kai; Huang, Chieh-Liang; Kuo, Hsiang-Wei; Wang, Sheng-Chang; Liu, Sheng-Wen; Ho, Ing-Kang; Liu, Yu-Li

    2016-03-01

    Methadone maintenance treatment (MMT) is commonly used for controlling opioid dependence, preventing withdrawal symptoms, and improving the quality of life of heroin-dependent patients. A steady-state plasma concentration of methadone enantiomers, a measure of methadone metabolism, is an index of treatment response and efficacy of MMT. Although the methadone metabolism pathway has been partially revealed, no genome-wide pharmacogenomic study has been performed to identify genetic determinants and characterize genetic mechanisms for the plasma concentrations of methadone R- and S-enantiomers. This study was the first genome-wide pharmacogenomic study to identify genes associated with the plasma concentrations of methadone R- and S-enantiomers and their respective metabolites in a methadone maintenance cohort. After data quality control was ensured, a dataset of 344 heroin-dependent patients in the Han Chinese population of Taiwan who underwent MMT was analyzed. Genome-wide single-locus and haplotype-based association tests were performed to analyze four quantitative traits: the plasma concentrations of methadone R- and S-enantiomers and their respective metabolites. A significant single nucleotide polymorphism (SNP), rs17180299 (raw p = 2.24 × 10(-8)), was identified, accounting for 9.541% of the variation in the plasma concentration of the methadone R-enantiomer. In addition, 17 haplotypes were identified on SPON1, GSG1L, and CYP450 genes associated with the plasma concentration of methadone S-enantiomer. These haplotypes accounted for approximately one-fourth of the variation of the overall S-methadone plasma concentration. The association between the S-methadone plasma concentration and CYP2B6, SPON1, and GSG1L were replicated in another independent study. A gene expression experiment revealed that CYP2B6, SPON1, and GSG1L can be activated concomitantly through a constitutive androstane receptor (CAR) activation pathway. In conclusion, this study revealed new

  17. Genome-Wide Pharmacogenomic Study on Methadone Maintenance Treatment Identifies SNP rs17180299 and Multiple Haplotypes on CYP2B6, SPON1, and GSG1L Associated with Plasma Concentrations of Methadone R- and S-enantiomers in Heroin-Dependent Patients

    PubMed Central

    Yang, Hsin-Chou; Chu, Shih-Kai; Huang, Chieh-Liang; Kuo, Hsiang-Wei; Wang, Sheng-Chang; Liu, Sheng-Wen; Ho, Ing-Kang; Liu, Yu-Li

    2016-01-01

    Methadone maintenance treatment (MMT) is commonly used for controlling opioid dependence, preventing withdrawal symptoms, and improving the quality of life of heroin-dependent patients. A steady-state plasma concentration of methadone enantiomers, a measure of methadone metabolism, is an index of treatment response and efficacy of MMT. Although the methadone metabolism pathway has been partially revealed, no genome-wide pharmacogenomic study has been performed to identify genetic determinants and characterize genetic mechanisms for the plasma concentrations of methadone R- and S-enantiomers. This study was the first genome-wide pharmacogenomic study to identify genes associated with the plasma concentrations of methadone R- and S-enantiomers and their respective metabolites in a methadone maintenance cohort. After data quality control was ensured, a dataset of 344 heroin-dependent patients in the Han Chinese population of Taiwan who underwent MMT was analyzed. Genome-wide single-locus and haplotype-based association tests were performed to analyze four quantitative traits: the plasma concentrations of methadone R- and S-enantiomers and their respective metabolites. A significant single nucleotide polymorphism (SNP), rs17180299 (raw p = 2.24 × 10−8), was identified, accounting for 9.541% of the variation in the plasma concentration of the methadone R-enantiomer. In addition, 17 haplotypes were identified on SPON1, GSG1L, and CYP450 genes associated with the plasma concentration of methadone S-enantiomer. These haplotypes accounted for approximately one-fourth of the variation of the overall S-methadone plasma concentration. The association between the S-methadone plasma concentration and CYP2B6, SPON1, and GSG1L were replicated in another independent study. A gene expression experiment revealed that CYP2B6, SPON1, and GSG1L can be activated concomitantly through a constitutive androstane receptor (CAR) activation pathway. In conclusion, this study revealed new

  18. 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.

  19. 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

  20. Psychiatric comorbidity and additional abuse of drugs in maintenance treatment with L- and D,L-methadone.

    PubMed

    Wedekind, Dirk; Jacobs, Stefan; Karg, Iris; Luedecke, Christel; Schneider, Udo; Cimander, Konrad; Baumann, Pierre; Ruether, Eckart; Poser, Wolfgang; Havemann-Reinecke, Ursula

    2010-03-01

    Sixty D,L- or L-methadone treated patients in maintenance therapy were interviewed for additional drug abuse and psychiatric comorbidity; 51.7% of the entire population had a comorbid Axis-I disorder, with a higher prevalence in females (P=0.05). Comorbid patients tended to have higher abuse of benzodiazepines, alcohol, cannabis, and cocaine, but not of heroin. They had received a significantly lower D,L- (P<0.05) and L-methadone dose than non-comorbid subjects. The duration of maintenance treatment showed an inverse relationship to frequency of additional heroin intake (P<0.01). Patients with additional heroin intake over the past 30 days had been treated with a significantly lower L-methadone dosage (P<0.05) than patients without. Axis-I comorbidity appears to be decreased when relatively higher dosages of D,L- (and L-methadone) are administered; comorbid individuals, however, were on significantly lower dosages. Finally, L-, but not D,L-methadone seems to be more effective in reducing additional heroin abuse.

  1. Cocaine

    MedlinePlus

    ... DEA 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 ...

  2. Cocaine

    MedlinePlus

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Cocaine KidsHealth > For Teens > Cocaine Print A A A ... Quit? Avoiding Cocaine en español Cocaína What Is Cocaine? Cocaine is a powerful and highly addictive drug ...

  3. [Efficacy diacetylmorphine (pharmaceutical heroin) for heroin treatment ].

    PubMed

    Demaret, I; Lemaître, A; Ansseau, M

    2010-12-01

    Before implementing the TADAM project in Belgium (a heroin-assisted treatment trial), our research team studied the trials in other countries. Since 1994, six randomised controlled trials have been developed using the same treatment model of heroin-assisted treatment (HAT). Each trial concluded that HAT had more efficacy than methadone treatment. We analysed those trials in order to find on which levels patients in a HAT treatment are expected to improve. Improvements appeared after at least six months on the level of street heroin use, (physical and mental) health and criminal behaviour. In the longer term, the continuation of treatment had positive but limited effects on the social level. Due to his higher cost, this treatment should remain a second-line treatment for this special target group: severe heroin addicts, using continuously street heroin in spite of a methadone treatment.

  4. Effects of prior cocaine versus morphine or heroin self-administration on extinction learning driven by over-expectation versus omission of reward

    PubMed Central

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

    2014-01-01

    Background 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 over-expectation. Methods In Experiment 1, we trained rats to self-administer cocaine, morphine, or sucrose for 3 hr/day (limited access). In Experiment 2, we trained rats to self-administer heroin or sucrose for 12 hr/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 over-expectation procedure and later by omitting the food reward. Results Rats trained under limited access conditions to self-administer sucrose or morphine demonstrated normal extinction in response to both over-expectation 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 over-expectation. Conclusions The specific long-lasting effects of cocaine and heroin show that drug exposure induces long-lasting deficits in the ability to extinguish reward seeking after changes in expected outcomes. These deficits were not observed in a standard extinction procedure but instead only affected extinction learning driven by a more complex phenomenon of over-expectation. PMID:25641634

  5. Application of pericardial fluid to the analysis of morphine (heroin) and cocaine in forensic toxicology.

    PubMed

    Contreras, María Teresa; Hernández, Antonio F; González, Marisa; González, Susana; Ventura, Rosa; Pla, Antonio; Valverde, Juan Luis; Segura, Jordi; de la Torre, Rafael

    2006-12-20

    In this study opiates (morphine and codeine) and cocaine and its related metabolites (benzoylecgonine and cocaethylene) were analyzed in pericardial fluid by GC/MS. This is the first study reporting levels of drugs of abuse in this body fluid. The analytical method used has been previously validated and then applied to 54 drug-related deaths in the Barcelona area (Spain). Median levels were as follows: morphine 589ng/ml, range 19-8857 (n=49); codeine 26ng/ml, range 15-343 (n=35); cocaine 78ng/ml, range 10-220 (n=14), benzoylecgonine 742ng/ml, range 20-3386 (n=15), and cocaethylene 36ng/ml, range 9-100 (n=13). In addition, a comparative study of the concentration of opiates and cocaine in pericardial fluid by both semi-quantitative EMIT d.a.u. and GC/MS (used as reference) was performed. Fairly good correlations for opiates (r=0.905) and cocaine (r=0.859) were found; however, the consistently low results of EMIT in the analysis of cocaine comparing to GC/MS could be caused by matrix effect. In spite of that, it raises the possibility of using the immunoassay as a preliminary technique in forensic toxicology.

  6. The Prevalence of Musculoskeletal Pain and Forward Head Posture among Heroin Users during their Withdrawal with Methadone

    PubMed Central

    Kamali-Sarvestani, Fahimeh; Motiallah, Tahereh; Ghaffarinejad, Farahnaz

    2014-01-01

    Background Heroin is an extremely addictive narcotic drug derived from morphine. Its continued use requires increased amounts of the drug to achieve the same effect, resulting in tolerance and addiction. This study was done in order to determine the prevalence of musculoskeletal pain and forward head posture among heroin users during their withdrawal. Methods This research was a cross-sectional study that was done on 90 heroin users (83 males, 7 females) aged between 20 to 40 years (32.5 ± 3.81) during their withdrawal in Shiraz, Iran. They were selected by simple randomized sampling. Data were collected by a form regarding age, sex, the duration of heroin use, and musculoskeletal pain. Pain was measured by VAS (visual analog scale) and forward head posture was evaluated by plumb line. Pearson correlation technique and chi-square were used for analyzing the data. Findings The results revealed that the majority of heroin users suffered from musculoskeletal pain during their withdrawal. At the end of withdrawal 53.4% had severe pain, 38.8% had moderate pain, and 7.8% of them had mild pain. Pain in the lower extremities and low back was more common than the upper extremities. The intensity of pain before withdrawal was mild, during withdrawal was moderate, and at the end was sever, but there was no significant correlation between them. The results also showed 43.3% of subjects had normal posture and 56.7% had forward posture. Conclusion According to the results, the intensity of pain increased during the withdrawal period; therefore, more attention must be paid to this complication in heroin users for better evaluation and a successful withdrawal. PMID:25140215

  7. 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…

  8. [Therapy in heroin addiction].

    PubMed

    Hosztafi, Sáandor; Fürst, Zsuzsanna

    2014-09-01

    Heroin addiction is one of the most devastating and expensive of public health problems. The most effective treatment is opioid replacement therapy. Replacement of heroin, a short-acting euphoriant with methadone or other opioids that have significantly longer duration of action provides a number of therapeutic benefits. Opioid detoxification has a role in both preventing acute withdrawal and maintaining long-term abstinence. Opioid-based detoxification is based on the principle of cross-tolerance, in which one opioid is replaced with another one that is slowly tapered. For the treatment of heroin addicts a wide range of psychosocial and pharmacotherapeutic treatments are available; of these, methadone maintenance therapy has the most evidence of benefit. Methadone maintenance reduces and/or eliminates the use of heroin, reduces the death rate 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 to reduce 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. There is growing interest in expanding treatment into primary care, allowing opioid addiction to be managed like other chronic illnesses. Buprenorphine which is a long-acting partial agonist was also approved as pharmacotherapy for opioid dependence. Opioid antagonists can reduce heroin self-administration and opioid craving in detoxified addicts. Naltrexone, which is a long-acting competitive antagonist at the opioid receptors, blocks the subjective and objective responses produced by intravenous opioids. Naltrexone is employed to accelerate opioid detoxification by displacing heroin and as a maintenance agent for detoxified formerly heroin-dependent patients who want to

  9. Neural Correlates of the Severity of Cocaine, Heroin, Alcohol, MDMA and Cannabis Use in Polysubstance Abusers: A Resting-PET Brain Metabolism Study

    PubMed Central

    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

    Introduction 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. Methods 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. Results 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. Conclusions 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. PMID:22768136

  10. 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

  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. Toxicokinetics of drugs of abuse: current knowledge of the isoenzymes involved in the human metabolism of tetrahydrocannabinol, cocaine, heroin, morphine, and codeine.

    PubMed

    Maurer, Hans H; Sauer, Christoph; Theobald, Denis S

    2006-06-01

    This review summarizes the major metabolic pathways of the drugs of abuse, tetrahydrocannabinol, cocaine, heroin, morphine, and codeine, in humans including the involvement of isoenzymes. This knowledge may be important for predicting their possible interactions with other xenobiotics, understanding pharmaco-/toxicokinetic and pharmacogenetic variations, toxicological risk assessment, developing suitable toxicological analysis procedures, and finally for understanding certain pitfalls in drug testing. The detection times of these drugs and/or their metabolites in biological samples are summarized and the implications of the presented data on the possible interactions of drugs of abuse with other xenobiotics, ie, inhibition or induction of individual polymorphic and nonpolymorphic isoenzymes, discussed.

  13. Discriminative stimulus effects of intravenous heroin and its metabolites in rhesus monkeys: opioid and dopaminergic mechanisms.

    PubMed

    Platt, D M; Rowlett, J K; Spealman, R D

    2001-11-01

    Heroin has characteristic subjective effects that contribute importantly to its widespread abuse. Drug discrimination procedures in animals have proven to be useful models for investigating pharmacological mechanisms underlying the subjective effects of drugs in humans. However, surprisingly little information exists concerning the mechanisms underlying the discriminative stimulus (DS) effects of heroin. This study characterized the DS effects of heroin in rhesus monkeys trained to discriminate i.v. heroin from saline. In drug substitution experiments, heroin, its metabolites 6-monoacetylmorphine, morphine, morphine-6-glucuronide, and morphine-3-glucuronide, and the mu-agonists fentanyl and methadone engendered dose-dependent increases in heroin-lever responding, reaching average maximums of >80% (full substitution) at doses that did not appreciably suppress response rate. In contrast, the delta-agonist SNC 80, the kappa-agonist spiradoline, and the dopamine uptake blockers/releasers cocaine, methamphetamine, and GBR 12909 did not engender heroin-like DS effects regardless of dose. In antagonism studies, in vivo apparent pA2 and pK(B) values for naltrexone combined with heroin, morphine, and 6-monoacetylmorphine (8.0-8.7) were comparable with those reported previously for naltrexone antagonism of prototypical mu-agonists. The results show that the DS effects of heroin are pharmacologically specific and mediated primarily at mu-opioid receptors. Moreover, the acetylated and glucuronated metabolites of heroin appear to play significant roles in these effects. Despite previous speculation that morphine-3-glucuronide lacks significant opioid activity, it substituted fully for heroin in our study, suggesting that it can exhibit prominent mu-agonist effects in vivo.

  14. Sexually transmitted infections among pregnant heroin- or cocaine-addicted women in treatment: the significance of psychiatric co-morbidity and sex trade.

    PubMed

    Cavanaugh, C E; Hedden, S L; Latimer, W W

    2010-02-01

    Psychiatric co-morbidity 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 programme 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. gonorrhoea, 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 co-morbidity (61.8%) and/or sex trade (60.5%). Participants with psychiatric co-morbidity (adjusted odds ratio [AOR] 3.9; 95% confidence interval [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 with 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 co-morbidity and/or sex trade were associated with greater STI risk. Findings underscore the importance of identifying and addressing co-morbid psychiatric disorders and sex trade behaviour in this population.

  15. 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.

  16. Optimum Methadone Compliance Testing

    PubMed Central

    2006-01-01

    Executive Summary Objective The objective of this analysis was to determine the diagnostic utility of oral fluid testing collected with the Intercept oral fluid collection device. Clinical Need: Target Population and Condition Opioids (opiates or narcotics) are a class of drugs derived from the opium poppy plant that typically relieve pain and produce a euphoric feeling. Methadone is a long-acting synthetic opioid used to treat opioid dependence and chronic pain. It prevents symptoms of opioid withdrawal, reduces opioid cravings and blocks the euphoric effects of short-acting opioids such as heroin and morphine. Opioid dependence is associated with harms including an increased risk of exposure to Human Immunodeficiency Virus and Hepatitis C as well as other health, social and psychological crises. The goal of methadone treatment is harm reduction. Treatment with methadone for opioid dependence is often a long-term therapy. The Ontario College of Physicians and Surgeons estimates that there are currently 250 physicians qualified to prescribe methadone, and 15,500 people in methadone maintenance programs across Ontario. Drug testing is a clinical tool whose purpose is to provide objective meaningful information, which will reinforce positive behavioral changes in patients and guide further treatment needs. Such information includes knowledge of whether the patient is taking their methadone as prescribed and reducing or abstaining from using opioid and other drugs of abuse use. The results of drug testing can be used with behavior modification techniques (contingency management techniques) where positive reinforcements such as increased methadone take-home privileges, sustained employment or parole are granted for drug screens negative for opioid use, and negative reinforcement including loss of these privileges for drug screens positive for opioid used. Body fluids including blood, oral fluid, often referred to as saliva, and urine may contain metabolites and the

  17. Methadone Maintenance as Law and Order

    ERIC Educational Resources Information Center

    Heyman, Florence

    1972-01-01

    Argues that substitution of methadone for heroin would not rehabilitate the drug addict, but it may be used as a method of tranquilizing a potentially troublesome ghetto and poor white population. (RJ)

  18. Short-term declines in CD4 levels associated with cocaine use in HIV-1 seropositive, minority injecting drug users.

    PubMed Central

    Siddiqui, N. S.; Brown, L. S.; Makuch, R. W.

    1993-01-01

    This study evaluates the association of cocaine use with short-term change in CD4 counts among human immunodeficiency virus type 1 (HIV-1) seropositive, minority injecting drug users prior to the introduction of zidovudine (AZT). Ninety-eight HIV-1 seropositive subjects were recruited from six inner-city, methadone maintenance clinics. A baseline assessment included a short questionnaire regarding drug behavior and quantitation of CD4 cell counts. These measures were repeated on all subjects 3 to 4 months later. Thirty-eight subjects reported using cocaine between baseline and 4-month follow-up evaluations. Males and African Americans were more likely to be cocaine users (P < .01). Cocaine users were more likely to engage in heroin and needle use (P < .001). Cocaine users experienced a significant decline in CD4 cells compared with nonusers (P = .013); no marked difference in CD4 decline was noted between heroin users and nonusers (P = .19). Multivariate analysis showed that a decline in CD4 counts was 2.82 times more likely to occur in cocaine users than in cocaine nonusers (90% two-sided confidence interval of 1.08, 7.37). These findings support the hypothesis of a possible link between cocaine use and short-term CD4 decline in HIV-1 seropositive injecting drug users. PMID:8478971

  19. Going Through the Changes: Methadone in New York City

    ERIC Educational Resources Information Center

    Agar, Michael

    1977-01-01

    Methadone has been defined as an agent to draw addicts out of the street life into "straight" society. However, the complementary perspective of the streets sees methadone as a new, widely available drug to be integrated into a subculture previously dominated by heroin. This article discusses the adaptation to methadone and its…

  20. Uses of diverted methadone and buprenorphine by opioid-addicted individuals in Baltimore, Maryland

    PubMed Central

    Mitchell, Shannon Gwin; Kelly, Sharon M.; Brown, Barry S.; Reisinger, Heather Schacht; Peterson, James A.; Ruhf, Adrienne; Agar, Michael H.; O'Grady, Kevin E.; Schwartz, Robert P.

    2009-01-01

    This study examined the uses of diverted methadone and buprenorphine among opiate-addicted individuals recruited from new admissions to methadone programs and from out-of-treatment individuals recruited from the streets. Self-report data regarding diversion were obtained from surveys and semi-structured qualitative interviews. Approximately 16% (n=84) of the total sample (N=515) reported using diverted (street) methadone 2–3 times per week for six months or more, and for an average of 7.8 days (SD=10.3) within the past month. The group reporting lifetime use of diverted methadone as compared to the group that did not report such use was less likely to use heroin and cocaine in the 30 days prior to admission (ps < .01) and had lower ASI Drug Composite scores (p < .05). Participants in our qualitative sub-sample (n=22) indicated that street methadone was more widely used than street buprenorphine and that both drugs were largely used as self-medication for detoxification and withdrawal symptoms. Participants reported using low dosages and no injection of either medication was reported. PMID:19874152

  1. Determining Effective Methadone Doses for Individual Opioid-Dependent Patients

    PubMed Central

    Trafton, Jodie A; Minkel, Jared; Humphreys, Keith

    2006-01-01

    Background Randomized clinical trials of methadone maintenance have found that on average high daily doses are more effective for reducing heroin use, and clinical practice guidelines recommend 60 mg/d as a minimum dosage. Nevertheless, many clinicians report that some patients can be stably maintained on lower methadone dosages to optimal effect, and clinic dosing practices vary substantially. Studies of individual responses to methadone treatment may be more easily translated into clinical practice. Methods and Findings A volunteer sample of 222 opioid-dependent US veterans initiating methadone treatment was prospectively observed over the year after treatment entry. In the 168 who achieved at least 1 mo of heroin abstinence, methadone dosages on which patients maintained heroin-free urine samples ranged from 1.5 mg to 191.2 mg (median = 69 mg). Among patients who achieved heroin abstinence, higher methadone dosages were predicted by having a diagnosis of posttraumatic stress disorder or depression, having a greater number of previous opioid detoxifications, living in a region with lower average heroin purity, attending a clinic where counselors discourage dosage reductions, and staying in treatment longer. These factors predicted 42% of the variance in dosage associated with heroin abstinence. Conclusions Effective and ineffective methadone dosages overlap substantially. Dosing guidelines should focus more heavily on appropriate processes of dosage determination rather than solely specifying recommended dosages. To optimize therapy, methadone dosages must be titrated until heroin abstinence is achieved. PMID:16448216

  2. A probability-based sampling approach for the analysis of drug seizures composed of multiple containers of either cocaine, heroin, or Cannabis.

    PubMed

    Mario, John R

    2010-04-15

    A probability-based analytical sampling approach for seized containers of cocaine, Cannabis, or heroin, to answer questions of both content weight and identity, is described. It utilizes the Student's t distribution, and, because of the lack of normality in studied populations, the power of the Central Limit Theorem with samples of size 20 to calculate the mean net weights of multiple item drug seizures. Populations studied ranged between 50 and 1200 units. Identity determination is based on chemical testing and sampling using the hypergeometric distribution fit to a program macro - created by the European Network of Forensic Science Institutes (ENFSI) Drugs Working Group. Formal random item selection is effected through use of an Excel-generated list of random numbers. Included, because of their impact on actual practice, are discussions of admissibility, sufficiency of proof, method validation, and harmony with the guidelines of international standardizing bodies.

  3. Heroin addiction and pregnancy.

    PubMed

    Bashore, R A; Ketchum, J S; Staisch, K J; Barrett, C T; Zimmermann, E G

    1981-06-01

    Pregnant heroin addicts tend to be younger than nonaddicted pregnant patients, unmarried or separated from spouses, and a disproportionately large number are members of minority ethnic groups. Heroin addiction during pregnancy is associated with several significant medical and obstetrical complications and may result in both acute and chronic abnormalities in neonates. Malnutrition, venereal disease, hepatitis, pulmonary complications, preeclampsia and third-trimester bleeding are the most common maternal complications, while fetal death, intrauterine growth retardation, prematurity and withdrawal symptoms affect the fetus and neonate. There is controversy about treating addicts with methadone during pregnancy. The findings of studies in animals suggest that there may be a long-lasting drug-induced syndrome, characterized by growth retardation, delayed motor development and behavior abnormalities in offspring of heroin-addicted or methadone-treated mothers.

  4. 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).

  5. A randomized controlled trial of the therapeutic workplace for community methadone patients: a partial failure to engage.

    PubMed

    Knealing, Todd W; Wong, Conrad J; Diemer, Karly N; Hampton, Jacqueline; Silverman, Kenneth

    2006-08-01

    The Therapeutic Workplace is an employment-based treatment for drug addiction that uses wages for work to reinforce drug abstinence. The Therapeutic Workplace has promoted abstinence from heroin and cocaine in treatment-resistant mothers in methadone treatment. This study attempted to replicate that effect in crack cocaine users recruited from community-based methadone programs. Participants were randomly assigned to a Therapeutic Workplace (n=22) or usual care control (n=25) group. Therapeutic Workplace participants were invited to work in the workplace and earn vouchers every weekday for 9 months contingent on documented opiate and cocaine abstinence. The two groups did not differ significantly on measures of cocaine or opiate use collected during study participation. Daily attendance and urinalysis results of the Therapeutic Workplace group were analyzed, and only 7 of the 22 participants initiated consistent periods of abstinence and workplace attendance. Two individuals gained access to the workplace on a few days, and 9 participants attempted to gain access to the workplace but never provided a drug-negative urine sample. Possible reasons for differences between the current study and the previous Therapeutic Workplace study are considered. Procedures that increase participant contact with the Therapeutic Workplace and its reinforcement contingencies might increase the likelihood of these individuals being successful in the treatment program.

  6. Foucault on methadone: beyond biopower.

    PubMed

    Keane, Helen

    2009-09-01

    This essay reviews four texts which critically analyse methadone maintenance therapy using Foucault as a key theoretical framework: [Friedman, J., & Alicea, M. (2001). Surviving heroin: Interviews with women in methadone clinics. Florida: University Press of Florida], [Bourgois, P. (2000). Disciplining addictions: The bio-politics of methadone and heroin in the United States. Culture Medicine and Psychiatry, 24, 165-195], [Bull, M. (2008). Governing the heroin trade: From treaties to treatment. Ashgate: Aldershot], and [Fraser, S., & valentine, k. (2008). Substance & substitution: Methadone subjects in liberal societies. New York: Palgrave Macmillan]. Taken together these works demonstrate one trajectory in the development of critical drug studies over the past decade. While all four view MMT as a regulatory technology which aims to create productive and obedient subjects, their understandings of the power relations of the clinic are quite distinct. The first two texts emphasise the social control of drug users, the third, issues of governmentality and liberal political practice, while the fourth engages with ontological questions about substances themselves. Thus while Foucauldian analysis has become familiar in social studies of drugs and alcohol, new uses for its conceptual tools continue to emerge.

  7. Methadone Maintenance: The Experience of Four Programs. The Drug Abuse Council Manuscript Series, No. 1.

    ERIC Educational Resources Information Center

    Danaceau, Paul

    Methadone maintenance is a relatively new method for treating heroin addiction. Controversy and questions remain about the drug itself and its use of methadone. The author was engaged by The Drug Abuse Council to prepare these descriptions of four methadone programs and the accompanying summary. The evolution of these programs is examined, and the…

  8. 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…

  9. Determination of cocaine and heroin with their respective metabolites in meconium by gas chromatography-mass spectrometry.

    PubMed

    López, P; Bermejo, A M; Tabernero, M J; Fernández, P; Alvarez, I

    2007-01-01

    The analysis of meconium specimens is a relatively accurate method for the detection of fetal exposure to drugs. The purpose of this study was to develop and validate a method for meconium sample preparation for a gas chromatography-mass spectrometry (GC-MS) confirmation of meconium extracts for cocaine, benzoylecgonine, codeine, morphine and 6-monoacetylmorphine. The analytes were initially extracted from the matrix by methanol. Subsequently a solid-phase extraction with Waters Oasis HLB cartridges was applied. Analytes were determined in GC-MS single monitoring mode. The method was validated in the range 40-2000 ng g(-1) using 0.5 g of meconium per assay. The detector response was linear over the studied range, and limits of quantitation and detection were found to be acceptable. Intra- and inter-batch coefficients of variation oscillated between 2.54% and 20.5%, and mean relative errors were in the range 0.79%-19.9%. The recoveries were higher than 42.1% in all cases. Finally the method was applied to analysis of meconium in newborns to assess fetal exposure to cocaine and opiates.

  10. Heroin reduces startle and cortisol response in opioid-maintained heroin-dependent patients.

    PubMed

    Walter, Marc; Wiesbeck, Gerhard A; Degen, Bigna; Albrich, Jürgen; Oppel, Monika; Schulz, André; Schächinger, Hartmut; Dürsteler-MacFarland, Kenneth M

    2011-01-01

    Heroin dependence (HD) is a chronic relapsing brain disorder characterized by a compulsion to seek and use heroin. Stress is seen as a key factor for heroin use. Methadone maintenance and the prescription of pharmaceutical heroin [diacetylmorphine (DAM)] are established treatments for HD in several countries. The present study examined whether DAM-maintained patients and methadone-maintained patients differ from healthy controls in startle reflex and cortisol levels. Fifty-seven participants, 19 of each group matched for age, sex and smoking status, completed a startle session which included the presentation of 24 bursts of white noise while eye-blink responses to startling noises were recorded. Salivary cortisol was collected three times after awakening, before, during and after the startle session. DAM was administered before the experiment, while methadone was administered afterwards. Both heroin-dependent patient groups exhibited significantly smaller startle responses than healthy controls (P < 0.05). Whereas the cortisol levels after awakening did not differ across the three groups, the experimental cortisol levels were significantly lower in DAM-maintained patients, who received their opioid before the experiment, than in methadone-maintained patients and healthy controls (P < 0.0001). Opioid maintenance treatment for HD is associated with reduced startle responses. Acute DAM administration may suppress cortisol levels, and DAM maintenance treatment may represent an effective alternative to methadone in stress-sensitive, heroin-dependent patients.

  11. Methadone-related deaths. A ten year overview.

    PubMed

    Vignali, Claudia; Stramesi, Cristiana; Morini, Luca; Pozzi, Fulvia; Groppi, Angelo

    2015-12-01

    Over the last 10 years we have registered in our district (about 500,000 inhabitants) 36 cases of fatal methadone poisoning, involving both patients on treatment and naive subjects: this is a significant increase of deaths due to methadone use, misuse or abuse compared with previous years. Twenty-four patients (66.7%) were on methadone maintenance programs for heroin detoxification, while 12 (33.3%) were taking the drug without a medical prescription. The average blood concentration of methadone in patients undergoing a maintenance program was 1.06 mg/L (0.21-3.37 mg/L), against 0.79 mg/L (0.2-3.15 mg/L) in those taking the non-prescribed drug. Since 111 heroin-related deaths were recorded in our district in the same period, the fact that there appear to be many methadone deaths (about a third of heroin-related deaths) cannot be overlooked. The aim of this work is to understand the possible reasons for such a large number of methadone-related deaths. On this subject, we have noticed that risks associated with methadone intake are often underestimated by clinicians prescribing the drug: sometimes methadone is prescribed without taking into account patient's tolerance to opiates, and a large number of subjects enrolled in methadone maintenance programs in Italy, have also been given take-home doses, thus increasing the risk of abuse and diversion.

  12. 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

    Fitzgerald, Paul J

    2013-10-13

    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.

  13. Should we prescribe heroin? A current Scottish debate.

    PubMed

    Gallagher, J; McKeganey, N

    2007-11-01

    There have been recent calls from within both Scotland and England for the wider prescription of heroin to heroin addicts as a way of coping with our burgeoning drug problem and as a route to reducing drug related criminality. But how feasible is heroin prescribing in this context? This paper considers some of the existing research evidence relating to heroin prescribing and looks also at the ethics and practicalities of prescribing heroin to heroin addicts in Scotland. We conclude that whilst the evidence on the benefits of heroin prescribing is far from clear cut there is a case for mounting a Scottish trial of heroin prescribing. Such a trial would need to be tightly controlled and rigorously evaluated. It would need to show that heroin prescribing was associated not only with a comparable level of harm reduction, as methadone prescribing, but that it was also an effective route towards drug users' eventual recovery and drug cessation.

  14. Analysis of opiates, cocaine and metabolites in urine by high-performance liquid chromatography with diode array detection (HPLC-DAD).

    PubMed

    Fernández, P; Vázquez, C; Morales, L; Bermejo, A M

    2005-01-01

    An analytical method is proposed for the simultaneous determination of morphine, codeine, 6-acetyl-morphine (MAM), cocaine, benzoylecgonine (BEG), cocaethylene, methadone and 2-ethylen-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) in urine using high performance liquid chromatography coupled to a diode array detector (HPLC-DAD). The selection of working wavelengths is based on the highest chromatographic response for each component: 233 nm for cocaine, BEG and cocaethylene; 285 nm for morphine, codeine and MAM; and 292 nm for methadone and EDDP. The mobile phase, which is a mixture of acetonitrile and 0.02 M phosphate buffer at pH 6.53, was eluted in gradient mode through an XTerra RP-8 column (250 mm x 4.6 mm i.d., 5 microm particle size). After applying a solid-phase extraction procedure with Bond Elut Certify cartridges, the recoveries obtained were between 60% (EDDP) and 97% (cocaethylene). A good linearity of the method in the 0.1-10 microg mL(-1) range of urinary concentrations was obtained because the coefficient of correlation exceeded 0.99 for each drug. The precision and accuracy were quite good, with values of <7% and within the range +/- 6%, respectively. Finally, the proposed method was applied to 23 urine samples from fatal intoxications related to methadone, heroin and[sol ]or cocaine.

  15. Changes in attitude toward methadone.

    PubMed

    Brown, B S; Jansen, D R; Benn, G J

    1975-02-01

    Staff and client attitudes toward heroin users and toward maintenance and abstient clients were assessed in 1970 and again in 1973. On each occasion there was striking agreement between the ratings made by staff and client groups. Abstinent clients were rated by all groups as significantly more effective and more responsible than either maintance clients or heroin users; maintenance clients were rated as more conservative, self-conscious, and self-effacing than were the other groups. While heroin users and abstinent clients were characterized similarly in the two rating periods, raters in the 1973 survey viewed methadone hydrochloride clients as more passive and less inclined to undertake adult responsibilities than was true of raters in the 1970 survey.

  16. Comparative toxicology of intentional and accidental heroin overdose.

    PubMed

    Darke, Shane; Duflou, Johan; Torok, Michelle

    2010-07-01

    The demographic and toxicological characteristics of deliberate (SUI, n = 50) and accidental (ACC, n = 927) fatal heroin overdose cases were examined. SUI cases were more likely to be female, had lower body mass indices, were more likely to be enrolled in treatment and less likely to have hepatic pathology. The median blood morphine concentration of SUI cases was significantly higher than that of ACC cases (0.70 vs. 0.40 mg/L, p < 0.001). Blood morphine concentrations of >1 mg/L were seen among 38.0% of SUI cases compared to 13.9% of ACC cases. Being a member of the SUI group remained a significant independent predictor of higher morphine concentrations after controlling for the effects of potential confounders (p < 0.001), other significant predictors being the absence of alcohol (p < 0.001), the presence of methadone (p < 0.05), and the presence of cocaine (p < 0.05). The current data are consistent with the view that suicide forms a small, but distinct, category of heroin overdose cases, rather than overdose being a parasuicidal phenomenon per se.

  17. Heroin Use: What Communities Should Know. Monthly Action Kit.

    ERIC Educational Resources Information Center

    Join Together, Boston, MA.

    This action kit was created in response to a rise in heroin use. Facts are provided about the scope of heroin use since it is the one illegal drug that is growing in popularity in some areas among young people. A brief explanation of some treatment options is provided including detoxification, methadone treatment, other medications, and behavioral…

  18. Methadone and alcohol.

    PubMed

    Freedman, L Z

    1976-01-01

    We have demonstrated the dangers of alcoholism that complicate methadone treatment of heroin addiction. In future papers, we will attempt to identify contributory factors and suggest interventionist techniques. In the final analysis, however, rehabilitation programs, vocational programs, and, above all, alleviation of the dreadful socioeconomic deprivations related to, among other factors, the racial bias under which most of these people have been born and have suffered during their lives will, in the long run, prove the most satisfactory means of reducing the heroin problem, except for a minority whose psychologic problems will then provide the irreducible minimum from which the majority of the addicts will come. As has so often been stated, the great drug problem in this country is alcoholism. We know that legal prohibition does not prevent the rise of alcoholism, and we know to our sorrow that not only does it give rise to enormous wealth and power to criminals and criminal gangs but that some of them are now also profiting from the great wealth to be made by dealing in heroin.

  19. 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

  20. Extended heroin access increases heroin choices over a potent nondrug alternative.

    PubMed

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

    2013-06-01

    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.

  1. Relationship between plasma concentrations of the l-enantiomer of methadone and response to methadone maintenance treatment.

    PubMed

    Meini, Milo; Moncini, Marco; Daini, Laura; Giarratana, Tania; Scaramelli, Daniela; Chericoni, Silvio; Stefanelli, Fabio; Rucci, Paola

    2015-08-05

    This study evaluated the relationship between the plasma concentration of l-methadone and response to methadone in real-world patients, in order to identify a minimum plasma concentration above which methadone treatment is effective. Ninety-four patients with opioid dependence under maintenance methadone treatment were consecutively recruited. Response was defined as negative urine analyses in the three weeks prior to the blood sampling. The percentage of participants with a plasma l-methadone concentration between 100 and 250 ng/ml was 54.2% among those with a methadone dosage ≥60 mg/day. Plasma l-methadone concentrations were significantly higher in patients with negative urine analyses compared with those with positive urine analyses (median 93 vs. 77 ng/ml, Mann-Whitney test, P<0.05). Above plasma l-methadone concentrations of 200 ng/ml no heroin use was reported and urine analyses were negative. Moreover, above concentrations of 250 ng/ml craving was absent. Examination of demographic correlates of treatment outcome indicated that older age, a stable job and being married were protective against the use of heroin. Mean plasma l-methadone concentration was significantly lower in patients who used cannabis compared with those who did not use cannabis, after adjusting for methadone dosage. In conclusion our results identify specific cut-offs for plasma l-methadone concentrations about which therapeutic response is observed and provide new evidence that therapeutic response is associated with patient׳s demographic characteristics. This underscores the need to monitor plasma methadone concentrations as part of Drug Addiction Services routine practice, in order to provide an objective framework for changing the methadone dosage.

  2. Cerebral vasculitis associated with cocaine abuse

    SciTech Connect

    Kaye, B.R.; Fainstat, M.

    1987-10-16

    A case of cerebral vasculitis in a previously healthy 22-year-old man with a history of cocaine abuse is described. Cerebral angiograms showed evidence of vasculitis. A search for possible causes other than cocaine produced no results. The authors include cocaine with methamphetamines, heroin, and ephedrine as illicit drugs that can cause cerebral vasculitis.

  3. Heroin Use, HIV-Risk, and Criminal Behavior in Baltimore: Findings from Clinical Research.

    PubMed

    Schwartz, Robert P; Kelly, Sharon M; Gryczynski, Jan; Mitchell, Shannon Gwin; O'Grady, Kevin E; Jaffe, Jerome H

    2015-01-01

    This article reviews research conducted in Baltimore over the past 15 years, examining the following: (1) What factors differentiate heroin-addicted individuals who enter methadone treatment from those who do not? (2) How difficult is gaining access to methadone treatment? (3) What are effective ways to overcome barriers to treatment entry? (4) Why do so many methadone patients drop out of treatment prematurely? (5) What are the added benefits of counseling when coupled with methadone or buprenorphine treatment? (6) Does increasing access to treatment have an impact on overdose deaths? Specific recommendations are made for policymakers concerned with addressing heroin addiction.

  4. The effect of parole on methadone patient behavior.

    PubMed

    Anglin, M D; McGlothlin, W H; Speckart, G

    1981-01-01

    A 7-year followup of three male samples of 1971-1973 methadone maintenance admissions was conducted: a random sample of 100; a sample of 136 who had a minimum of 30 months remaining on civil addict parole status at the time of methadone entry; and a matched sample of 136 not on parole. Ninety percent of those not decreased were interviewed. The overall sample spent 58% of the nonincarcerated follow-up interval on methadone. This resulted in a large decline in daily heroin use and associated criminal behavior measures. The addition of parole supervision with urine testing resulted in only marginal improvements in behavior over that attributable to maintenance alone; however, the parole status did significantly reduce the length of intervals of daily heroin use both prior and subsequent to methadone entry.

  5. Quantitation of methadone and metabolite in patients under maintenance treatment.

    PubMed

    Diong, Shiau Hui; Mohd Yusoff, Nor Shuhadah; Sim, Maw Shin; Raja Aziddin, Raja Elina; Chik, Zamri; Rajan, Poppy; Abdul Rashid, Rusdi; Chemi, Norliza; Mohamed, Zahurin

    2014-01-01

    Gas chromatography-mass spectrometry quantitative method was developed to monitor concentrations of methadone and its metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) in plasma and urine of patients. The developed method was simple, accurate and reproducible to quantify methadone and EDDP in plasma and urine samples in the concentration range of 15-1,000 and 50-2,000 ng/mL, respectively. The proposed analytical method was applied to plasma and urine samples obtained from 96 patients undergoing methadone maintenance treatment (MMT) with daily methadone doses of 2-120 mg/day. Urinary methadone excretion was observed to be significantly affected by pH, in which the ratio of methadone to EDDP was two times higher in acidic urine (P = 0.029). The findings of this study further enhance the guidelines for monitoring of methadone treatment among outpatients. Methadone-to-EDDP ratio in urine was found to be consistent at 24 and 4 h, hence suggesting the possibility that outpatients may be monitored with single urine sample in order to check for compliance. This study which provides data on peak concentrations of methadone and EDDP as well as the ratio of both compounds has added to the body of knowledge regarding pharmacokinetic properties of methadone among heroin-dependent patients under MMT.

  6. Evaluation of Drug Abuse Treatment: A Repeated Measures Design Assessing Methadone Maintenance.

    ERIC Educational Resources Information Center

    Hser, Yih-Ing; And Others

    1988-01-01

    A repeated measures design was used to evaluate methadone maintenance (MM) treatment effects for 720 heroin addicts who entered MM in Southern California in 1971-1978. Compared to pretreatment measures, results show significant improvement for methadone users. Level of improvement was affected by sex, ethnicity, and treatment duration. (TJH)

  7. Pharmacokinetics and pharmacokinetic variability of heroin and its metabolites: review of the literature.

    PubMed

    Rook, Elisabeth J; Huitema, Alwin D R; van den Brink, Wim; van Ree, Jan M; Beijnen, Jos H

    2006-01-01

    This article reviews the pharmacokinetics of heroin after intravenous, oral, intranasal, intramuscular and rectal application and after inhalation in humans, with a special focus on heroin maintenance therapy in heroin dependent patients. In heroin maintenance therapy high doses pharmaceutically prepared heroin (up to 1000 mg/day) are prescribed to chronic heroin dependents, who do not respond to conventional interventions such as methadone maintenance treatment. Possible drug-drug interactions with the hydrolysis of heroin into 6-monoacetylmorphine and morphine, the glucuronidation of morphine and interactions with drug transporting proteins are described. Since renal and hepatic impairment is common in the special population of heroin dependent patients, specific attention was paid on the impact of renal and hepatic impairment. Hepatic impairment did not seem to have a clinically relevant effect on the pharmacokinetics of heroin and its metabolites. However, some modest effects of renal impairment have been noted, and therefore control of the creatinine clearance during heroin-assisted treatment seems recommendable.

  8. Pupil responses to intravenous heroin (diamorphine) in dependent and non-dependent humans.

    PubMed

    Tress, K H; El-Sobky, A A

    1979-02-01

    1. Intravenous heroin was administered to volunteers, in doses of 2.5 and 5 mg to non-dependent subjects and does of 1/6, 1/3 and 1/2 of their prescribed daily does of opiates to dependent subjects, and pupillary responses measured before and three times during the 2 h after injection. 2. Tolerance to the miotic effects of heroin in the dependent subjects was demonstrated--larger doses of heroin were needed to produce the same pupil response in dependent subjects than in non-dependent subjects and the duration of action was shorter in the former group. 3. The effect of concurrent oral methadone medication on pupil response to heroin was demonstrated. Subjects prescribed both methadone and heroin showed smaller control pupil diameters and a reduced dose effect to heroin than did subjects prescribed heroin alone.

  9. 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.

  10. Gas chromatography-mass spectrometry method for the determination of methadone and 2-ethylidene-1,5-dimethyl-3, 3-diphenylpyrrolidine (EDDP).

    PubMed

    Snozek, Christine L H; Bjergum, Matthew W; Langman, Loralie J

    2010-01-01

    Methadone is a synthetic opioid used to relieve pain, treat opioid withdrawal, and wean heroin addicts. Measurement of methadone and its major metabolite EDDP in urine is useful for assessing compliance with addiction rehabilitation and pain management programs. This method quantitatively measures methadone and its metabolite EDDP in urine. Methadone and EDDP are recovered from urine by solid phase extraction at pH 6.0. Analysis is performed by gas chromatography with mass spectrometry detection, using selective ion monitoring.

  11. [Heroin addiction].

    PubMed

    Hosztafi, Sándor

    2011-01-01

    Heroin is an illicit, highly addictive drug. It is either the most abused or the most rapidly acting member of opioids. Abusers describe a feeling of a surge of pleasurable sensation, named as "rush" or "high". Repeated administration of high doses of heroin results in the induction of physical dependence. Physical dependence refers to an altered physiological state produced by chronic administration of heroin which necessitates the continued administration of the drug to prevent the appearance of a characteristic syndrome, the opioid withdrawal or abstinence syndrome. Withdrawal symptoms may occur within a few hours after the last administration of heroin. Symptoms of the withdrawal include restlessness, insomnia, drug craving, diarrhea, muscle and bone pain, cold flashes with goose bumps, and leg movements. Major withdrawal symptoms peak between 48 and 72 hours after the last dose of heroin and subside after about a week. At this time, weakness and depression are pronounced and nausea and vomiting are common. Nevertheless, some chronic addicts have shown persistent withdrawal signs for many months or even years. Heroin addiction is considered as a behavioural state of compulsive drug use and a high tendency to relapse after periods of abstinence. It is generally accepted that compulsive use and relapse are typically associated with the status of heroin craving or heroin hunger that are difficult to define but appear to be powerful motivational significance in the addiction process. The route of administering heroin varies largely and may indicate the degree of seriousness of the individual's addiction. Intravenous administration seems to be the predominant method of heroin use, but recently a shift in heroin use pattern has been found, i.e. from injection to sniffing and smoking. Frequent injections coupled with widespread sharing of syringes increase the risk of contracting HIV, hepatitis B, C and other blood-borne infectious diseases. Long-term use of heroin

  12. Interaction of counseling rapport and topics discussed in sessions with methadone treatment clients.

    PubMed

    Joe, George W; Simpson, D Dwayne; Rowan-Szal, Grace A

    2009-01-01

    Therapeutic rapport between counselors and clients in drug user treatment has been shown to be an important predictor of follow-up outcomes. This naturalistic study investigated the relationship of counseling rapport to drug-related topics discussed in counseling sessions in a sample of 330 clients and nine counselors. These voluntary clients had been admitted to a private, for-profit outpatient methadone treatment in Texas between September 1995 and August 1997 and received no-fee services for a year for participation in this study. The data were gathered using forms in the TCU community treatment assessments (www.ibr.tcu.edu) that measured intake information, counseling session topics, and counselor evaluation of the client. A majority were males, Hispanic, had a pending legal status and the average age was 39. Co-occurring drug dependence for these heroin users included cocaine (38%) and alcohol (31%). The results supported the hypothesis that higher rapport would be associated with addressing clients in a more "supportive approach" that emphasized relapse prevention and strengths-building while lower rapport would be associated with a punitive counseling style that stressed program rules and compliance. The influences of client background, counselor differences, and during-treatment positive urines were also examined. Although counselors differed in their general manner of dealing with clients, each also showed flexibility determined in part by client behavior (such as continued cocaine use). The findings indicate that focusing on constructive solutions is the preferred counseling approach.

  13. Search for Genetic Markers and Functional Variants Involved in the Development of Opiate and Cocaine Addiction, and Treatment

    PubMed Central

    Yuferov, Vadim; Levran, Orna; Proudnikov, Dmitri; Nielsen, David A.; Kreek, Mary Jeanne

    2013-01-01

    Addiction to opiates and illicit use of psychostimulants is a chronic, relapsing brain disease that, if left untreated, can cause major medical, social and economic problems. This article reviews recent progress in studies of association of gene variants with vulnerability to develop opiate and cocaine addictions, focusing primarily on genes of the opioid and monoaminergic systems. In addition, we provide the first evidence of a cis-acting polymorphism and a functional haplotype in the PDYN gene, of significantly higher DNA methylation rate of the OPRM1 gene in the lymphocytes of heroin addicts, and significant differences in genotype frequencies of three single nucleotide polymorphisms of the P-glycoprotein gene (ABCB1) between “higher” and “lower” methadone doses in methadone-maintained patients. In genome-wide and multi-gene association studies, we have found association of a number of new genes and new variants of known genes with heroin addiction. Finally, we have described the development and application of a novel technique: molecular haplotyping for studies in genetics of drug addiction. PMID:20201854

  14. 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.

  15. 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

  16. Route of administration influences substitution patterns in rats trained to discriminate methadone vs. vehicle.

    PubMed

    Vann, Robert E; Wise, Laura E; Varvel, Stephen A; Philibin, Scott D; Walentiny, D Matthew; Porter, Joseph H

    2009-08-01

    Replacement therapy with the synthetic mu-opioid agonist methadone is an efficacious treatment for opioid abuse. While much is known about methadone's pharmacology, its discriminative stimulus properties remain largely unexplored. The present study sought to establish methadone discrimination in rats. Moreover, some research suggests that route of administration alters the discriminative stimulus of methadone. Thus, the present study also compared intraperitoneal (i.p.) and subcutaneous (s.c.) routes of administration. Male Sprague-Dawley rats were trained to discriminate 3.0mg/kg methadone (i.p.) from vehicle in a two-lever discrimination procedure. Generalization tests were conducted with a variety of compounds administered i.p. and s.c. Methadone fully substituted for itself, yielding ED(50)s of 1.5mg/kg (i.p.) and 0.2mg/kg (s.c.). Naltrexone (i.p.), an opioid antagonist produced a dose-dependent reduction in methadone-appropriate responding. The methadone stereoisomers fully substituted for methadone when given s.c.; however, when administered i.p., (+) and (-) methadone produced partial and no substitution, respectively. Heroin fully generalized to methadone regardless of administration route, while morphine fully substituted when given s.c., but not i.p. The kappa-agonist U50-488 failed to generalize to methadone with either route of administration. These results demonstrated that methadone's discriminative stimulus is mediated through mu-opioid receptor activity and is similar to that of commonly abused opioids (heroin, morphine). Additionally, route of administration produced differential results for many of the drugs tested, suggesting decreased drug bioavailability following i.p. administration due to hepatic first pass metabolism. Taken together, these results suggest that methadone's shared subjective effects with abused opioids, as well as its unique metabolic properties contribute to its efficacy in opioid maintenance therapy.

  17. Attitudes of Employers toward Hiring Methadone Maintenance Patients.

    ERIC Educational Resources Information Center

    Pugliese, Anthony

    1978-01-01

    Results of this study indicate that at present employers are not ready to accept methadone maintained patients into their firms. The stigma placed on heroin addicts by employers is a very important issue when the treated patient tries to make it in the employment field. More employer education is needed. (Author)

  18. Online extraction LC-MS/MS method for the simultaneous quantitative confirmation of urine drugs of abuse and metabolites: amphetamines, opiates, cocaine, cannabis, benzodiazepines and methadone.

    PubMed

    de Jager, Andrew D; Bailey, Neville L

    2011-09-01

    A rapid LC-MS/MS method for confirmatory testing of five major categories of drugs of abuse (amphetamine-type substances, opiates, cocaine, cannabis metabolites and benzodiazepines) in urine has been developed. All drugs of abuse mandated by the Australian/New Zealand Standard AS/NZS 4308:2008 are quantified in a single chromatographic run. Urine samples are diluted with a mixture of isotope labelled internal standards. An on-line trap-and-flush approach, followed by LC-ESI-MS/MS has been successfully used to process samples in a functioning drugs of abuse laboratory. Following injection of diluted urine samples, compounds retained on the trap cartridge are flushed onto a reverse-phase C18 HPLC column (5-μm particle size) with embedded hydrophylic functionality. A total chromatographic run-time of 15 min is required for adequate resolution. Automated quantitation software algorithms have been developed in-house using XML scripting to partially automate the identification of positive samples, taking into account ion ratio (IR) and retention times (Rt). The sensitivity of the assay was found to be adequate for the quantitation of drugs in urine at and below the confirmation cut-off concentrations prescribed by AS/NZS 4308:2008.

  19. Heroin overdose

    MedlinePlus

    ... overdose. This type of medicine is called an antidote. Naloxone is injected under the skin or into ... effects of the heroin Outlook (Prognosis) If an antidote can be given, recovery from an acute overdose ...

  20. Gender differences in health related quality of life of young heroin users

    PubMed Central

    2010-01-01

    Background Health Related Quality of Life (HRQL) of opiate users has been studied in treatment settings, where assistance for drug use was sought. In this study we ascertain factors related to HRQL of young opiate users recruited outside treatment facilities, considering both genders separately. Methods Current opiate users (18-30 y) were recruited in outdoor settings in three Spanish cities (Barcelona, Madrid, Sevilla). Standardised laptop interviews included socio-demographic data, drug use patterns, health related issues, the Severity of Dependence Scale (SDS) and the Nottingham Health Profile (NHP). Results A total of 991 subjects (73% males), mean age = 25.7 years were interviewed. The mean global NHP score differed by gender (women: 41.2 (sd:23.8); men:34.1(sd:23.6);p < 0.05). Multivariate analysis was implemented separately by gender, variables independently related with global NHP score, both for males and females, were heroin and cocaine SDS scores. For women, only other drug related variables (alcohol intake and length of cocaine use) were independently associated with their HRQL. HIV+ males who suffered an opiate overdose or had psychiatric care in the last 12 months perceived their health as poorer, while those who had ever been in methadone treatment in the last 12 months perceived it as better. The model with both genders showed all factors for males plus quantity of alcohol and an interaction between gender and HIV status. Conclusions Heroin users were found to be at a considerable risk of impaired HRQL, even in these young ages. A score approaching severity of dependence was the factor with the strongest relation with it. PMID:21122134

  1. Staff concerns in heroin-assisted treatment centres.

    PubMed

    Demaret, I; Lemaître, A; Ansseau, M

    2012-08-01

    Heroin-assisted treatment (HAT) is a solution for improving the condition of treatment-resistant heroin addicts. Since 1994, six randomized controlled trials have concluded that HAT is more efficacious than oral methadone for severe heroin addicts. We visited seven HAT treatment centres in four countries in order to observe diacetylmorphine (DAM) administration and to study the main concerns of the staff. Nurses were concerned by the risk taken if a previously intoxicated patient received his dose of DAM. Another concern was the smuggling of DAM doses. The HAT centres face a dilemma: treating patients while at the same time allowing their risky street habits in the centre.

  2. Diazepam and methadone interactions in methadone maintenance.

    PubMed

    Preston, K L; Griffiths, R R; Stitzer, M L; Bigelow, G E; Liebson, I A

    1984-10-01

    Survey study data and high rates of diazepam use/abuse in methadone maintenance suggest that acute administration of diazepam with daily methadone doses may enhance methadone effects. Acute subjective and physiologic effects of single oral doses of placebo, diazepam (20 and 40 mg), methadone (100%, 150%, and 200% of the maintenance dose), and four diazepam-methadone dose combinations (20 and 40 mg diazepam in combination with 100% and 150% of the maintenance dose) were assessed under double-blind conditions. The subjects were five adult male patients on methadone maintenance with histories of diazepam abuse who were receiving 50 to 60 mg methadone a day. Physiologic measures were continuously monitored for 30 min before and for 2 hr after dosing. Pupil diameter and subjective responses were measured 15 min before dosing and 15, 30, 45, 60, 90, and 120 min after dosing. Methadone induced dose-dependent increases in pupil constriction and scores on a subjective opioid effects rating scale, but diazepam had no significant effect on either. The combination of methadone at 150% of the maintenance dose with 40 mg diazepam induced increases in these measures greater than those induced by either drug dose alone. Drug combinations, however, were more frequently identified as being benzodiazepine/barbiturate-like than as methadone-like. Thus although the subjective effects of the drug combination are distinguishable from those of methadone alone, diazepam with methadone in methadone maintenance appears to increase some physiologic and subjective opioid effects that may be related to the relatively great use/abuse of diazepam in this population.

  3. HIV transmission and the cost-effectiveness of methadone maintenance.

    PubMed Central

    Zaric, G S; Barnett, P G; Brandeau, M L

    2000-01-01

    OBJECTIVES: This study determined the cost-effectiveness of expanding methadone maintenance treatment for heroin addiction, particularly its effect on the HIV epidemic. METHODS: We developed a dynamic epidemic model to study the effects of increased methadone maintenance capacity on health care costs and survival, measured as quality-adjusted life-years (QALYs). We considered communities with HIV prevalence among injection drug users of 5% and 40%. RESULTS: Additional methadone maintenance capacity costs $8200 per QALY gained in the high-prevalence community and $10,900 per QALY gained in the low-prevalence community. More than half of the benefits are gained by individuals who do not inject drugs. Even if the benefits realized by treated and untreated injection drug users are ignored, methadone maintenance expansion costs between $14,100 and $15,200 per QALY gained. Additional capacity remains cost-effective even if it is twice as expensive and half as effective as current methadone maintenance slots. CONCLUSIONS: Expansion of methadone maintenance is cost-effective on the basis of commonly accepted criteria for medical interventions. Barriers to methadone maintenance deny injection drug users access to a cost-effective intervention that generates significant health benefits for the general population. PMID:10897189

  4. The GABAB receptor agonist baclofen prevents heroin-induced reinstatement of heroin-seeking behavior in rats.

    PubMed

    Spano, Maria Sabrina; Fattore, Liana; Fratta, Walter; Fadda, Paola

    2007-06-01

    Opiate addiction is a chronic relapsing disorder characterized by high rates of relapse. The gamma-aminobutyric acid GABA(B) receptor agonist baclofen is known to affect the reinforcing effects of several drugs of abuse, including heroin, as well as to decrease cue-maintained responding for heroin, cocaine and nicotine and suppress alcohol deprivation effect in rats. Here we studied the effect of baclofen on the reinstatement of extinguished heroin-seeking behavior triggered by a priming injection of heroin in abstinent rats trained to stably self-administer heroin (30 microg/kg per infusion) under a continuous reinforcement schedule. Following extinction, the effect of non-contingent non-reinforced primings with heroin, baclofen or heroin/baclofen combination on the resumption of responding was evaluated. Results indicate that heroin priming (0.25mg/kg) promptly reinitiated heroin-seeking behavior, an effect dose-dependently reduced by baclofen at doses (0.625 and 1.25mg/kg) not affecting responding per sè. Importantly, baclofen did not affect locomotion either alone or in combination with heroin, dispelling any doubt as to the eliciting of possible non-specific (motor) effects. The present results show that GABA(B) receptor activation may reduce the propensity to resume drug-induced heroin-seeking behavior thus offering a possible approach in maintaining opiate abstinence.

  5. Methadone-related deaths in Palm Beach County.

    PubMed

    Wolf, Barbara C; Lavezzi, Wendy A; Sullivan, Linda M; Flannagan, Lisa M

    2004-03-01

    The authors reviewed cases investigated by the Palm Beach Medical Examiner's Office in which postmortem toxicologic studies indicated the presence of methadone over the period from 1998 to 2002, to examine the role of the drug in these deaths. There were 139 methadone-positive cases, including 75 in which the death was attributed to combined drug toxicity and 23 to methadone toxicity alone. Methadone was most frequently used in conjunction with other prescription or illicit drugs, most commonly benzodiazepines and/or cocaine. There was considerable overlap in the postmortem blood methadone concentrations among the groups. Concentrations ranged from 0.114 mg/L-1.939 mg/L (mean .0559 mg/L) in cases where death was attributed to methadone toxicity; 0.050 mg/L-1.903 mg/L (mean 0.411 mg/L) in cases of combined drug toxicity; 0.069 mg/L-0.644 mg/L (mean 0.224 mg/L) in deaths attributed to other drugs; 0.062 mg/L-1.090 mg/L (mean 0.344 mg/L) among deaths attributed to natural causes and 0.072 mg/L-2.7 mg/L (mean 0.605 mg/L) among deaths due to trauma. The concentrations of methadone detected indicate that it may not be possible to establish a lethal methadone range because some deaths occurred at methadone concentrations below previously reported lethal ranges, and because of the presence of other drugs. Determining the cause of death in methadone-positive cases necessitates correlation with autopsy results and investigative findings.

  6. 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…

  7. Deuterodiacetylmorphine as a marker for use of illicit heroin by addicts in a heroin-assisted treatment program.

    PubMed

    Klous, Marjolein G; Rook, Elisabeth J; Hillebrand, Michel J X; van den Brink, Wim; van Ree, Jan M; Beijnen, Jos H

    2005-09-01

    In preparation for a treatment program concerning the medical coprescription of heroin and methadone to treatment-resistant addicts in the Netherlands, we studied a novel strategy for monitoring co-use of illicit (nonprescribed) heroin. A deuterated analogue of heroin was added (1:20) to pharmaceutical, smokable heroin (a powder mixture of 75% w/w diacetylmorphine base and 25% w/w caffeine anhydrate), to be used by inhalation after volatilization ("chasing the dragon"). Plasma and urine samples were collected from nine male patients who had used pharmaceutical, smokable heroin during a four-day stay in a closed clinical research unit, and these samples were analyzed by liquid chromatography coupled with tandem mass spectrometry. Ratios of deuterated and undeuterated diacetylmorphine and 6-acetylmorphine (MAM/MAM-d3) in plasma and urine were calculated from peak areas of these substances in the respective chromatograms. The MAM/MAM-d3 ratios in plasma and urine were normally distributed (with small standard deviations) and independent from concentrations of 6-acetylmorphine and from time after use of pharmaceutical heroin. A MAM/MAM-d3 ratio in urine above 32.8 was considered indicative of co-use of illicit heroin, and this value was associated with a false-positive rate of only 1% (95% confidence interval: -1 to 3%). The MAM/MAM-d3 ratio was detectable in urine for 4-9.5 h after use of pharmaceutical, smokable heroin. Addition of stable, isotopically labelled heroin to pharmaceutical, smokable heroin is considered to be a feasible strategy for the detection of co-use of illicit heroin by patients in heroin-assisted treatment.

  8. Treatment-refractory substance use disorder: Focus on alcohol, opioids, and cocaine.

    PubMed

    Soyka, Michael; Mutschler, Jochen

    2016-10-03

    Substance use disorders are common, but only a small minority of patients receive adequate treatment. Although psychosocial therapies are effective, relapse is common. This review focusses on novel pharmacological and other treatments for patients with alcohol, opioid, or cocaine use disorders who do not respond to conventional treatments. Disulfiram, acamprosate, and the opioid antagonist naltrexone have been approved for the treatment of alcoholism. A novel, "as needed" approach is the use of the mu-opioid antagonist and partial kappa agonist nalmefene to reduce alcohol consumption. Other novel pharmacological approaches include the GABA-B receptor agonist baclofen, anticonvulsants such as topiramate and gabapentin, the partial nicotine receptor agonist varenicline, and other drugs. For opioid dependence, opioid agonist therapy with methadone or buprenorphine is the first-line treatment option. Other options include oral or depot naltrexone, morphine sulfate, depot or implant formulations, and heroin (diacetylmorphine) in treatment-refractory patients. To date, no pharmacological treatment has been approved for cocaine addiction; however, 3 potential pharmacological treatments are being studied, disulfiram, methylphenidate, and modafinil. Pharmacogenetic approaches may help to optimize treatment response in otherwise treatment-refractory patients and to identify which patients are more likely to respond to treatment, and neuromodulation techniques such as repeated transcranial magnetic stimulation and deep brain stimulation also may play a role in the treatment of substance use disorders. Although no magic bullet is in sight for treatment-refractory patients, some novel medications and brain stimulation techniques have the potential to enrich treatment options at least for some patients.

  9. 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…

  10. 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…

  11. 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.

  12. [The history of heroin].

    PubMed

    Hosztafi, S

    2001-08-01

    The discovery of heroin and the development of heroin abuse are introduced. Heroin, the hydrochloride of diacetylmorphine, was discovered by acetylation of morphine. Heroin, in pharmacological studies, proved to be more effective than morphine or codeine. The Bayer Company started the production of heroin in 1898 on a commercial scale. The first clinical results were so promising that heroin was considered a wonder drug. Indeed, heroin was more effective than codeine in respiratory diseases. It has turned out, however, that repeated administration of heroin results in the development of tolerance and the patients become heroin-addicts soon. In the early 1910s morphine addicts "discovered" the euphorising properties of heroin and this effect was enhanced by intravenous administration. Heroin became a narcotic drug and its abuse began to spread quickly. Restrictions on its production, use and distribution were regulated by international treties. The total ban on heroin production was also proposed. As a result of the strict regulations the production and cosumption of heroin showed a significant decrease after 1931. At the same time the underworld recognized the shortage of heroin and started the illicit production and trafficking. The quantity of heroin seized by law enforcement agencies in the past decades rose gradually. As an indicator of the worldwide heroin market, the quantity of confiscated heroin underwent a tenfold increase since 1970. The paper surveys the most important heroin-producing and trafficking countries. Heroin, prepared in clandestine ("kitchen" or "jungle") laboratories, is diluted ("cut") by every member of the illegal heroin distributing chain, i.e. smugglers, traffickers, dealers and vendors.

  13. Pregnant heroin addict: what about the baby?

    PubMed Central

    Namboodiri, Vasudevan; George, Sanju; Boulay, Sylvie; Fair, Mandy

    2010-01-01

    Heroin misuse in pregnancy is a significant health and social problem, and it can have an adverse effect on the mother and the baby. Although heroin and methadone have no specific teratogenic potential, 48–94% of children exposed in utero will have neonatal abstinence syndrome (NAS). The primary aim of this case report is to raise awareness of NAS among clinicians and to remind them that although very common, it is not inevitable. The risk of NAS can be further minimised by offering comprehensive and co-ordinated antenatal care that addresses the various biopsychosocial needs of the pregnant woman. Further, a brief description of NAS and a review of evidence in the field of management of opioid misuse in pregnancy, as relevant to this case, are provided. We have also included the patient’s own reflections on her pregnancy and treatment. PMID:22328902

  14. Sexual Dysfunction in Men Receiving Methadone Maintenance Treatment: Clinical History and Psychobiological Correlates.

    PubMed

    Gerra, Gilberto; Manfredini, Matteo; Somaini, Lorenzo; Maremmani, Icro; Leonardi, Claudio; Donnini, Claudia

    2016-01-01

    A variety of studies evidenced a relationship between drug use disorders and sexual dysfunction. In particular, heroin and opioid agonist medications to treat heroin dependence have been found to be associated with erectile dysfunction and reduced libido. Controversial findings also indicate the possibility of factors other than the pharmacological effects of opioid drugs concurring to sexual dysfunction. With the present study, we investigated the link between sexual dysfunction and long-term exposure to opioid receptor stimulation (heroin dependence, methadone maintenance treatment, methadone dosage), the potentially related hormonal changes reflecting hypothalamus-pituitary-gonadal axis function and prolactin (PRL) pituitary release, the role of adverse childhood experiences in the clinical history and the concomitant symptoms of comorbid mental health disorders in contributing to sexual problems. Forty male patients participating in a long-term methadone treatment program were included in the present study and compared with 40 healthy control subjects who never used drugs nor abused alcohol. All patients and controls were submitted to the Arizona Sexual Experiences Scale (ASEX), Child Experiences of Care and Abuse-Questionnaire (CECA-Q) and the Symptom Check List-90 Scale. A blood sample for testosterone and PRL assays was collected. Methadone dosages were recorded among heroin-dependent patients on maintenance treatment. Methadone patients scored significantly higher than controls on the 5-item rating ASEX scale, on CECA-Q and on Symptoms Check List 90 (SCL 90) scale. Testosterone plasma levels were significantly lower and PRL levels significantly higher in methadone patients with respect to the healthy control group. ASEX scores reflecting sexual dysfunction were directly and significantly correlated with CECA-Q neglect scores and SCL 90 psychiatric symptoms total score. The linear regression model, when applied only to addicted patients, showed that

  15. Methadone maintenance in general practice: patients, workload, and outcomes.

    PubMed Central

    Wilson, P.; Watson, R.; Ralston, G. E.

    1994-01-01

    OBJECTIVE--To assess recruitment to and work-load associated with methadone maintenance clinics in general practice; to investigate the characteristics of patients and outcomes associated with treatment. DESIGN--Study of case notes. SETTING--Methadone maintenance clinics run jointly by general practitioners and drug counsellors in two practices in Glasgow. PARTICIPANTS--46 injecting drug users receiving methadone maintenance during an 18 month period, 31 of whom were recruited to clinic based methadone maintenance treatment and 15 of whom were already receiving methadone maintenance treatment from the general practitioners. Mean (SD) age of patients entering treatment was 29.6 (5.5) years; 29 were male. They had been injecting opiates for a mean 9.9 (5.1) years, and most had a concurrent history of benzodiazepine misuse. Average reported daily intake of heroin was approximately 0.75 g. Participants in treatment had high levels of preexisting morbidity, and most stated that they committed crime daily. RESULTS--2232 patient weeks of treatment were studied. Mean duration of treatment during the study period was 50.7 (21.1) weeks and retention in treatment at 26 weeks was 83%. No evidence of illicit opiate use was obtained at an average of 78% of patients' consultations where methadone had been prescribed in the previous week; for opiate injection the corresponding figure was 86%. CONCLUSIONS--Providing methadone maintenance in general practice is feasible. Although costs are considerable, the reduction in drug use, especially of intravenous opiates, is encouraging. Attending clinics also allows this population, in which morbidity is considerable, to receive other health care. PMID:8086989

  16. 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…

  17. Serum concentrations of macro and trace elements in heroin addicts of the Canary Islands.

    PubMed

    Díaz-Flores, José F; Sañudo, Ricardo I; Rodríguez, Elena M; Romero, Carlos Díaz

    2004-01-01

    Na, K, Ca, Mg, P, Fe, Cu, Zn and Se concentrations were determined in the serum of 106 heroin addicts and were compared with the concentrations obtained in a control group formed of 186 apparently healthy individuals. Heroin addicts displayed K and Se mean concentrations lower (p < 0.05), and Na, Mg, P mean concentrations and a Cu/Zn ratio higher (p < 0.05) than those mean values observed in the control group. The Mg and P concentrations in the serum of heroin addicts tended to normalize when age increased. The heroin addicts included in the methadone maintenance treatment program had higher serum mean concentrations of K and Mg than the heroin addicts in the detoxification process. The Na, K and Mg concentrations displayed highly significant correlations, with a different behavior for the heroin addicts group and the control group. When applying factor analysis and representing the scores of the first and second factors, the heroin addicts tended to differentiation from the control group. However, methadone substitution treatment was not able to normalize these concentrations.

  18. Methadone maintenance: some client opinions.

    PubMed

    Brown, B S; Benn, G J; Jansen, D R

    1975-06-01

    The authors found similar attitudes toward methadone and methadone treatment programs in 75 detoxification and 115 methadone maintenance clients. Both groups expressed considerable ambivalence--although they viewed methadone as capable of helping them end their herioin addiction, they were concerned about possible methadone dependence and about side effects, both real and imagined. The authors stress the societal context of such concern and suggest that, althought they are not easily allayed, limiting the duration of methadone maintenace from the outset of treatment may be an ameliorative factor.

  19. 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- ...

  20. DrugFacts: Heroin

    MedlinePlus

    ... Badge NIDA TV Spotlight: Heroin in the Twin Cities YouTube embedded video: http://www.youtube-nocookie.com/ ... a highlight on heroin use in the Twin Cities from her June 2013 Report on "Drug Abuse ...

  1. Neuroelectrophysiological approaches in heroin addiction research: A review of literatures.

    PubMed

    Motlagh, Farid; Ibrahim, Fatimah; Menke, J Michael; Rashid, Rusdi; Seghatoleslam, Tahereh; Habil, Hussain

    2016-04-01

    Neuroelectrophysiological properties have been used in human heroin addiction studies. These studies vary in their approach, experimental conditions, paradigms, and outcomes. However, it is essential to integrate previous findings and experimental methods for a better demonstration of current issues and challenges in designing such studies. This Review examines methodologies and experimental conditions of neuroelectrophysiological research among heroin addicts during withdrawal, abstinence, and methadone maintenance treatment and presents the findings. The results show decrements in attentional processing and dysfunctions in brain response inhibition as well as brain activity abnormalities induced by chronic heroin abuse. Chronic heroin addiction causes increased β and α2 power activity, latency of P300 and P600, and diminished P300 and P600 amplitude. Findings confirm that electroencephalography (EEG) band power and coherence are associated with craving indices and heroin abuse history. First symptoms of withdrawal can be seen in high-frequency EEG bands, and the severity of these symptoms is associated with brain functional connectivity. EEG spectral changes and event-related potential (ERP) properties have been shown to be associated with abstinence length and tend to normalize within 3-6 months of abstinence. From the conflicting criteria and confounding effects in neuroelectrophysiological studies, the authors suggest a comprehensive longitudinal study with a multimethod approach for monitoring EEG and ERP attributes of heroin addicts from early stages of withdrawal until long-term abstinence to control the confounding effects, such as nicotine abuse and other comorbid and premorbid conditions.

  2. Functional Genetic Polymorphisms in CYP2C19 Gene in Relation to Cardiac Side Effects and Treatment Dose in a Methadone Maintenance Cohort

    PubMed Central

    Wang, Sheng-Chang; Ho, Ing-Kang; Tsou, Hsiao-Hui; Liu, Sheng-Wen; Hsiao, Chin-Fu; Chen, Chia-Hui; Tan, Happy Kuy-Lok; Lin, Linen; Wu, Chi-Shin; Su, Lien-Wen; Huang, Chieh-Liang; Yang, Yi-Hong; Liu, Ming-Lun; Lin, Keh-Ming; Liu, Shu Chih; Wu, Hsiao-Yu; Kuo, Hsiang-Wei; Chen, Andrew C.H.; Chang, Yao-Sheng

    2013-01-01

    Abstract Methadone maintenance therapy is an established treatment for heroin dependence. This study tested the influence of functional genetic polymorphisms in CYP2C19 gene encoding a CYP450 enzyme that contributes to methadone metabolism on treatment dose, plasma concentration, and side effects of methadone. Two single nucleotide polymorphisms (SNPs), rs4986893 (exon 4) and rs4244285 (exon 5), were selected and genotyped in 366 patients receiving methadone maintenance therapy in Taiwan. The steady-state plasma concentrations of both methadone and its EDDP metabolite enantiomers were measured. SNP rs4244285 allele was significantly associated with the corrected QT interval (QTc) change in the electrocardiogram (p=0.021), and the Treatment Emergent Symptom Scale (TESS) total score (p=0.021) in patients who continued using heroin, as demonstrated with a positive urine opiate test. Using the gene dose (GD) models where the CYP2C19 SNPs were clustered into poor (0 GD) versus intermediate (1 GD) and extensive (2 GD) metabolizers, we found that the extensive metabolizers required a higher dose of methadone (p=0.035), and showed a lower plasma R-methadone/methadone dose ratio (p=0.007) in urine opiate test negative patients, as well as a greater QTc change (p=0.008) and higher total scores of TESS (p=0.018) in urine opiate test positive patients, than poor metabolizers. These results in a large study sample from Taiwan suggest that the gene dose of CYP2C19 may potentially serve as an indicator for the plasma R-methadone/methadone dose ratio and cardiac side effect in patients receiving methadone maintenance therapy. Further studies of pharmacogenetic variation in methadone pharmacokinetics and pharmacodynamics are warranted in different world populations. PMID:24016178

  3. Functional genetic polymorphisms in CYP2C19 gene in relation to cardiac side effects and treatment dose in a methadone maintenance cohort.

    PubMed

    Wang, Sheng-Chang; Ho, Ing-Kang; Tsou, Hsiao-Hui; Liu, Sheng-Wen; Hsiao, Chin-Fu; Chen, Chia-Hui; Tan, Happy Kuy-Lok; Lin, Linen; Wu, Chi-Shin; Su, Lien-Wen; Huang, Chieh-Liang; Yang, Yi-Hong; Liu, Ming-Lun; Lin, Keh-Ming; Liu, Shu Chih; Wu, Hsiao-Yu; Kuo, Hsiang-Wei; Chen, Andrew C H; Chang, Yao-Sheng; Liu, Yu-Li

    2013-10-01

    Abstract Methadone maintenance therapy is an established treatment for heroin dependence. This study tested the influence of functional genetic polymorphisms in CYP2C19 gene encoding a CYP450 enzyme that contributes to methadone metabolism on treatment dose, plasma concentration, and side effects of methadone. Two single nucleotide polymorphisms (SNPs), rs4986893 (exon 4) and rs4244285 (exon 5), were selected and genotyped in 366 patients receiving methadone maintenance therapy in Taiwan. The steady-state plasma concentrations of both methadone and its EDDP metabolite enantiomers were measured. SNP rs4244285 allele was significantly associated with the corrected QT interval (QTc) change in the electrocardiogram (p=0.021), and the Treatment Emergent Symptom Scale (TESS) total score (p=0.021) in patients who continued using heroin, as demonstrated with a positive urine opiate test. Using the gene dose (GD) models where the CYP2C19 SNPs were clustered into poor (0 GD) versus intermediate (1 GD) and extensive (2 GD) metabolizers, we found that the extensive metabolizers required a higher dose of methadone (p=0.035), and showed a lower plasma R-methadone/methadone dose ratio (p=0.007) in urine opiate test negative patients, as well as a greater QTc change (p=0.008) and higher total scores of TESS (p=0.018) in urine opiate test positive patients, than poor metabolizers. These results in a large study sample from Taiwan suggest that the gene dose of CYP2C19 may potentially serve as an indicator for the plasma R-methadone/methadone dose ratio and cardiac side effect in patients receiving methadone maintenance therapy. Further studies of pharmacogenetic variation in methadone pharmacokinetics and pharmacodynamics are warranted in different world populations.

  4. Cocaine withdrawal

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/000947.htm Cocaine withdrawal To use the sharing features on this page, please enable JavaScript. Cocaine withdrawal occurs when someone who has used a ...

  5. 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.

  6. Understanding Heroin Overdose: A Study of the Acute Respiratory Depressant Effects of Injected Pharmaceutical Heroin.

    PubMed

    Jolley, Caroline J; Bell, James; Rafferty, Gerrard F; Moxham, John; Strang, John

    2015-01-01

    Opioids are respiratory depressants and heroin/opioid overdose is a major contributor to the excess mortality of heroin addicts. The individual and situational variability of respiratory depression caused by intravenous heroin is poorly understood. This study used advanced respiratory monitoring to follow the time course and severity of acute opioid-induced respiratory depression. 10 patients (9/10 with chronic airflow obstruction) undergoing supervised injectable opioid treatment for heroin addiction received their usual prescribed dose of injectable opioid (diamorphine or methadone) (IOT), and their usual prescribed dose of oral opioid (methadone or sustained release oral morphine) after 30 minutes. The main outcome measures were pulse oximetry (SpO2%), end-tidal CO2% (ETCO2%) and neural respiratory drive (NRD) (quantified using parasternal intercostal muscle electromyography). Significant respiratory depression was defined as absence of inspiratory airflow >10s, SpO2% < 90% for >10s and ETCO2% per breath >6.5%. Increases in ETCO2% indicated significant respiratory depression following IOT in 8/10 patients at 30 minutes. In contrast, SpO2% indicated significant respiratory depression in only 4/10 patients, with small absolute changes in SpO2% at 30 minutes. A decline in NRD from baseline to 30 minutes post IOT was also observed, but was not statistically significant. Baseline NRD and opioid-induced drop in SpO2% were inversely related. We conclude that significant acute respiratory depression is commonly induced by opioid drugs prescribed to treat opioid addiction. Hypoventilation is reliably detected by capnography, but not by SpO2% alone. Chronic suppression of NRD in the presence of underlying lung disease may be a risk factor for acute opioid-induced respiratory depression.

  7. Disaccharides in urine samples as markers of intravenous abuse of methadone and buprenorphine.

    PubMed

    Jungen, Hilke; Andresen-Streichert, Hilke; Müller, Alexander; Iwersen-Bergmann, Stefanie

    2013-01-01

    Methadone and buprenorphine are commonly used as oral substitutes in opiate maintenance programs to treat persons who are dependent on heroin. During these programs, patients are not allowed to continue using illicit drugs. Abstinence can easily be monitored by urine tests with immunochemical methods. It is well known that the intravenous abuse of heroin substitutes like methadone or buprenorphine has become common as well. The methadone-prescribing physician has no opportunity to check whether the opiate maintenance treatment patient takes his substitution medicines orally as intended or continues with his intravenous misuse now substituting the methadone instead of injecting heroin. In Germany, substitutes are available as liquids and tablets that contain carbohydrates as adjuvants. Sucrose is used to increase viscosity in liquids, while lactose is needed for pressing tablets (e.g., Methaddict® and Subutex®). In case of oral ingestion, disaccharides are broken down into monosaccharides by disaccharidases in the small intestine. These monosaccharides are absorbed into the blood stream by special monosaccharide transporters. Disaccharidases do not exist in blood, thus sucrose and lactose are not split if substitute medicines are injected intravenously. Our assumption, therefore, was that they are excreted unchanged in urine. We investigated a method for the detection of disaccharides in urine as markers of intravenous abuse of substitutes. Urine samples of 26 intravenous substitute abusers showed all positive results for lactose (76.9%) and/or sucrose (73.1%). The method is assumed to be useful to detect intravenous abuse of substitutes.

  8. 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

  9. Methadone versus buprenorphine for the treatment of opioid abuse in pregnancy: science and stigma.

    PubMed

    Holbrook, Amber M

    2015-01-01

    The past decade has seen an increase in rates of opioid abuse during pregnancy. This clinical challenge has been met with debate regarding whether or not illicit and prescription opioid-dependent individuals require different treatment approaches; whether detoxification is preferable to maintenance; and the efficacy of methadone versus buprenorphine as treatment options during pregnancy. The clinical recommendations resulting from these discussions are frequently influenced by the comparative stigma attached to heroin abuse and methadone maintenance versus prescription opioid abuse and maintenance treatment with buprenorphine. While some studies have suggested that a subset of individuals who abuse prescription opioids may have different characteristics than heroin users, there is currently no evidence to suggest that buprenorphine is better suited to treatment of prescription opioid abuse than methadone. Similarly, despite its perennial popularity, there is no evidence to recommend detoxification as an efficacious approach to treatment of opioid dependence during pregnancy. While increased access to treatment is important, particularly in rural areas, there are multiple medical and psychosocial reasons to recommend comprehensive substance abuse treatment for pregnant women suffering from substance use disorders rather than office-based provision of maintenance medication. Both methadone and buprenorphine are important treatment options for opioid abuse during pregnancy. Methadone may still remain the preferred treatment choice for some women who require higher doses for stabilization, have a higher risk of treatment discontinuation, or who have had unsuccessful treatment attempts with buprenorphine. As treatment providers, we should advocate to expand available treatment options for pregnant women in all States.

  10. 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…

  11. 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…

  12. [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.

  13. Quantitative analysis of 26 opioids, cocaine, and their metabolites in human blood by ultra performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Fernández, María del Mar Ramírez; Wille, Sarah M R; Kummer, Nathalie; Di Fazio, Vincent; Ruyssinckx, Evi; Samyn, Nele

    2013-08-01

    use of heroin, cocaine, tramadol, and methadone, and to proficiency testing schemes.

  14. Opiate-dependent patients receiving methadone. How physicians should manage therapy.

    PubMed Central

    Kahan, M.; Sutton, N.

    1996-01-01

    Methadone treatment can reduce illicit drug use, needle sharing, and the social costs and health risks of heroin addiction. It is superior to no treatment, detoxification, or treatment programs lasting less than 3 months. For most patients, the optimal methadone dose is 50 to 120 mg daily. Supervised, random urine drug specimens should be collected at least twice weekly. Long-term counseling is essential and should include information on the risks of needle sharing and on screening for HIV and hepatitis B and C. PMID:8828879

  15. Methadone-induced hypoglycemia.

    PubMed

    Faskowitz, Andrew J; Kramskiy, Vladimir N; Pasternak, Gavril W

    2013-05-01

    To determine if recent observations of hypoglycemia in patients receiving high-dose methadone extended to an animal model, we explored the effects of methadone and other mu-opioids on blood glucose levels in mice. Methadone lowered blood glucose in a dose-dependent manner with 20 mg/kg yielding a nadir in average glucose levels to 55 ± 6 mg/dL from a baseline of 172 ± 7 mg/dL, an effect that was antagonized by naloxone and mu selective antagonists β-funaltrexamine and naloxonazine. The effect was stereoselective and limited to only the l-isomer, while the d-isomer was ineffective. Despite the robust decrease in blood glucose produced by methadone, a series of other mu-opioids, including morphine, fentanyl, levorphanol, oxycodone or morphine-6β-glucuronide failed to lower blood glucose levels. Similar differences among mu-opioid agonists have been observed in other systems, suggesting the possible role of selected splice variants of the mu-opioid receptor gene Oprm1. This mouse model recapitulates our clinical observations and emphasizes the need to carefully monitor glucose levels when using high methadone doses, particularly intravenously, and the need for controlled clinical trials.

  16. 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

  17. Therapeutic and recreational methadone cardiotoxicity.

    PubMed

    Lusetti, Monia; Licata, Manuela; Silingardi, Enrico; Reggiani Bonetti, Luca; Palmiere, Cristian

    2016-04-01

    Several classes of drugs have been associated with an increased risk of cardiovascular disease and occurrence of arrhythmias potentially involved in sudden deaths in chronic users even at therapeutic doses. The study presented herein focuses on pathological changes involving the heart possibly due to methadone use. 60 cases were included in the study in total and were divided into three groups (therapeutic methadone users: 20 cases, recreational methadone users: 20 cases, and sudden death group in subjects who had never taken methadone: 20 cases). Autopsies, histology, biochemistry and toxicology were performed in all cases. Macroscopic and microscopic investigation results in therapeutic methadone users were similar to those observed in sudden, unexpected deaths in non-methadone users. In recreational methadone consumers, macroscopic and microscopic examination of the heart failed to provide results consistent with acute or chronic myocardial or coronary damage, thereby corroborating the hypothesis of death most likely following respiratory depression.

  18. Drug-Related HIV Risk Behaviors and Cocaine Preference among Injection Drug Users in Los Angeles.

    ERIC Educational Resources Information Center

    Longshore, Douglas; And Others

    1993-01-01

    Compared drug-related risk behavior of drug users whose preferred injection drug was cocaine and users with preference for heroin or no preference between the two drugs (total n=422). Found cocaine preference unrelated to likelihood of needle sharing overall, needle sharing with strangers, needle sharing at shooting galleries, and failure to use…

  19. Sex trading and psychological distress among women on methadone.

    PubMed

    El-Bassel, N; Simoni, J M; Cooper, D K; Gilbert, L; Schilling, R F

    2001-09-01

    This study examined the relationship between sex trading and psychological distress among a nonrandom sample of women recruited from 3 methadone maintenance clinics in New York City. Face-to-face interviews with 280 women (M age = 40.7) revealed that 32% had traded sex for money or drugs in the previous year. Compared to other participants, these women reported less education and higher rates of incarceration in the past year, sexually transmitted diseases, childhood sexual abuse, partner abuse, and current regular crack/cocaine and alcohol use. Hierarchical multiple regression analysis indicated that sex traders scored 0.41 units higher than non-sex traders on the General Severity Index of the Brief Symptom Inventory after controlling for all relevant covariates. The findings emphasize the need to consider the interrelation of psychological distress, abuse, and addiction in designing public health interventions addressing methadone maintained women.

  20. 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…

  1. Is there a need for heroin substitution treatment in Vancouver's Downtown Eastside? Yes there is, and in many other places too.

    PubMed

    Schechter, Martin T; Kendall, Perry

    2011-01-01

    The prescription of medically-supervised diacetylmorphine, the active ingredient in heroin, to individuals with treatment-refractory opioid dependence is a controversial and often politically charged subject. Just as methadone maintenance was opposed in the 1960s by some treatment providers who preferred abstinence-based therapies, heroin-assisted therapy is now being opposed by some methadone treatment providers--this despite the fact that the effectiveness of heroin-assisted treatment has been demonstrated in no less than six randomized trials in Switzerland, the Netherlands, Spain, Germany, Canada and the UK. The North American Opiate Medication Initiative (NAOMI) trial in Canada clearly showed heroin-assisted therapy to be superior to methadone in individuals with chronic, treatment-refractory heroin addiction both in terms of retention in addiction treatment and clinical response. An international internal review panel, three Research Ethics Boards, the CIHR RCT review panel, the Therapeutic Products Directorate of Health Canada, and several journal peer-reviewers reviewed the NAOMI trial. Nevertheless, authors of a commentary in this issue of CJPH find fault with the trial in terms of methadone prescribing, use of intention-to-treat analysis, safety and cost. We take this opportunity to respond to the numerous misconceptions and errors in their commentary.

  2. Methadone and prescription drug overdose.

    PubMed

    Hendrikson, Hollie; Hansen, Melissa

    2014-12-01

    (1) Methadone accounted for 2 percent of painkiller prescriptions and more than 30 percent of prescription painkiller deaths in 2009. (2) Data suggest that the rise in deaths from methadone overdose is not related to its use in treating drug abuse but, rather, to its use for pain management. (3) Preferred drug lists in most Medicaid programs identify methadone as a preferred drug for managing chronic pain, but most experts do no recommend it as a first choice.

  3. Long-acting opioid-agonists in the treatment of heroin addiction: why should we call them "substitution"?

    PubMed

    Gerra, G; Maremmani, I; Capovani, B; Somaini, L; Berterame, S; Tomas-Rossello, J; Saenz, E; Busse, A; Kleber, H

    2009-01-01

    Many studies have documented the safety, efficacy, and effectiveness of long-acting opioids (L-AOs), such as methadone and buprenorphine, in the treatment of heroin addiction. This article reviews the pharmacological differences between L-AO medications and short-acting opioids (heroin) in terms of reinforcing properties, pharmacokinetics, effects on the endocrine and immune systems. Given their specific pharmacological profile, L-AOs contribute to control addictive behavior, reduce craving, and restore the balance of disrupted endocrine function. The use of the term "substitution," referring to the fact that methadone or buprenorphine replace heroin in binding to brain opioid receptors, has been generalized to consider L-AOs as simple replacement of street drugs, thus contributing to the widespread misunderstanding of this treatment approach.

  4. CYP2B6 SNPs are associated with methadone dose required for effective treatment of opioid addiction.

    PubMed

    Levran, Orna; Peles, Einat; Hamon, Sara; Randesi, Matthew; Adelson, Miriam; Kreek, Mary Jeanne

    2013-07-01

    Adequate methadone dosing in methadone maintenance treatment (MMT) for opioid addiction is critical for therapeutic success. One of the challenges in dose determination is the inter-individual variability in dose-response. Methadone metabolism is attributed primarily to cytochrome P450 enzymes CYP3A4, CYP2B6 and CYP2D6. The CYP2B6*6 allele [single nucleotide polymorphisms (SNPs) 785A>G (rs2279343) and 516G>T (rs3745274)] was associated with slow methadone metabolism. To explore the effects of CYP2B6*6 allele on methadone dose requirement, it was genotyped in a well-characterized sample of 74 Israeli former heroin addicts in MMT. The sample is primarily of Middle Eastern/European ancestry, based on ancestry informative markers (AIMs). Only patients with no major co-medication that may affect methadone metabolism were included. The stabilizing daily methadone dose in this sample ranges between 13 and 260mg (mean 140±52mg). The mean methadone doses required by subjects homozygous for the variant alleles of the CYP2B6 SNPs 785A>G and 516G>T (88, 96mg, respectively) were significantly lower than those of the heterozygotes (133, 129mg, respectively) and the non-carriers (150, 151mg, respectively) (nominal P=0.012, 0.048, respectively). The results remain significant after controlling for age, sex and the ABCB1 SNP 1236C>T (rs1128503), which was previously shown to be associated with high methadone dose requirement in this population (P=0.006, 0.030, respectively). An additional 77 CYP2B6, CYP3A4 and CYP2D6 SNPs were genotyped. Of these, 24 SNPs were polymorphic and none showed significant association with methadone dose. Further studies are necessary to replicate these preliminary findings in additional subjects and other populations.

  5. Pharmacogenomics study on cadherin 2 network with regard to HIV infection and methadone treatment outcome

    PubMed Central

    Kuo, Hsiang-Wei; Shih, Chia-Lung; Tsung, Jieh-Hen; Liu, Sheng-Wen; Chu, Shih-Kai; Yang, Hsin-Chou; Tsou, Hsiao-Hui; Wang, Zih-Hsiang; Chen, Andrew C. H.; Liu, Yu-Li

    2017-01-01

    Heroin dependent patients have a high incidence of HIV infection. In contrast to the gene expression method, we developed a systemic correlation analysis method built upon the results of pharmacogenomics study in a methadone maintenance treatment (MMT) cohort consisting of 344 Taiwanese heroin dependent patients. We identified genetic variants and their encoding proteins that may be involved with HIV infection and MMT treatment outcome. Cadherin 2 (CDH2) genetic determinants were identified through the genome-wide pharmacogenomic study. We found significant correlations among HIV infection status, plasma levels of CDH2, cytokine IL-7, ADAM10, and the treatment responses to methadone. Two single nucleotide polymorphisms located within CDH2 gene showed associations with blood pressure and plasma CDH2 concentration. Plasma concentration of CDH2 showed correlations with the level of cytokine IL-7, status of HIV infection, and urine morphine test result. Plasma level of IL-7 was correlated with corrected QT interval (QTc) and gooseflesh skin withdrawal symptom score, while level of ADAM10 was correlated with plasma concentrations of vitamin D metabolite, nicotine metabolite, and R-methadone. The results suggest a novel network involving HIV infection and methadone treatment outcome. PMID:28358908

  6. The effects of gabapentin on methadone based addiction treatment: a randomized controlled trial.

    PubMed

    Moghadam, Mohsen Saber; Alavinia, Mohammad

    2013-09-01

    Gabapentin is a potentially useful drug in alleviating the hyperexcitatory painful states in the control of opiate dependence in acute detoxification and the stabilization phase. This study aim was to evaluate the effectiveness of gabapentin adds-on methadone therapy on lowering the methadone. This randomized double blind controlled clinical trial conducted at an outpatient rehabilitation clinic. Sixty patients using opium, opium extract and heroin were randomly assigned to two groups (34 in treatment group and 26 in control group); one group was prescribed combination of methadone (40-120 mg) and gabapentin (300 mg) as group A, and the other group was given methadone (40-120) and placebo as group B. The subjects were followed up for three weeks after intervention. There were 60 outpatients including 51 males with the mean age of 40.9±9.2. Daily dose and cumulative dose of methadone during the treatment was found to be significantly higher in group B (73.8±19.5 mg daily vs. 58.9±11 mg daily and cumulatively 1550.7±409.7 mg vs. 238.3±238.2 mg, p= 0.001). When the patients were stratified based on the kind of abused drug, the methadone dose was seen to be significantly reduced in the opium addicted patients in the group A. Group A showed more withdrawal symptoms whereas the most common complain of group B was sedation particularly during the first three days. The results showed that gabapentin is an effective adds-on therapy when is added to methadone. This drug leads to relief of withdrawal symptoms and lower methadone consumption.

  7. 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

  8. Greater Avoidance of a Heroin-Paired Taste Cue is Associated with Greater Escalation of Heroin Self-Administration in Rats

    PubMed Central

    Imperio, Caesar G.; Grigson, Patricia S.

    2015-01-01

    Heroin addiction is a disease of chronic relapse affecting over half of its users. Therefore, modeling individual differences in addiction-like behavior is needed to better reflect the human condition. In a rodent model, avoidance of a cocaine-paired saccharin cue is associated with greater cocaine seeking and taking. Here, we tested whether rats would avoid a saccharin cue when paired with the opportunity to self-administer heroin and whether the rats that most greatly avoid the heroin-paired taste cue would exhibit the greatest drug escalation over time, the greatest willingness to work for drug, and the greatest heroin-induced relapse. Adult male Sprague-Dawley rats received 5 min access to a 0.15% saccharin solution followed by the opportunity to self-administer either saline or heroin for 3 h (short access) or 6 h (extended access). Following 16 – 18 pairings, terminal saccharin intake was used to categorize the rats into small (>200 licks/5min) or large (<200 licks/5min) suppressors and responding for drug was examined accordingly. Only 5% of the short access rats reached the criteria for large suppressors. This large suppressor did not differ from the small suppressors in drug taking behavior. Conversely, 50% of the extended access saccharin-heroin rats were large suppressors and showed the largest escalation of drug intake, drug-loading behavior, and the greatest relapse-like behaviors. Extended access small suppressors displayed drug-taking behaviors that were similar to rats in the short access heroin condition. Avoidance of a heroin-paired taste cue reliably identifies individual differences in addiction-like behavior for heroin using extended drug access. PMID:26214212

  9. Greater avoidance of a heroin-paired taste cue is associated with greater escalation of heroin self-administration in rats.

    PubMed

    Imperio, Caesar G; Grigson, Patricia S

    2015-08-01

    Heroin addiction is a disease of chronic relapse affecting over half of its users. Therefore, modeling individual differences in addiction-like behavior is needed to better reflect the human condition. In a rodent model, avoidance of a cocaine-paired saccharin cue is associated with greater cocaine seeking and taking. Here, we tested whether rats would avoid a saccharin cue when paired with the opportunity to self-administer heroin and whether the rats that most greatly avoid the heroin-paired taste cue would exhibit the greatest drug escalation over time, the greatest willingness to work for drug, and the greatest heroin-induced relapse. Adult male Sprague-Dawley rats received 5 min access to a 0.15% saccharin solution followed by the opportunity to self-administer either saline or heroin for 3 hr (short access) or 6 hr (extended access). Following 16 to 18 pairings, terminal saccharin intake was used to categorize the rats into small (>200 licks/5min) or large (<200 licks/5min) suppressors and responding for drug was examined accordingly. Only 5% of the short access rats reached the criteria for large suppressors. This large suppressor did not differ from the small suppressors in drug-taking behavior. On the other hand, 50% of the extended access saccharin-heroin rats were large suppressors and showed the largest escalation of drug intake, drug-loading behavior, and the greatest relapse-like behaviors. Extended access small suppressors displayed drug-taking behaviors that were similar to rats in the short access heroin condition. Avoidance of a heroin-paired taste cue reliably identifies individual differences in addiction-like behavior for heroin using extended drug access.

  10. Cocaine and kidney injury: a kaleidoscope of pathology

    PubMed Central

    Goel, Narender; Pullman, James M.; Coco, Maria

    2014-01-01

    Cocaine is abused worldwide as a recreational drug. It is a potent activator of the sympathetic nervous system leading to intense vasoconstriction, endothelial dysfunction, oxidative stress, platelet activation and decrease in prostaglandins E2 and prostacyclin. Cocaine can lead to widespread systemic adverse effects such as stroke, myocardial infarction, arterial dissection, vascular thrombosis and rhabdomyolysis. In human and rat kidneys, cocaine has been associated with glomerular, tubular, vascular and interstitial injury. It is not uncommon to diagnose cocaine-related acute kidney injury (AKI), malignant hypertension and chronic kidney disease. Cocaine abuse can lead to AKI by rhabdomyolysis, vasculitis, infarction, thrombotic microangiopathy and malignant hypertension. It is reported that 50–60% of people who use both cocaine and heroin are at increased risk of HIV, hepatitis and additional risk factors that can cause kidney diseases. While acute interstitial nephritis (AIN) is a known cause of AKI, an association of AIN with cocaine is unusual and seldom reported. We describe a patient with diabetes mellitus, hypertension and chronic hepatitis C, who presented with AKI. Urine toxicology was positive for cocaine and a kidney biopsy was consistent with AIN. Illicit drugs such as cocaine or contaminants may have caused AIN in this case and should be considered in the differential diagnosis of causes of AKI in a patient with substance abuse. We review the many ways that cocaine adversely impacts on kidney function. PMID:25859366

  11. Heroin crystal nephropathy.

    PubMed

    Bautista, Josef Edrik Keith; Merhi, Basma; Gregory, Oliver; Hu, Susie; Henriksen, Kammi; Gohh, Reginald

    2015-06-01

    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.

  12. The Problem of Heroin

    ERIC Educational Resources Information Center

    Wilson, James Q.; And Others

    1972-01-01

    Argues that most of the underlying assumptions of presently recommended solutions to the problem of heroin addiction are unreasonable, unwarranted, or at least open to more than one interpretation. (DM)

  13. Heroin (Smack, Junk) Facts

    MedlinePlus

    ... Families? Why Is It So Hard to Quit Drugs? Effects of Drugs Drug Use Hurts Other People Drug ... was addicted to heroin. Here, he describes the drug's effects on his life. Read Deon's story The Prescription ...

  14. Heroin and Pregnancy

    MedlinePlus

    ... seeds from poppy plants. Prescription opioids , like oxycodone, morphine and codeine, are used as painkillers after an ... a street (illegal) drug made from the opioid morphine. Heroin can be a white or brown powder, ...

  15. Methadone diversion as a protective strategy: the harm reduction potential of 'generous constraints'.

    PubMed

    Harris, Magdalena; Rhodes, Tim

    2013-11-01

    Methadone maintenance treatment is evidenced as a successful harm reduction initiative in regard to the prevention of blood borne viruses and other injecting related harms. This is attributable to reductions in heroin use and injecting equipment sharing incidents, yet the means by which these are achieved are rarely elaborated. Methadone diversion is predominantly presented in a negative light; associated with overdose and other harms. In our qualitative London-based study with 37 people who inject drugs, 35 on substitution therapies, we found that methadone self regulation and diversion played a prominent role in helping participants to manage their drug use, prevent withdrawal, cement social relationships, and inadvertently protect against hepatitis C transmission. The ability of participants to enact these 'indigenous harm reduction strategies' was constrained to various degrees by their treatment dosing protocols. In this article we explore the strategies participants enacted with methadone, the role of 'generous constraints' in this enactment and the associated production and reduction of risk. In order to reengage people who inject drugs with harm reduction interventions, it is necessary for initiatives to take stock of the indigenous strategies that individuals are already utilising and - in the case of methadone self regulation - support them by the implementation of more generous constraints.

  16. 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.

  17. Chronic opiate treatment enhances both cocaine-reinforced and cocaine-seeking behaviors following opiate withdrawal.

    PubMed

    He, Shaunteng; Grasing, Kenneth

    2004-08-16

    After chronic exposure to psychostimulants or opiates, self-administration or conditioned place preference with either class is increased (sensitized). Cross-sensitization of conditioned place preference, i.e., enhancement of psychostimulant-induced preferences after exposure to opiates, has also been described, but increases in cocaine self-administration after morphine pretreatment have not been reported. The present study evaluated effects of chronic morphine treatment on cocaine reinforcement. Opiate dependence was established in Wistar rats by administration of morphine as a constant infusion that was gradually increased to a dose of 50mg/kg per day over a 1-week period. Immediately after discontinuation of chronic morphine treatment, animals were allowed to acquire cocaine self-administration under a simple fixed-ratio schedule (FR-1), and were subsequently advanced to a progressive ratio schedule. Acquisition of cocaine self-administration under the FR-1 did not differ in saline- and morphine-pretreated animals. For cocaine self-administration under a progressive ratio schedule measured at 5 or more days after the onset of opiate withdrawal, chronic pretreatment with morphine increased the number of ratios completed, augmented final response requirements, and produced a more stable pattern of cocaine self-administration. Responding was also increased in morphine-pretreated animals during an initial extinction session. These results show that chronic opiate treatment can enhance both cocaine-reinforced and cocaine-seeking behaviors following opiate withdrawal. A similar effect may occur in human patients who discontinue methadone or other forms of replacement therapy for opiate abuse, and may contribute to relapse involving use of cocaine or other psychostimulants.

  18. Pharmacokinetic comparison of two methods of heroin smoking: 'chasing the dragon' versus the use of a heating device.

    PubMed

    Klous, Marjolein G; Huitema, Alwin D R; Rook, Elisabeth J; Hillebrand, Michel J X; Hendriks, Vincent M; Van den Brink, Wim; Beijnen, Jos H; Van Ree, Jan M

    2005-05-01

    In preparation for a trial on co-prescription of inhalable heroin and methadone, two methods for inhalation of heroin/caffeine tablets were compared: the commonly used method of 'chasing the dragon' and a standardised procedure for inhalation of volatilised heroin, using a heating device. Five male addicts inhaled a tablet of smokable heroin daily for 5 days, alternating the inhalation method. Plasma concentrations of heroin, 6-acetylmorphine, morphine and morphine-3- and -6-glucuronide were determined using a liquid chromatography method with tandem mass spectrometric detection. The exposure to heroin and its metabolites (expressed as areas under the concentration-time curve) was significantly lower after smoking via the heating device than after 'chasing the dragon': heroin 80% and 6-acetylmorphine 73% lower (p < 0.05). Maximal concentrations of heroin and 6-acetylmorphine were also 80% and 70% lower (p < 0.05) after using the heating device. 'Chasing the dragon' is a more efficient inhalation method than inhalation via the heating device.

  19. Concentrations of cocaine and benzoylecgonine in femoral blood from cocaine-related deaths compared with venous blood from impaired drivers.

    PubMed

    Jones, Alan Wayne; Holmgren, Anita

    2014-01-01

    The concentrations of cocaine and its major metabolite benzoylecgonine (BZE) were determined in femoral blood from 132 cocaine-related deaths and compared with venous blood from 988 apprehended drivers. Cocaine and BZE were determined by solid-phase extraction and isotope dilution gas chromatography-mass spectrometry with limits of quantitation of 0.02 mg/L for both substances. Significantly more men (95-98%) than women (2-5%) abused cocaine, although their mean age was about the same (29-30 years). Mean age (±SD) of cocaine-related deaths was 29 ± 7 years, which was not significantly different from 30 ± 8 years in traffic cases (P > 0.05). The median concentration of cocaine in blood in 61 fatalities was 0.10 mg/L compared with 0.06 mg/L in traffic cases (P < 0.001). In drug intoxication deaths, the median concentration of cocaine was 0.13 mg/L (N = 25), which was not significantly different from 0.09 mg/L (N = 36) in other causes of death. Cocaine-related deaths mostly involved mixed drug intoxications including co-ingestion of heroin, cannabis, amphetamines as well as legal drugs, such as benzodiazepines and/or ethanol. The concentrations of cocaine in blood from living and deceased persons overlapped, which makes it infeasible to predict toxicity from the analytical toxicology results alone.

  20. Enhanced development of dispositional tolerance to methadone by desipramine given together with methadone

    SciTech Connect

    Liu, S.J.; Wang, R.I.H.

    1985-02-25

    Rats given 2-day oral administration of methadone (15 mg/kg, twice on day 1 and once on day 2) by gastric tube developed dispositional tolerance to methadone analgesia as demonstrated by a decrease in analgesic response and by an increase in methadone metabolism. The increased metabolism of methadone was evidenced by a decrease in brain concentration of /sup 14/C-methadone and increases in the percentages of total /sup 14/C in liver or urine as /sup 14/C-water-soluble metabolites (/sup 14/C-WSM) after the rats were challenged with a test dose of /sup 14/C-methadone. Two-day pretreatment with a combination of desipramine (DMI) (10 mg/kg, ip) and methadone (15 mg/kg, po) enhanced the development of dispositional tolerance to methadone analgesia which was evidenced by a greater decrease in the brain concentration of methadone and a greater increase in methadone metabolism as compared to those changes in rats pretreated with only methadone. Repeated treatment with DMI alone neither decreased the analgesic effect of methadone nor stimulated methadone metabolism. It is suggested that DMI given together with methadone promoted the induction of methadone metabolism in the liver by prolonging the enzyme-stimulating state of methadone, thus enhancing the development of dispositional tolerance to methadone. 20 references, 1 figure, 1 table.

  1. 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.

  2. Scaling up the national methadone maintenance treatment program in China: achievements and challenges

    PubMed Central

    Yin, Wenyuan; Hao, Yang; Sun, Xinhua; Gong, Xiuli; Li, Fang; Li, Jianhua; Rou, Keming; Sullivan, Sheena G; Wang, Changhe; Cao, Xiaobin; Luo, Wei; Wu, Zunyou

    2010-01-01

    China’s methadone maintenance treatment program was initiated in 2004 as a small pilot project in just eight sites. It has since expanded into a nationwide program encompassing more than 680 clinics covering 27 provinces and serving some 242 000 heroin users by the end of 2009. The agencies that were tasked with the program’s expansion have been confronted with many challenges, including high drop-out rates, poor cooperation between local governing authorities and poor service quality at the counter. In spite of these difficulties, ongoing evaluation has suggested reductions in heroin use, risky injection practices and, importantly, criminal behaviours among clients, which has thus provided the impetus for further expansion. Clinic services have been extended to offer clients a range of ancillary services, including HIV, syphilis and hepatitis C testing, information, education and communication, psychosocial support services and referrals for treatment of HIV, tuberculosis and sexually transmitted diseases. Cooperation between health and public security officials has improved through regular meetings and dialogue. However, institutional capacity building is still needed to deliver sustainable and standardized services that will ultimately improve retention rates. This article documents the steps China made in overcoming the many barriers to success of its methadone program. These lessons might be useful for other countries in the region that are scaling-up their methadone programs. PMID:21113034

  3. Scaling up the national methadone maintenance treatment program in China: achievements and challenges.

    PubMed

    Yin, Wenyuan; Hao, Yang; Sun, Xinhua; Gong, Xiuli; Li, Fang; Li, Jianhua; Rou, Keming; Sullivan, Sheena G; Wang, Changhe; Cao, Xiaobin; Luo, Wei; Wu, Zunyou

    2010-12-01

    China's methadone maintenance treatment program was initiated in 2004 as a small pilot project in just eight sites. It has since expanded into a nationwide program encompassing more than 680 clinics covering 27 provinces and serving some 242 000 heroin users by the end of 2009. The agencies that were tasked with the program's expansion have been confronted with many challenges, including high drop-out rates, poor cooperation between local governing authorities and poor service quality at the counter. In spite of these difficulties, ongoing evaluation has suggested reductions in heroin use, risky injection practices and, importantly, criminal behaviours among clients, which has thus provided the impetus for further expansion. Clinic services have been extended to offer clients a range of ancillary services, including HIV, syphilis and hepatitis C testing, information, education and communication, psychosocial support services and referrals for treatment of HIV, tuberculosis and sexually transmitted diseases. Cooperation between health and public security officials has improved through regular meetings and dialogue. However, institutional capacity building is still needed to deliver sustainable and standardized services that will ultimately improve retention rates. This article documents the steps China made in overcoming the many barriers to success of its methadone program. These lessons might be useful for other countries in the region that are scaling-up their methadone programs.

  4. Quality of life among former Soviet Union and Israeli origin methadone users.

    PubMed

    Isralowitz, Richard; Reznik, Alexander; Pruginin, Itay

    2016-01-01

    A common treatment intervention for heroin addiction is methadone maintenance. In recent years a wider perspective has been adapted to understand and evaluate addiction through quality of life. This article examines quality of life conditions of 170 male former Soviet Union and Israeli origin drug users in methadone maintenance and provides an understanding of conditions linked to the World Health Organization Quality of Life project's best available techniques reference document. Having a partner or spouse and less chronic illness are positive factors affecting quality of life regardless of country of origin. Israeli born drug users reported better quality of life based on their psychological health and environment domain responses; no difference was found for the physical health and social relationship domains of the Israeli and former Soviet Union origin males. Because heroin addiction is a chronic and relapsing illness, one of the goals of methadone maintenance is to address patients' health status from a broad perspective. Based on clinical observations, the treatment of special populations may be enhanced if their particular needs are considered and met. Quality of life factors are relevant for assessing high risk groups, including those from different ethnic origins, in poor physical and psychological health, their treatment and personal adjustment, and their service personnel training needs.

  5. Absence of neurocognitive impairment in a large Chinese sample of HCV-infected injection drug users receiving methadone treatment

    PubMed Central

    Gupta, Saurabh; Iudicello, Jennifer E.; Shi, Chuan; Letendre, Scott; Knight, Adam; Li, Jianhua; Riggs, Patricia K.; Franklin, Donald R.; Duarte, Nichole; Jin, Hua; Atkinson, J. Hampton; Yu, Xin; Wu, Zunyou; Grant, Igor; Heaton, Robert K.

    2014-01-01

    Background Prior research has demonstrated neuropsychological (NP) impairment in persons with histories of injection drug use (IDU), hepatitis C virus (HCV) infection, and methadone maintenance treatment (MMT), individually, but little is known about the NP effects of these three risk factors in combination. This issue is particularly important in China, which is addressing its highly HCV-comorbid IDU epidemic with widespread government sponsored MMT, especially in light of recent evidence suggesting that methadone may be neuroprotective in some circumstances. Methods We administered a comprehensive NP test battery to 195 Chinese heroin IDU individuals taking MMT (IDU+ group), the majority of whom were also HCV+ (87%; n = 169), and compared their NP performance to that of 198 demographically comparable, non-IDU Chinese controls (IDU− group). All participants in both groups tested negative for HIV infection, which is also a common comorbidity in the Chinese IDU population. Results The IDU+ group did not have an increased rate of global NP impairment, or perform significantly worse on any individual NP test measure. Within the IDU+ group, liver disease characteristics and reported details of heroin use were not significantly associated with NP performance. Conclusion Failure to detect NP impairment in IDU+ subjects with or without HCV infection was surprising, particularly considering the previously demonstrated sensitivity of our NP battery to neurocognitive disorders associated with HIV infection in China. One possible explanation, which should be explored in future research, is the potential neuroprotective effect of methadone in the context of HCV infection and/or heroin withdrawal. PMID:24508003

  6. Impact of the heroin 'drought' on patterns of drug use and drug-related harms.

    PubMed

    Longo, Marie C; Henry-Edwards, Susan M; Humeniuk, Rachel E; Christie, Paul; Ali, Robert L

    2004-06-01

    Since late 2000, anecdotal reports from drug users and health professionals have suggested that there was a reduction in the supply of heroin in Adelaide in the first half of 2001, referred to as a heroin 'drought'. The aim of this paper was to critically review evidence for this, using data obtained from 100 injecting drug users surveyed for the 2001 Illicit Drug Reporting System (IDRS). This project is carried out annually in all Australian jurisdictions, and collects up-to-date information on the markets for heroin, methamphetamine, cocaine and cannabis. This paper also investigates the possible implications of this 'drought' on patterns of drug use and drug-related harms. The 2001 IDRS found consistent reports by users of an increase in the price of heroin, together with decreases in purity and availability. These factors resulted in a decrease in the frequency of self-reported heroin use among those surveyed in 2001, and a concomitant increase in the use of other drugs, in particular methamphetamine and morphine. The heroin 'drought' appears to have had a substantial impact on several indices of drug-related harm. There was a marked decrease in the number of opioid-related fatalities, and hospital data also showed reductions in heroin-related presentations. Treatment service data showed an increase in the number of admissions related to amphetamines. There is a need for health promotion and education on the adverse effects of methamphetamine use, and the development of improved treatment protocols for methamphetamine abuse and dependence.

  7. Cocaine and Pregnancy

    MedlinePlus

    ... my baby’s body too? Yes. Cocaine crosses the placenta and enters the developing baby. Cocaine can be ... Later in pregnancy, cocaine use can cause the placenta to pull away from the wall of the ...

  8. 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.

  9. A reduction in blood morphine concentrations amongst heroin overdose fatalities associated with a sustained reduction in street heroin purity.

    PubMed

    Darke, Shane; Duflou, Johan; Torok, Michelle

    2010-05-20

    To determine the effects of a sudden and sustained reduction in heroin purity on the toxicology of heroin overdose, 959 consecutive heroin overdose cases autopsied at the NSW Department of Forensic Medicine (1/1/1998-31/12/2006) were analysed. There was a significant reduction in blood morphine concentration across the study period (beta=-0.07), declining from a median of 0.50mg/L in the years 1998-2000 prior to 0.40mg/L in the period 2001-2006. There was no significant change in the proportion of alcohol positive cases, but the proportion of benzodiazepine positive cases increased across time (OR 1.11), as did methadone positive cases (OR 1.12). The decline in blood morphine concentrations remained significant after controlling for these factors (beta=-0.07). In determining toxic and lethal morphine concentrations, the fact that the toxicology of overdose is responsive to changes in the opioid street market needs to be borne in mind.

  10. "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

  11. Correlates of Alcohol Use among Methadone-Maintained Adults

    PubMed Central

    Nyamathi, Adeline; Cohen, Allan; Marfisee, Mary; Shoptaw, Steven; Greengold, Barbara; de Castro, Viviane; George, Daniel; Leake, Barbara

    2009-01-01

    This prospective study (n = 190) examined correlates of alcohol use from baseline data of a longitudinal trial conducted among moderate and heavy alcohol users receiving methadone maintenance therapy (MMT). The sample included MMT clients who were 18-55 years of age, and were receiving MMT from five large methadone maintenance clinics in the Los Angeles area. Half of the sample were heavy drinkers and nearly half (46%) reported heroin use. Using a structured questionnaire, correlates of heavy alcohol use included White and Hispanic ethnicity, and fair or poor physical health combined with older age (≥ 50 years). We also found that MMT clients who were younger than 50 years, regardless of health status, were more likely to be heavy drinkers. Compared with moderate alcohol consumers, a greater number of heavy alcohol users also experienced recent victimization. To optimize MMT, alcohol screening should be part of routine assessment and alcohol treatment should be made available within MMT programs. Moreover, special consideration should be provided to the most vulnerable clients, such as the younger user, those with a long-term and current history of heavy drug use, and those victimized and reporting fair or poor health. In addition, promoting attention to general physical and mental health problems within MMT programs may be beneficial in enhancing health outcomes of this population. PMID:19081204

  12. Towards "evidence-making intervention" approaches in the social science of implementation science: The making of methadone in East Africa.

    PubMed

    Rhodes, Tim; Closson, Elizabeth F; Paparini, Sara; Guise, Andy; Strathdee, Steffanie

    2016-04-01

    In this commentary, we take the recent introduction of methadone treatment in response to emerging problems of HIV linked to heroin addiction in Kenya as a case for reflecting on the social science of implementation science. We offer a framework of 'evidence-making intervention' which we hold as distinct from mainstream 'evidence-based intervention' approaches. Whilst accepting that interventions are shaped in their contexts, evidence-based intervention approaches tend to imagine a stable intervention object with universal effect potential. By contrast, an evidence-making intervention approach investigates how an intervention, and the knowledge which constitutes it, is made locally, through its processes of implementation. Drawing on qualitative research generated in Kenya prior to (2012-2013) and during (2014-2015) the implementation of methadone treatment, we explore the making of 'methadone promise' as a case of evidence-making intervention. We show how enactments of methadone promise make multiple methadones, through which a binary is negotiated between the narratives of methadone as hope for addiction recovery and methadone as hope for HIV prevention. Addiction recovery narratives predominate, despite methadone's incorporation into policy via its globally supported HIV prevention evidence-base. Key practices in the making of methadone promise in Kenya include its medicalization, and renaming, as 'medically assisted treatment' - or simply 'MAT' - which distance it from prior constitutions elsewhere as a drug of substitution, and the visualisation of its effects wherein unhealthy people can be seen and shown to have become well. We also show how actors seek to protect the story of methadone promise from counter narratives, including through mass media projects. We conclude that there is no single biomedical object of methadone intervening on a single biological body across contexts, and no single universe of evidence. By giving weight to local rather than

  13. Methadone Recycling Sustains Drug Reservoir in Tissue.

    PubMed

    Linares, Oscar A; Fudin, Jeffrey; Daly, Annemarie; Schiesser, William E; Boston, Raymond C

    2015-09-01

    We hypothesize that there is a tissue store of methadone content in humans that is not directly accessible, but is quantifiable. Further, we hypothesize the mechanism by which methadone content is sustained in tissue stores involves methadone uptake, storage, and release from tissue depots in the body (recycling). Accordingly, we hypothesize that such tissue stores, in part, determine plasma methadone levels. We studied a random sample of six opioid-naïve healthy subjects. We performed a clinical trial simulation in silico using pharmacokinetic modeling. We found a large tissue store of methadone content whose size was much larger than methadone's size in plasma in response to a single oral dose of methadone 10 mg. The tissue store measured 13-17 mg. This finding could only be explained by the contemporaneous storage of methadone in tissue with dose recycling. We found that methadone recycles 2-5 times through an inaccessible extravascular compartment (IAC), from an accessible plasma-containing compartment (AC), before exiting irreversibly. We estimate the rate of accumulation (or storage) of methadone in tissue was 0.029-7.29 mg/h. We predict 39 ± 13% to 83 ± 6% of methadone's tissue stores "spillover" into the circulation. Our results indicate that there exists a large quantifiable tissue store of methadone in humans. Our results support the notion that methadone in humans undergoes tissue uptake, storage, release into the circulation, reuptake from the circulation, and re-release into the circulation, and that spillover of methadone from tissue stores, in part, maintain plasma methadone levels in humans.

  14. Opiate addiction and cocaine addiction: underlying molecular neurobiology and genetics.

    PubMed

    Kreek, Mary Jeanne; Levran, Orna; Reed, Brian; Schlussman, Stefan D; Zhou, Yan; Butelman, Eduardo R

    2012-10-01

    Addictive diseases, including addiction to heroin, prescription opioids, or cocaine, pose massive personal and public health costs. Addictions are chronic relapsing diseases of the brain caused by drug-induced direct effects and persisting neuroadaptations at the epigenetic, mRNA, neuropeptide, neurotransmitter, or protein levels. These neuroadaptations, which can be specific to drug type, and their resultant behaviors are modified by various internal and external environmental factors, including stress responsivity, addict mindset, and social setting. Specific gene variants, including variants encoding pharmacological target proteins or genes mediating neuroadaptations, also modify vulnerability at particular stages of addiction. Greater understanding of these interacting factors through laboratory-based and translational studies have the potential to optimize early interventions for the therapy of chronic addictive diseases and to reduce the burden of relapse. Here, we review the molecular neurobiology and genetics of opiate addiction, including heroin and prescription opioids, and cocaine addiction.

  15. Changes in patterns of drug injection concurrent with a sustained reduction in the availability of heroin in Australia.

    PubMed

    Topp, Libby; Day, Carolyn; Degenhardt, Louisa

    2003-06-05

    Between 1996 and 2000, heroin was the drug most frequently injected in Australia, and viable heroin markets existed in six of Australia's eight jurisdictions. In 2001, there was a dramatic and sustained reduction in the availability of heroin that was accompanied by a substantial increase in its price, and a 14% decline in the average purity of seizures analysed by forensic laboratories. The shortage of heroin constitutes a unique natural experiment within which to examine the impact of supply reduction. This paper reviews one important correlate of the shortage, namely changes in patterns of illicit drug injection. A number of studies have consistently suggested that between 2000 and 2001, there was a sizeable decrease in both prevalence and frequency of heroin injection among injecting drug users. These changes were accompanied by increased prevalence and frequency of stimulant injection. Cocaine was favoured in NSW, the sole jurisdiction in which a cocaine market was established prior to the heroin shortage; whereas methamphetamine predominated in other jurisdictions. Some data suggest that, at least in the short-term, some drug injectors left the market altogether subsequent to the reduced heroin availability. However, the findings that (1) some former heroin users switched their drug preference to a stimulant; and (2) subsequently attributed this change to the reduced availability of heroin, suggests that reducing the supply of one drug may serve to increase the use of others. Given the differential harms associated with the use of stimulants and opiates, this possibility has grave implications for Australia, where the intervention and treatment system is designed primarily to accommodate opiate use and dependence.

  16. Genetic susceptibility to heroin addiction; a candidate-gene association study

    PubMed Central

    Levran, O.; Londono, D.; O’Hara, K.; Nielsen, D. A.; Peles, E.; Rotrosen, J.; Casadonte, P.; Linzy, S.; Randesi, M.; Ott, J.; Adelson, M.; Kreek, M. J.

    2010-01-01

    Heroin addiction is a chronic complex disease with a substantial genetic contribution. This study was designed to identify genetic variants that are associated with susceptibility to develop heroin addiction, by analyzing 1350 variants in 130 candidate genes. All subjects had Caucasian ancestry. The sample consisted of 412 former severe heroin addicts in methadone treatment, and 184 healthy controls with no history of drug abuse. Nine variants, in six genes, showed the lowest nominal P values in the association tests (P < 0.01). These variants were in non-coding regions of the genes encoding the mu (OPRM1; rs510769, rs3778151), kappa (OPRK1; rs6473797), and delta opioid receptors, (OPRD1; rs2236861, rs2236857 and rs3766951), the neuropeptide galanin (GAL; rs694066), the serotonin receptor subtype 3B (HTR3B; rs3758987) and the casein kinase 1 isoform epsilon (CSNK1E; rs1534891). Several haplotypes and multi-locus genotype patterns showed nominally significant associations (e.g. OPRM1; P = 0.0006 and CSNK1E; P = 0.0007). Analysis of a combined effect of OPRM1 and OPRD1 showed that rs510769 and rs2236861 increase the risk of heroin addiction (P = 0.0005). None of these associations remained significant after adjustment for multiple testing. This study suggests the involvement of several genes and variants in heroin addiction that is worthy of future study. PMID:18518925

  17. Conglomerate pulmonary disease: a form of talcosis in intravenous methadone abusers.

    PubMed

    Sieniewicz, D J; Nidecker, A C

    1980-10-01

    A program of detoxification of heroin addicts by the use of oral methadone produced a series of patients who developed pulmonary granulomatous mass lesions as the result of the intravenous use of the oral form of the drug. Talc, used in the preparation of the tablet, seems to be the offending substance. Besides producing a diffuse interstitial granulomatous reaction, conglomerate masses in the upper lung zones were also noted. This radiographic pattern can occur rather rapidly from the background of fine diffuse interstitial micronodularity. The latter may be subtle, but can change to mass lesions associated with lung contraction, volume loss in the upper lung zones, and hyperinflation in the lower lungs. The mechanism of formation of mass lesions is unknown, but individual host reaction and immunologic mechanisms probably play a role. The development and progress of such a process is described in four heroin addicts.

  18. Pharmacokinetic interaction between telaprevir and methadone.

    PubMed

    van Heeswijk, Rolf; Verboven, Peter; Vandevoorde, Ann; Vinck, Petra; Snoeys, Jan; Boogaerts, Griet; De Paepe, Els; Van Solingen-Ristea, Rodica; Witek, James; Garg, Varun

    2013-05-01

    Hepatitis C virus (HCV) antibody is present in most patients enrolled in methadone maintenance programs. Therefore, interactions between the HCV protease inhibitor telaprevir and methadone were investigated. The pharmacokinetics of R- and S-methadone were measured after administration of methadone alone and after 7 days of telaprevir (750 mg every 8 h [q8h]) coadministration in HCV-negative subjects on stable, individualized methadone therapy. Unbound R-methadone was measured in predose plasma samples before and during telaprevir coadministration. Safety and symptoms of opioid withdrawal were evaluated throughout the study. In total, 18 subjects were enrolled; 2 discontinued prior to receiving telaprevir. The minimum plasma concentration in the dosing interval (C(min)), the maximum plasma concentration (Cmax), and the area under the plasma concentration-time curve from h 0 (time of administration) to 24 h postdose (AUC(0-24)) for R-methadone were reduced by 31%, 29%, and 29%, respectively, in the presence of telaprevir. The AUC0-24 ratio of S-methadone/R-methadone was not altered. The median unbound percentage of R-methadone increased by 26% in the presence of telaprevir. The R-methadone median (absolute) unbound C(min) values in the absence (10.63 ng/ml) and presence (10.45 ng/ml) of telaprevir were similar. There were no symptoms of opioid withdrawal and no discontinuations due to adverse events. In summary, exposure to total R-methadone was reduced by approximately 30% in the presence of telaprevir, while the exposure to unbound R-methadone was unchanged. No symptoms of opioid withdrawal were observed. These results suggest that dose adjustment of methadone is not required when initiating telaprevir treatment. (This study has been registered at ClinicalTrials.gov under registration no. NCT00933283.).

  19. Patterns in admission delays to outpatient methadone treatment in the United States.

    PubMed

    Gryczynski, Jan; Schwartz, Robert P; Salkever, David S; Mitchell, Shannon Gwin; Jaffe, Jerome H

    2011-12-01

    Waiting lists for methadone treatment have existed in many U.S. communities, but little is known nationally about what patient and service system factors are related to admission delays that stem from program capacity shortfalls. Using a combination of national data sources, this study examined patterns in capacity-related admission delays to outpatient methadone treatment in 40 U.S. metropolitan areas (N = 28,920). Patient characteristics associated with admission delays included racial/ethnic minority status, lower education, criminal justice referral, prior treatment experience, secondary cocaine or alcohol use, and co-occurring psychiatric problems. Injection drug users experienced fewer delays, as did self-pay patients and referrals from health care and addiction treatment providers. Higher community-level utilization of methadone treatment was associated with delay, whereas delays were less common in communities with higher utilization of alternative modalities. These findings highlight potential disparities in timely admission to outpatient methadone treatment. Implications for improving treatment access and service system monitoring are discussed.

  20. Development and manufacture of diacetylmorphine/caffeine sachets for inhalation via 'chasing the dragon' by heroin addicts.

    PubMed

    Klous, M G; Nuijen, B; van den Brink, W; van Ree, J M; Beijnen, J H

    2004-08-01

    In 1998, two clinical trials were started in The Netherlands to evaluate the effect of coprescription of heroin and methadone on the mental and physical health and social functioning of chronic, treatment-resistant, heroin-dependent patients. Since 75-85% of the heroin addicts in The Netherlands use their heroin by "chasing the dragon," one of the two study arms concerned the coprescription of inhalable heroin. A pharmaceutical dosage form for inhalable heroin was developed for this trial, consisting of a 3:1 powder mixture of diacetylmorphine base and caffeine anhydrate. We describe the manufacturing process that was developed for filling sachets with this mixture in four dosages using a micro dose auger filler. In order to control product quality, in-process controls were developed to monitor the filling process and quality control tests were performed on the finished product. In-process control results have shown the filling process to be accurate and precise. The diacetylmorphine/caffeine sachets were shown to comply with the specifications for content and uniformity of mass. The finished product was found to be stable for 2 years when stored at 25 degrees C, 60% relative humidity and for 6 months when stored at 40 degrees C, 75% relative humidity.

  1. Comparison of methadone and buprenorphine for opiate detoxification (LEEDS trial): a randomised controlled trial

    PubMed Central

    Wright, Nat MJ; Sheard, Laura; Adams, Clive E; Rushforth, Bruno J; Harrison, Wendy; Bound, Nicole; Hart, Roger; Tompkins, Charlotte NE

    2011-01-01

    Background Many opiate users require prescribed medication to help them achieve abstinence, commonly taking the form of a detoxification regime. In UK prisons, drug users are nearly universally treated for their opiate use by primary care clinicians, and once released access GP services where 40% of practices now treat drug users. There is a paucity of evidence evaluating methadone and buprenorphine (the two most commonly prescribed agents in the UK) for opiate detoxification. Aim To evaluate whether buprenorphine or methadone help to achieve drug abstinence at completion of a reducing regimen for heroin users presenting to UK prison health care for detoxification. Design Open-label, pragmatic, randomised controlled trial in three prison primary healthcare departments in the north of England. Method Prisoners (n = 306) using illicit opiates were recruited and given daily sublingual buprenorphine or oral methadone, in the context of routine care, over a standard reduced regimen of not more than 20 days. The primary outcome measure was abstinence from illicit opiates at 8 days post detoxification, as indicated by urine test (self-report/clinical notes where urine sample was not feasible). Secondary outcomes were also recorded. Results Abstinence was ascertained for 73.7% at 8 days post detoxification (urine sample = 52.6%, self report = 15.2%, clinical notes = 5.9%). There was no statistically significant difference in the odds of achieving abstinence between methadone and buprenorphine (odds ratio [OR] = 1.69; 95% confidence interval [CI] = 0.81 to 3.51; P = 0.163). Abstinence was associated solely with whether or not the participant was still in prison at that time (15.22 times the odds; 95% CI = 4.19 to 55.28). The strongest association for lasting abstinence was abstinence at an earlier time point. Conclusion There is equal clinical effectiveness between methadone and buprenorphine in achieving abstinence from opiates at 8 days post detoxification within prison

  2. Improvement of saccadic functions after dosing with methadone in opioid addicted individuals.

    PubMed

    Gorzelańczyk, Edward Jacek; Walecki, Piotr; Feit, Julia; Kunc, Marek; Fareed, Ayman

    2016-01-01

    In the current experiment, we used the saccadometric test to study the effect of a single therapeutic dose of methadone on the integrity of cortico-subcortical brain functioning. In this prospective study, we used the Saccadometer System (Advanced Clinical Instrumentation, Cambridge, UK). The saccadometric test was performed before and 1.5 hours after methadone dosing. We analyzed the following saccadic parameters: latency, duration, amplitude, average and peak velocity, and processing performance (promptness) as well as a number of different types of saccades (like correct/incorrect, under/overshoot, and left-sided/right-sided). The sample consists of 40 subjects with an average 18 years of opioid addiction. The mean age is 35.3 ± 7 (80% males and 20% females). The mean period of heroin dependence is 15.3 ± 6.3 years. The mean daily dose of methadone in substitution therapy is 90 ± 26.5 mg. After administration of a single therapeutic dose of methadone, there were statistically significant differences in the values of saccade duration and latency when compared to the values before the drug administration. Average duration of saccade was significantly longer [51.40 ± 8.75 ms versus 48.93 ± 6.91 ms, z = 2.53, p = .01] and average latency was significantly longer [198.85 ± 52.57 ms versus 183.05 ± 30.95 ms, z = 2.09 p < .03]. This is the first study to test the therapeutic effect of daily methadone dosing on the integrity of the cortico-subcortical brain functions as measured by the saccadometry. More research is needed to explore the effect of illicit opioid use on the integrity of brain structures and functions, and the protective effect of opioid agonist therapy on reversing the damaging effects of illicit opioid use.

  3. Inhibition of cocaine self-administration by fluoxetine or D-fenfluramine combined with phentermine.

    PubMed

    Glatz, Andrew C; Ehrlich, Michelle; Bae, Richard S; Clarke, Michelle J; Quinlan, Patricia A; Brown, Emily C; Rada, Pedro; Hoebel, Bartley G

    2002-01-01

    Instrumental responding for intravenous cocaine in rats at 85% of free-feeding weight was significantly decreased 50% by D-fenfluramine plus phentermine (D-Fen/Phen, 5 mg/kg of each for 1 day). A similar effect was obtained in normal-weight rats self-administering a cocaine-heroin mixture. Treating normal-weight animals with fluoxetine (5 mg/kg) for 4 days also significantly decreased cocaine self-administration by half, and then adding phentermine caused an additional decrease in cocaine intake. Animals that were well trained to self-administer drug did not self-administer intravenous D-Fen/Phen or Flu/Phen. The present results confirm that serotonergic drugs can decrease cocaine, or cocaine/heroin, self-administration in rats, and that phentermine adds to the effect. Based on related research with the same dose of D-Fen/Phen, it is suggested that effectiveness in reducing cocaine reinforcement is due in part to a satiating effect in which dopamine and acetylcholine are released in the nucleus accumbens.

  4. Revisiting the effectiveness of methadone treatment on crime reductions in the 1990s.

    PubMed

    Rothbard, A; Alterman, A; Rutherford, M; Liu, F; Zelinski, S; McKay, J

    1999-06-01

    This study examines the relationship between methadone treatment and the criminal activity of 126 individuals participating in treatment during the early 1990s. The primary question addressed is to what extent is methadone maintenance treatment associated with reductions in crime? Although prior studies in the 1970s and early 1980s showed significant decreases in crime for individuals in treatment programs, criteria for remaining in this treatment modality have changed in recent years, particularly with the advent of acquired immune deficiency syndrome and the need to reduce intravenous drug use. A pre-post study design is employed spanning a 6-year time period of subject recruitment and follow-up (1987-1993). Uniform administrative records on arrests are used for the analyses. A multiple regression model is employed to explain the variance in the number of arrests 2 years following program admission, with prior criminal history, prior and current drug treatment, and current cocaine use employed as explanatory variables. Results indicate that treatment retention has only a slight, though significant, effect on reducing criminal activity during treatment. Two other factors that appear to increase arrest activity are the use of cocaine and prior criminal history. The fact that arrests did not decrease during a treatment period of 18 months on average requires more investigation in light of the increase in cocaine use in this population.

  5. [8 years experience with heroin-assited treatment in Switzerland--current results and future improvements].

    PubMed

    Gschwend, P; Eschmann, S; Güttinger, F; Hosek, M; Rehm, J; Uchtenhagen, A

    2003-06-01

    In 1994, Switzerland introduced experimental heroin assisted treatment for refractory opioid addicts as last line of treatment. An evaluation research was established examining effectiveness and cost-benefit of heroin-assisted treatment for the first project phase between 1994 and 1996. The present publication intends to provide an overview for the newer results of the evaluation. In summary, the positive outcomes found at first follow-ups continued to persist regarding somatic and mental improvements, social integration including reduction of criminal behaviour, and reduction of use of illicit drugs. In future, treatment of co-morbid mental disorders, integration into the labour market and persistent consumption of cocaine in some patients still need focussed attention. Different efforts to assure quality control and development hopefully will serve towards further optimisation of heroin-assisted treatment.

  6. Methadone-Induced Toxic Brain Damage

    PubMed Central

    Corré, Jérôme; Pillot, Jérôme; Hilbert, Gilles

    2013-01-01

    A 29-year-old man presented with comatose after methadone intoxication. Cerebral tomography only showed cortico-subcortical hypodense signal in the right cerebellar hemisphere. Brain MRI showed a rare imaging of FLAIR and DWI hyperintensities in the two cerebellar hemispheres as well as basal ganglia (globi pallidi), compatible with methadone overdose. To our knowledge this is the first reported case of both cerebellar and basal ganglia involvement in methadone overdose. PMID:23762729

  7. 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.

  8. Methadone Maintenance Therapy in Vietnam: An Overview and Scaling-Up Plan

    PubMed Central

    Nguyen, Tam T. M.; Nguyen, Long T.; Pham, Manh D.; Vu, Hoang H.; Mulvey, Kevin P.

    2012-01-01

    Vietnam is among the countries with the highest rate of HIV transmission through injecting drug users. HIV prevalence among injecting drug users is 20% and up to 50% in many provinces. An estimated number of drug users in the country by the end of 2011 were 171,000 in which the most common is heroin (85%). Detoxification at home, community, and in rehabilitation centers have been the main modalities for managing heroin addiction until Methadone Maintenance Treatment (MMT) was piloted in 2008. Recent reports have demonstrated positive treatment outcomes. Incidence of HIV was found remarkably low among patients on MMT. Treatment has significantly improved the quality of life as well as stability for society. The government has granted the Ministry of Health (MoH) to expand Methadone treatment to at least 30 provinces to provide treatment for more than 80,000 drug users by 2015. The Vietnam Administration for HIV/AIDS Control (VAAC) and MOH have outlined the role and responsibility of key departments at the central and local levels in implementing and maintaining MMT treatment. This paper will describe the achievements of the MMT pilot program and the scaling-up plan as well as strategies to ensure quality and sustainability and to overcome the challenges in the coming years. PMID:23227351

  9. Methadone induced lysis of mammalian cells.

    PubMed

    Will, P C; Noteboom, W D

    1978-08-01

    Methadone induced lysis of human erythrocytes and mouse leukemic cells was studied. The cells lyse without prior swelling that is a necessary step of colloid osmotic lysis. Methadone is accumulated by both cell types, and is widely distributed intracellurly in mouse leukemic cells. The maximum lytic rate is roughly proportional to the amount of methadone uptake and the Q10 for lysis is equal to the Q10 for methadone partitioning between octanol and water. It is concluded that the cells lyse as a result of a non-specific disruption of the plasma membrane.

  10. [Heroin abuse among Danish prisoners on remand. I. Prevalence related to form of administration].

    PubMed

    Andersen, H S; Sestoft, D M; Lillebaek, T; Gabrielsen, G

    1996-08-19

    Two groups of Danish prisoners on remand (in solitary confinement and not in solitary confinement) were examined by interview on reception (n = 133 & n = 95) in order to evaluate the prevalence and form of administration of opioid abuse/dependence. About 50% had abused opioids during their lifetime; one third were dependent at the time of reception. Twenty percent of opioid dependent prisoners administered opioids by smoking. More intravenous users were treated with methadone before and during imprisonment than those who were dependent on smoking opioids. Few were objectively suffering from withdrawal symptoms. The psycho-social impact of dependence on smoking heroin and intravenous heroin one month prior to imprisonment was at the same level and substantial as measured by the Global Assessment Scale.

  11. 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.

  12. 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

  13. Genetic signatures of heroin addiction.

    PubMed

    Chen, Shaw-Ji; Liao, Ding-Lieh; Shen, Tsu-Wang; Yang, Hsin-Chou; Chen, Kuang-Chi; Chen, Chia-Hsiang

    2016-08-01

    Heroin addiction is a complex psychiatric disorder with a chronic course and a high relapse rate, which results from the interaction between genetic and environmental factors. Heroin addiction has a substantial heritability in its etiology; hence, identification of individuals with a high genetic propensity to heroin addiction may help prevent the occurrence and relapse of heroin addiction and its complications. The study aimed to identify a small set of genetic signatures that may reliably predict the individuals with a high genetic propensity to heroin addiction. We first measured the transcript level of 13 genes (RASA1, PRKCB, PDK1, JUN, CEBPG, CD74, CEBPB, AUTS2, ENO2, IMPDH2, HAT1, MBD1, and RGS3) in lymphoblastoid cell lines in a sample of 124 male heroin addicts and 124 male control subjects using real-time quantitative PCR. Seven genes (PRKCB, PDK1, JUN, CEBPG, CEBPB, ENO2, and HAT1) showed significant differential expression between the 2 groups. Further analysis using 3 statistical methods including logistic regression analysis, support vector machine learning analysis, and a computer software BIASLESS revealed that a set of 4 genes (JUN, CEBPB, PRKCB, ENO2, or CEBPG) could predict the diagnosis of heroin addiction with the accuracy rate around 85% in our dataset. Our findings support the idea that it is possible to identify genetic signatures of heroin addiction using a small set of expressed genes. However, the study can only be considered as a proof-of-concept study. As the establishment of lymphoblastoid cell line is a laborious and lengthy process, it would be more practical in clinical settings to identify genetic signatures for heroin addiction directly from peripheral blood cells in the future study.

  14. Mind Over Matter: Cocaine

    MedlinePlus

    ... Over Matter Teaching Guide and Series / Cocaine Print Mind Over Matter: Cocaine Order Free Publication in: English ... how drugs affect the brain and nervous system. Mind Over Matter is produced by the National Institute ...

  15. Cocaine and Cardiovascular Events.

    ERIC Educational Resources Information Center

    Cantwell, John D.; Rose, Fred D.

    1986-01-01

    The case of a 21-year-old man who suffered a myocardial infarction after using cocaine and amphetamines is reported. A brief literature review provides evidence of cocaine's potential cardiovascular effects. (Author/MT)

  16. Self-Administration of cocaine-opioid combinations by rhesus monkeys: evaluation of the role of mu receptor efficacy using labor supply analysis.

    PubMed

    Rowlett, James K; Rodefer, Joshua S; Spealman, Roger D

    2005-03-01

    Cocaine and heroin often are abused by self-administering the drugs in combination as a "speedball". We evaluated the extent to which intrinsic efficacy at the mu-opioid receptor influences combined cocaine-opioid self-administration and used the behavioral economic model termed "labor supply" to quantitatively evaluate the reinforcing effects of cocaine-opioid combinations. Rhesus monkeys (n = 8) were trained under a progressive-ratio schedule of i.v. cocaine injection in which the response requirement increased during the experimental session and the initial response requirement was varied. Combination of cocaine with heroin enhanced self-administration compared with the drugs individually, with ineffective doses of both drugs maintaining self-administration when combined. These effects also were observed with the high-efficacy mu agonist alfentanil and low-efficacy agonist nalbuphine. Using the labor supply economic model, combinations of heroin, alfentanil, or nalbuphine with relatively low doses of cocaine were found to increase the number of injections per session ("income") and total responses per session ("labor"). Combination of a relatively high dose of cocaine with either heroin or alfentanil, but not nalbuphine, also resulted in only a small reduction in income concomitant with increased labor, suggesting that heroin and alfentanil made cocaine consumption more resistant to increasing response costs, or more "inelastic." Collectively, these findings suggest that speedball self-administration may occur even with relatively low levels of intrinsic efficacy at mu-opioid receptors and that an inelastic relationship between drug consumption and labor may contribute to the persistence of speedball abuse.

  17. Predicting subsequent relapse by drug-related cue-induced brain activation in heroin addiction: an event-related functional magnetic resonance imaging study.

    PubMed

    Li, Qiang; Li, Wei; Wang, Hanyue; Wang, Yarong; Zhang, Yi; Zhu, Jia; Zheng, Ying; Zhang, Dongsheng; Wang, Lina; Li, Yongbin; Yan, Xuejiao; Chang, Haifeng; Fan, Min; Li, Zhe; Tian, Jie; Gold, Mark S; Wang, Wei; Liu, Yijun

    2015-09-01

    Abnormal salience attribution is implicated in heroin addiction. Previously, combining functional magnetic resonance imaging (fMRI) and a drug cue-reactivity task, we demonstrated abnormal patterns of subjective response and brain reactivity in heroin-dependent individuals. However, whether the changes in cue-induced brain response were related to relapse was unknown. In a prospective study, we recruited 49 heroin-dependent patients under methadone maintenance treatment, a gold standard treatment (average daily dose 41.8 ± 16.0 mg), and 20 healthy subjects to perform the heroin cue-reactivity task during fMRI. The patients' subjective craving was evaluated. They participated in a follow-up assessment for 3 months, during which heroin use was assessed and relapse was confirmed by self-reported relapse or urine toxicology. Differences between relapsers and non-relapsers were analyzed with respect to the results from heroin-cue responses. Compared with healthy subjects, relapsers and non-relapsers commonly demonstrated significantly increased brain responses during the processing of heroin cues in the mesolimbic system, prefrontal regions and visuospatial-attention regions. However, compared with non-relapsers, relapsers demonstrated significantly greater cue-induced craving and the brain response mainly in the bilateral nucleus accumbens/subcallosal cortex and cerebellum. Although the cue-induced heroin craving was low in absolute measures, the change in craving positively correlated with the activation of the nucleus accumbens/subcallosal cortex among the patients. These findings suggest that in treatment-seeking heroin-dependent individuals, greater cue-induced craving and greater specific regional activations might be related to reward/craving and memory retrieval processes. These responses may predict relapse and represent important targets for the development of new treatment for heroin addiction.

  18. Pharmaceutical heroin for inhalation: thermal analysis and recovery experiments after volatilisation.

    PubMed

    Klous, Marjolein G; Bronner, Gaby M; Nuijen, Bastiaan; van Ree, Jan M; Beijnen, Jos H

    2005-10-04

    Pharmaceutical heroin for inhalation was developed for a clinical trial on co-prescription of heroin and methadone to chronic treatment-resistant heroin addicts. Diacetylmorphine base was selected as the active pharmaceutical ingredient for this product with caffeine anhydrate added as an excipient. Differential scanning calorimetry and thermogravimetric analysis showed that addition of caffeine resulted in a lower melting temperature and a higher volatilisation rate for the mixture than for diacetylmorphine base alone. Recovery experiments showed that 40.8+/-5.3% of diacetylmorphine base could be found in smoke condensate after volatilisation of diacetylmorphine-caffeine tablets. All of the caffeine from each tablet was recovered unchanged in the fumes, while 85.6% of the diacetylmorphine from each tablet was recovered, either unchanged in the fumes or as non-volatilised residue. Recovery was found to be reproducible and only small differences were found between the tablet types. The experimental set-up was found to efficiently collect the vapours resulting from heating the powder. Under the tested experimental conditions, no evidence was found that degradation products of diacetylmorphine or caffeine, other than 6-acetylmorphine (5.9%) had volatilised, even though a decomposed residue was present after heating diacetylmorphine-caffeine samples. Diacetylmorphine-caffeine was found to be a suitable basis for pharmaceutical heroin to be used by 'chasing the dragon'.

  19. Reduced methadone clearance during aromatase inhibition.

    PubMed

    Lu, Wenjie Jessie; Thong, Nancy; Flockhart, David A

    2012-08-01

    Methadone is increasingly used in pain management and is a cornerstone in the treatment of opiate withdrawal. It is subject to highly variable clearance among patients. The complete metabolic disposition of methadone is likely to involve a number of enzymes, including specifically CYP2B6. Previous studies in vitro suggest that metabolism by aromatase may also contribute. Single-dose methadone pharmacokinetics (2 mg, intravenous) were studied in 15 healthy postmenopausal women in the presence and absence of a potent aromatase inhibitor, letrozole. A sequential design was used, involving a control period followed by treatment with letrozole (2.5 mg/d, 11 days), in which each subject served as her own control. On average, letrozole treatment reduced methadone systemic clearance by 22% (P = 0.001), increased methadone AUC by 23% (P = 0.007), and increased elimination half-life by 21% (P = 0.042). The plasma parent-to-metabolite ratio also increased (P = 0.009), and there was a linear relationship (R2 = 0.74) between change in this plasma ratio and change in methadone AUC0-∞. In contrast, there was no such association with change in apparent urinary methadone clearance. Letrozole did not change methadone distribution half-life or its volume of distribution. Overall, these data demonstrate a significant decrease in methadone clearance during coadministration of letrozole, consistent with decreased metabolism brought about by aromatase inhibition. An involvement of aromatase in the disposition of methadone may help explain the difficulty in methadone dosing and suggests a broader role for this catalyst of endogenous steroid metabolism in xenobiotic drug disposition.

  20. 21 CFR 862.3620 - Methadone test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Methadone test system. 862.3620 Section 862.3620....3620 Methadone test system. (a) Identification. A methadone test system is a device intended to measure methadone, an addictive narcotic pain-relieving drug, in serum and urine. Measurements obtained by...

  1. 21 CFR 862.3620 - Methadone test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Methadone test system. 862.3620 Section 862.3620....3620 Methadone test system. (a) Identification. A methadone test system is a device intended to measure methadone, an addictive narcotic pain-relieving drug, in serum and urine. Measurements obtained by...

  2. 21 CFR 862.3620 - Methadone test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Methadone test system. 862.3620 Section 862.3620....3620 Methadone test system. (a) Identification. A methadone test system is a device intended to measure methadone, an addictive narcotic pain-relieving drug, in serum and urine. Measurements obtained by...

  3. 21 CFR 862.3620 - Methadone test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Methadone test system. 862.3620 Section 862.3620....3620 Methadone test system. (a) Identification. A methadone test system is a device intended to measure methadone, an addictive narcotic pain-relieving drug, in serum and urine. Measurements obtained by...

  4. 21 CFR 862.3620 - Methadone test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Methadone test system. 862.3620 Section 862.3620....3620 Methadone test system. (a) Identification. A methadone test system is a device intended to measure methadone, an addictive narcotic pain-relieving drug, in serum and urine. Measurements obtained by...

  5. The Dreams of Heroin Addicts

    ERIC Educational Resources Information Center

    Looney, Maryanne

    1972-01-01

    Few heroin addicts get high'' in their dreams. An exploration of the reasons for this failure provides some clues to the conflicts and other problems that retard an addict's progress in therapy. (Author)

  6. 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…

  7. Methadone Medical Maintenance: An Early 21st-Century Perspective.

    PubMed

    Novick, David M; Salsitz, Edwin A; Joseph, Herman; Kreek, Mary Jeanne

    2015-01-01

    Methadone medical maintenance is the treatment of stable methadone-maintained patients in primary care physicians' offices under an exemption from federal methadone regulations. Reports from seven such programs in six states show high retention and low frequencies of illicit drug use. Patients and physicians indicate high levels of satisfaction. Although methadone maintenance has a long history of safety and efficacy, most methadone medical maintenance programs are no longer operating or accepting new patients. Federal regulations for standard methadone clinics allow some features of methadone medical maintenance, and advocacy for state approval of these changes is strongly recommended.

  8. Concentrations of delta 9-tetrahydrocannabinol, cocaine and 6-monoacetylmorphine in hair of drug abusers.

    PubMed

    Kauert, G; Röhrich, J

    1996-01-01

    Hair samples taken from 850 individuals with presumed drug abuse were tested simultaneously for delta 9-tetrahydrocannabinol (THC), cocaine, heroin, the primary heroin metabolite 6-monoacetylmorphine (6-MAM) and morphine. The drugs were extracted with methanol under sonication. Compared to other extraction procedures this solvent extraction technique provides high extraction yields and less experimental effort. The analyses were carried out using gas chromatography-mass spectrometry (GCMS) in selected ion monitoring (SIM) mode. This procedure allows the simultaneous detection of amphetamine, methylenedioxyamphetamine (MDA), methylenedioxymethamphetamine (MDMA) and methylenedioxylamphetamine (MDE). THC was found in 104 (12.2%), cocaine in 230 (27%) and 6-MAM in 141 (16.6%) samples. In addition to 6-MAM, morphine was detected in 87 (10.2%) and heroin in 38 samples (4.5%). The concentrations found were in a range 0.009-16.7 ng/mg for THC, 0.037-129.68 ng/mg for cocaine, 0.028-79.82 ng/mg for 6-MAM, 0.045-53.14 ng/mg for heroin and 0.011-7.800 ng/mg for morphine. The statistical distribution of the drug concentrations compared with the self-reported consumption behaviour of the users may possibly lead to a better understanding of the relationship between drug dosage and corresponding concentrations in hair.

  9. Involvement of exon 11-associated variants of the mu opioid receptor MOR-1 in heroin, but not morphine, actions.

    PubMed

    Pan, Ying-Xian; Xu, Jin; Xu, Mingming; Rossi, Grace C; Matulonis, Joshua E; Pasternak, Gavril W

    2009-03-24

    Heroin remains a major drug of abuse and is preferred by addicts over morphine. Like morphine, heroin has high affinity and selectivity for mu-receptors, but its residual analgesia in exon 1 MOR-1 knockout mice that do not respond to morphine suggests a different mechanism of action. MOR-1 splice variants lacking exon 1 have been observed in mice, humans, and rats, raising the possibility that they might be responsible for the residual heroin and morphine-6beta-glucuronide (M6G) analgesia in the exon 1 knockout mice. To test this possibility, we disrupted exon 11 of MOR-1, which eliminates all of the variants that do not contain exon 1. Morphine and methadone analgesia in the exon 11 knockout mouse was normal, but the analgesic actions of heroin, M6G, and fentanyl were markedly diminished in the radiant heat tail-flick and hot-plate assays. Similarly, the ability of M6G to inhibit gastrointestinal transit was greatly diminished in these exon 11 knockout mice, whereas the ability of morphine was unchanged. These findings identify receptors selectively involved with heroin and M6G actions and confirm the relevance of the exon 11-associated variants and raise important issues regarding the importance of atypical truncated G-protein-coupled receptors.

  10. 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

  11. Heroin-assisted treatment as a response to the public health problem of opiate dependence.

    PubMed

    Fischer, Benedikt; Rehm, Jürgen; Kirst, Maritt; Casas, Miguel; Hall, Wayne; Krausz, Michael; Metrebian, Nicky; Reggers, Jean; Uchtenhagen, Ambros; van den Brink, Wim; van Ree, Jan M

    2002-09-01

    Injection drug use (involving the injection of illicit opiates) poses serious public health problems in many countries. Research has indicated that injection drug users are at higher risk for morbidity in the form of HIV/AIDS and Hepatitis B and C, and drug-related mortality, as well as increased criminal activity. Methadone maintenance treatment is the most prominent form of pharmacotherapy treatment for illicit opiate dependence in several countries, and its application varies internationally with respect to treatment regulations and delivery modes. In order to effectively treat those patients who have previously been resistant to methadone maintenance treatment, several countries have been studying and/or considering heroin-assisted treatment as a complementary form of opiate pharmacotherapy treatment. This paper provides an overview of the prevalence of injection drug use and the opiate dependence problem internationally, the current opiate dependence treatment landscape in several countries, and the status of ongoing or planned heroin-assisted treatment trials in Australia, Canada and certain European countries.

  12. Heroin Epidemic Expands Its Grip on America

    MedlinePlus

    ... gov/news/fullstory_164350.html Heroin Epidemic Expands Its Grip on America Use of the narcotic grew ... people transition from painkillers to heroin, Martins explained. It is also related to availability, lower cost and ...

  13. Tips for Teens: The Truth about Heroin

    MedlinePlus

    ... glamorization of “heroin chic” in films, fashion, and music, heroin use can have tragic consequences that extend far beyond its users. Fetal effects, HIV/AIDS, tuberculosis, violence, and crime are all ...

  14. Opioids: The Prescription Drug & Heroin Overdose Epidemic

    MedlinePlus

    ... Resources Law Enforcement Resources Opioids: The Prescription Drug & Heroin Overdose Epidemic Opioids are natural or synthetic chemicals ... in your brain or body. Common opioids include heroin and prescription drugs such as oxycodone, hydrocodone, and ...

  15. [X-ray diffraction spectrum of heroin].

    PubMed

    Hu, X; Kan, J; Yuan, B

    1999-06-01

    In this paper, practical measured X-ray diffraction spectra of heroin and opium are given and the parameters of each diffraction peak of the heroin are listed. The heroin belongs to orthorhombic crystal system; the basic vectors of the primitive cell are: a = 8.003, b = 14.373, c = 16.092 x 10(-10) m. As compared with the standard spectra of pure heroin and sucrose, the main doped additive checked by us, is sugar affirmatively.

  16. 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.

  17. Evaluation of ongoing oxycodone abuse among methadone-maintained patients.

    PubMed

    Dunn, Kelly E; Sigmon, Stacey C; McGee, Mark R; Heil, Sarah H; Higgins, Stephen T

    2008-12-01

    Prevalence of prescription opioid abuse has increased dramatically in recent years in the United States generally, and a similar pattern of increasing prescription opioid use has also been noted among patients seeking treatment for opioid dependence. This study presents results from an internal quality assurance project conducted by an outpatient methadone maintenance (MM) treatment clinic which sought to examine the extent of ongoing oxycodone abuse among patients that might be going undetected with current urinalysis-testing methods. One hundred five MM patients provided 437 urine samples over a 6-week period. Samples were analyzed using the clinic's usual enzyme multiplied immunoassay test (EMIT) opiate assay (300 ng/ml opiate cutpoint) and a supplemental oxycodone test strip (100 ng/ml oxycodone cutpoint). The EMIT assay identified only 6% (20/437) of samples as positive for oxycodone, whereas the oxycodone test strip indicated that 19% (83/437) tested positive for recent oxycodone use. Inspection of patient characteristics revealed that oxycodone users were more likely to report a prescription opioid as their primary drug at intake, be in MM treatment for a significantly shorter duration, and provide significantly more opioid- and cocaine-positive urine samples. Overall, these data illustrate the potential importance of monitoring for ongoing oxycodone use in MM clinics. Although future efforts should examine this question using more rigorous experimental methods, findings from this initial project have implications for clinical issues such as evaluating patient stability in treatment, making medication-dosing decisions, and determining patient eligibility for methadone take-home privileges.

  18. 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

  19. Methadone's effect on nAChRs--a link between methadone use and smoking?

    PubMed

    Talka, Reeta; Tuominen, Raimo K; Salminen, Outi

    2015-10-15

    Methadone is a long-acting opioid agonist that is frequently prescribed as a treatment for opioid addiction. Almost all methadone maintenance patients are smokers, and there is a correlation between smoking habit and use of methadone. Methadone administration increases tobacco smoking, and heavy smokers use higher doses of methadone. Nevertheless, methadone maintenance patients are willing to quit smoking although their quit rates are low. Studies on nicotine-methadone interactions provide an example of the bedside-to-bench approach, i.e., observations in clinical settings have been studied experimentally in vivo and in vitro. In vivo studies have revealed the interplay between nicotine and the endogenous opioid system. At the receptor level, methadone has been shown to be an agonist of human α7 nAChRs and a non-competitive antagonist of human α4β2 and α3* nAChRs. These drugs do not have significant interactions at the level of drug metabolism, and thus the interaction is most likely pharmacodynamic. The net effect of the interaction may depend on individual characteristics because pharmacogenetic factors influence the disposition of both methadone and nicotine.

  20. 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)

  1. Methadone and buprenorphine toxicity in children.

    PubMed

    Boyer, Edward W; McCance-Katz, Elinore F; Marcus, Steven

    2010-01-01

    Recent years have seen very large increases in the prescribing of methadone and buprenorphine formulations for treatment of opioid addiction as well as the increasing utilization of methadone for the treatment of chronic pain. Coincident with the rise in the prescribing of these drugs has been a substantial increase in pediatric opioid toxicities and adverse events. This review will address the current state of methadone- and buprenorphine-related adverse events in children in the United States. We will also discuss treatment of opioid toxicity in pediatric populations and make recommendations aimed at reducing these occurrences.

  2. Cocaine and the heart

    PubMed Central

    Egred, M; Davis, G

    2005-01-01

    Cocaine is the second commonest illicit drug used and the most frequent cause of drug related deaths. Its use is associated with both acute and chronic complications that may involve any system, the most common being the cardiovascular system. Cocaine misuse has a major effect in young adult drug users with resulting loss of productivity and undue morbidity with cocaine related cardiac and cerebrovascular effects. Many cocaine users have little or no idea of the risks associated with its use. Patients, health care professionals, and the public should be educated about the dangers and the considerable risks of cocaine use. This review concentrates on the cardiovascular effects of cocaine and their management. PMID:16143686

  3. Cocaine-Induced Vasculitis

    PubMed Central

    Berman, Mark; Paran, Daphna; Elkayam, Ori

    2016-01-01

    The use of cocaine continues to grow worldwide. One of the possible side-effects of cocaine is vasculitis. Two distinct vasculitic syndromes have been described due to cocaine. One is cocaine-induced midline destructive lesion, secondary to a direct vasoconstrictor effect of cocaine, inducing ischemic necrosis of the septal cartilage and perforation of the nasal septum, mimicking findings of granulomatosis with polyangiitis in the upper airways. The other is ANCA-associated vasculitis, attributed to the levamisole component that contaminates about 70% of the cocaine. This type of vasculitis may be myeloperoxidase (MPO) and proteinase 3 (PR3) positive, and its main manifestations are typical cutaneous findings, arthralgia, otolaryngologic involvement, and agranulocytosis. A high degree of suspicion and awareness is needed in order properly to diagnose and treat these patients. PMID:27824551

  4. Pharmacokinetic correlates of the effects of a heroin vaccine on heroin self-administration in rats.

    PubMed

    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.

  5. 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

  6. Forensic Investigation of Methadone Concentrations in Deceased Breastfed Infants.

    PubMed

    Madadi, Parvaz; Kelly, Lauren E; Ross, Colin J; Kepron, Charis; Edwards, James N; Koren, Gideon

    2016-03-01

    There is a paucity of data to aid in assessing whether postmortem methadone findings in breastfed infants are clinically and/or toxicologically significant. Two cases are reported in which methadone was detected in deceased neonates whose mothers were enrolled in methadone maintenance programs and were breastfeeding. In addition to a complete autopsy and toxicological testing for alcohol, prescription medications, and drugs of abuse, pharmacogenetic analysis was performed for variants in genes related to methadone metabolism and response. In both cases, the postmortem methadone concentration measured in neonatal heart blood was higher than the maximum serum methadone concentration reported in living breastfed infants whose mothers were receiving methadone. However, additional analysis of antemortem blood indicated postmortem redistribution of methadone. Pharmacogenetic results were suggestive of a potential predisposition to methadone toxicity based on studies in adults; the significance of these findings in breastfed neonates requires further research. The medical cause of death was unascertained in both cases.

  7. Economical synthesis of 13C-labeled opiates, cocaine derivatives and selected urinary metabolites by derivatization of the natural products.

    PubMed

    Karlsen, Morten; Liu, Huiling; Johansen, Jon Eigill; Hoff, Bård Helge

    2015-03-25

    The illegal use of opiates and cocaine is a challenge world-wide, but some derivatives are also valuable pharmaceuticals. Reference samples of the active ingredients and their metabolites are needed both for controlling administration in the clinic and to detect drugs of abuse. Especially, (13)C-labeled compounds are useful for identification and quantification purposes by mass spectroscopic techniques, potentially increasing accuracy by minimizing ion alteration/suppression effects. Thus, the synthesis of [acetyl-(13)C4]heroin, [acetyl-(13)C4-methyl-(13)C]heroin, [acetyl-(13)C2-methyl-(13)C]6-acetylmorphine, [N-methyl-(13)C-O-metyl-(13)C]codeine and phenyl-(13)C6-labeled derivatives of cocaine, benzoylecgonine, norcocaine and cocaethylene was undertaken to provide such reference materials. The synthetic work has focused on identifying (13)C atom-efficient routes towards these derivatives. Therefore, the (13)C-labeled opiates and cocaine derivatives were made from the corresponding natural products.

  8. Medical consequences of cocaine.

    PubMed Central

    Gray, J. D.

    1993-01-01

    Cocaine use among middle-class North Americans increased dramatically during the 1980s. Medical complications involve almost every organ system and are produced by intense vasoconstriction. Managing cocaine-induced disease requires careful identification and the use of alpha-adrenergic blocking agents, in addition to standard therapy and referral to specialists to manage cocaine withdrawal. Images p1976-a p1980-a PMID:8106032

  9. Cocaine withdrawal in Planaria.

    PubMed

    Raffa, R B; Valdez, J M

    2001-10-26

    Cocaine-exposed planarians displayed abstinence-induced withdrawal behavior when placed into cocaine-free, but not cocaine-containing, water. The effect, manifested and quantified using a new spontaneous locomotor velocity metric, was dose-dependently related to cocaine exposure (8x10(-9) to 8x10(-5) M). Ultraviolet light (254 nm=7.83x10(-19) J), which was previously shown to interfere with drug-receptor interactions in Planaria, enhanced the abstinence-induced decreased locomotor velocity.

  10. [The message from heroin overdoses].

    PubMed

    Pap, Ágota; Hegedűs, Katalin

    2015-03-01

    Drug use can be defined as a kind of self destruction, and it is directly linked to attitudes toward death and suicide occurring in a significant number of users of different narcotics. The aim of the authors was to look for the background of this relationship between drug and death and examine the origin, development, and motives behind heroin overdose based on an analysis of previous studies. It seems clear that pure heroin overdose increased gradually over the years. The fear of the police is the inhibitory factor of the overdose prevention and notification of emergency health care service. Signs of suicide could be the own home as the chosen location for heroin overdose and the presence of partners ("moment of death companion"). Interventions should include simple techniques such as first aid, naloxone administration, resuscitation, prevention of relapse of prisoners and social network extension involving maintenance programs.

  11. 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

  12. Lifetime history of heroin use is associated with greater drug severity among prescription opioid abusers

    PubMed Central

    Meyer, Andrew C.; Patrick, Mollie E.; Sigmon, Stacey C.

    2014-01-01

    Background While research suggests primary prescription opioid (PO) abusers may exhibit less severe demographic and drug use characteristics than primary heroin abusers, less is known about whether a lifetime history of heroin use confers greater severity among PO abusers. Objective In this secondary analysis, we examined demographic and drug use characteristics as a function of lifetime heroin use among 89 PO-dependent adults screened for a trial evaluating the relative efficacy of buprenorphine taper durations. Exploratory analyses also examined contribution of lifetime heroin use to treatment response among a subset of participants who received a uniform set of study procedures. Methods Baseline characteristics were compared between participants reporting lifetime heroin use ≥5 (H+; n=41) vs. <5 (H−; n=48) times. Treatment response (i.e., illicit opioid abstinence and treatment retention at end of study) was examined in the subset of H+ and H− participants randomized to receive the 4-week taper condition (N=22). Results H+ participants were significantly older and more likely to be male. They reported longer durations of illicit opioid use, greater alcohol-related problems, more past-month cocaine use, greater lifetime IV drug use, and greater lifetime use of cigarettes, amphetamines and hallucinogens. H+ participants also had lower scores on the Positive Symptom Distress and Depression subscales of the Brief Symptom Inventory. Finally, there was a trend toward poorer treatment outcomes among H+ participants. Conclusion A lifetime history of heroin use may be associated with elevated drug severity and unique treatment needs among treatment-seeking PO abusers. PMID:25481453

  13. [Breast feeding during methadon- and buprenorphin therapy].

    PubMed

    Müller, M J; Lange, M; Paul, T; Seeliger, S

    2011-12-01

    The number of opiate addicted patients treated with opioid replacement therapy is continuously increasing. In Germany, 57.7% of these patients are treated with methadone and 18.6% with buprenorphine. This maintenance therapy provides several advantages while addicted pregnant women and their foetus have a high benefit from appropriate replacement therapy. However, the recommendations concerning breast feeding during an opioid replacement therapy are discussed controversially, because methadone as well as buprenorphine accumulate in breast milk. This accumulation might cause damages to the newborn's health; so, child benefits of breast feeding have to be balanced with possible health risks.This review provides an overview of a selective literature search based on the PubMed-database and german consensus recommendations. Used search terms included: (methadone*) AND (breastfeeding OR lactation), (methadone*) AND (human milk), (buprenorphine*) AND (breastfeeding OR lactation) and (buprenorphine*) AND (human milk).According to the available literature, addicted women, substinated with methadone or buprenorphine are allowed to breast feed their newborns. The advantages of breast feeding prevail the risks of an infant opiate intoxication caused by methadone or buprenorphine.

  14. Manifest and Latent Components in Methadone Maintenance: The Methadone Maintenance Game

    ERIC Educational Resources Information Center

    King, Charles H.

    1975-01-01

    This paper discusses various difficulties which arise when the staff of a methadone maintenance clinic must come to grips with the manifest and latent issues in service delivery. A solution is suggested which involves severing the tie between methadone and the behaviors which are reinforced by its use. (Author)

  15. Analysis of diacetylmorphine, caffeine, and degradation products after volatilization of pharmaceutical heroin for inhalation.

    PubMed

    Klous, Marjolein G; Lee, WeiChing; Hillebrand, Michel J X; van den Brink, Wim; van Ree, Jan M; Beijnen, Jos H

    2006-01-01

    Pharmaceutical smokable heroin was developed for a clinical trial on medical co-prescription of heroin and methadone. This product, consisting of 75% w/w diacetylmorphine base and 25% w/w caffeine anhydrate, was intended for use via "chasing the dragon", that is, inhalation after volatilization. This procedure involves heating the powder mixture, which may lead to formation of degradation products that could subsequently be inhaled. We developed a method that used a high-performance liquid chromatography system that was compatible with photodiode-array detection and mass spectrometric detection to separate diacetylmorphine- and caffeine-related compounds in a wide polarity range for analysis of the vapor. This method was used to analyze the contents of the plastic drinking straws that were used by patients to inhale the vapors from pharmaceutical heroin used via chasing the dragon, which were considered to be representative of the vapors the patients inhaled. They contained primarily unchanged diacetylmorphine, its main metabolite 6-acetylmorphine, caffeine, and some morphine. Several unidentified peaks were observed in the straw chromatograms. Chemical structures were proposed for nine degradation products: morphine derivatives with different substitution patterns of the C(3), C(6), and/or N(17) positions, which comprised 0.4-9.7% of the straw sample residue weight. Activity and toxicity of most of these compounds are unknown and require further investigation.

  16. Cocaine (Coke, Crack) Facts

    MedlinePlus

    ... Families? Why Is It So Hard to Quit Drugs? Effects of Drugs Drug Use Hurts Other People Drug Use Hurts ... This Section Signs of Cocaine Use and Addiction Effects of Cocaine on Brains and Bodies Previous Index Next ... About the National Institute on Drug Abuse (NIDA) | About This Website Tools and Resources | ...

  17. 21 CFR 862.3250 - Cocaine and cocaine metabolite test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Cocaine and cocaine metabolite test system. 862... Test Systems § 862.3250 Cocaine and cocaine metabolite test system. (a) Identification. A cocaine and cocaine metabolite test system is a device intended to measure cocaine and a cocaine...

  18. 21 CFR 862.3250 - Cocaine and cocaine metabolite test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Cocaine and cocaine metabolite test system. 862... Test Systems § 862.3250 Cocaine and cocaine metabolite test system. (a) Identification. A cocaine and cocaine metabolite test system is a device intended to measure cocaine and a cocaine...

  19. 21 CFR 862.3250 - Cocaine and cocaine metabolite test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Cocaine and cocaine metabolite test system. 862... Test Systems § 862.3250 Cocaine and cocaine metabolite test system. (a) Identification. A cocaine and cocaine metabolite test system is a device intended to measure cocaine and a cocaine...

  20. 21 CFR 862.3250 - Cocaine and cocaine metabolite test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Cocaine and cocaine metabolite test system. 862... Test Systems § 862.3250 Cocaine and cocaine metabolite test system. (a) Identification. A cocaine and cocaine metabolite test system is a device intended to measure cocaine and a cocaine...

  1. 21 CFR 862.3250 - Cocaine and cocaine metabolite test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cocaine and cocaine metabolite test system. 862... Test Systems § 862.3250 Cocaine and cocaine metabolite test system. (a) Identification. A cocaine and cocaine metabolite test system is a device intended to measure cocaine and a cocaine...

  2. Lay theories of heroin addiction.

    PubMed

    Furnham, A; Thomson, L

    1996-07-01

    This study examined the structure and determinants of lay people's implicit theories of heroin addiction. A questionnaire was derived from interviews with lay people about their beliefs and theories of heroin addiction and academic literature on the subject. One hundred and forty-four subjects completed the questionnaire, in which they rated 105 statements about the causes, correlates and cures of heroin addiction. The three parts of the questionnaire were individually factor analyzed and a clear, interpretable factor structure emerged for each. The factors seemed similar to explicit academic theories, but the exception was beliefs about cure, which did not show overall support for the most clinically used models. When the three factor analyses were combined into a single 'higher-order' factor analysis four factors emerged, labelled moralistic, psychosocial, sociocultural and drug treatment, which reflect more or less coherent views on the nature of heroin addiction. Subjects' political beliefs was the greatest (demographic and attitudinal) determinant of lay beliefs in these factors, with experience of addiction, addicts, drugs and age also highly correlated. Vote was the main determinant and best predictor of the four 'higher-order' structured lay theories: right-wing voters emphasizing moralistic and individualistic theory and left-wing voters supporting the psychological and societal ideas. Implications for policy and interventions to addicts of these lay theories are considered.

  3. Rapid simultaneous determination of ephedrines, amphetamines, cocaine, cocaine metabolites, and opiates in human urine by GC-MS.

    PubMed

    Saito, Takeshi; Mase, Hiroyasu; Takeichi, Sanae; Inokuchi, Sadaki

    2007-01-04

    This paper presents a simple and sensitive chromatographic procedure for the simultaneous determination and quantification of ephedrines, amphetamines, cocaine, cocaine metabolites, and opiates in human urine by gas chromatography-mass spectrometry. This method involves enzyme hydrolysis in the presence of a deuterated internal standard, liquid-liquid extraction, and derivatization with pentafluoropropionic anhydride and pentafluoropropanol. The recovery of each compound averaged at 65.8% or more. The limits of detection determined for each compound by using a 2-mL sample volume ranged from 5 to 50 ng/mL. The calibration curves were linear to 100 ng/mL for all compounds when determined using methamphetamine-d4 and MDMA-d5 as internal standards. This method was successfully applied for the analysis of urine samples suspected to contain intoxicants such as methamphetamine and heroin.

  4. [Cocaine - Characteristics and addiction].

    PubMed

    Girczys-Połedniok, Katarzyna; Pudlo, Robert; Jarząb, Magdalena; Szymlak, Agnieszka

    Cocaine use leads to health, social and legal problems. The aim of this paper is to discuss cocaine action, addicts characteristics, use patterns and consequences, as well as addiction treatment methods. A literature review was based on the Medline, PubMed, Polish Medical Bibliography databases and the Silesian Library resources. The Police and Central Statistical Office statistics, as well as the World Health Organization, the European Monitoring Centre for Drugs and Drug Addiction and the National Office for Combating Drug Addiction reports were used. Cocaine leads to mood improvement, appetite decrease, physical and intellectual activity enhancement, euphoria, inflated self-esteem, social networking ease and increased sexual desire. Cocaine hydrochloride is mainly used intranasaly, but also as intravenous and subcutaneous injections. Cocaine use and first addiction treatment fall in later age compared to other psychoactive substances. There is a high men to women ratio among addicts. There is a relationship between cocaine addiction, the presence of other disorders and genetic predisposition to addiction development. Polish reports indicate higher popularity of cocaine among people with a high economic and social status. Although Poland is a country with the low percentage of cocaine use, its popularity is growing. The consequences of cocaine use concern somatic and mental health problems, socioeconomic and legal conditions. The drug plays a role in crimes and traffic accidents. Because of the risks associated with cocaine use, it has been listed in a register of drugs attached to the Act on Counteracting Drug Addiction. Addiction treatment includes psychological, pharmacological and harm reduction strategies. Med Pr 2016;67(4):537-544.

  5. 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

  6. The MTHFR C677T Variant is Associated with Responsiveness to Disulfiram Treatment for Cocaine Dependency

    PubMed Central

    Spellicy, Catherine J.; Kosten, Thomas R.; Hamon, Sara C.; Harding, Mark J.; Nielsen, David A.

    2013-01-01

    Objective: Disulfiram is a one of the few pharmacotherapies for cocaine addiction that shows promise. Since disulfiram and cocaine both affect levels of global methylation we hypothesized the MTHFR gene, whose product is involved in supplying methyl groups for DNA and protein methylation, may be associated with responsiveness to disulfiram in cocaine-dependent individuals. Methods: Sixty-seven cocaine-dependent patients were stabilized on methadone for 2 weeks and then randomized into disulfiram (250 mg/day, N = 32) and placebo groups (N = 35) for 10 weeks. Patients were genotyped for the MTHFR (rs1801133, also known as C677T) polymorphism and the data was evaluated for association with cocaine-free urines in the disulfiram or placebo groups. Data from patients that completed all 10 weeks of the study (N = 56) were analyzed using repeated measures analysis of variance (ANOVA), corrected for population structure. Results: The CT or TT MTHFR genotype group (N = 32) dropped from 73 to 52% cocaine-positive urines on disulfiram (p = 0.0001), while the placebo group showed no treatment effect. The CC MTHFR genotype group (N = 24) showed a smaller, but still significant, reduction in cocaine-positive urines on disulfiram compared to placebo; 81–69% (p = 0.007). Conclusion: This study indicates that a patient’s MTHFR genotype may be used to identify individuals who might show improved response to disulfiram treatment for cocaine dependence. Clinical Trial: Pharmacogenetics of Disulfiram for Cocaine, clinicaltrials.gov/ct2/show/NCT00149630, NIDA-18197-2, NCT00149630. PMID:23335901

  7. Cocaine and the nervous system.

    PubMed

    Prakash, A; Das, G

    1993-12-01

    Cocaine abuse today has reached greater heights than it did during the first cocaine epidemic in the late nineteenth century. It is estimated that one out of every four Americans has used cocaine and some six million people in the US use it regularly. Although cocaine affects all systems in the body, the central nervous system (CNS) is the primary target. Cocaine blocks the reuptake of neurotransmitters in the neuronal synapses. Almost all CNS effects of cocaine can be attributed to this mechanism. Euphoria, pharmacological pleasure and intense cocaine craving share basis in this system. The effects of cocaine on other organ systems, in addition to its effects on the CNS, account for the majority of the complications associated with cocaine abuse. In this paper, the CNS effects following cocaine administration and their treatment are discussed.

  8. 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.

  9. Methadone

    MedlinePlus

    ... were addicted to opiate drugs by producing similar effects and preventing withdrawal symptoms in people who have ... your medications or monitor you carefully for side effects.tell your doctor what herbal products you are ...

  10. Intradialytic clearance of opioids: methadone versus hydromorphone.

    PubMed

    Perlman, Ryan; Giladi, Hili; Brecht, Krista; Ware, Mark A; Hebert, Terence E; Joseph, Lawrence; Shir, Yoram

    2013-12-01

    Opioids are commonly prescribed to patients with chronic pain associated with end-stage renal disease requiring hemodialysis. The stability of opioid analgesia during dialysis may vary among different opioids. No studies to date have corroborated this clinical observation by directly comparing plasma concentrations of different opioids during dialysis. We compared changes in peridialysis plasma concentrations of 2 pharmacokinetically distinct opioids, methadone and hydromorphone (HM). Fourteen dialysis patients with chronic pain received either methadone or HM for at least 2 weeks before beginning the study. Blood samples were obtained immediately before, during, and after hemodialysis in 2 separate dialysis sessions, 1 week apart, and were analyzed for opioid concentrations. Methadone plasma concentrations were more stable during hemodialysis compared to HM: the mean percent change of methadone plasma levels was 14.9% ± 8.2% (± SD) compared with 55.1% ± 8.1% in the HM treatment group, a difference of 40.2% (95% confidence interval 17.14 to 63.14). The mean plasma clearance of methadone was 19.9 ± 8.5 mL/min (± SD) compared with 105.7 ± 8.3 mL/min for HM, a difference of 85.7 mL/min (95% confidence interval 61.9 to 109.1). There were no differences between the 2 opioid groups in pain scores, side effect profile, and quality of life. Methadone therapy was not associated with an increased rate of adverse events. If confirmed by larger clinical studies, methadone could be considered as one of the opioids of choice in dialysis patients.

  11. Work Adjustment of the Methadone-Maintained Corporate Employee

    ERIC Educational Resources Information Center

    Yankowitz, Robert; Randell, Joan

    1977-01-01

    The work adjustment of 26 methadone-maintained corporate employees was evaluated. Results indicated: (a) relative to their nonmethadone-maintained coworkers, the methadone-maintained employees had comparable job performance and superior punctuality and attendance; and (b) the methadone-maintained skilled laborers were satisfied with their…

  12. Australian heroin seizures and the causes of the 2001 heroin shortage.

    PubMed

    Jiggens, John

    2008-08-01

    This paper uses Australian heroin seizure data, along with estimates of the size of the Australian heroin market to evaluate the impact of drug law enforcement on the 2001 Australian heroin shortage from the percentage of the market seized. It also critically examines international heroin production trends and published reports on the causes of the Australian heroin shortage. Its conclusion is that previous studies may have overstated the success of drug law enforcement and that the most likely explanation for Australia's 2001 heroin shortage was a significant decline in heroin production world-wide, due to a general move away from heroin production in the countries of Southeast Asia and the prohibition on opium growing by the Taliban regime in Afghanistan.

  13. 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

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

    PubMed

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

    2014-02-01

    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.

  15. Mortality risk factors and excess mortality in a cohort of cocaine users admitted to drug treatment in Spain.

    PubMed

    de la Fuente, Luis; Molist, Gemma; Espelt, Albert; Barrio, Gregorio; Guitart, Anna; Bravo, Maria J; Brugal, M Teresa

    2014-02-01

    We assessed mortality risk factors and excess mortality compared to the general population in two Spanish sub-cohorts of 8,825 cocaine and heroin users (CHUs) and 11,905 only cocaine users (OCUs) aged 15-49 admitted to drug treatment. Heroin use (among all cocaine users), no-regular employment and drug injection (among CHUs and OCUs), daily cocaine use and previous drug treatment (among CUs), and death before 2005 and >10 years of heroin use (among CHUs) were clearly associated with higher mortality in Cox regression. Excess mortality was assessed by the directly standardized mortality rate ratio, which was higher in CHUs (14.3; 95% CI: 12.6-16.2) than CUs (5.1; 95% CI: 4.3-6.0) and in women than men, especially among OCUs (8.6; 95% CI: 7.5-10.0 vs. 3.5; 95% CI: 3.3-3.8); it decreased with age among CHUs, but did not decrease overall during 1997-2008. OCUs excess mortality was considerable and showed no signs of decline, suggesting the need for improved treatment and prevention interventions.

  16. Investigation of the interactions between methadone and elvitegravir-cobicistat in subjects receiving chronic methadone maintenance.

    PubMed

    Bruce, R Douglas; Winkle, P; Custodio, J M; Wei, X; Rhee, M S; Kearney, B P; Ramanathan, S; Friedland, Gerald H

    2013-12-01

    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.

  17. [Rapid analysis of added ingredients in heroin].

    PubMed

    Wang, Ji-fen; Yu, Jing; Guo, Xin; Sun, Xing-long; Wang, Ding-fang

    2011-07-01

    The method of rapid analysis of added ingredients in heroin was studied in the present paper. Adding sucrose, fructose, glucose, starch, caffeine and phenacetin to heroin with a certain percentage, the changes in the infrared spectrum with the concentration of heroin increasing and the detection limit of the additives were determined. Whether or not heroin can be detected in the sample with high concentration of added ingredients was studied using Raman spectroscopy. Similarly, in high purity of heroin, whether or not Raman spectroscopy can detect the added ingredients was tested. Through systematic experiments, the results showed that: using infrared spectroscopy and Raman spectroscopy to test the added ingredients of heroin is a rapid and effective method. Each has both advantages and disadvantages. We should select the appropriate method according to the actual cases.

  18. [Fatal methadone poisoning of a child].

    PubMed

    Klupp, N; Risser, D; Stichenwirth, M; Hönigschnabl, S; Stimpfl, T; Bauer, G

    2000-04-21

    The substance methadone is used for substitution therapy since the 1960s in the U.S. Mainly because of the endemic spread of HIV-1 infections among intravenous drug abusers methadone was made legally available through medical prescription in Austria in 1987. Legal authorities today also allow the patient to take home the necessary daily consumption for weekends or public holidays. The drug is distributed as a watery solution in tiny bottles, which are fitted with an ordinary screw cap. This kind of distribution may, however, have fatal consequences. This is demonstrated in the following case of accidental poisoning of an infant: A two-year-old girl whose parents were both participating in the substitution scheme was found dead in her bed in Vienna in 1997. Forensic autopsy revealed a methadone concentration in the liver tissue of 640 ng/g. The criminal investigation determined that the girl had opened a bottle of methadone solution and subsequently had taken the drug. Considering the circumstances of this accident, from the medical point of view safety devices for the screw caps of the methadone bottles should be required by law, in order to avoid future accidental poisoning.

  19. 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

  20. 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

  1. Genetic polymorphisms in the opioid receptor mu1 gene are associated with changes in libido and insomnia in methadone maintenance patients.

    PubMed

    Wang, Sheng-Chang; Tsou, Hsiao-Hui; Chen, Chia-Hui; Chen, Yu-Ting; Ho, Ing-Kang; Hsiao, Chin-Fu; Chou, Sun-Yuan; Lin, Yen-Feng; Fang, Kai-Chi; Huang, Chieh-Liang; Su, Lien-Wen; Fang, Yung-Chun; Liu, Ming-Lun; Wu, Hsiao-Yu; Lin, Keh-Ming; Liu, Shu Chih; Kuo, Hsiang-Wei; Chiang, I-Chen; Chen, Andrew C H; Tian, Jia-Ni; Liu, Yu-Li

    2012-10-01

    Methadone, a synthetic racemic opioid that primarily works as a μ-opioid receptor (OPRM1) agonist, is commonly used for the treatment of heroin addiction. Genetic association studies have reported that the OPRM1 gene is involved in the physiology of heroin and alcohol addiction. Our current study is designed to test the hypothesis that genetic polymorphisms in the OPRM1 gene region are associated with methadone dosage, plasma concentrations, treatment responses, adverse reactions and withdrawal symptoms in a methadone maintenance treatment (MMT) cohort from Taiwan. Fifteen OPRM1 single nucleotide polymorphisms (SNPs) were selected and genotyped using DNA samples from 366 MMT patients. The plasma concentrations of methadone and its metabolite were measured by high performance liquid chromatography. The results obtained using dominant model analysis indicate that the OPRM1 SNPs rs1074287, rs6912029, rs12209447, rs510769, rs3798676, rs7748401, rs495491, rs10457090, rs589046, rs3778152, rs563649, and rs2075572 are significantly associated with change-in-libido side effects (adjusted p<0.042). Using recessive model analysis, these SNPs were also found to be significantly associated with insomnia side effects in this cohort (p<0.009). The significance of the insomnia findings was mainly contributed by a subgroup of patients who had a positive urine morphine test (p<0.022), and by individuals who did not use benzodiazepine hypnotics (p<0.034). Our current data thus suggest that genetic polymorphisms in OPRM1 may influence the change-in-libido and insomnia side effects sometimes found in MMT patients.

  2. Heroin fatality due to penile injection.

    PubMed

    Winek, C L; Wahba, W W; Rozin, L

    1999-03-01

    Death due to heroin overdose and/or rapid injection of heroin is a frequent occurrence among opioid addicts. We present an unusual case of heroin fatality due to the injection of the drug in the penis. Blood, urine, bile, and vitreous humor concentrations of morphine were 0.68, 0.49, 0.32 and 0.062 microg/ml, respectively. Ethanol was detected at concentrations of 104, 124, 106, and 94 mg/dl in the blood, urine, bile, and vitreous humor, respectively. The cause of death was determined to be due to heroin and ethanol intoxication.

  3. Body Composition Changes Associated With Methadone Treatment

    PubMed Central

    Sadek, Gamal E.; Chiu, Simon; Cernovsky, Zack Z.

    2016-01-01

    Background: Methadone is associated with a statistically significant increase in BMI in the first 2 years of treatment. Objectives: To evaluate the changes of body composition (bone mass, % fat, % muscle mass, % water, and basal metabolic rate) related to this increase. Patients and Methods: Changes in body composition were monitored, via bioelectrical impedance, in 29 patients in methadone treatment for opiate dependency (age 18 to 44, mean = 29.3, SD = 7.0, 13 men, 16 women). Results: Within one year from admission to treatment, a statistically significant (t-tests, P < 0.05) increase was noted in their body mass index (BMI), % of body fat, average body mass, and average basal metabolic rate, and relative decrease in their % of muscle mass and % of bone mass. Neither absolute bone mass nor muscle mass changed significantly. Conclusions: Physicians involved in care of methadone patients should recommend dietary and lifestyle changes to improve their overall health. PMID:27162765

  4. Pharmacogenomics of methadone maintenance treatment.

    PubMed

    Somogyi, Andrew A; Barratt, Daniel T; Ali, Robert L; Coller, Janet K

    2014-05-01

    Methadone is the major opioid substitution therapy for opioid dependence. Dosage is highly variable and is often controlled by the patient and prescriber according to local and national policy and guidelines. Nevertheless many genetic factors have been investigated including those affecting its metabolism (CYP2B6-consistent results), efflux transport (P-gp-inconsistent results), target μ-opioid receptor (μ-opioid receptor-inconsistent results) and a host of other receptors (DRD2) and signaling elements (GIRK2 and ARRB2; not replicated). None by themselves have been able to substantially explain dosage variation (the major but not sole end point). When multiple genes have been combined such as ABCB1, CYP2B6, OPRM1 and DRD2 a greater contribution to dosage variation was found but not as yet replicated. As stabilization of dosage needs to be made rapidly, it is imperative that larger internationally based studies be instigated so that genetic contribution to dosage can be properly assessed, which may or may not tailor to different ethnic groups and each country's policy towards an outcome that benefits all.

  5. NAOMI: The trials and tribulations of implementing a heroin assisted treatment study in North America

    PubMed Central

    Gartry, Candice C; Oviedo-Joekes, Eugenia; Laliberté, Nancy; Schechter, Martin T

    2009-01-01

    Background Opioid addiction is a chronic, relapsing disease and remains a major public health challenge. Despite important expansions of access to conventional treatments, there are still significant proportions of affected individuals who remain outside the reach of the current treatment system and who contribute disproportionately to health care and criminal justice costs as well as to public disorder associated with drug addiction. The NAOMI study is a Phase III randomized clinical trial comparing injectable heroin maintenance to oral methadone. The study has ethics board approval at its Montréal and Vancouver sites, as well as from the University of Toronto, the New York Academy of Medicine and Johns Hopkins University. The main objective of the NAOMI Study is to determine whether the closely supervised provision of injectable, pharmaceutical-grade opioid agonist is more effective than methadone alone in recruiting, retaining, and benefiting chronic, opioid-dependent, injection drug users who are resistant to current standard treatment options. Methods The case study submitted chronicles the challenges of getting a heroin assisted treatment trial up and running in North America. It describes: a brief background on opioid addiction; current standard therapies for opioid addiction; why there is/was a need for a heroin assisted treatment trial; a description of heroin assisted treatment; the beginnings of creating the NAOMI study in North America; what is the NAOMI study; the science and politics of the NAOMI study; getting NAOMI started in Canada; various requirements and restrictions in getting the study up and running; recruitment into the study; working with the media; a status report on the study; and a brief conclusion from the authors' perspectives. Results and conclusion As this is a case study, there are no specific results or main findings listed. The case study focuses on: the background of the study; what it took to get the study started in Canada

  6. The Effects of Maternally Administered Methadone, Buprenorphine and Naltrexone on Offspring: Review of Human and Animal Data

    PubMed Central

    Farid, W.O; Dunlop, S.A; Tait, R.J; Hulse, G.K

    2008-01-01

    Most women using heroin are of reproductive age with major risks for their infants. We review clinical and experimental data on fetal, neonatal and postnatal complications associated with methadone, the current “gold standard”, and compare these with more recent, but limited, data on developmental effects of buprenorphine, and naltrexone. Methadone is a µ-opioid receptor agonist and is commonly recommended for treatment of opioid dependence during pregnancy. However, it has undesired outcomes including neonatal abstinence syndrome (NAS). Animal studies also indicate detrimental effects on growth, behaviour, neuroanatomy and biochemistry, and increased perinatal mortality. Buprenorphine is a partial µ-opioid receptor agonist and a κ-opioid receptor antagonist. Clinical observations suggest that buprenorphine during pregnancy is similar to methadone on developmental measures but is potentially superior in reducing the incidence and prognosis of NAS. However, small animal studies demonstrate that low doses of buprenorphine during pregnancy and lactation lead to changes in offspring behaviour, neuroanatomy and biochemistry. Naltrexone is a non-selective opioid receptor antagonist. Although data are limited, humans treated with oral or sustained-release implantable naltrexone suggest outcomes potentially superior to those with methadone or buprenorphine. However, animal studies using oral or injectable naltrexone have shown developmental changes following exposure during pregnancy and lactation, raising concerns about its use in humans. Animal studies using chronic exposure, equivalent to clinical depot formulations, are required to evaluate safety. While each treatment is likely to have maternal advantages and disadvantages, studies are urgently required to determine which is optimal for offspring in the short and long term. PMID:19305793

  7. 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

  8. [Heroin. II. Preparation, hydrolysis, stability, pharmacokinetics].

    PubMed

    Hosztafi, S

    2001-10-01

    Heroin is prepared by treating morphine with acetyl chloride or acetic anhydride. It is a simple reaction and the yields are generally quantitative. Nowadays the whole process is illegal. Morphine is the major alkaloid present in the opium poppy. Opium is manufactured illicitly then morphine is extracted from it in clandestine laboratories. Numerous studies were carried out on heroin to investigate its rate of hydrolysis. It has been shown that heroin is rapidly deacylated in aqueous solution at alkaline or acidic pH to form 6-acethylmorphine and finally, to morphine. Heroin also rapidly decomposes in biological medium yielding first 6-acetylmorphine and then morphine. Hydrolysis can be performed in blood and in tissue homogenates. Heroin can be administered by several routes. Smoking and intravenous administration are preferred, but intranasal, intramuscular and subcutaneous administration are also common. Recently, there has been a shift in heroin use patterns from injection to sniffing and smoking. Sharing of the injection equipment can result in several severe infectious diseases, such as AIDS, hepatitis B and C. Soon after administration, heroin metabolizes to 6-acetylmorphine and morphine. Most of the pharmacological activities of heroin are due to these active metabolites. Therefore, knowledge of distribution of 6-acetylmorphine and morphine is essential to understand pharmacological properties of heroin. Heroin, which is relatively nonpolar compound compared with morphine, has high lipid solubility facilitating rapid absorption from the bloodstream and passage through the blood-brain barrier. When heroin is administered by intravenously the drug takes 10 s to reach the brain i.e. pharmacological effects appear quickly.

  9. Implication of gender differences in heroin-assisted treatment: results from the German randomized controlled trial.

    PubMed

    Eiroá-Orosa, Francisco José; Verthein, Uwe; Kuhn, Silke; Lindemann, Christina; Karow, Anne; Haasen, Christian; Reimer, Jens

    2010-01-01

    Despite a lower prevalence of opioid dependence among females, drug-related problems and risk factors such as prostitution have a negative effect for women in treatment. This study was conducted with the purpose of analyzing gender differences in the German trial on heroin-assisted treatment (HAT), which compared HAT with methadone maintenance treatment (MMT). Significant baseline gender differences were found, with females showing a greater extent of mental distress. Differences in retention and outcome were significant for male patients, but no differences between treatment options were found for female patients. Ongoing prostitution was found to influence drug use outcomes. Other outcome criteria may need to be stressed when assessing the effect of HAT for women.

  10. Knowledge and stigma regarding methadone maintenance treatment among personnel of methadone maintenance treatment and non-methadone maintenance treatment addiction facilities in Israel.

    PubMed

    Shidlansik, Lia; Adelson, Miriam; Peles, Einat

    2017-01-01

    Stigma attached to methadone maintenance treatment is very common. The objective of the current article is to evaluate the presence of stigma and its relation to the extent of knowledge about methadone maintenance treatment. The authors conducted a survey among methadone maintenance treatment and non-methadone maintenance treatment addiction therapists from different treatment centers in Israel, including methadone maintenance treatment clinics (Ministry of Health) and non-methadone maintenance treatment addiction facilities (Ministry of Social Services), using an anonymous questionnaire about methadone maintenance treatment stigma and knowledge. There were 63 therapists from methadone maintenance treatment clinics (63%) and 46 therapists from the social services department (SSD) non-methadone maintenance treatment addiction facilities (9.2%) who responded. Methadone maintenance treatment versus social services department personnel were older (42.7 ± 12.8 versus 37.5 ± 8.2 years; p = 0.03), with fewer females (48 versus 75%; p = 0.006), and 50% were social workers compared to 100% social workers in the SSD group (p < 0.0005). Stigma score was lower among methadone maintenance treatment personnel compared to the social services department personnel (3 ± 2.5 versus 5.0 ± 3.5; p = 0.0001), while the knowledge score about methadone maintenance treatment was higher among the methadone maintenance treatment personnel (10.3 ± 2.9 versus 7.7 ± 2.8; p < 0.0005). The difference in both the stigma and knowledge scores remained significant after controlling for age, gender, and profession. There was a negative correlation between the stigma and knowledge scores among both the methadone maintenance treatment (R = -0.5, p < 0.0005) and the social services department personnel (R = -0.33, p = 0.03). These results revealed a significant correlation between the presence of stigma and the extent of education and knowledge about methadone maintenance treatment, with ignorance

  11. 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

  12. 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.

  13. 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.

  14. Heroin: Challenge for the 21st Century.

    ERIC Educational Resources Information Center

    Gordon, Susan M.

    The rise in heroin use in the 1990s is attributed to an increase in snorting and smoking heroin as opposed to earlier epidemics that relied on intravenous use. An increase in purity has also added to the addiction problem. The trend towards use by young people was confirmed by the 2000 Monitoring the Future Study, which reported that 10.6% of high…

  15. Treatment of Heroin Dependence: Effectiveness, Costs, and Benefits of Methadone Maintenance

    ERIC Educational Resources Information Center

    Schilling, Robert; Dornig, Katrina; Lungren, Lena

    2006-01-01

    Objectives: Social workers will increasingly be required to attend to the cost-effectiveness of practices, programs, and policies. In the area of substance abuse, there is little evidence to suggest that social workers' decisions are based on evidence of either effectiveness or costs. Method: This article provides an overview of existing evidence…

  16. Concurrent detection of heroin, fentanyl, and xylazine in seven drug-related deaths reported from the Philadelphia Medical Examiner's Office.

    PubMed

    Wong, Stella C; Curtis, John A; Wingert, William E

    2008-03-01

    Recreational drugs, such as cocaine and heroin, are often adulterated with other pharmacological agents to either enhance or diminish the drug effects. Between April 21, 2006 and August 8, 2006, the Philadelphia Medical Examiner's Office detected xylazine (a veterinary sedative) and fentanyl (a synthetic opioid) in specimens taken from seven cases. Initial immunoassay screening was performed on urine and blood for fentanyl, opiate, cocaine, phencyclidine (PCP), and benzodiazepines. All tests reported positive were confirmed by gas chromatography-mass spectrometry. All seven xylazine positive cases tested positive for fentanyl and six cases tested positive for 6-acetylmorphine (a metabolite and definitive marker for heroin). The seventh case was positive for morphine and had a history of heroin abuse. Xylazine was present in urine in all seven cases and blood levels were detected in three cases. The blood concentrations ranged from trace to 130 ng/mL. Fentanyl was present in the blood and urine in each case and blood concentrations ranged from 4.7 to 47 ng/mL. Adulteration of illicit drugs has become an epidemic health concern for drug users. Healthcare professionals need to be aware of this issue, so the patients can be treated in an effective, timely manner.

  17. Methadone maintenance and drug-related crime.

    PubMed

    Bell, J; Mattick, R; Hay, A; Chan, J; Hall, W

    1997-01-01

    Using data from an evaluation of methadone maintenance treatment, this study investigated factors associated with continued involvement in crime during treatment, and in particular whether there appeared to be differences in effectiveness of treatment between different methadone clinics. The methodology was an observational study, in which 304 patients attending three low-intervention, private methadone clinics in Sydney were interviewed on three occasions over a twelve month period. Outcome measures were self-reported criminal activity and police department records of convictions. By self-report, crime dropped promptly and substantially on entry to treatment, to a level of acquisitive crime about one-eighth that reported during the last addiction period. Analysis of official records indicated that rates of acquisitive convictions were significantly lower in the in-treatment period compared to prior to entry to treatment, corroborating the changes suggested by self-report. Persisting involvement in crime in treatment was predicted by two factors: the cost of persisting use of illicit drugs, particularly cannabis, and ASPD symptom count. Treatment factors also were independently predictive of continued involvement in crime. By both self-report and official records, and adjusting for subject factors, treatment at one clinic was associated with greater involvement in crime. This clinic operated in a chaotic and poorly organized way. It is concluded that crime during methadone treatment is substantially lower than during street addiction, although the extent of reduction depends on the quality of treatment being delivered.

  18. Methadone Maintenance: The Addict's Family Recreated.

    ERIC Educational Resources Information Center

    Schwartzman, John; Bokos, Peter

    1979-01-01

    A study of four methadone clinics, the addicts treated at these clinics, and their families, reveals basic dissonances in treatment ideology and professional-paraprofessional relationships which, combined with the addict's particular mode of functioning, make significant change in his behavior improbable. (Author)

  19. Employment Patterns of Methadone Maintenance Clients

    ERIC Educational Resources Information Center

    Bloch, Harriet I.; And Others

    1977-01-01

    Analysis of employment patterns of methadone maintenance clients had indicated that the majority were not employed at time of program admission. At time of evaluation, 70 percent of the sample were employed; 88 percent of these clients had previous work histories and brought marketable skills with them. (Author)

  20. 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…

  1. Heroin addiction and voluntary choice: the case of informed consent.

    PubMed

    Henden, Edmund

    2013-09-01

    Does addiction to heroin undermine the voluntariness of heroin addicts' consent to take part in research which involves giving them free and legal heroin? This question has been raised in connection with research into the effectiveness of heroin prescription as a way of treating dependent heroin users. Participants in such research are required to give their informed consent to take part. Louis C. Charland has argued that we should not presume that heroin addicts are competent to do this since heroin addiction by nature involves a loss of ability to resist the desire for heroin. In this article, I argue that Charland is right that we should not presume that heroin addicts are competent to consent, but not for the reason he thinks. In fact, as Charland's critics correctly point out, there is plenty of evidence showing that heroin addicts can resist their desire for heroin. These critics are wrong, however, to conclude from this that we should presume that heroin addicts are competent to give their voluntary consent. There are, I shall argue, other conditions associated with heroin addiction that might constrain heroin addicts' choice in ways likely to undermine the voluntariness of their consent. In order to see this, we need to move beyond the focus on the addicts' desires for heroin and instead consider the wider social and psychological circumstances of heroin addiction, as well as the effects these circumstances may have on the addicts' beliefs about the nature of their options.

  2. Is the promise of methadone Kenya’s solution to managing HIV and addiction? A mixed-method mathematical modelling and qualitative study

    PubMed Central

    Rhodes, Tim; Guise, Andy; Ndimbii, James; Strathdee, Steffanie; Ngugi, Elizabeth; Platt, Lucy; Kurth, Ann; Cleland, Charles; Vickerman, Peter

    2015-01-01

    Background and objectives Promoted globally as an evidence-based intervention in the prevention of HIV and treatment of heroin addiction among people who inject drugs (PWID), opioid substitution treatment (OST) can help control emerging HIV epidemics among PWID. With implementation in December 2014, Kenya is the third Sub-Saharan African country to have introduced OST. We combine dynamic mathematical modelling with qualitative sociological research to examine the ‘promise of methadone’ to Kenya. Methods, setting and participants We model the HIV prevention impact of OST in Nairobi, Kenya, at different levels of intervention coverage. We draw on thematic analyses of 109 qualitative interviews with PWID, and 43 with stakeholders, to chart their narratives of expectation in relation to the promise of methadone. Results The modelled impact of OST shows relatively slight reductions in HIV incidence (5–10%) and prevalence (2–4%) over 5 years at coverage levels (around 10%) anticipated in the planned roll-out of OST. However, there is a higher impact with increased coverage, with 40% coverage producing a 20% reduction in HIV incidence, even when accounting for relatively high sexual transmissions. Qualitative findings emphasise a culture of ‘rationed expectation’ in relation to access to care and a ‘poverty of drug treatment opportunity’. In this context, the promise of methadone may be narrated as a symbol of hope—both for individuals and community—in relation to addiction recovery. Conclusions Methadone offers HIV prevention potential, but there is a need to better model the effects of sexual HIV transmission in mediating the impact of OST among PWID in settings characterised by a combination of generalised and concentrated epidemics. We find that individual and community narratives of methadone as hope for recovery coexist with policy narratives positioning methadone primarily in relation to HIV prevention. Our analyses show the value of mixed

  3. Neurovascular complications of cocaine.

    PubMed

    Daras, M; Tuchman, A J; Koppel, B S; Samkoff, L M; Weitzner, I; Marc, J

    1994-08-01

    Use of cocaine in the USA, has reached epidemic proportions since 1983, when "crack" was introduced, its higher potency compared with cocaine HCl has been associated with a tremendous increase in the incidence of strokes. This study reports our experience with 55 cases of neurovascular events (25 ischemic and 30 hemorrhagic) related to cocaine use in 54 patients. Only 15 patients had other risk factors for stroke. Twenty six patients smoked "crack", 10 snorted cocaine and 12 injected it intravenously. Strokes occurred within 3 h of cocaine use in 15 patients with infarcts and 17 with hemorrhages. Ten infarcts occurred after an overnight binge. Of the hemorrhage group 9 were subarachnoid, 16 intracerebral (8 basal ganglia, 7 hemispheric and one brain stem) and 5 intraventricular. Computerized tomography (CT) showed an aneurysm of the anterior communicating artery, as well as one of the vein of Galen. Four aneurysms and 3 AVMs were identified on angiography. CT revealed 15 infarcts; it was normal in 7 patients with pure motor hemiparesis and in 3 with findings consistent with anterior spinal artery infarction. Several mechanisms may be responsible for the cerebrovascular complications. A sudden rise in systemic arterial pressure may cause hemorrhages, frequently in association with an underlying aneurysm or AVM. Vasospasm, arteritis, myocardial infarction with cardiac arrhythmias and increased platelet aggregation may provoke infarcts.

  4. Mechanism of ritonavir changes in methadone pharmacokinetics and pharmacodynamics: I. Evidence against CYP3A mediation of methadone clearance.

    PubMed

    Kharasch, E D; Bedynek, P S; Park, S; Whittington, D; Walker, A; Hoffer, C

    2008-10-01

    Ritonavir diminishes methadone plasma concentrations, an effect attributed to CYP3A induction, but the actual mechanisms are unknown. We determined ritonavir effects on stereoselective methadone pharmacokinetics and clinical effects (pupillary miosis) in healthy human immunodeficiency virus-negative volunteers. Subjects received intravenous plus oral (deuterium-labeled) racemic methadone after no ritonavir, short-term (3-day) ritonavir, and steady-state ritonavir. Acute and steady-state ritonavir, respectively, caused 1.5- and 2-fold induction of systemic and apparent oral R- and S-methadone clearances. Ritonavir increased renal clearance 40-50%, and stereoselectively (S > R) increased hepatic methadone N-demethylation 50-80%, extraction twofold, and clearance twofold. Bioavailability was unchanged despite significant inhibition of intestinal P-glycoprotein. Intestinal and hepatic CYP3A was inhibited > 70%. Ritonavir shifted methadone plasma concentration-miosis curves leftward and upward. Rapid ritonavir induction of methadone clearance results from increased renal clearance and induced hepatic metabolism. Induction of methadone metabolism occurred despite profound CYP3A inhibition, suggesting no role for CYP3A in clinical methadone metabolism and clearance. Ritonavir may alter methadone pharmacodynamics.

  5. Reaction Pathway for Cocaine Hydrolase-Catalyzed Hydrolysis of (+)-Cocaine

    PubMed Central

    Yao, Yuan; Liu, Junjun; Zheng, Fang; Zhan, Chang-Guo

    2017-01-01

    A recently designed and discovered cocaine hydrolase (CocH), engineered from human butyrylcholinesterase (BChE), has been proven promising as a novel enzyme therapy for treatment of cocaine overdose and addiction because it is highly efficient in catalyzing hydrolysis of naturally occurring (−)-cocaine. It has been known that the CocH also has a high catalytic efficiency against (+)-cocaine, a synthetic enantiomer of cocaine. Reaction pathway and the corresponding free energy profile for the CocH-catalyzed hydrolysis of (+)-cocaine have been determined, in the present study, by performing first-principles pseudobond quantum mechanical/molecular mechanical (QM/MM)-free energy (FE) calculations. Acordingt to the QM/MM-FE results, the catalytic hydrolysis process is initiated by the nucleophilic attack on carbonyl carbon of (−)-cocaine benzoyl ester via hydroxyl oxygen of S198 side chain, and the second reaction step (i.e. dissociation of benzoyl ester) is rate-determining. This finding for CocH-catalyzed hydrolysis of (+)-cocaine is remarkably different from that for the (+)-cocaine hydrolysis catalyzed by bacterial cocaine esterase in which the first reaction step of the deacylation is associated with the highest free energy barrier (~17.9 kcal/mol). The overall free energy barrier (~16.0 kcal/mol) calculated for the acylation stage of CocH-catalyzed hydrolysis of (+)-cocaine is in good agreement with the experimental free energy barrier of ~14.5 kcal/mol derivated from the experimental kinetic data.

  6. Heroin-induced suppression of saccharin intake in water-deprived and water-replete rats.

    PubMed

    Grigson, P S; Twining, R C; Carelli, R M

    2000-07-01

    Rats suppress intake of a saccharin conditioned stimulus (CS) when paired with an aversive unconditioned stimulus such as lithium chloride. This phenomenon is referred to as a conditioned taste aversion (CTA). Rats also suppress intake of a saccharin CS when paired with a rewarding sucrose solution and when paired with a drug of abuse. Although the suppressive effects of drugs of abuse have long been interpreted as CTAs, evidence suggests that rats may suppress intake of the saccharin CS following taste-drug pairings because they are anticipating the rewarding rather than the aversive properties of the drug. Oddly, however, while all other drugs of abuse tested suppress intake of a gustatory CS, the highly reinforcing drug, heroin, is reportedly ineffective. The present study reexamined this issue in both water-deprived and water-replete rats using procedures that sustain both morphine- and cocaine-induced suppression of CS intake. The results showed that heroin greatly reduced CS intake following saccharin-heroin pairings and that this effect was less variable when assessed in water-replete subjects. When taken with other reports, these data suggest that rats suppress intake of a saccharin CS in anticipation of the availability of all drugs of abuse tested.

  7. Gamma-vinyl GABA inhibits methamphetamine, heroin, or ethanol-induced increases in nucleus accumbens dopamine.

    PubMed

    Gerasimov, M R; Ashby, C R; Gardner, E L; Mills, M J; Brodie, J D; Dewey, S L

    1999-10-01

    We examined the acute effect of the irreversible GABA-transaminase inhibitor, gamma-vinyl GABA (GVG, Sabril((R)), Vigabatrin((R))) on increases in nucleus accumbens (NAc) dopamine (DA) following acute administration of methamphetamine, heroin, or ethanol. Methamphetamine (2.5 mg/kg) produced a dose-dependent increase (2, 700%) in NAc DA. GVG preadministration (300 or 600 mg/kg), however, inhibited this response by approximately 39 and 61%, respectively. The lower dose of methamphetamine (1.25 mg/kg), increased DA by 1, 700%. This response was inhibited to a similar extent (44%) regardless of the GVG dose preadministered (300 or 600 mg/kg). In addition, heroin-induced increases in NAc DA (0.5 mg/kg, 170%) were inhibited or completely abolished by GVG (150 or 300 mg/kg, 65 and 100%, respectively). Finally, at half the dose necessary for heroin, GVG (150 mg/kg) also completely abolished ethanol-induced increases in NAc DA following a 0.25 g/kg challenge dose (140%). Taken with our previous findings using nicotine or cocaine as the challenge drug, these results indicate that GVG attenuates increases in NAc DA by a mechanism common to many drugs of abuse. However, it appears unlikely that an acute dose of GVG can completely inhibit increases in NAc DA following challenges with a drug whose mechanism of action is mediated primarily through the DA reuptake site.

  8. Characteristics of methadone-related fatalities in Norway.

    PubMed

    Bernard, Jean-Paul; Khiabani, Hassan Z; Hilberg, Thor; Karinen, Ritva; Slørdal, Lars; Waal, Helge; Mørland, Jørg

    2015-11-01

    There are currently over 7000 patients enrolled in opioid maintenance treatment (OMT) programs in Norway. A rise in methadone-related deaths proportional to increasing methadone sales over the period 2000-2006 has been observed, but the causative factors for these fatalities have been elusive. In the present study, individual characteristics, methadone concentrations and additional toxicological findings were analyzed. Methadone intoxication deaths (n = 264) were divided into 3 groups according to toxicological findings in whole blood: group 1 - methadone detected alone, or together with one additional drug at low or therapeutic levels, or a low concentration of ethanol (<1 g/L) (n = 21); group 2 - multiple additional drugs/substances detected below lethal levels (n = 175); group 3 - one or more additional drugs/substances detected at lethal levels, or ethanol >3 g/L (n = 55). Methadone blood concentrations in decedents who had been enrolled in OMT were higher than for decedents not in treatment, in all groups. Blood methadone concentrations around 1 mg/L were present in fatal multi-drug intoxications in OMT patients. Results suggest that some patients may be at risk of dying when combining therapeutic concentrations of methadone with other psychoactive substances. Somatic disease was a common finding among deceased OMT patients. Concentrations in methadone users not enrolled in OMT were predominantly between 0.3 and 0.4 mg/L and were not related to the presence of other drugs. However, methadone concentrations below 0.1 mg/L may be associated with intoxication following methadone use, both alone and in combination with other drugs. Younger male users (mean age 34 years) seemed to have a higher susceptibility to methadone intoxication.

  9. Effects of heroin-assisted treatment on alcohol consumption: findings of the German randomized controlled trial.

    PubMed

    Haasen, C; Eiroa-Orosa, F J; Verthein, U; Soyka, M; Dilg, C; Schäfer, I; Reimer, J

    2009-06-01

    Alcohol has been suggested to be a risk factor for opioid-dependent patients in methadone maintenance treatment (MMT). Literature shows that MMT has limited effects on alcohol use. Nevertheless, a decrease in alcohol use was detected in the Swiss heroin-assisted treatment (HAT) study. In this article, we carry out an in-depth analysis of the German HAT trial with the aim of determining whether alcohol use was affected among patients undergoing HAT and MMT. Analysis was carried out using self-reported data on consumption units of alcohol used (CU), Addiction Severity Index composite scores (ASI CSs), and carbohydrate-deficient transferrin (CDT) measures. Results suggest significant reduction of CU and CDT in both groups, yet larger effects in the HAT group. ASI CS significantly decreased in the HAT but not in the MMT group. The greater benefit of HAT in reducing alcohol use may be due to the greater daily frequency of dispensing heroin coupled with a requirement of sobriety at each dosing occasion.

  10. Cocaine detection using piezoresistive microcantilevers

    NASA Astrophysics Data System (ADS)

    Srijanto, Bernadeta; Cheney, Christine P.; Hedden, David L.; Gehl, Anthony; Ferrell, Thomas L.

    2008-03-01

    Sensitive and inexpensive sensors play a significant role in the analysis of drugs and drug metabolites. Specifically, reliable in vivo detection of cocaine and cocaine metabolites serves as a useful tool in research of the body's reaction to the drug and in the treatment of the drug addiction. We present here a promising cocaine biosensor to be used in the human body. The sensor's active element consists of piezoresistive microcantilevers coated with an oligonucleotide-based aptamer as the cocaine binder. In vitro cocaine detection was carried out by flowing a cocaine solution over the microcantilevers. Advantages of this device are its low power consumption, its high sensitivity, and its potential for miniaturization into an implantable capsule. The limit of detection for cocaine in distilled water was found to be 1 ng/ml.

  11. Detection of opiate use in a methadone maintenance treatment population with the CEDIA 6-acetylmorphine and CEDIA DAU opiate assays.

    PubMed

    Spanbauer, A C; Casseday, S; Davoudzadeh, D; Preston, K L; Huestis, M A

    2001-10-01

    Heroin, with a plasma half-life of approximately 5 min, is rapidly metabolized to 6-acetylmorphine (6-AM). 6-AM, a specific marker for heroin use, which also has a short half-life of only 0.6 h, is detected in urine for only a few hours after heroin exposure. Ingestion of poppy seeds and/or licit opiate analgesics can produce positive urine opiate tests. This has complicated the interpretation of positive opiate results and contributed to the decision to raise opiate cutoff concentrations and to require 6-AM confirmation in federally mandated workplace drug-testing programs. Microgenics Corp. has developed the CEDIA 6-AM assay, a homogeneous enzyme immunoassay for semiquantitative determination of 6-AM in human urine, in addition to its CEDIA DAU opiate assay. Urine specimens were collected 3 times per week from 27 participants enrolled in a clinical research trial evaluating a contingency management treatment program for heroin and cocaine abuse. Of the 1377 urine specimens screened, 261 (18.9%) were positive for opiates at > or = 300 ng/mL, 153 (11.1%) were positive for opiates at > or = 2000 ng/mL, and 55 (4.0%) were positive for 6-AM at > or = 10 ng/mL. For opiate-positive screens > or = 300 and > or = 2000 ng/mL, 91.3% and 80.8% confirmed positive for morphine or codeine at the respective gas chromatography-mass spectrometry (GC-MS) cutoffs. All specimens screening positive for 6-AM also confirmed positive by GC-MS at > or = 10 ng/mL. Increasing the opiate screening and confirmation cutoffs for the federal workplace drug-testing program resulted in 8% fewer opiate-positive tests; however, recent heroin use was not affected by this change.

  12. Mechanism of efavirenz influence on methadone pharmacokinetics and pharmacodynamics.

    PubMed

    Kharasch, E D; Whittington, D; Ensign, D; Hoffer, C; Bedynek, P S; Campbell, S; Stubbert, K; Crafford, A; London, A; Kim, T

    2012-04-01

    Mechanisms by which efavirenz diminishes methadone plasma concentrations are unknown. This investigation determined efavirenz influence on clinical methadone disposition and miosis, intravenous and oral alfentanil clearance (hepatic and intestinal cytochrome P450 3A4/5 (CYP3A4/5) activity), fexofenadine disposition (intestinal transporters activity), and efavirenz clearance and 8-hydroxylation (CYP2B6 activity), and human hepatocyte effects. Efavirenz induced systemic and oral alfentanil clearances two- to fivefold and induced efavirenz 8-hydroxylation. Efavirenz stereoselectively decreased methadone plasma concentrations 50-70%. Methadone systemic and oral clearances, hepatic clearance and extraction ratio, N-demethylation, and metabolite formation clearance were stereoselectively increased two- to threefold. Bioavailability decreased. Efavirenz shifted methadone concentration-miosis curves leftward and upward. Efavirenz induced hepatocyte CYP2B6 and CYP3A4 expression, activity, and methadone N-demethylation. Results show that efavirenz coinduced hepatic CYP2B6 and CYP3A4/5, coinduced hepatic and intestinal CYP3A4/5, and coinduced gastrointestinal CYP3A4/5 and efflux transporters. Methadone disposition was most consistent with efavirenz induction of hepatic CYP2B6-mediated methadone N-demethylation. Efavirenz may alter methadone pharmacodynamics.

  13. Cocaine withdrawal symptoms identify "Type B" cocaine-dependent patients.

    PubMed

    Ahmadi, Jamshid; Kampman, Kyle; Dackis, Charles; Sparkman, Thorne; Pettinati, Helen

    2008-01-01

    Recent studies of substance dependence typologies briefly show that multivariate systems originally developed for identifying subtypes of alcoholics, such as Babor's Type A and B system, may also be valid in abusers of other substances, such as cocaine. Type B patients are characterized by an earlier onset of addiction and more severe symptoms of their addiction, psychopathology, and impulsivity. The Type B classification has also been associated with deficits in serotonergic function. We have found that patients who exhibit more severe cocaine withdrawal symptoms, as measured by scores on the Cocaine Selective Severity Assessment (CSSA), have poor treatment outcome and share many characteristics with "Type B" patients. In this paper, we review baseline characteristics of cocaine-dependent patients from several recently completed outpatient cocaine dependence treatment trials to assess the association of cocaine withdrawal symptom severity and the Type B profile. Identifying subtypes of cocaine-dependent patients may improve our ability to treat cocaine dependence by targeting treatments for specific subtypes of patients. We examined the ability of the CSSA scores to capture Type B characteristics in cocaine dependence by analyzing a series of cocaine medication trials that included 255 cocaine-dependent subjects. High CSSA scores at baseline were associated with a history of violent behavior, a family history of substance abuse, antisocial personality disorder, higher addiction severity, and co-morbid psychiatric diseases. Patients with high CSSA scores are also more likely to meet criteria for Type B (Type II) cocaine dependence. Identifying Type B cocaine-dependent patients may help to develop targeted psychosocial or pharmacological treatments for these difficult-to-treat patients.

  14. An enhanced positive reinforcement model for the severely impaired cocaine abuser.

    PubMed

    Foote, J; Seligman, M; Magura, S; Handelsman, L; Rosenblum, A; Lovejoy, M; Arrington, K; Stimmel, B

    1994-01-01

    This article describes a cognitive-behavioral treatment approach that has been extensively modified to work with inner-city methadone-maintained cocaine users. Modifications were deemed essential to address the problems of engagement and retention in treatment that are typically encountered with this population. While this approach relies on such basic tenets of treatment as relapse prevention, cognitive restructuring, and psychoeducation, an understanding of the particular psychological vulnerabilities of this population has been incorporated into the model. The modified approach utilizes positive reinforcement extensively. This includes use of concrete reinforcers to facilitate initial engagement, and use of interpersonal reinforcers (therapist positive regard, attention, and respect) to increase program retention and sustain posttreatment change. Preliminary results indicate that 63% of patients can complete this intensive 6-month program, with considerable reductions in cocaine use and significant change in drug injection behavior.

  15. An Exploratory Study of Inhalers and Injectors Who Used Black Tar Heroin

    PubMed Central

    Maxwell, Jane Carlisle; Spence, Richard T.

    2011-01-01

    Aims To undertake an exploratory study to examine the characteristics of patients in narcotic treatment programs who started their use of black tar heroin either as inhalers or as injectors and to compare them with those who started as inhalers but shifted to injecting. Other studies in this area have used subjects using other forms of heroin more amenable to inhaling. Participants, Design, and Measurement A purposive sample of 199 patients in 6 methadone programs in Texas were interviewed in 2002-2003 using a structured instrument. Findings At admission to treatment, those who were heroin inhalers were more likely to be African American, to live with their families, to have income from wages, and to report fewer days of problems on most of the ASI measures. Those who shifted from inhaling to injecting were more likely to be Hispanic and to have had mental health problems that interfered with their lives and to have had less nurturing while growing up. Injectors were older at this treatment admission, had more treatment episodes and more times in jail, and were more likely to have hepatitis C, AIDS, or gonorrhea. There were high levels of physical and mental problems and histories of traumatization as children and adults for almost all the respondents. Males were as likely as females to have been sexually abused as children or as adults. Conclusions The high rates of mental and physical problems among all the clients interviewed showed the need for comprehensive services to be delivered within the substance abuse treatment programs. Histories of trauma and sexual abuse should be addressed for both male and female clients. PMID:21552428

  16. Substance use -- cocaine

    MedlinePlus

    ... can be monitored as you recover. At this time, there is no medicine that can help reduce the use of cocaine by blocking its effects. But, scientists are researching such medicines. ... that involved your drug use. Spend more time with family and friends you lost touch with ...

  17. Correlates of cocaine/crack use among inner-city incarcerated adolescents.

    PubMed

    Kang, S Y; Magura, S; Shapiro, J L

    1994-11-01

    Inner-city male adolescents in jail in New York City (N = 427) were interviewed to examine correlates of cocaine or crack use. Twenty-three percent had used cocaine or crack in the month before arrest and 32% reported lifetime use. Substantial rates of robbery, murder, other violent crime, weapons possession, and drug dealing were found. However, type of crime, including violent crime, was not related either to cocaine/crack use or to drug dealing. Current cocaine/crack users were more likely to use alcohol, marijuana, and intranasal heroin; to have multiple previous arrests; to be out of school; to be psychologically distressed; to have been sexually molested as a child; to have substance abusing parents; and to have cocaine/crack-using friends. They were also more likely to have frequent sex with girls, to be gay or bisexual, and to engage in anal intercourse. The findings should be considered in developing more effective drug abuse prevention and treatment interventions, and HIV prevention education, for incarcerated at-risk adolescents.

  18. Combined cocaine hydrolase gene transfer and anti-cocaine vaccine synergistically block cocaine-induced locomotion.

    PubMed

    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.

  19. Pharmacotherapy in the Treatment of Addiction: Methadone

    PubMed Central

    Kreek, Mary Jeanne; Borg, Lisa; Ducat, Elizabeth; Ray, Brenda

    2010-01-01

    Methadone maintenance treatment is the most widely available pharmacotherapy for opioid addiction and has been shown over a period of 40 years to be an effective and safe treatment. While women comprise approximately 40% of clients currently being treated in MMT programs, comparatively little research geared specifically toward this group has been published. This article begins with an overview of neurobiological studies on opioid addiction, including a discussion of gender differences, followed by a review of the pharmacology of methadone The authors then examine the particular needs and differences of women being treated in MMTs, including co-dependence with other substances, women’s health issues and psychosocial needs unique to this population. In conclusion, research shows that women have different substance abuse treatment needs in comparison to their male counterparts. One New York City MMT program that has attempted to address these differences is highlighted. PMID:20407977

  20. Toxic effects of xylazine on endothelial cells in combination with cocaine and 6-monoacetylmorphine.

    PubMed

    Silva-Torres, L A; Vélez, C; Lyvia Alvarez, J; Ortiz, J G; Zayas, B

    2014-10-01

    The use of xylazine as a drug of abuse has emerged worldwide in the last 7 years, including Puerto Rico. Clinical findings reported that xylazine users present greater physiological deterioration, than heroin users. The aim of this study was to assess the xylazine toxicity on endothelial cells, as this is one of the first tissues impact upon administration. Human umbilical vein endothelial cells in culture were treated with xylazine, cocaine, 6-monoacetylmorphine (heroin metabolite) and its combinations, at concentrations of 0.10-400 μM, for periods of 24, 48 and 72 h. IC50 were calculated and the Annexin V assay implemented to determine the cell death mechanism. Results indicated IC50 values at 24h as follow: xylazine 62 μM, cocaine 210 μM, 6-monoacetylmorphine 300 μM. When these drugs were combined the IC50 value was 57 μM. Annexin V results indicated cell death by an apoptosis mechanism in cells treated with xylazine or in combination. Results demonstrated that xylazine use inhibits the endothelial cell proliferation, at lower concentrations than cocaine and 6-monoacetylmorphine. These findings contribute to the understanding of the toxicity mechanisms induced by xylazine on endothelial cells.

  1. Toxic Effects of Xylazine on Endothelial Cells in Combination with Cocaine and 6-monoacetylmorphine

    PubMed Central

    Silva-Torres, L.A.; Vélez, C.; Alvarez, J. Lyvia; Ortiz, J.G.; Zayas, B.

    2014-01-01

    The use of xylazine as a drug of abuse has emerged worldwide in the last 7 years, including Puerto Rico. Clinical findings reported that xylazine users present greater physiological deterioration, than heroin users. The aim of this study was to assess the xylazine toxicity on endothelial cells, as this is one of the first tissues impact upon administration. Human umbilical vein endothelial cells in culture were treated with xylazine, cocaine, 6-monoacetylmorphine (heroin metabolite) and its combinations, at concentrations of 0.10 µM to 400 µM, for periods of 24, 48 and 72 hours. IC50 were calculated and the Annexin V assay implemented to determine the cell death mechanism. Results indicated IC50 values at 24 hours as follow: xylazine 62 µM, cocaine 210 µM, 6-monoacetylmorphine 300 µM. When these drugs were combined the IC50 value was 57 µM. Annexin V results indicated cell death by an apoptosis mechanism in cells treated with xylazine or in combination. Results demonstrated that xylazine use inhibits the endothelial cell proliferation, at lower concentrations than cocaine and 6-monoacetylmorphine. These findings contribute to the understanding of the toxicity mechanisms induced by xylazine on endothelial cells. PMID:25017475

  2. Heroin: MedlinePlus Health Topic

    MedlinePlus

    ... Substance Abuse and Mental Health Services Administration) - PDF Topic Image MedlinePlus Email Updates Get Heroin updates by ... Opiate and opioid withdrawal Opioid intoxication Related Health Topics Drug Abuse Opioid Abuse and Addiction National Institutes ...

  3. "Addiction Proneness" and Personality in Heroin Addicts

    ERIC Educational Resources Information Center

    Platt, Jerome J.

    1975-01-01

    A carefully controlled comparison of the personality characteristics of heroin addict (n=27) and nonaddict (n=20) offenders was carried out so as to avoid methodological problems associated with earlier studies. (Editor)

  4. Signs of Heroin Abuse and Addiction

    MedlinePlus

    ... Families? Why Is It So Hard to Quit Drugs? Effects of Drugs Drug Use Hurts Other People Drug ... was addicted to heroin. Here, he describes the drug's effects on his life. Read Deon's story About the ...

  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.

  6. Heroin-associated anthrax with minimal morbidity.

    PubMed

    Black, Heather; Chapman, Ann; Inverarity, Donald; Sinha, Satyajit

    2017-03-08

    In 2010, during an outbreak of anthrax affecting people who inject drugs, a heroin user aged 37 years presented with soft tissue infection. He subsequently was found to have anthrax. We describe his management and the difficulty in distinguishing anthrax from non-anthrax lesions. His full recovery, despite an overall mortality of 30% for injectional anthrax, demonstrates that some heroin-related anthrax cases can be managed predominately with oral antibiotics and minimal surgical intervention.

  7. Enhanced Choice for Viewing Cocaine Pictures in Cocaine Addiction

    SciTech Connect

    Moeller, S.J.; Goldstein, R.; Moeller, S.J.; Maloney, T. Parvaz, M.A.; Dunning, J.P.; Alia-Klein, N.; Woicik, P.A.; Hajcak, G.; Telang, F.; Wang, G.-J.; Volkow, N.D.; Goldstein, R.Z.

    2009-02-01

    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 that 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.

  8. Heroin

    MedlinePlus

    ... En Español Making a Change – Your Personal Plan Hot Topics Am I in a Healthy Relationship? Who ... restlessness muscle and bone pain diarrhea vomiting alternating hot and cold flashes with goosebumps kicking movements severe ...

  9. The "lessons" of the Australian "heroin shortage".

    PubMed

    Degenhardt, Louisa; Day, Carolyn; Gilmour, Stuart; Hall, Wayne

    2006-05-02

    Heroin use causes considerable harm to individual users including dependence, fatal and nonfatal overdose, mental health problems, and blood borne virus transmission. It also adversely affects the community through drug dealing, property crime and reduced public amenity. During the mid to late 1990s in Australia the prevalence of heroin use increased as reflected in steeply rising overdose deaths. In January 2001, there were reports of an unpredicted and unprecedented reduction in heroin supply with an abrupt onset in all Australian jurisdictions. The shortage was most marked in New South Wales, the State with the largest heroin market, which saw increases in price, dramatic decreases in purity at the street level, and reductions in the ease with which injecting drug users reported being able to obtain the drug. The abrupt onset of the shortage and a subsequent dramatic reduction in overdose deaths prompted national debate about the causes of the shortage and later international debate about the policy significance of what has come to be called the "Australian heroin shortage". In this paper we summarise insights from four years' research into the causes, consequences and policy implications of the "heroin shortage".

  10. 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.

  11. Anti-cocaine vaccine development

    PubMed Central

    Kinsey, Berma M; Kosten, Thomas R; Orson, Frank M

    2010-01-01

    Cocaine abuse is an ongoing and serious problem which has lead to the growth of a brutal criminal enterprise, particularly in the Americas and Europe. At present, there are no effective pharmacological agents available to treat the addiction by blocking cocaine or reversing its effects. In order to help motivated addicts conquer their addiction, vaccines against cocaine are being developed, and one has progressed to clinical trials. This review will discuss the concept of anti-drug vaccines in general, the successes and limitations of the various anti-cocaine vaccine approaches, the results of the clinical trials with an anti-cocaine vaccine, and some new vaccine-mediated approaches to combat cocaine addiction. PMID:20822352

  12. Trends in Methadone Distribution for Pain Treatment, Methadone Diversion, and Overdose Deaths - United States, 2002-2014.

    PubMed

    Jones, Christopher M; Baldwin, Grant T; Manocchio, Teresa; White, Jessica O; Mack, Karin A

    2016-07-08

    Use of the prescription opioid methadone for treatment of pain, as opposed to treatment of opioid use disorder (e.g., addiction), has been identified as a contributor to the U.S. opioid overdose epidemic. Although methadone accounted for only 2% of opioid prescriptions in 2009 (1), it was involved in approximately 30% of overdose deaths. Beginning with 2006 warnings from the Food and Drug Administration (FDA), efforts to reduce methadone use for pain have accelerated (2,3). The Office of the Assistant Secretary for Planning and Evaluation of the U.S. Department of Health and Human Services and CDC analyzed methadone distribution, reports of diversion (the transfer of legally manufactured methadone into illegal markets), and overdose deaths during 2002-2014. On average, the rate of grams of methadone distributed increased 25.1% per year during 2002-2006 and declined 3.2% per year during 2006-2013. Methadone-involved overdose deaths increased 22.1% per year during 2002-2006 and then declined 6.5% per year during 2006-2014. During 2002-2006, rates of methadone diversion increased 24.3% per year; during 2006-2009, the rate increased at a slower rate, and after 2009, the rate declined 12.8% per year through 2014. Across sex, most age groups, racial/ethnic populations, and U.S. Census regions, the methadone overdose death rate peaked during 2005-2007 and declined in subsequent years. There was no change among persons aged ≥65 years, and among persons aged 55-64 years the methadone overdose death rate continued to increase through 2014. Additional clinical and public health policy changes are needed to reduce harm associated with methadone use for pain, especially among persons aged ≥55 years.

  13. Employment-based abstinence reinforcement as a maintenance intervention for the treatment of cocaine dependence: post-intervention outcomes

    PubMed Central

    DeFulio, Anthony; Silverman, Kenneth

    2011-01-01

    Aims 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. Design 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 independent 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. Setting A nonprofit data entry business. Participants Unemployed welfare recipients who persistently used cocaine while in methadone treatment. Measurements Urine samples and self-reports were collected every six months for 30 months. Findings During the employment year, abstinence-contingent employment participants provided significantly more cocaine-negative samples than controls (82.7% and 54.2%; P = .01, OR = 4.61). During the follow-up year, the groups had similar rates of cocaine-negative samples (44.2% and 50.0%; P = .93), and HIV-risk behaviors. Participants’ social, employment, economic, and legal conditions were similar in the two groups across all phases of the study. Conclusions 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. PMID:21226886

  14. Opioid addiction and abuse in primary care practice: a comparison of methadone and buprenorphine as treatment options.

    PubMed

    Bonhomme, Jean; Shim, Ruth S; Gooden, Richard; Tyus, Dawn; Rust, George

    2012-01-01

    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, 200000 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.

  15. 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

  16. 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.

  17. 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…

  18. The metabolism of methadone by cultured mammalian cells.

    PubMed

    Will, P C; Noteboom, W D

    1978-02-15

    Rat hepatoma tissue culture cells and mouse leukemic cells were found to metabolize [1-3H] methadone to at least 2 unidentified radioactive compounds. These results suggest that cultured cells may be useful models for studying methadone metabolism by specific cell types.

  19. Factors Associated with Illegal Drug Use among Older Methadone Clients

    ERIC Educational Resources Information Center

    Rosen, Daniel

    2004-01-01

    Purpose. The overall aims of this study are to describe the life stressors of, exposure to illegal drug use of, and illegal drug use by older methadone clients. Design and Methods. The current study focuses on a sub-sample of the larger administrative data of a methadone clinic that is limited to African American and White clients over the age of…

  20. Methadone Diversion: Experiences and Issues. Services Research Monograph Series.

    ERIC Educational Resources Information Center

    Inciardi, James A.

    This report is a description of the phenomenon of methadone diversion as it exists now and places it in the context of prior research in this area. The intent here is to clarify issues around methadone diversion and to provide guidance to treatment administrators and program planners regarding efforts they can initiate to monitor this significant…

  1. Decreasing Methadone Dose Via Anxiety Reduction: A Treatment Manual.

    ERIC Educational Resources Information Center

    Kushner, Marlene; And Others

    This manual describes a Relaxation-Information Presentation program based on the clinical observation that anxiety is a serious barrier to detoxification for many methadone clients, and on experimental evidence indicating that expectations may play a greater role in the discomfort experienced during detoxification than the actual methadone dose.…

  2. Multimodality Approach to Methadone Treatment of Narcotic Addicts

    ERIC Educational Resources Information Center

    Brill, Leon; Chambers, Carl D.

    1971-01-01

    This multimodality approach is geared primarily to the goal of abstinence. For addicts who cannot achieve this goal, methadone maintenance is suggested as the next step. The modalities described range from low-dose maintenance for clinic outpatients to intensive rehabilitation in a methadone maintenance residential center facility. (Author)

  3. 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.

  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. 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

  6. Orbitofrontal response to drug-related stimuli after heroin administration.

    PubMed

    Walter, Marc; Denier, Niklaus; Gerber, Hana; Schmid, Otto; Lanz, Christian; Brenneisen, Rudolf; Riecher-Rössler, Anita; Wiesbeck, Gerhard A; Scheffler, Klaus; Seifritz, Erich; McGuire, Philip; Fusar-Poli, Paolo; Borgwardt, Stefan

    2015-05-01

    The compulsion to seek and use heroin is frequently driven by stress and craving during drug-cue exposure. Although previous neuroimaging studies have indicated that craving is mediated by increased prefrontal cortex activity, it remains unknown how heroin administration modulates the prefrontal cortex response. This study examines the acute effects of heroin on brain function in heroin-maintained patients. Using a crossover, double-blind, placebo-controlled design, 27 heroin-maintained patients performed functional magnetic resonance imaging 20 minutes after the administration of heroin or placebo (saline) while drug-related and neutral stimuli were presented. Images were processed and analysed with statistical parametric mapping. Plasma concentrations of heroin and its main metabolites were assessed using high-performance liquid chromatography. Region of interest analyses showed a drug-related cue-associated blood-oxygen-level-dependent activation in the orbitofrontal cortex (OFC) in heroin-dependent patients during both treatment conditions (heroin and placebo). This activation of the OFC was significantly higher after heroin than after placebo administration. These findings may indicate the importance of OFC activity for impulse control and decision-making after regular heroin administration and may emphasize the benefit of the heroin-assisted treatment in heroin dependence.

  7. Modeling the Demand for Cocaine

    DTIC Science & Technology

    1994-01-01

    the Demand for Cocaine Susan S. Everingham C. Peter Rydell Pre~redfor the Office of NatinalDrug Control Policy United States Army DRUG POLICY...Demand for Cocaine . 60 50- sm 40- squared 30- delta prevalence 20- 10- 0.2 0 0.15 0.15 󈧄 b C; 0 i Sum squared delta 0.2 prevalence 0.195 EQ 50-50 0,19...model of the demand for cocaine that was fit to 20 years of data on the current cocaine epidemic in the United States. It also describes the analysis

  8. Cocaine-induced mesenteric ischaemia.

    PubMed

    Osorio, J; Farreras, N; Ortiz De Zárate L; Bachs, E

    2000-01-01

    We report a 33-year-old man with distal ileum infarction after intravenous abuse of cocaine. He underwent resection of a gangrenous bowel segment and survived. We review the literature regarding intestinal ischaemia related to cocaine. To date, 19 cases have been published. Like most previously reported cases, our patient was young and had no previous history of arteriosclerosis. He suffered cocaine-induced rhabdomyolysis and acute renal failure. Mesenteric ischaemia should be considered in the differential diagnosis of acute or chronic abdominal pain in cocaine consumers.

  9. Heroin users in Australia: population trends.

    PubMed

    Kaya, C Yalçin; Tugai, Yuliya; Filar, Jerzy A; Agrawal, Manju R; Ali, Robert L; Gowing, Linda R; Cooke, Richard

    2004-03-01

    The aim of this paper is to identify certain important population trends among heroin users in Australia for the period 1971 - 97, such as: population growth, initiation, i.e. the number who were initiated to heroin in a given year, and quitting, i.e. the number that quit using heroin. For this purpose, we summarize and extract relevant characteristics from data from National Drug Strategy Household Survey (NDSHS 1998) conducted in Australia in 1998. We devise a systematic procedure to estimate historical trends from questions concerning past events. It is observed from our findings that the size of the heroin user population in Australia is in a sharp increase, especially from the early 1980s onwards. The general trend obtained for the period 1971 - 97 is strikingly similar to that obtained by Hall et al. (2000) for the dependent heroin user population in Australia, even though their study was based on different datasets and a different methodology. In our reconstruction of the time history we also detect a levelling-off prior to 1990. Initiation is also observed to be on a sharp increase. The latter trend is accompanied by a similar trend of quitting, perhaps indicating a relatively short heroin use career. A sharp decrease in both initiation and quitting is observed after 1990. In conclusion, in the case of the trend in the population of heroin users a high rate of growth has been identified that is consistent with the existing literature. In the process, we demonstrated that even a static survey such as NDSHS 1998 can, sometimes, be used to extract historical (dynamic) trends of certain important variables.

  10. Birth Order and Polydrug Abuse Among Heroin Addicts

    ERIC Educational Resources Information Center

    Lerner, Steven E.; Linder, Ronald L.

    1975-01-01

    The purpose of this study was to determine the significance of possible relationships between birth order and polydrug use patterns of heroin addicts prior to undergoing treatment. Overrepresentation of "only child" heroin addicts was evident among the population studied. (Author)

  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. Contingency management in cocaine abusers: a dose-effect comparison of goods-based versus cash-based incentives.

    PubMed

    Vandrey, Ryan; Bigelow, George E; Stitzer, Maxine L

    2007-08-01

    Goods-based contingency management interventions (e.g., those using vouchers or prizes as incentives) have demonstrated efficacy in reducing cocaine use, but cost has limited dissemination to community clinics. Recent research suggests that development of a cash-based contingency management approach may improve treatment outcomes while reducing operational costs of the intervention. However, the clinical safety of providing cash-based incentives to substance abusers has been a concern. The present 16-week study compared the effects of goods-based versus cash-based incentives worth $0, $25, $50, and $100 on short-term cocaine abstinence in a small sample of cocaine-dependent methadone patients (N = 12). A within-subject design was used; a 9-day washout period separated each of 8 incentive conditions. Higher magnitude ($50 and $100) cash-based incentives (checks) produced greater cocaine abstinence compared with the control ($0) condition, but a magnitude effect was not seen for goods-based incentives (vouchers). A trend was observed for greater rates of abstinence in the cash-based versus goods-based incentives at the $50 and $100 magnitudes. Receipt of $100 checks did not increase subsequent rates of cocaine use above those seen in control conditions. The efficacy and safety data provided in this and other recent studies suggest that use of cash-based incentives deserves consideration for clinical applications of contingency management, but additional confirmation in research using larger samples and more prolonged periods of incentive delivery is needed.

  13. Copper thiocyanato complexes and cocaine - a case of 'black cocaine'.

    PubMed

    Laussmann, Tim; Grzesiak, Ireneus; Krest, Alexander; Stirnat, Kathrin; Meier-Giebing, Sigrid; Ruschewitz, Uwe; Klein, Axel

    2015-01-01

    The chemical composition of a black powder confiscated by German customs was elucidated. Black powders are occasionally used as a 'transporter' for cocaine and are obviously especially designed to cloak the presence of the drug. The material consisting of cocaine, copper, iron, thiocyanate, and graphite was approached by analytical tools and chemical modelling. Graphite is added to the material probably with the intention of masking the typical infrared (IR) fingerprints of cocaine and can be clearly detected by powder X-ray diffraction (XRD) and Raman spectroscopy. Cu(2+) and NCS(-) ions, when carefully reacted with cocaine hydrochloride, form the novel compound (CocH)2 [Cu(NCS)4 ] (CocH(+)  = protonated cocaine), which has been characterised by single crystal XRD, IR, NMR, UV/Vis absorption and EPR spectroscopy. Based on some further experiments the assumed composition of the original black powder is discussed.

  14. An investigation into the microflora of heroin.

    PubMed

    McLauchlin, J; Mithani, V; Bolton, F J; Nichols, G L; Bellis, M A; Syed, Q; Thomson, R P M; Ashton, J R

    2002-11-01

    In 2000, an unusual increase of morbidity and mortality among illegal injecting drug users in the UK and Ireland was reported and Clostridium novyi was identified as the likely source of the serious infection, although infections due to C. botulinum and Bacillus cereus were also reported. Because heroin was a possibile source of infection, this study investigated the microflora of heroin samples seized in England during 2000 and 2002. Two methods were developed for the examination of the microflora of heroin. The first consisted of suspension of the drug in maximum recovery diluent (MRD) which was inoculated directly into Clostridium Botulinum Isolation Cooked Meat Broth (CBI). The second method rendered the heroin soluble in citric acid, concentrated particulate material (and bacterial cells) by filtration and removed heroin residues by washing with citric acid and phosphate-buffered saline before placing the filter in CBI broth. Duplicate CBI broths from both methods were incubated without heating and after heating at 60 degrees C for 30 min. Subcultures were made after incubation for 7 and 14 days on to eight different solid media. The methods were evaluated with heroin samples spiked with either C. botulinum or C. novyi spore suspensions; recovery of 10 spores in the original sample was demonstrated. Fifty-eight heroin samples were tested by citric acid solubilisation and 34 by the MRD suspension technique. Fifteen different gram-positive species of four genera were recognised. No fungi were isolated. Aerobic endospore-forming bacteria (Bacillus spp. and Paenibacillus macerans) were the predominant microflora isolated and at least one species was isolated from each sample. B. cereus was the most common species and was isolated from 95% of all samples, with B. licheniformis isolated from 40%. Between one and five samples yielded cultures of B. coagulans, B. laterosporus, B. pumilus, B. subtilis and P. macerans. Staphylococcus spp. were isolated from 23 (40

  15. Orexin / hypocretin 1 receptor antagonist reduces heroin self-administration and cue-induced heroin seeking.

    PubMed

    Smith, Rachel J; Aston-Jones, Gary

    2012-03-01

    The orexin/hypocretin system is involved in several addiction-related behaviors. In the present experiments, we examined the involvement of orexin in heroin reinforcement and relapse by administering the orexin 1 receptor antagonist SB-334867 prior to heroin self-administration or prior to cue-induced or heroin-induced reinstatement of extinguished heroin seeking in male Sprague Dawley rats. SB-334867 (30 mg/kg, intraperitoneal) reduced heroin intake during self-administration under fixed ratio-1 and progressive ratio schedules. SB-334867 also attenuated reinstatement of heroin seeking elicited by cues, but not reinstatement elicited by a heroin prime. These results indicate that orexin antagonism reduces heroin self-administration, and they support a role for orexin in cue-triggered drug relapse.

  16. The resurgence of heroin abuse in the District of Columbia.

    PubMed

    Greene, M H

    1975-01-01

    Prospectively collected drug abuse trend surveillance data suggest that the rate of heroin use in Washington, D.C. is rising following a two year decline in the magnitude of this problem. Supportive data include increased potency of street level heroin, increased numbers of heroin-related deaths, increased detection of heroin positive urine specimens in the D.C. Superior Court arrestee population, increased demand for addiction treatment services and rising property crime rates. Increased prevalence of heroin use has not yet been associated with an increase in incidence, suggesting that former heroin users have begun to use once again following a period of abstinence. Analysis of heroin specimens seized across the United States suggests that cities formerly dependant upon European (white) heroin have now developed a new heroin distribution system which supplies Mexican (brown) heroin. This has offset the reduction in heroin use observed during 1972-1973 concomitant with the East Coast heroin shortage and widespread introduction of addiction treatment services.

  17. What You Need to Know About Drugs: Heroin

    MedlinePlus

    ... Room? What You Need to Know About Drugs: Heroin KidsHealth > For Kids > What You Need to Know About Drugs: Heroin A A A en español Lo que necesitas ... sobre las drogas: La heroína What It Is: Heroin (say: HAIR-uh-win) comes from the opium ...

  18. Isolation and purification of heroin from heroin street samples by preparative high performance liquid chromatography.

    PubMed

    Guo, Zhen; Zheng, Hui; Lu, Yanzhen; Wei, Yun

    2012-09-10

    The present study established a novel method using preparative high performance liquid chromatography to isolate and purify heroin·HCl from heroin street samples to be used as a reference standard. Different kinds of mobile phases and columns were used, ultimately the mobile phase consisting of hexane-isopropanol-methanol (65:28:7, v/v) and the SIL preparative column prepared in laboratory were selected as the final condition. Heroin was further purified by the drowning-out crystallization method using isopropanol-methanol (50:1, v/v) and hexane as drowning-out anti-solvents and salting-out agents, respectively. The purity was assessed by analytical high performance liquid chromatography and the confirmation of the chemical structure was performed by IR and NMR. About 110.7mg of heroin·HCl at a purity of over 99.52% was obtained from 180mg of heroin street samples which contained 156.15mg of heroin·HCl component by preparative high performance liquid chromatography. This method is suitable for preparing heroin standards in forensic science area.

  19. Takotsubo cardiomyopathy due to iatrogenic methadone withdrawal.

    PubMed

    Saiful, Faisal B; Lafferty, James; Jun, Chin Hee; Teli, Sumaya; Duvvuri, Srinivas; Khattri, Saakshi; Bhat, Tariq

    2011-01-01

    Takotsubo cardiomyopathy is a syndrome characterized by transient apical ballooning or reversible midventricular systolic dysfunction. Most cases occur in postmenopausal women and are typically triggered by an acute medical illness or emotional or physical stress. Its presentation is highly suggestive of myocardial ischemia, but there is little or no evidence of epicardial coronary artery disease. To our knowledge there are only three reported cases in the literature of Takotsubo cardiomyopathy induced by opioid agonist withdrawal in adults; ours is the first reported case of iatrogenic methadone withdrawal leading to Takotsubo cardiomyopathy.

  20. A systematic review of the cardiotoxicity of methadone

    PubMed Central

    Alinejad, Samira; Kazemi, Toba; Zamani, Nasim; Hoffman, Robert S.; Mehrpour, Omid

    2015-01-01

    Methadone is one of the most popular synthetic opioids in the world with some favorable properties making it useful both in the treatment of moderate to severe pain and for opioid addiction. Increased use of methadone has resulted in an increased prevalence of its toxicity, one aspect of which is cardiotoxicity. In this paper, we review the effects of methadone on the heart as well as cardiac concerns in some special situations such as pregnancy and childhood. Methods: We searched for the terms methadone, toxicity, poisoning, cardiotoxicity, heart, dysrhythmia, arrhythmia, QT interval prolongation, torsade de pointes, and Electrocardiogram (ECG) in bibliographical databases including TUMS digital library, PubMed, Scopus, and Google Scholar. This review includes relevant articles published between 2000 and 2013. The main cardiac effects of methadone include prolongation of QT interval and torsade de pointes. Other effects include changes in QT dispersion, pathological U waves, Taku-Tsubo syndrome (stress cardiomyopathy), Brugada-like syndrome, and coronary artery diseases. The aim of this paper is to inform physicians and health care staff about these adverse effects. Effectiveness of methadone in the treatment of pain and addiction should be weighed against these adverse effects and physicians should consider the ways to lessen such undesirable effects. This article presents some recommendations to prevent heart toxicity in methadone users. PMID:26869865

  1. Contingent methadone delivery: effects on illicit-opiate use.

    PubMed

    Higgins, S T; Stitzer, M L; Bigelow, G E; Liebson, I A

    1986-07-01

    This study examined the effects of contingent vs. non-contingent delivery of a methadone dose supplement on relapse to illicit opiate use in the context of a methadone outpatient detoxification program. Following a 3-week methadone stabilization period on 30 mg, patients (N = 39) were randomly assigned to a contingent, a non-contingent, or a control treatment group. All patients received identical gradual reductions in their assigned methadone dose. During the dose reduction period (weeks 4-11), members of the contingent (N = 13) and non-contingent groups (N = 13) could obtain daily methadone-dose supplements up to 20 mg, but contingent group members could obtain supplements only if their most recent urinalysis results were opiate negative. Control subjects (N = 13) did not have dose increases available. The contingent group presented significantly lower opiate-positive urines during weeks 8-11 (14% positive) of the detox than the non-contingent (38% positive) or control (50% positive) groups. Additionally, the availability of extra methadone improved treatment retention and increased clinic attendance above levels observed in the control group. The potential for further use of methadone's reinforcing properties in the treatment of opiate dependence is discussed.

  2. Cocaine/Crack: The Big Lie.

    ERIC Educational Resources Information Center

    National Inst. on Drug Abuse (DHHS/PHS), Rockville, MD.

    This pamphlet focuses on cocaine and crack use and the addictive nature of cocaine/crack. It contains a set of 21 questions about crack and cocaine, each accompanied by a clear and complete response. Interspersed throughout the booklet are photographs and quotes from former cocaine or crack users/addicts. Questions and answers focus on what…

  3. Evaluation of a low-threshold/high-tolerance methadone maintenance treatment clinic in saint john, new brunswick, Canada: one year retention rate and illicit drug use.

    PubMed

    Christie, Timothy K S; Murugesan, Alli; Manzer, Dana; O'Shaughnessey, Michael V; Webster, Duncan

    2013-01-01

    Objective. To report the one-year retention rate and the prevalence of illicit opioid use and cocaine use in the Low-Threshold/High-Tolerance (LTHT) methadone maintenance treatment (MMT) clinic located in Saint John, New Brunswick, Canada. Methods. A description of the LTHT MMT clinic is provided. The one-year retention rate was determined by collecting data on patients who enrolled in the LTHT MMT clinic between August 04, 2009 and August 04, 2010. The prevalence of illicit drug use was determined using a randomly selected retrospective cohort of 84 participants. For each participant the results of six consecutive urine tests for the most recent three months were compared to the results of the first six consecutive urine tests after program entry. Results. The one-year retention rate was 95%, 67% of the cohort achieved abstinence from illicit opioids and an additional 13% abstained from cocaine use. Conclusion. The novel feature of the LTHT MMT clinic is that patients are not denied methadone because of lack of ancillary services. Traditional comprehensive MMT programs invest the majority of financial resources in ancillary services that support the biopsychosocial model, whereas the LTHT approach utilizes a medical model and directs resources at medical management.

  4. Methadone-induced respiratory depression in the neonatal guinea pig.

    PubMed

    Nettleton, Rosemary T; Ransom, Ty A; Abraham, Stephanie L; Nelson, Cole S; Olsen, George D

    2007-12-01

    Respiratory depression, the most serious side-effect of opioid treatment, is well documented for morphine, the most commonly used opioid in neonatal care. Less is known about methadone, a clinically relevant opioid analgesic, especially during neonatal development. This study was undertaken to determine the neonatal respiratory effects of methadone. We hypothesize that methadone is equipotent to morphine, compared to our previous morphine results in the same animal model, but has a much longer duration of action, due to its longer elimination half-life. Neonatal guinea pigs (3-14 days old) randomly received a single subcutaneous dose of methadone or saline. Using a non-invasive plethysmographic method, we measured ventilatory and metabolic parameters before injection and at intervals for 32 hr after injection while pups breathed "room air" or 5% CO(2) gas mixtures. Methadone-induced depression of ventilation was most evident during 5% CO(2) challenge. The onset of drug effects was within 15 min for all ages and doses, but the duration of action decreased with age. While the depth of methadone-induced respiratory depression did not depend on pup age, the control of breathing was different in 3-day-old pups, where inspiratory time increased fourfold; twice that of older pups. We conclude that methadone induces a naloxone reversible respiratory depression in guinea pig neonates and, in the very young, causes an abnormal breathing pattern due to changes in respiratory timing. Methadone is more potent than morphine with respect to neonatal respiratory depression, but surprisingly, the duration of methadone action was not longer than morphine.

  5. Plasma cholesterol and triglycerides in heroin addicts.

    PubMed

    Maccari, S; Bassi, C; Zanoni, P; Plancher, A C

    1991-12-31

    We examined total cholesterolemia, triglyceridemia, high density lipoproteins- (HDL) cholesterolemia, apolipoproteins A1 and B, body mass index, albuminemia and alanine aminotransferase in 60 heroin addicts. After comparing 23 control subjects with the heroin addicts the result was that the latter have significantly lower mean values of total cholesterolemia and of HDL-cholesterolemia and higher values of triglyceridemia. They also have significantly higher prevalences of cases of hypocholesterolemia and of hypo-HDL-cholesterolemia. Within the addict group there is no linear correlation between total cholesterolemia and body mass index; there is, however, an inverse linear correlation between total cholesterolemia and alanine aminotransferase. Therefore, the alterations found in the lipid pattern of heroin addicts are not due to malnutrition but hypothetically to liver diseases which are frequent in these patients.

  6. Toxicological criterion of the heroin poisoning.

    PubMed

    Shigeev, S

    2007-01-01

    The paper presents toxicological characteristics of 198 cases of acute parenteral heroin intoxication, analyzes the clinically encountered range of blood and urinary concentrations of its metabolites. The principal causes of death are elucidated in victims of heroin poisoning at the hospital stage. Where there is a relationship of death probability to the detection of morphine in the victims' biological fluids is considered; its blood and urinary concentrations are determined, which undoubtedly suggests the occurrence of poisoning-related death. It has been established that death from poisoning by heroin may occur in the whole range of its detectable concentrations. There is no doubt that the blood morphine concentrations of at least 2.0 microg/ml should be considered to be fatal.

  7. Crystal in Iran: methamphetamine or heroin kerack

    PubMed Central

    2013-01-01

    In recent years, methamphetamine use has dramatically increased in Iran while there is a crucial misunderstanding about the colloquial words related to methamphetamine among health providers, policy makers, clinicians, scholars and people in the community. The word Crystal refers to methamphetamine in some parts of Iran while in some other parts of the country, Crystal refers to a high purity street-level heroin which is called Kerack and its abuse is epidemic. Methamphetamine and heroin Kerack are different drugs in Iran. Methamphetamine is a stimulant drug while heroin Kerack is an opioid. Health providers especially clinicians and emergency medicine specialists should consider colloquial words that Iranian drug users apply. Special training courses should be designed and implemented for clinicians in Iran to inform them about methamphetamine and its frequently used colloquial words in the community. This issue has important clinical and health implications. PMID:23497450

  8. From victim to heroine: children's stories revisited.

    PubMed

    Turkel, Ann Ruth

    2002-01-01

    The need to escape reality and the taste for adventure with the unknown fills a universal need for both adults and children. Fairy tales have a powerful grip on the imagination because they are homespun versions of myths and have passionate intensity without epic grandeur. The happy ending of fairy tales reflects gender stereotyping because the heroine usually does very little except sit, wish, and wait for marriage. She has no control over her destiny and no active involvement in selecting or planning her future. These heroines are really passive victims. Sexism was once rampant in children's books. The Oz books, with their independent, courageous, and active heroine were way ahead of their time. The advent of women's liberation has led to a reappraisal of the female in folk literature. Anthropologists have now discovered stories of admirable women who were strong characters in their own epic dramas.

  9. [Gender heteronomy of heroin addiction in adolescences].

    PubMed

    Bokhan, N A; Baturin, E V

    2010-01-01

    On the model of heroin addiction in adolescents the premises for grounding the concept of gender heteronomy of addictions have been identified. The clinical-dynamic patterns associated with gender--so called gender associated types of disease in which the leading factors of difference formation are biological sex, valuable orientation structure, sexual experience and social status were singled out. The gender-associated types of heroin addiction in boys and girls were specified as dominant, repressive, partner, utilitarian, integrating and independent. Gender-differentiated programs of pharmaco- and psychotherapy are proposed.

  10. Sigma receptors and cocaine abuse.

    PubMed

    Narayanan, Sanju; Mesangeau, Christophe; Poupaert, Jacques H; McCurdy, Christopher R

    2011-01-01

    Sigma receptors have been well documented as a protein target for cocaine and have been shown to be involved in the toxic and stimulant actions of cocaine. Strategies to reduce the access of cocaine to sigma receptors have included antisense oligonucleotides to the sigma-1 receptor protein as well as small molecule ligand with affinity for sigma receptor sites. These results have been encouraging as novel protein targets that can attenuate the actions of cocaine are desperately needed as there are currently no medications approved for treatment of cocaine toxicity or addiction. Many years of research in this area have yet to produce an effective treatment and much focus was on dopamine systems. A flurry of research has been carried out to elucidate the role of sigma receptors in the blockade of cocaine effects but this research has yet to yield a clinical agent. This review summarizes the work to date on the linkage of sigma receptors and the actions of cocaine and the progress that has been made with regard to small molecules. Although there is still a lack of an agent in clinical trials with a sigma receptor mechanism of action, work is progressing and the ligands are becoming more selective for sigma systems and the potential remains high.

  11. 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

  12. Neural correlates of adherence to extended-release naltrexone pharmacotherapy in heroin dependence.

    PubMed

    Wang, A-L; Elman, I; Lowen, S B; Blady, S J; Lynch, K G; Hyatt, J M; O'Brien, C P; Langleben, D D

    2015-03-17

    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.

  13. Effects of cortisol administration on craving in heroin addicts

    PubMed Central

    Walter, M; Bentz, D; Schicktanz, N; Milnik, A; Aerni, A; Gerhards, C; Schwegler, K; Vogel, M; Blum, J; Schmid, O; Roozendaal, B; Lang, U E; Borgwardt, S; de Quervain, D

    2015-01-01

    Heroin dependence is a severe and chronically relapsing substance use disorder with limited treatment options. Stress is known to increase craving and drug-taking behavior, but it is not known whether the stress hormone cortisol mediates these stress effects or whether cortisol may rather reduce craving, for example, by interfering with addiction memory. The aim of the present study was to determine the effects of cortisol administration on craving in heroin-dependent patients and to determine whether the effects depend on the daily dose of heroin consumption. We used a double-blind, placebo-controlled, cross-over study in 29 heroin-dependent patients in a stable heroin-assisted treatment setting. A single oral dose of 20 mg of cortisol or placebo was administered 105 min before the daily heroin administration. The primary outcome measure was cortisol-induced change in craving. Secondary measures included anxiety, anger and withdrawal symptoms. For the visual analog scale for craving, we found a significant interaction (P=0.0027) between study medication and heroin-dose group (that is, daily low, medium or high dose of heroin). Cortisol administration reduced craving in patients receiving a low dose of heroin (before heroin administration: P=0.0019; after heroin administration: P=0.0074), but not in patients receiving a medium or high dose of heroin. In a picture-rating task with drug-related pictures, cortisol administration did not affect the ratings for the picture-characteristic craving in all the three heroin-dose groups. Cortisol also did not significantly affect secondary outcome measures. In conclusion, a single administration of cortisol leads to reduced craving in low-dose heroin addicts. The present findings might have important clinical implications with regard to understanding stress effects and regarding treatment of addiction. PMID:26218852

  14. Effects of cortisol administration on craving in heroin addicts.

    PubMed

    Walter, M; Bentz, D; Schicktanz, N; Milnik, A; Aerni, A; Gerhards, C; Schwegler, K; Vogel, M; Blum, J; Schmid, O; Roozendaal, B; Lang, U E; Borgwardt, S; de Quervain, D

    2015-07-28

    Heroin dependence is a severe and chronically relapsing substance use disorder with limited treatment options. Stress is known to increase craving and drug-taking behavior, but it is not known whether the stress hormone cortisol mediates these stress effects or whether cortisol may rather reduce craving, for example, by interfering with addiction memory. The aim of the present study was to determine the effects of cortisol administration on craving in heroin-dependent patients and to determine whether the effects depend on the daily dose of heroin consumption. We used a double-blind, placebo-controlled, cross-over study in 29 heroin-dependent patients in a stable heroin-assisted treatment setting. A single oral dose of 20 mg of cortisol or placebo was administered 105 min before the daily heroin administration. The primary outcome measure was cortisol-induced change in craving. Secondary measures included anxiety, anger and withdrawal symptoms. For the visual analog scale for craving, we found a significant interaction (P = 0.0027) between study medication and heroin-dose group (that is, daily low, medium or high dose of heroin). Cortisol administration reduced craving in patients receiving a low dose of heroin (before heroin administration: P = 0.0019; after heroin administration: P = 0.0074), but not in patients receiving a medium or high dose of heroin. In a picture-rating task with drug-related pictures, cortisol administration did not affect the ratings for the picture-characteristic craving in all the three heroin-dose groups. Cortisol also did not significantly affect secondary outcome measures. In conclusion, a single administration of cortisol leads to reduced craving in low-dose heroin addicts. The present findings might have important clinical implications with regard to understanding stress effects and regarding treatment of addiction.

  15. Selective effects of a morphine conjugate vaccine on heroin and metabolite distribution and heroin-induced behaviors in rats.

    PubMed

    Raleigh, M D; Pravetoni, M; Harris, A C; Birnbaum, A K; Pentel, P R

    2013-02-01

    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.

  16. 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

  17. Differences in Methadone Metabolism by CYP2B6 Variants.

    PubMed

    Gadel, Sarah; Friedel, Christina; Kharasch, Evan D

    2015-07-01

    Methadone is a long-acting opioid with considerable unexplained interindividual variability in clearance. Cytochrome P450 2B6 (CYP2B6) mediates clinical methadone clearance and metabolic inactivation via N-demethylation to 2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP). Retrospective studies suggest that individuals with the CYP2B6*6 allelic variant have higher methadone plasma concentrations. Catalytic activities of CYP2B6 variants are highly substrate- and expression-system dependent. This investigation evaluated methadone N-demethylation by expressed human CYP2B6 allelic variants in an insect cell coexpression system containing P450 reductase. Additionally, the influence of coexpressing cytochrome b5, whose role in metabolism can be inhibitory or stimulatory depending on the P450 isoform and substrate, on methadone metabolism, was evaluated. EDDP formation from therapeutic (0.25-1 μM) R- and S-methadone concentrations was CYP2B6.4 ≥ CYP2B6.1 ≥ CYP2B6.5 > CYP2B6.9 ≈ CYP2B6.6, and undetectable from CYP2B6.18. Coexpression of b5 had small and variant-specific effects at therapeutic methadone concentrations but at higher concentrations stimulated EDDP formation by CYP2B6.1, CYP2B6.4, CYP2B6.5, and CYP2B6.9 but not CYP2B6.6. In vitro intrinsic clearances were generally CYP2B6.4 ≥ CYP2B6.1 > CYP2B6.5 > CYP2B6.9 ≥ CYP2B6.6. Stereoselective methadone metabolism (S>R) was maintained with all CYP2B6 variants. These results show that methadone N-demethylation by CYP2B6.4 is greater compared with CYP2B6.1, whereas CYP2B6.9 and CYP2B6.6 (which both contain the 516G>T, Q172H polymorphism), are catalytically deficient. The presence or absence of b5 in expression systems may explain previously reported disparate catalytic activities of CYP2B6 variants for specific substrates. Differences in methadone metabolism by CYP2B6 allelic variants provide a mechanistic understanding of pharmacogenetic variability in clinical methadone metabolism and clearance.

  18. Cocaine esterase: interactions with cocaine and immune responses in mice.

    PubMed

    Ko, Mei-Chuan; Bowen, Luvina D; Narasimhan, Diwahar; Berlin, Aaron A; Lukacs, Nicholas W; Sunahara, Roger K; Cooper, Ziva D; Woods, James H

    2007-02-01

    Cocaine esterase (CocE) is the most efficient protein catalyst for the hydrolysis of cocaine characterized to date. The aim of this study was to investigate the in vivo potency of CocE in blocking cocaine-induced toxicity in the mouse and to assess CocE's potential immunogenicity. Cocaine toxicity was quantified by measuring the occurrence of convulsions and lethality. Intravenous administration of CocE (0.1-1 mg) 1 min before cocaine administration produced dose-dependent rightward shifts of the dose-response curve for cocaine toxicity. More important, i.v. CocE (0.1-1 mg), given 1 min after the occurrence of cocaine-induced convulsions, shortened the recovery time after the convulsions and saved the mice from subsequent death. Effects of repeated exposures to CocE were evaluated by measuring anti-CocE antibody titers and the protective effects of i.v. CocE (0.32 mg) against toxicity elicited by i.p. cocaine (320 mg/kg) (i.e., 0-17% occurrence of convulsions and lethality). CocE retained its potency against cocaine toxicity in mice after a single prior CocE exposure (0.1-1 mg), and these mice did not show an immune response. CocE retained similar effectiveness in mice after three prior CocE exposures (0.1-1 mg/week for 3 weeks), although these mice displayed 10-fold higher antibody titers. CocE partially lost effectiveness (i.e., 33-50% occurrence of convulsions and lethality) in mice with four prior exposures to CocE (0.1-1 mg/2 week for four times), and these mice displayed approximately 100-fold higher antibody titers. These results suggest that CocE produces robust protection and reversal of cocaine toxicity, indicating CocE's therapeutic potential for acute cocaine toxicity. Repeated CocE exposures may increase its immunogenicity and partially reduce its protective ability.

  19. Are empty methadone bottles empty? An analytic study

    PubMed Central

    2014-01-01

    Background Methadone maintenance treatment is the most widely prescribed treatment for opiate dependence with proven benefits for patients. In naïve users or in case of recreational misuse, methadone can be a source of potentially lethal intoxications, resulting in fatal overdoses. A few cases of infantile intoxications have been described in the literature, some of which resulted in death. Nowadays, more than 50,000 bottles are used every day in France, most of which are thrown away in the bin. Relatives at home, especially children, can have access to these empty bottles. This study aims to determine whether the residual quantity of methadone in the bottles is associated with a risk of intoxication for someone who has a low tolerance to opiates, such as a child. Methods The methadone dosage left in a sample of 175 bottles recapped after use by the patients taking their maintenance treatment in an addiction treatment program centre was analysed during a 2-week period in March 2013. Results The mean residual quantity of methadone left in each bottle after use is 1.9 ± 1.8 mg and 3.3 ± 2.4 mg in the sample of 60 mg bottles. Conclusions There is a potential danger of accidental overdose with empty bottles of methadone syrup, especially for children. To take into account this hazard, several harm reduction strategies can be proposed, such as favouring the taking of the treatment within the delivery centres rather than the ‘take home’ doses, asking methadone users to bring back their used bottles, and raising patients’ awareness of the intoxication risks and the necessary everyday precautions. For stable patients with take home methadone, the use of capsules could be considered. PMID:24990630

  20. Sudden sensorineural hearing loss after heroin injection.

    PubMed

    Schrock, Andreas; Jakob, Mark; Wirz, Stefan; Bootz, Friedrich

    2008-05-01

    Sudden sensorineural hearing loss is a symptom of cochlear injury. Potential aetiologies are vascular diseases, viral infections, allergic reactions, autoimmune disorders, and traumatic rupture of the intralabyrinthe membrane. Unlike in unilateral cases bilateral sensorineural hearing loss is often associated with specific disease entities. We report a case of sudden bilateral deafness after intravenous heroin abuse. The putative pathophysiological mechanisms are discussed.

  1. Martha E. Rogers: heretic and heroine.

    PubMed

    Phillips, John R

    2015-01-01

    Rhythms of Martha Rogers' life and work are presented showing her evolution as a heretic and a heroine through her heretical thinking. New concepts of unitariology, energyspirit, wellbecoming, integral presence, and soul are presented with their relevance for advancing Rogers' science of unitary human beings. New dimensions of practice make explicit pandimensional ministering to humankind and living in the universe.

  2. Interdependent Group Contingency Management for Cocaine-Dependent Methadone Maintenance Patients

    ERIC Educational Resources Information Center

    Kirby, Kimberly C.; Kerwin, MaryLouise E.; Carpenedo, Carolyn M.; Rosenwasser, Beth J.; Gardner, Robert S.

    2008-01-01

    Contingency management (CM) for drug abstinence has been applied to individuals independently even when delivered in groups. We developed a group CM intervention in which the behavior of a single, randomly selected, anonymous individual determined reinforcement delivery for the entire group. We also compared contingencies placed only on cocaine…

  3. 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

  4. Cocaine, Appetitive Memory and Neural Connectivity

    PubMed Central

    Ray, Suchismita

    2013-01-01

    This review examines existing cognitive experimental and brain imaging research related to cocaine addiction. In section 1, previous studies that have examined cognitive processes, such as implicit and explicit memory processes in cocaine users are reported. Next, in section 2, brain imaging studies are reported that have used chronic users of cocaine as study participants. In section 3, several conclusions are drawn. They are: (a) in cognitive experimental literature, no study has examined both implicit and explicit memory processes involving cocaine related visual information in the same cocaine user, (b) neural mechanisms underlying implicit and explicit memory processes for cocaine-related visual cues have not been directly investigated in cocaine users in the imaging literature, and (c) none of the previous imaging studies has examined connectivity between the memory system and craving system in the brain of chronic users of cocaine. Finally, future directions in the field of cocaine addiction are suggested. PMID:25009766

  5. Sustained incentive value of heroin-related cues in short- and long-term abstinent heroin users.

    PubMed

    Preller, Katrin H; Wagner, Michael; Sulzbach, Christian; Hoenig, Klaus; Neubauer, Julia; Franke, Petra E; Petrovsky, Nadine; Frommann, Ingo; Rehme, Anne K; Quednow, Boris B

    2013-10-01

    Models of addiction and addiction memory propose that drug-associated cues elicit incentive effects in drug users, which play an important role in maintenance of drug use and relapse. Incentive effects have been demonstrated for smoking and alcohol-related cues but evidence for heroin-related cues has been inconclusive. Furthermore, it is unknown whether appetitive effects of heroin-related cues persist after prolonged abstinence, although heroin addiction is known to have high relapse rates. Therefore, we investigated implicit and explicit valence of heroin-related cues in dependent users at different stages of abstinence using affective startle modulation. In Study I, 15 current heroin users were measured before and after detoxification. Correspondingly, 15 healthy control participants were tested twice at an interval of 14 days. In Study II, 14 long-term abstinent heroin users were additionally measured in a single session. Implicit processing of drug-related stimuli was assessed using affective startle modulation by pictures of heroin and smoking scenes. Explicit reactions were measured using ratings of valence and craving. In contrast to controls, heroin-dependent participants showed a clear reduction of startle response during heroin-related pictures (p<0.05). Detoxification did not significantly change their startle responses to heroin-cues. No difference between non-detoxified current and long-term abstinent heroin users was found in implicit reactions to heroin-cues, whereas explicit measures differed between both groups (all p<0.05). After detoxification and even after prolonged abstinence, heroin cues still exert implicit appetitive effects in heroin users. This implies that drug-induced adaptations of reward circuits are long-lasting, resulting in a highly stable addiction memory.

  6. The North American Opiate Medication Initiative (NAOMI): profile of participants in North America's first trial of heroin-assisted treatment.

    PubMed

    Oviedo-Joekes, Eugenia; Nosyk, Bohdan; Brissette, Suzanne; Chettiar, Jill; Schneeberger, Pascal; Marsh, David C; Krausz, Michael; Anis, Aslam; Schechter, Martin T

    2008-11-01

    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.

  7. Gender differences in pharmacokinetics and pharmacodynamics of methadone substitution therapy

    PubMed Central

    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. Method: 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. Results: 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. Conclusion: 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. PMID:26106330

  8. [Fatal methadone poisoning: observations at the CHU of Liege].

    PubMed

    Denooz, R; Charlier, C

    2006-01-01

    All methadone-associated deaths from October 2002 to April 2005 are analysed. A regular increase in these fatal intoxications has been recorded, in Belgium as in other countries, due, in particular, to an intensified prescription of this product, of which illicit use as street dope becomes problematic. Over the 30 months period covered by the study, 26 deaths related to methadone were listed, of which 3 occurred in accidental circumstances. In the other 23 cases, methadone can be found, yet always associated with psychotropic substances, mainly benzodiazepines (18 cases), narcotics (15 cases) and finally alcohol (5 cases). Based upon the nature of the products combined with methadone, records have been divided in two groups: In the first group (17 observations), xenobiotics at (infra)therapeutic levels are detected. In the other group (6 observations), xenobiotics at high and toxic levels are detected. Blood methadone concentrations are not so different between the 2 groups of individuals since the median values and the extreme values are worth respectively 308, and 110-11300 microg/L, for the first group and 776 and 93-2080 microg/L for the second group. There is thus an important overlap between the therapeutic blood methadone concentrations (150-400 microg/L) and blood concentrations observed in fatalities.Thus, it is necessary that all information and post-mortem results must be examined in a critical way to identify and justify cause of the death.

  9. 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

  10. Employment-Based Reinforcement to Motivate Naltrexone Ingestion and Drug Abstinence in the Treatment of Drug Addiction. - 1

    ClinicalTrials.gov

    2005-11-03

    Behavior Therapy; Cocaine; Cocaine (IV); Cocaine Abuse; Cocaine Dependence; Contingency Management; HIV Risk Behaviors; Heroin; Heroin Dependence; Naltrexone; Opioid Dependence; Substance Abuse, Intravenous; Sexual Risk Behaviors

  11. Cocaine Conditioned Behavior: A Cocaine Memory Trace or an Anti-Habituation Effect

    PubMed Central

    Carey, Robert J.; Damianopoulos, Ernest N.; Shanahan, Arielle B.

    2008-01-01

    Whether cocaine locomotor conditioning represents a cocaine positive effect; i.e., a Pavlovian cocaine conditioned response; or, a cocaine negative effect; i.e., interference with habituation to the test environment, is a subject of some controversy. Three separate experiments were conducted to compare the behavior (locomotion and grooming) of separate groups of rats given 1, 9 or 14 cocaine (10 mg/kg) treatments paired/unpaired with placement into an open-field arena. The behavior of the cocaine groups on subsequent saline tests were compared with the habituation rates of saline treated rats. After one cocaine pairing with the test environment, the subsequent behavior of the cocaine-paired group on saline tests was similar to a non-habituated control group. In the two experiments with repeated cocaine pairings to the test environment, the subsequent behavior of the cocaine treated groups did not parallel that of the non-habituated saline control groups. These results were not explicable in terms of cocaine anti-habituation effects. It is suggested that cocaine contextual cues paired with cocaine treatment can activate cocaine memory traces which with subsequent cocaine treatments are reinforced and strengthened. In this way repeated cocaine use can forge conditioned stimulus connections to the cocaine behavioral response that are highly resistant to extinction. PMID:18571225

  12. Recreational drugs, methadone and protease inhibitors.

    PubMed

    Timour, K

    1998-01-01

    The Treatment Education Project, an initiative of the Staten Island AIDS Task Force, often responds to requests for information on the effects of recreational drugs on people taking anti-HIV medications. There is very little research on the topic because the drugs are illegal and the effects tested with chemically pure street drugs are not likely to mirror those in the population using varied strengths and qualities of the drugs. There have been some controlled studies with methadone, and there is a trial underway to test the use of Marinol and marijuana with Crixivan. The Treatment Education Project also provides counseling, maintains Internet sites in both English and Spanish, and sets up treatment libraries. They also provide workshops for social service agencies and staff.

  13. Cocaine Use: 2002 and 2003. The NSDUH Report

    ERIC Educational Resources Information Center

    Substance Abuse and Mental Health Services Administration, 2005

    2005-01-01

    Cocaine, including crack cocaine, was responsible for 12.8 percent of admissions to substance abuse treatment services in 2002.1 The National Survey on Drug Use and Health (NSDUH) asks persons aged 12 or older to report their use of illicit drugs, including cocaine. NSDUH defines cocaine use as use of cocaine in any form, including crack cocaine.…

  14. Effects of cocaine, cocaine metabolites and cocaine pyrolysis products on the hindbrain cardiac and respiratory centers of the rabbit.

    PubMed

    Erzouki, H K; Allen, A C; Newman, A H; Goldberg, S R; Schindler, C W

    1995-01-01

    Hemodynamic and respiratory effects of vertebral artery or i.v. administration of cocaine, cocaine metabolites and cocaine pyrolysis products were measured in anesthetized rabbits. Vertebral artery administration of 1 mg of cocaine produced decreases in blood pressure and heart rate and respiratory arrest. Cocaethylene (1 mg), a cocaine metabolite produced following co-administration of cocaine and ethanol, had comparable effects except that the respiratory arrest following cocaethylene had a longer duration of action than did cocaine. A decrease in blood pressure was also observed following 1 mg of norcocaine; however, unlike cocaine, norcocaine did not affect respiration. Acute tolerance was not observed to any of the effects of 1 mg of cocaine, cocaethylene or norcocaine following vertebral artery administration. None of these compounds had significant effects following i.v. administration of the same dose. The cocaine metabolites benzoylecgonine and ecgonine methyl ester were without effect by either route in doses up to 3 mg. In contrast to cocaine, the cocaine pyrolysis products anhydroecgonine methyl ester (3 mg) and noranhydroecgonine methyl ester (3 mg) produced similar effects via both routes of administration. Both compounds produced decreases in blood pressure and heart rate and an increase in respiratory rate. Anhydroecgonine ethyl ester (3 mg), a metabolite hypothetically formed from the cocaine pyrolysis product in individuals co-administering ethanol, had effects similar to the other pyrolysis products, although its effects were not as prominent via the i.v. route of administration. Acute tolerance was observed upon administration of the cocaine pyrolysis products. These results indicate that the cocaine pyrolysis products do not share a common mechanism of action with either cocaine or the cocaine metabolites.

  15. 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

  16. Detection of clinical interactions between methadone and anti-retroviral compounds using an enantioselective capillary electrophoresis for methadone analysis.

    PubMed

    Esteban, Javier; de la Cruz Pellín, María; Gimeno, Carmen; Barril, José; Mora, Eva; Giménez, Jesús; Vilanova, Eugenio

    2004-06-15

    A capillary electrophoresis method was developed to detect interactions between methadone and anti-retroviral compounds. Eight subjects, who underwent methadone maintenance treatment in the Province of Alicante (Spain), consented to participate in the present study. Of those, one subject was followed up for 123 days to detect drug-drug interactions. The enantiomers of methadone and those of its main metabolite were conveniently resolved within 4 min using a chiral electrophoresis buffer mixture which consisted of phosphate buffer, pH 5, plus 0.2% highly sulphated-(beta)-cyclodextrin. The effective mobility of the analytes was in the 0.061-0.140 cm(2)/(kV s) range at pH 5. The R-methadone plasma concentration range for seven patients was 91-318 ng/mL, it decreased from 186 to 46 ng/mL in a patient followed-up on commencement of the anti-retroviral therapy, returning to the previous higher levels after progressive dose increases. We conclude that monitoring R-methadone plasma levels can be a useful tool for the dose adjustment of methadone.

  17. Determination and Validation of a Solid-phase Extraction Gas Chromatography-mass Spectrometry for the Quantification of Methadone and Its Principal Metabolite in Human Plasma

    PubMed Central

    Chiadmi, Fouad; Schlatter, Joël

    2015-01-01

    This study aimed to develop a solid-phase extraction gas chromatography-selected ion monitoring-mass spectrometry method for the determination of methadone (MDN) and 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) in human plasma. The linear response was obtained over the concentration range from 10 to 2000 ng/mL for MDN and EDDP. The absolute recoveries of MDN and EDDP were 95.9%–98.9% and 94.8%–102.4%, with relative standard deviation (RSD) ranging from 1.8% to 2.7% and 1.8% to 3.9%, respectively. The intra- and interday precisions were found to be less than 5% for both analytes. The limits of detection of MDN and EDDP were 4 and 5 ng/mL, respectively. The presented method was convenient for therapeutic drug monitoring and pharmacokinetic studies in patients on heroin-assisted MDN therapy. PMID:26339186

  18. Using chi-Squared Automatic Interaction Detection (CHAID) modelling to identify groups of methadone treatment clients experiencing significantly poorer treatment outcomes.

    PubMed

    Murphy, Emma L; Comiskey, Catherine M

    2013-10-01

    In times of scarce resources it is important for services to make evidence based decisions when identifying clients with poor outcomes. chi-Squared Automatic Interaction Detection (CHAID) modelling was used to identify characteristics of clients experiencing statistically significant poor outcomes. A national, longitudinal study recruited and interviewed, using the Maudsley Addiction Profile (MAP), 215 clients starting methadone treatment and 78% were interviewed one year later. Four CHAID analyses were conducted to model the interactions between the primary outcome variable, used heroin in the last 90 days prior to one year interview and variables on drug use, treatment history, social functioning and demographics. Results revealed that regardless of these other variables, males over 22 years of age consistently demonstrated significantly poorer outcomes than all other clients. CHAID models can be easily applied by service providers to provide ongoing evidence on clients exhibiting poor outcomes and requiring priority within services.

  19. Response to cocaine, alone and in combination with methylphenidate, in cocaine abusers with ADHD.

    PubMed

    Collins, Stephanie L; Levin, Frances R; Foltin, Richard W; Kleber, Herbert D; Evans, Suzette M

    2006-04-28

    Attention deficit hyperactivity disorder (ADHD) is prevalent in adult cocaine abusers. Yet, it remains to be determined how the response to cocaine differs in cocaine abusers with ADHD compared to cocaine abusers without ADHD. Further, since ADHD is commonly treated with stimulants, such as methylphenidate (MPH), it is important to examine whether MPH maintenance alters the response to cocaine in cocaine abusers with ADHD. Thus, the first phase of this study compared the response to cocaine in adult cocaine abusers with ADHD to those without ADHD. The second phase assessed the effects of oral sustained-release methylphenidate (MPH-SR) maintenance (40 and 60 mg) on the response to cocaine only in those with ADHD. Cocaine abusers with ADHD (N=7) and without ADHD (N=7) who were not seeking treatment remained inpatient initially for 1 week, when the effects of cocaine alone were tested (Phase 1). Cocaine abusers with ADHD remained inpatient for an additional 3 weeks, during which the effects of cocaine during oral MPH-SR maintenance were tested (Phase 2). During cocaine fixed dosing sessions, participants received four injections of i.v. cocaine (0, 16 or 48 mg/70 kg), spaced 14 min apart. During cocaine choice sessions, participants had a choice between receiving i.v. cocaine (16 or 48 mg/70 kg) or two tokens, each exchangeable for 2 US dollars. Subjective effects related to ADHD symptoms (e.g. ratings of "Able to Concentrate") were significantly lower in cocaine abusers with ADHD compared to those without ADHD when placebo cocaine was administered. Active cocaine produced similar increases in cardiovascular and positive subjective effects in both groups and there was no difference in cocaine choice between the two groups. These data suggest that the response to cocaine is not different between cocaine abusers with ADHD compared to those without ADHD. When the cocaine abusers with ADHD were maintained on MPH-SR, cardiovascular effects were increased, however, this did

  20. The phosphodiesterase-4 inhibitor rolipram attenuates heroin-seeking behavior induced by cues or heroin priming in rats.

    PubMed

    Lai, Miaojun; Zhu, Huaqiang; Sun, Anna; Zhuang, Dingding; Fu, Dan; Chen, Weisheng; Zhang, Han-Ting; Zhou, Wenhua

    2014-09-01

    Inhibition of phosphodiesterase-4 (PDE4), an enzyme that specifically hydrolyzes cyclic adenosine monophosphate (cAMP) increases intracellular cAMP/cAMP-response element binding protein (CREB) signaling. Activation of this signaling is considered as an important compensatory response that decreases motivational properties of drugs of abuse. However, it is not known whether PDE4 is involved in heroin seeking. Self-administration of heroin (50 μg/kg/infusion) was performed under the fixed ratio 1 (FR1) schedule for 14 d and then drug seeking was extinguished for 10 d. The progressive ratio schedule was used to evaluate the relative motivational value of heroin reinforcement. After training, the conditioned cue or heroin priming (250 μg/kg) was introduced for the reinstatement of heroin-seeking behavior. Pretreatment (i.p.) with rolipram (0.03-0.3 mg/kg), a prototypical, selective PDE4 inhibitor, failed to inhibit heroin self-administration under the FR1 schedule, but decreased the reward values under the progressive ratio schedule in a dose-dependent manner. In addition, rolipram decreased the reinstatement of heroin seeking induced by cues or heroin priming even at the lowest dose (0.03 mg/kg); in contrast, the highest dose (0.3 mg/kg) of rolipram was required to decrease sucrose reinforcement. Finally, the effects of rolipram on heroin-seeking behavior were correlated with the increases in expression of phosphorylated CREB in the nucleus accumbens. The study demonstrated that rolipram inhibited heroin reward and heroin-seeking behavior. The results suggest that PDE4 plays an essential role in mediating heroin seeking and that PDE4 inhibitors may be used as a potential pharmacotherapeutic approach for heroin addiction.

  1. Substance use and response to psychiatric treatment in methadone-treated outpatients with comorbid psychiatric disorder

    PubMed Central

    Kidorf, Michael; King, Van L.; Peirce, Jessica; Gandotra, Neeraj; Ghazarian, Sharon; Brooner, Robert K.

    2014-01-01

    The psychiatric care of opioid users receiving agonist therapies is often complicated by high rates of illicit drug use (Brooner et al., 2013). The present study evaluates if illicit drug use (i.e., opioids, cocaine, sedatives) detected at the start of psychiatric care affects treatment response. Methadone maintenance patients (n = 125) with at least one current psychiatric disorder completed a 3-month randomized clinical trial evaluating the efficacy of financial incentives on attendance to on-site integrated substance abuse and psychiatric services (Kidorf et al., 2013). The present study re-analyzes the data set by grouping participants into one of two conditions based on the 4-week baseline observation: 1) no illicit drug use (Baseline Negative; n = 50), or 2) any illicit drug use (Baseline Positive; n = 75). All participants received a similar schedule of psychiatric services, and had good access to prescribed psychiatric medications. The Global Severity Index (GSI) of the Hopkins Symptom Checklist-Revised was administered monthly to evaluate changes in psychiatric distress. Results showed that while both conditions evidenced similar utilization of on-site psychiatric services, Baseline Negative participants remained in treatment somewhat longer (80.7 vs. 74.8 days, p = .04) and demonstrated greater reductions in GSI scores than Baseline Positive participants at Month 3 (p = .004). These results have implications for interpreting previous studies that have shown inconsistent efficacy of pharmacotherapy and other psychiatric treatments, and for providing clinical care for patients with co-occurring substance use and psychiatric disorders. PMID:25468006

  2. Alcohol administration increases cocaine craving but not cocaine cue attentional bias

    PubMed Central

    Marks, Katherine R.; Pike, Erika; Stoops, William W.; Rush, Craig R.

    2015-01-01

    Background Alcohol consumption is a known antecedent to cocaine relapse. Through associative conditioning, it is hypothesized that alcohol increases incentive motivation for cocaine and thus the salience of cocaine-related cues, which are important in maintaining drug-taking behavior. Cocaine-using individuals display a robust cocaine cue attentional bias as measured by fixation time during the visual probe task. The purpose of the present study was to evaluate the influence of alcohol administration on cocaine cue attentional bias using eye-tracking technology to directly measure attentional allocation. Methods Twenty current cocaine users completed a double-blind, placebo-controlled, within-subjects study that tested the effect of three doses of alcohol (0.00, 0.325, 0.65 g/kg alcohol) on cocaine cue attentional bias using the visual probe task with eye-tracking technology. The participant-rated and physiological effects of alcohol were also assessed. Results Participants displayed a robust cocaine cue attentional bias following both placebo and alcohol administration as measured by fixation time, but not response time. Alcohol administration did not influence cocaine cue attentional bias, but increased craving for cocaine in a dose dependent manner. Alcohol produced prototypic psychomotor and participant-rated effects. Conclusions Alcohol administration increases cocaine craving but not cocaine cue attentional bias. Alcohol-induced cocaine craving suggests that alcohol increases incentive motivation for cocaine but not the salience of cocaine-related cues. PMID:26331880

  3. Pain Among High-Risk Patients on Methadone Maintenance Treatment.

    PubMed

    Voon, Pauline; Hayashi, Kanna; Milloy, M-J; Nguyen, Paul; Wood, Evan; Montaner, Julio; Kerr, Thomas

    2015-09-01

    The complexity of treating concurrent pain and opioid dependence among many methadone-maintained individuals presents a major challenge in many clinical settings. Furthermore, recent expert guidelines have called for increased research on the safety of methadone in the context of chronic pain. This study explores the prevalence and correlates of pain among a prospective cohort of people who use illicit drugs in Vancouver, British Columbia, Canada, who reported enrollment in methadone maintenance treatment (MMT) between 2011 and 2014. Among the 823 participants eligible for this analysis, 338 (40.9%) reported moderate pain and 91 (11.1%) reported extreme pain at the first study visit. In multivariable, generalized, linear mixed model analyses, higher pain severity was positively and independently associated with self-managing pain (adjusted odds ratio [AOR] 2.15, 95% confidence interval [CI] 1.77-2.60), patient perception of methadone dose being too low (AOR 1.82, 95% CI 1.41-2.34), older age (AOR 1.31, 95% CI 1.13-1.51), having a physical disability (AOR 4.59, 95% CI 3.73-5.64), having ever been diagnosed with a mental illness (AOR 1.44, 95% CI 1.13-1.84), white ethnicity (AOR 1.42, 95% CI 1.10-1.83), and marijuana use (AOR 1.25, 95% CI 1.02-1.52). These findings suggest several areas for clinical intervention, particularly related to patient education and alternative analgesic approaches for MMT patients experiencing pain. Perspective: To better understand the complexity of concurrent pain and opioid dependency among individuals on methadone maintenance treatment, this article describes the prevalence and correlates of higher pain severity among methadone-maintained people who use illicit drugs. Patients on methadone with comorbid pain may benefit from education and alternative analgesic approaches.

  4. Cause of death conundrum with methadone use: a case report.

    PubMed

    Letsky, Michael C; Zumwalt, Ross E; Seifert, Steven A; Benson, Blaine E

    2011-06-01

    Deaths caused by a methadone intoxication or overdose are becoming more frequent. We report a case involving a patient who had extremely high methadone blood concentrations but whose cause of death may have been unrelated to the drug. A 51-year-old woman was found deceased in bed by her daughter. At the scene were numerous bottles of methadone, with the chronic dosage of 240 mg 3 times a day. There was no history of prior suicide attempts, there were no reports of suicidal ideation having been voiced and there was no suicide note. At autopsy, there were no pills found in the stomach. Microscopic tissue examination revealed lobar pneumonia of the right lower lobe. Postmortem lung cultures grew out Streptococcus pneumoniae. Femoral blood contained methadone, 5.7 mg/L; EDDP, 2.1 mg/L; oxycodone, 0.017 mg/L; doxylamine, 0.022 mg/L; and ethanol, 13.0 mg/dL. The postmortem methadone concentration was consistent with her known dose, plausible pharmacokinetics and conditions of discovery. Various causes of death, such as a methadone-related arrhythmia from QTc prolongation or the contribution of methadone to the development of the pneumonia, cannot be ruled out and may well have caused or contributed to death, but the pneumonia was felt to be a competent cause of death. Ultimately, the most likely cause(s) of death, is a decision left to the individual medical examiner. This case is illustrative of the growing number of similar cases facing forensic pathologists. The cause of death cannot be solely based on drug concentrations and it may not be possible to come to a conclusion as to "the" cause of death and the forensic pathologist must be content with "a" cause of death.

  5. Heroin self-administration by means of 'chasing the dragon': pharmacodynamics and bioavailability of inhaled heroin.

    PubMed

    Hendriks, V M; van den Brink, W; Blanken, P; Bosman, I J; van Ree, J M

    2001-06-01

    In this controlled clinical study, the bioavailability and pharmacodynamics of inhaled heroin are evaluated and compared between 'chasing the dragon' and inhalation from a heating device, and at three dose levels, 25, 50 and 100 mg heroin, in two separate study phases. In study phase 1, no differences between the inhalation methods were detected on any of the physiological or behavioral measures, nor in bioavailability. Subjectively, the participants had a strong preference for the method of chasing, which was therefore used in study phase 2. In phase 2, heroin produced a dose-related increase in subjective drug-liking, body temperature and heart rate, and a clear, dose-related decline in reaction time. Linearly dose-related differences were found in the amount of total morphine in urine, amounting to an average of 45% of the parent heroin base received. Based on these findings, it is concluded that chasing is quite an effective route of heroin administration, producing rapid, dose-related subjective and objective effects and a sufficiently high and reproducible bioavailability.

  6. Methadone disposition in oral fluid during pharmacotherapy for opioid-dependence

    PubMed Central

    Gray, Teresa R.; Dams, Riet; Choo, Robin E.; Jones, Hendree E.; Huestis, Marilyn A.

    2010-01-01

    Introduction Oral fluid testing is widely used for detecting drug exposure, but data describing methadone and metabolites in oral fluid during pharmacotherapy for opioid-dependence are relatively limited. Method 414 oral fluid specimens from 16 opioid-dependent pregnant women receiving daily methadone were analyzed for methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), and methadol by liquid chromatography-mass spectrometry. Results All oral fluid specimens contained methadone greater than 1 ng/mL; 88% were positive for EDDP and 12% for methadol. Over 95% of oral fluid specimens exceeded the 20 ng/mL methadone cutoff set by the European Driving Under the Influence of Drugs, Alcohol and Medicines (DRUID) study. Methadone and EDDP oral fluid concentrations were highly variable within and between participants, did not predict methadone dose, but were negatively correlated with pH. Conclusion Methadone was readily identified in oral fluid at concentrations greater than 20 ng/mL following daily 30–110 mg/day methadone pharmacotherapy. As no specimens contained only EDDP or methadol, there was no advantage to including these analytes for identification of methadone exposure. As nearly all oral fluid specimens from methadone-maintained patients exceeded the DRUID guideline, the 20 ng/mL cutoff appears to be sensitive enough to detect daily methadone exposure; however, additional indicators of behavioral and/or motor impairment would be necessary to provide evidence of driving impairment. PMID:20667673

  7. [Analysis of two year heroin seizures in the Liege area].

    PubMed

    Denooz, R; Dubois, N; Charlier, C

    2005-09-01

    The results of heroin analysis from seizures in the Liege area during the last two years are presented in this article. Between January 2003 and January 2005, 50 samples were analysed in the Laboratory of Clinical Toxicology and Forensic Toxicology of the University of Liege. Mean heroin concentration was 14,7%. Noscapine and papaverine, other opium alcaloïds, were simultaneously present with heroin. As diluents, we only identified caffein and acetaminophen.

  8. Lemon juice as a solvent for heroin in Spain.

    PubMed

    Page, J B; Fraile, J S

    1999-06-01

    Preliminary observations and responses to interviews in Valencia, Spain reveal that injecting drug users (IDUs) dissolve heroin before injection with two or three drops of lemon juice. Solution in lemon juice makes heating of heroin in water unnecessary. This pattern apparently developed spontaneously in Spain, but is almost unknown elsewhere in the world. Its implications for IDUs' health remain speculative, but use of lemon juice to dissolve heroin for injection deserves further scientific study.

  9. Tips for Teens: The Truth about Cocaine

    MedlinePlus

    ... crack) form. It is made from the coca plant and causes a short-lived high that is ... permanently damage their nasal tissue. Cocaine affects your emotions. Using cocaine can make you feel paranoid, angry, ...

  10. Pyrolysis and volatilization of cocaine

    SciTech Connect

    Martin, B.R.; Lue, L.P.; Boni, J.P. )

    1989-05-01

    The increasing popularity of inhaling cocaine vapor prompted the present study, to determine cocaine's fate during this process. The free base of (3H)cocaine (1 microCi/50 mg) was added to a glass pipe, which was then heated in a furnace to simulate freebasing. Negative pressure was used to draw the vapor through a series of glass wool, ethanol, acidic, and basic traps. Air flow rate and temperature were found to have profound effects on the volatilization and pyrolysis of cocaine. At a temperature of 260 degrees C and a flow rate of 400 mL/min, 37% of the radioactivity remained in the pipe, 39% was found in the glass wool trap, and less than 1% in the remainder of the volatilization apparatus after a 10-min volatilization. Reducing the air flow rate to 100 mL/min reduced the amount of radioactivity collected in the glass wool trap to less than 10% of the starting material and increased the amount that remained in the pipe to 58%. GC/MS analysis of the contents of the glass wool trap after volatilization at 260 degrees C and a flow rate of 400 mL/min revealed that 60% of the cocaine remained intact, while approximately 6 and 2% of the starting material was recovered as benzoic acid and methylecgonidine, respectively. As the temperature was increased to 650 degrees C, benzoic acid and methylecgonidine accounted for 83 and 89% of the starting material, respectively, whereas only 2% of the cocaine remained intact. Quantitation of cocaine in the vapor during the course of volatilization revealed high concentrations during the first two min and low concentrations for the remaining time.

  11. Documentation of a heroin manufacturing process in Afghanistan.

    PubMed

    Zerell, U; Ahrens, B; Gerz, P

    2005-01-01

    The present article documents an authentic process of heroin manufacturing in Afghanistan: white heroin hydrochloride produced using simple equipment and a small quantity of chemicals. The quantities of chemicals actually used corresponded to the minimum needed for manufacturing heroin. The only organic solvent used was acetone, and only a very small quantity of it was used. Because the chemicals used in the demonstration were from actual seizures in Afghanistan, some of the chemicals had been disguised or repackaged by smugglers. Others had been put into labelled containers that proved to be counterfeit, and some glass containers used were not the original containers of the manufacturer displayed on the label. The brown heroin base prepared as an intermediate step in the process shares some of the characteristics of the South-West Asia type of heroin preparations often seized in Germany. The final product of the documented heroin manufacturing process was white heroin hydrochloride, which shares the key characteristics of the white heroin occasionally seized in Germany and other countries in Western Europe since 2000. The present article demonstrates that this kind of heroin can be produced in Afghanistan.

  12. Rethinking Informed Consent in Research on Heroin-Assisted Treatment.

    PubMed

    Uusitalo, Susanne; Broers, Barbara

    2015-09-01

    Can heroin addicts give consent to research on trials in which heroin is prescribed to them? Analyses of addicts and informed consent have been objects of debate in several articles. Informed consent requires the agent not only to be competent but also to give consent voluntarily. This has been questioned because of alleged features of heroin addiction. Until recently the discussion has focused on heroin addicts' desires for heroin, whether these are irresistible and thus pose a problem for giving consent. Still, in light of empirical evidence, there seems to be a consensus more or less that the problem is not whether the addicts can resist their desire for heroin. A recent article concentrates specifically on heroin addicts' false assumptions of options and voluntariness. We argue that the prevailing framing of the options in this discussion in terms of heroin and access to it is problematic. The way in which the options are typically laid out suggests an assumption that participation in the research is allegedly based on the addicts' views on using the drug. We argue that this way of presenting the options is, first, a mismatch to the studies carried out and, second, symptomatic of potential misconceptions about heroin addiction and addicts. Furthermore, we also suggest that the account of voluntariness needs to be realistic in order for subjects to be able to give consent voluntarily in actual situations, and for medical research to carry out studies on improving outcomes in addiction treatment in an ethical way.

  13. Contact allergy and respiratory/mucosal complaints from heroin (diacetylmorphine).

    PubMed

    Hogen Esch, A J; van der Heide, S; van den Brink, W; van Ree, J M; Bruynzeel, D P; Coenraads, P J

    2006-01-01

    After the start of heroin (diacetylmorphine)-assisted treatment to a selected group of chronic treatment-resistant heroin-dependent patients in the Netherlands, we reported about work-related eczema and positive patch tests to heroin in some nurses and nasal and respiratory complaints. To investigate the prevalence of heroin contact allergy, we started a questionnaire-based study with follow-up by allergological examinations. Of 120 questionnaires sent, 101 (84%) was returned: 67 from nurses and 34 from other employees. Of 101 workers, 38 (38%) had reported work-related complaints: 33 of 67 (49%) nurses and 5 of 34 (15%) other employees. Patch tests to heroin were performed in 24 nurses and were positive in 8 (33%). All the 8 had eyelid or facial eczema and, in 6, accompanied by mucosal or respiratory complaints. The prevalence of heroin contact allergy in this study was 8% (8/101) among all employees and 12% (8/67) among nurses. Respiratory and mucosal complaints could not be ascribed to a contact allergy, and in these cases, serum was analysed for specific immunoglobulin E to heroin. A type 1 allergy to heroin could not be shown. These complaints are possibly due to the histamine-liberating effect of heroin, to atopic constitution, to a combination of these factors or - less likely - to other non-allergic factors.

  14. A heroin addict with focal weakness.

    PubMed

    Galassi, Giuliana; Ariatti, Alessandra; Gozzi, Manuela; Cavazza, Stefano

    2013-05-01

    A 24-year-old female with 5 year history of heroin abuse experienced painless stiffness of elbow joints and weakness of shoulder and upper limb muscles. She was injecting herself 4-6 times daily alternatively in the upper extremities, sparing the lower limbs. Electromyography (EMG) showed myopathic changes in clinically affected and unaffected muscles. Magnetic resonance imaging (MRI) revealed muscle fibrosis in directly injected muscles, whereas in subcutaneous fat and within muscles of anterior and posterior compartments of both thighs, not directly injected, there were signal changes supportive of oedema and inflammation. EMG and MRI were congruent in showing abnormalities in muscles not directly injected, suggesting long distant effects of heroin or adulterants with a mechanism either toxic or immunologically mediated.

  15. A System Description of the Heroin Trade

    DTIC Science & Technology

    1994-01-01

    104 Bibliography .............................................. log vii Figures 1.1. Worldwide Opium Production: NNICC and INCSR Estimates from 1983 to...United States (18 to 25 Years Old) ........................................ 5 2.1. The World’s Three Principal Opium Producing Regions ......... 10 2.2... Opium Production by the Major Producing Countries in 1991 ..... 11 2.3. Heroin Availability in the United States by Source Region ....... 14 3.1

  16. [Efficiency of noophen in heroin addiction].

    PubMed

    Kuchkarov, U I; Ashurov, Z Sh; Sultanov, Sh Kh

    2009-01-01

    24 patients with heroin addiction have been observed with the purpose to assess cognitive and neurosis-like disorders during the treatment with Noofen. The methods of research included clinical-psychopathological examination. The course therapy with Noofen reduced intensity of memory and attention disorders and improved general cognitive status of the patients. The therapy with Noofen has not increased a pathological drive to narcotics. Noofen use has improve cognitive sphere alongside with reduction in concomitant psychopathological symptoms including depressive and other disorders.

  17. Signs of Cocaine Abuse and Addiction

    MedlinePlus

    ... Signs of Cocaine Use and Addiction Signs of Cocaine Use and Addiction Listen ©istock.com/ AntonioGuillern After ... English Español "My life was built around getting cocaine and getting high." ©istock.com/ Marjot Stacey is ...

  18. Prenatal Cocaine Exposure and Infant Cortisol Reactivity

    ERIC Educational Resources Information Center

    Eiden, Rina D.; Veira, Yvette; Granger, Douglas A.

    2009-01-01

    This study examined the effects of prenatal cocaine exposure on infant hypothalamic-pituitary-adrenal axis activity and reactivity at 7 months of infant age. Participants were 168 caregiver-infant dyads (87 cocaine exposed, 81 not cocaine exposed; 47% boys). Maternal behavior, caregiving instability, and infant growth and behavior were assessed,…

  19. Increases in body mass index following initiation of methadone treatment.

    PubMed

    Fenn, Jennifer M; Laurent, Jennifer S; Sigmon, Stacey C

    2015-04-01

    Despite the clear efficacy of methadone for opioid dependence, one less desirable phenomenon associated with methadone may be weight gain. We examined changes in body mass index (BMI) among patients entering methadone treatment. A retrospective chart review was conducted for 96 patients enrolled in an outpatient methadone clinic for ≥ 6 months. The primary outcome of BMI was assessed at intake and a subsequent physical examination approximately 1.8 ± 0.95 years later. Demographic, drug use and treatment characteristics were also examined. There was a significant increase in BMI following intake (p<0.001). Mean BMIs increased from 27.2 ± 6.8 to 30.1 ± 7.7 kg/m(2), translating to a 17.8-pound increase (10% increase in body weight) in the overall patient sample. Gender was the strongest predictor of BMI changes (p < 0.001), with significantly greater BMI increases in females than males (5.2 vs. 1.7 kg/m(2), respectively). This translates to a 28-pound (17.5%) increase in females vs. a 12-pound (6.4%) increase in males. In summary, methadone treatment enrollment was associated with clinically significant weight gain, particularly among female patients. This study highlights the importance of efforts to help patients mitigate weight gain during treatment, particularly considering the significant health and economic consequences of obesity for individuals and society more generally.

  20. Interim versus standard methadone treatment: a benefit-cost analysis.

    PubMed

    Schwartz, Robert P; Alexandre, Pierre K; Kelly, Sharon M; O'Grady, Kevin E; Gryczynski, Jan; Jaffe, Jerome H

    2014-03-01

    A benefit-cost analysis was conducted as part of a clinical trial in which newly-admitted methadone patients were randomly assigned to interim methadone (IM; methadone without counseling) for the first 4 months of 12 months of methadone treatment or 12 months of methadone with one of two counseling conditions. Health, residential drug treatment, criminal justice costs, and income data in 2010 dollars were obtained at treatment entry, and 4- and 12-month follow-up from 200 participants and program costs were obtained. The net benefits of treatment were greater for the IM condition but controlling for the baseline variables noted above, the difference between conditions in net monetary benefits was not significant. For the combined sample, there was a pre- to post-treatment net benefit of $1470 (95% CI: -$625; $3584) and a benefit-cost ratio of 1.5 (95% CI: 0.8, 2.3), but using our conservative approach to calculating benefits, these values were not significant.

  1. Methadone in healthy goats - pharmacokinetics, behaviour and blood pressure.

    PubMed

    Olsén, L; Olsson, K; Hydbring-Sandberg, E; Bondesson, U; Ingvast-Larsson, C

    2013-08-01

    The pharmacokinetics and effects of the opioid methadone on behaviour, arterial blood pressure, heart rate and haematocrit were studied in goats. Two goats received methadone (0.2mg/kg) intravenously and the terminal half-life was 88 and 91 min, the volume of distribution 8.4 and 6.1L/kg, and clearance 86 and 123 mL/min/kg. In a crossover study eight goats received methadone (0.6 mg/kg) or 0.15M NaCl subcutaneously (SC). After SC administration bioavailability was complete and the terminal half-life was 215 ± 84 min (mean ± SD), Tmax 31 ± 15 min and Cmax 45 ±11 ng/mL. Blood pressure and haematocrit increased while heart rate did not change. The goats did not ruminate and they climbed, scratched, gnawed and showed tail-flicking after SC methadone in contrast to NaCl administration. The use of methadone in goats may be restricted due to the inhibition of rumination and the rather short half-life.

  2. Discriminative and reinforcing stimulus effects of nicotine, cocaine, and cocaine + nicotine combinations in rhesus monkeys.

    PubMed

    Mello, Nancy K; Newman, Jennifer L

    2011-06-01

    Concurrent cigarette smoking and cocaine use is well documented. However, the behavioral pharmacology of cocaine and nicotine combinations is poorly understood, and there is a need for animal models to examine this form of polydrug abuse. The purpose of this study was twofold: first to assess the effects of nicotine on the discriminative stimulus effects of cocaine, and second, to study self-administration of nicotine/cocaine combinations in a novel polydrug abuse model. In drug discrimination experiments, nicotine increased the discriminative stimulus effects of low cocaine doses in two of three monkeys, but nicotine did not substitute for cocaine in any monkey. Self-administration of cocaine and nicotine alone, and cocaine + nicotine combinations was studied under a second-order fixed ratio 2, variable ratio 16 (FR2[VR16:S]) schedule of reinforcement. Cocaine and nicotine alone were self-administered in a dose-dependent manner. The combination of marginally reinforcing doses of cocaine and nicotine increased drug self-administration behavior above levels observed with the same dose of either cocaine or nicotine alone. These findings indicate that nicotine may increase cocaine's discriminative stimulus and reinforcing effects in rhesus monkeys, and illustrate the feasibility of combining cocaine and nicotine in a preclinical model of polydrug abuse. Further studies of the behavioral effects of nicotine + cocaine combinations will contribute to our understanding the pharmacology of dual nicotine and cocaine dependence, and will be useful for evaluation of new treatment medications.

  3. Bacillus cereus cellulitis from contaminated heroin.

    PubMed

    Dancer, S J; McNair, D; Finn, P; Kolsto, A B

    2002-03-01

    Concern exists over recent unexplained deaths among intravenous drug users. This report describes a patient with crepitant cellulitis who was admitted complaining of severe pain in the right forearm. Ultrasonography demonstrated gas in the tissues and he was referred for early surgical debridement of the arm. He was treated with intravenous benzyl penicillin, gentamicin and metronidazole and made a full recovery. Aspirate samples grew Bacillus cereus, morphologically similar to the isolate obtained from a sample of the patient's own heroin. Antibiogram and API 50CHB profiles were also similar. Further typing included 'H' flagellar serotyping, which found both blood and heroin strains to be non-typable, and amplified fragment polymorphism analysis, which showed that the strains were indistinguishable. Genotyping of two selected genes from B. cereus confirmed almost certain identity between the two strains. This case illustrates the potential virulence of B. cereus when inoculated into tissues, and to our knowledge, is the first report to demonstrate a conclusive microbiological link between contaminated heroin and serious sepsis in a drug user due to B. cereus.

  4. Synthesis and immunological effects of heroin vaccines.

    PubMed

    Li, Fuying; Cheng, Kejun; Antoline, Joshua F G; Iyer, Malliga R; Matyas, Gary R; Torres, Oscar B; Jalah, Rashmi; Beck, Zoltan; Alving, Carl R; Parrish, Damon A; Deschamps, Jeffrey R; Jacobson, Arthur E; Rice, Kenner C

    2014-10-07

    Three haptens have been synthesized with linkers for attachment to carrier macromolecules at either the piperidino-nitrogen or via an introduced 3-amino group. Two of the haptens, with a 2-oxopropyl functionality at either C6, or at both the C3 and C6 positions on the 4,5-epoxymorphinan framework, as well as the third hapten (DiAmHap) with diamido moieties at both the C3 and C6 positions, should be much more stable in solution, or in vivo in a vaccine, than a hapten with an ester in one of those positions, as found in many heroin-based haptens. A "classical" opioid synthetic scheme enabled the formation of a 3-amino-4,5-epoxymorphinan which could not be obtained using palladium chemistry. Our vaccines are aimed at the reduction of the abuse of heroin and, as well, at the reduction of the effects of its predominant metabolites, 6-acetylmorphine and morphine. One of the haptens, DiAmHap, has given interesting results in a heroin vaccine and is clearly more suited for the purpose than the other two haptens.

  5. Mechanisms of withdrawal-associated increases in heroin self-administration: pharmacologic modulation of heroin vs food choice in heroin-dependent rhesus monkeys.

    PubMed

    Negus, S Stevens; Rice, Kenner C

    2009-03-01

    Opioid withdrawal can produce a constellation of physiological and behavioral signs, including an increase in opioid self-administration. Different mechanisms mediate different withdrawal signs, and the present study used pharmacologic tools to assess mechanisms underlying withdrawal-associated increases in opioid reinforcement. Five rhesus monkeys were rendered heroin dependent via daily 21-h heroin self-administration sessions. One hour after each heroin self-administration session, monkeys chose between heroin (0-0.1 mg/kg per injection) and food (1 g pellets) during 2-h choice sessions. Under these conditions, heroin maintained a dose-dependent increase in heroin choice, such that monkeys responded primarily for food when low heroin doses were available (0-0.01 mg/kg per injection) and primarily for heroin when higher heroin doses were available (0.032-0.1 mg/kg per injection). Periods of spontaneous withdrawal were intermittently introduced by omitting one 21-h heroin self-administration session, and test drugs were administered during these withdrawal periods. Untreated withdrawal robustly increased heroin choice during choice sessions. Withdrawal-associated increases in heroin choice were completely suppressed by the mu opioid agonist morphine (0.032-0.32 mg/kg/h, i.v.), but not by the alpha-2 noradrenergic agonist clonidine (0.01-0.1 mg/kg/h, i.v.), the dopamine/norepinephrine releaser amphetamine (0.032-0.1 mg/kg/h, i.v.), or the kappa-opioid antagonist 5'-guanidinonaltrindole (1.0 mg/kg, i.m.). The corticotropin-releasing factor 1 antagonist antalarmin (1.0-10 mg/kg per day, i.m.) produced a morphine-like suppression of withdrawal-associated increases in heroin choice in one of three monkeys. These results suggest that mechanisms of withdrawal-associated increases in the relative reinforcing efficacy of opioid agonists may be different from mechanisms of many other somatic, mood-related, and motivational signs of opioid withdrawal.

  6. Testing human hair for drugs of abuse. III. Identification of heroin and 6-acetylmorphine as indicators of heroin use.

    PubMed

    Goldberger, B A; Caplan, Y H; Maguire, T; Cone, E J

    1991-01-01

    Hair samples from 20 documented heroin users contained 6-acetylmorphine, a unique metabolite of heroin, in all samples. Heroin was identified in smaller amounts in seven of these samples. The identity of 6-acetylmorphine and heroin was established by comparison of full scan spectra of extracts to standard reference materials. The presence of 6-acetylmorphine generally predominated over heroin, morphine, and codeine. The mean concentrations of analytes were as follows: 6-acetylmorphine, 0.90 ng/mg, N = 20; heroin, 0.17 ng/mg, N = 7; morphine, 0.26 ng/mg, N = 20; codeine, 0.18 ng/mg, N = 15. Analysis of hair samples obtained from 10 drug-free control subjects were negative for 6-acetylmorphine, morphine, and codeine. However, a small interfering peak was observed at the retention time for heroin. Control samples soaked in aqueous solutions of heroin and 6-acetylmorphine were found to be contaminated, even though an initial wash step was included in the analysis. These data suggest that hair analysis for 6-acetylmorphine can be used to differentiate heroin users from other types of opiate exposure (e.g., poppy seed, licit morphine, and codeine); however, environmental contamination can potentially produce false positives during opiate testing.

  7. Description and quantification of cocaine withdrawal signs in Planaria.

    PubMed

    Raffa, Robert B; Desai, Prarthna

    2005-01-25

    Previous work provided indirect evidence that planarians undergo abstinence-induced withdrawal from cocaine. The present study's purpose was to determine if planarians display withdrawal signs and, if so, to quantify the behaviors. Planarians were soaked in cocaine then transferred to either the same cocaine concentration or cocaine-free water. Compared to the cocaine/cocaine group, the cocaine/water group displayed a significant number of atypical behaviors, providing direct evidence of a 'withdrawal phenomenon' in planarians.

  8. Aminorex associated with possible idiopathic pulmonary hypertension in a cocaine user.

    PubMed

    Karch, Steven B; Defraia, Beatrice; Messerini, Luca; Mari, Francesco; Vaiano, Fabio; Bertol, Elisabetta

    2014-07-01

    The conversion of levamisole to aminorex in horses was first described in 2009 and, for the first time, confirmed in humans two years later by our laboratory. Aminorex and levamisole interfere with serotonin metabolism and both are proven cause of potentially fatal idiopathic pulmonary hypertension (IPH). Because most of the world's seizures of illicit cocaine is now contaminated with levamisole, this raises the possibility that users of levamisole adulterated cocaine users may be at risk for IPH. Here we describe the first case of IPH in a user of levamisole-contaminated cocaine. Levamisole and aminorex were both identified and quantified in hair and other biological specimens by means gas chromatography/mass spectrometry system (levamisole: urine, 75.05ng/mL; blood, 15.05ng/mL; brain, >0.15ng/g; liver, >0.15ng/g; hair, 12.15ngmg; aminorex: urine, 38.62ng/mL; blood, 8.92ng/mL, brain >0.15ng/g; liver, 0.15ng/g; hair 7.35ng/mg; cocaine, benzoylecgonine, morphine, 6-acetylmorphine, methadone, 2-ethylidine-1, 5-dimetil-3, 3 diphenylpyrrolidine were also detected). Moreover histological changes associated with IPH were observed in the lung. As IPH produces relatively non-specific symptoms in its early stages, this index case may serve as a harbinger of many more cases to come. It should also alert clinicians to the possibility that their patient may be suffering from this relatively rare disorder.

  9. Multilevel Predictors of Concurrent Opioid Use during Methadone Maintenance Treatment among Drug Users with HIV/AIDS

    PubMed Central

    Tran, Bach Xuan; Ohinmaa, Arto; Mills, Steve; Duong, Anh Thuy; Nguyen, Long Thanh; Jacobs, Philip; Houston, Stan

    2012-01-01

    Background Ongoing drug use during methadone maintenance treatment (MMT) negatively affects outcomes of HIV/AIDS care and treatment for drug users. This study assessed changes in opioid use, and longitudinal predictors of continued opioid use during MMT among HIV-positive drug users in Vietnam, with the aim of identifying changes that might enhance program efficacy. Methods We analyze data of 370 HIV-positive drug users (mean age 29.5; 95.7% male) taking MMT at multi-sites. Opioid use was assessed at baseline, 3, 6, and 9 months using interviews and heroin confirmatory urine tests. A social ecological model was applied to explore multilevel predictors of continued opioid use, including individual, interpersonal, community and service influences. Generalized estimating equations (GEE) statistical models were constructed to adjust for intra-individual correlations. Results Over 9 month follow-up, self-reported opioid use and positive heroin urine test substantially decreased to 14.6% and 14.4%. MMT helped improve referrals and access to health care and social services. However, utilization of social integration services was small. GEE models determined that participants who were older (Adjusted Odd Ratio - AOR = 0.97 for 1 year increase), had economic dependents (AOR = 0.33), or were referred to TB treatment (AOR = 0.53) were less likely to continue opioid use. Significant positive predictors of ongoing opioid use included frequency of opioid use prior to MMT, peer pressure, living with sexual partners, taking antiretroviral treatment, other health concerns and TB treatment. Conclusion These findings show that MMT in the Vietnamese context can dramatically reduce opioid use, which is known to be associated with reduced antiretroviral (ART) adherence. Disease stage and drug interactions between antiretrovirals or TB drugs and MMT could explain some of the observed predictors of ongoing drug use; these findings could inform changes in MMT program design and

  10. 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

    2017-01-16

    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 (Vdss /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.

  11. Prevalence of executive dysfunction in cocaine, heroin and alcohol users enrolled in therapeutic communities.

    PubMed

    Fernández-Serrano, María José; Pérez-García, Miguel; Perales, José C; Verdejo-García, Antonio

    2010-01-10

    Many studies have observed relevant executive alterations in polysubstance users but no data have been generated in terms of prevalence of these alterations. Studies of the prevalence of neuropsychological impairment can be useful in the design and implementations of interventional programs for substance abusers. The present study was conducted to estimate the prevalence of neuropsychological impairment in different components of executive functions in polysubstance users enrolled in therapeutic communities. Moreover, we estimated the effect size of the differences in the executive performance between polysubstance users and non substance users in order to know which neuropsychological tasks can be useful to detect alterations in the executive functions. Study results showed a high prevalence of executive function impairment in polysubstance users. Working memory was the component with the highest impairment proportion, followed by fluency, shifting, planning, multi-tasking and interference. Comparisons between user groups showed very similar executive impairment prevalence for all the analyzed executive components. The best discriminating task between users and controls was Arithmetic (Wechsler Adult Intelligence Scale, WAIS-III). Moreover FAS and Ruff Figural Fluency Test was discriminating for fluency, Category Test for shifting, Stroop Colour-Word Interference Test for interference, Zoo Map (Behavioural Assessment of the Dysexecutive Syndrome, BADS) for planning and Six Elements (BADS) for multi-tasking. The existence of significant prevalence of executive impairment in polysubstance users reveals the need to redirect the actuation policies in the field of drug-dependency towards the creation of treatments addressed at the executive deficits of the participants, which in turn would facilitate the individuals' compliance and final rehabilitation.

  12. Odor impact of volatiles emitted from marijuana, cocaine, heroin and their surrogate scents

    PubMed Central

    Rice, Somchai; Koziel, Jacek A.

    2015-01-01

    Volatile compounds emitted into headspace from illicit street drugs have been identified, but until now odor impact of these compounds have not been reported. Data in support of identification of these compounds and their odor impact to human nose are presented. In addition, data is reported on odor detection thresholds for canines highlighting differences with human ODTs and needs to address gaps in knowledge. New data presented here include: (1) compound identification, (2) gas chromatography (GC) column retention times, (3) mass spectral data, (4) odor descriptors from 2 databases, (5) human odor detection thresholds from 2 databases, (6) calculated odor activity values, and (7) subsequent ranking of compounds by concentration and ranking of compounds by odor impact (reported as calculated odor activity values). For further interpretation and discussion, see Rice and Koziel [1] and Rice [2]. PMID:26958621

  13. Model of methadone-induced hyperalgesia in rats and effect of memantine.

    PubMed

    Hay, Justin L; Kaboutari, Jahangir; White, Jason M; Salem, Abdallah; Irvine, Rod

    2010-01-25

    Methadone used for opioid dependence therapy is associated with increased pain sensitivity. This study aimed to investigate whether methadone administration lowers nociceptive threshold in adult male Sprague-Dawley (SD) rats, and if this threshold could be altered by the NMDA receptor antagonist memantine. Rats were implanted with osmotic pumps delivering 1mg/kg/day methadone (n=6), or saline placebo (n=6) (0.51 microl/h). A separate cohort of rats received either methadone 1mg/kg/day (n=8) or methadone 1mg/kg/day with 20mg/kg/day memantine (n=8). Nociception was measured by the Hargreave's paw withdrawal test. Baseline nociception was measured on day 0 prior to osmotic pump implantation and was measured daily for the following 21 days. Osmotic pumps were removed following nociceptive testing on day 14. Methadone only treated rats had a mean paw withdrawal latency significantly lower than the corresponding values for saline on days 8, 9, 10, 11, 12, 14, and 17 (P<0.05). At all other time points the mean paw withdrawal latency was not significantly different from saline (P>0.05). Paw withdrawal latency of rats treated with methadone co-administered with memantine did not differ significantly compared to methadone only (P>0.05). This demonstrates that methadone induces hyperalgesia in the SD rat yet this hyperalgesia resolves following discontinuation of methadone administration. Furthermore, memantine does not alter the development of methadone-induced hyperalgesia.

  14. Multiple mononeuropathy following cocaine abuse

    PubMed Central

    Beniczky, Sándor; Tfelt-Hansen, Peer; Fabricius, Martin; Andersen, Kjeld V

    2009-01-01

    A 31-year-old man with acute-onset of left-sided weakness following the sniffing of cocaine was admitted with rhabdomyolysis. Neurophysiological studies showed axonal degeneration in 4/10 sensory and 3/8 motor nerves, and conduction block outside the typical compression-sites in 3/8 motor nerves. The findings are consistent with a diagnosis of multiple mononeuropathy. Ischaemia due to vasoconstriction is currently believed to be the cause of muscle necrosis following cocaine abuse and we hypothesise that it also explains the neuropathy in this case. PMID:21686808

  15. HIV Risk Reduction With Buprenorphine-Naloxone or Methadone: Findings From A Randomized Trial

    PubMed Central

    Woody, George; Bruce, Douglas; Korthuis, P. Todd; Chhatre, Sumedha; Hillhouse, Maureen; Jacobs, Petra; Sorensen, James; Saxon, Andrew J.; Metzger, David; Ling, Walter

    2014-01-01

    Objectives Compare HIV injecting and sex risk in patients being treated with methadone (MET) or buprenorphine-naloxone (BUP). Methods Secondary analysis from a study of liver enzyme changes in patients randomized to MET or BUP who completed 24-weeks of treatment and had 4 or more blood draws. The initial 1:1 randomization was changed to 2:1 (BUP: MET) after 18 months due to higher dropout in BUP. The Risk Behavior Survey (RBS) measured past 30-day HIV risk at baseline and weeks 12 and 24. Results Among 529 patients randomized to MET, 391 (74%) were completers; among 740 randomized to BUP, 340 (46%) were completers; 700 completed the RBS. There were significant reductions in injecting risk (p< 0.0008) with no differences between groups in mean number of times reported injecting heroin, speedball, other opiates, and number of injections; or percent who shared needles, did not clean shared needles with bleach, shared cookers, or engaged in front/back loading of syringes. The percent having multiple sex partners decreased equally in both groups (p<0.03). For males on BUP the sex risk composite increased; for males on MET, the sex risk decreased resulting in significant group differences over time (p<0.03). For females, there was a significant reduction in sex risk (p<0.02) with no group differences. Conclusions Among MET and BUP patients that remained in treatment, HIV injecting risk was equally and markedly reduced, however MET retained more patients. Sex risk was equally and significantly reduced among females in both treatment conditions, but increased for males on BUP, and decreased for males on MET. PMID:24751432

  16. Quantitation of methadone enantiomers in humans using stable isotope-labeled (2H3)-, (2H5)-, and (2H8)Methadone

    SciTech Connect

    Nakamura, K.; Hachey, D.L.; Kreek, M.J.; Irving, C.S.; Klein, P.D.

    1982-01-01

    A new technique for simultaneous stereoselective kinetic studies of methadone enantiomers was developed using three deuterium-labeled forms of methadone and GLC-chemical-ionization mass spectrometry. A racemic mixture (1:1) of (R)-(-)-(2H5)methadone (l-form) and (S)-(R)-(2H3)methadone (d-form) was administered orally in place of a single daily dose of unlabeled (+/-)-(2H0)methadone in long-term maintenance patients. Racemic (+/-)-(2H8)methadone was used as an internal standard for the simultaneous quantitation of (2H0)-, (2H3)-, and (2H5)methadone in plasma and urine. A newly developed extraction procedure, using a short, disposable C18 reversed-phase cartridge and improved chemical-ionization procedures employing ammonia gas, resulted in significant reduction of the background impurities contributing to the ions used for isotopic abundance measurements. These improvements enabled the measurement of labeled plasma methadone levels for 120 hr following a single dose. This methodology was applied to the study of methadone kinetics in two patients; in both patients, the analgesically active l-enantiomer of the drug had a longer plasma elimination half-life and a smaller area under the plasma disappearance curve than did the inactive d-form.

  17. 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.

  18. Altered prefrontal connectivity after acute heroin administration during cognitive control.

    PubMed

    Schmidt, André; Borgwardt, Stefan; Gerber, Hana; Schmid, Otto; Wiesbeck, Gerhard A; Riecher-Rössler, Anita; Bendfeldt, Kerstin; Smieskova, Renata; Lang, Undine E; Rubia, Katya; Walter, Marc

    2014-09-01

    Neuroimaging studies have reported reduced activity in a broad network of brain regions during response inhibition in heroin-dependent patients. However, how heroin in an acute dose modulates the neural correlates of response inhibition and the underlying brain connectivity has not yet been investigated. In this double-blind placebo-controlled study, we used functional magnetic resonance imaging to examine whether acute heroin administration changed whole brain activity during response inhibition in 26 heroin-dependent patients. We then applied dynamic causal modelling to investigate the effect of an acute dose of heroin on the functional interactions between the dorsal anterior cingulate cortex (dACC) and the bilateral inferior frontal gyri (IFG). Heroin acutely reduced dACC activity, as well as the inhibition-induced modulation of connectivity from the dACC to the right IFG compared with placebo. Furthermore, dACC activity was positively related to false alarm rates after placebo but not heroin administration. These results suggest that acute heroin administration impairs cognitive control in dependent patients by reducing the activity in the dACC activity and the functional connectivity from the dACC to the right IFG.

  19. 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)

  20. Neurobiological underpinnings of sensation seeking trait in heroin abusers.

    PubMed

    Cheng, Gordon L F; Liu, Yu-Pin; Chan, Chetwyn C H; So, Kwok-Fai; Zeng, Hong; Lee, Tatia M C

    2015-11-01

    Neurobiological investigation of heroin revealed that abusers of this highly addictive substance show dysregulation in brain circuits for reward processing and cognitive control. Psychologically, personality traits related to reward processing and cognitive control differed between heroin abusers and non-abusers. Yet, there is no direct evidence on the relationship between these neurobiological and psychological findings on heroin abusers, and whether such relationship is altered in these abusers. The present study filled this research gap by integrating findings obtained via magnetic resonance imaging (structural volume and resting-state functional connectivity) and self-reported personality trait measures (Zuckerman׳s Sensation Seeking Scale and Barratt Impulsivity Scale) on 33 abstinent heroin users and 30 matched healthy controls. The key finding is a negative relationship between high sensation seeking tendency and midbrain structural volume in the heroin users. Importantly, there was stronger coupling between the midbrain and ventromedial prefrontal cortex and weaker coupling between the midbrain and dorsolateral prefrontal cortex in heroin users. Our findings offer significant insight into the neural underpinning of sensation seeking in heroin users. Importantly, the data shed light on a novel relationship between the mesolimbic-prefrontal pathway of the reward system and the high sensation seeking personality trait in heroin abusers.

  1. Effects of a cocaine hydrolase engineered from human butyrylcholinesterase on metabolic profile of cocaine in rats.

    PubMed

    Chen, Xiabin; Zheng, Xirong; Zhou, Ziyuan; Zhan, Chang-Guo; Zheng, Fang

    2016-11-25

    Accelerating cocaine metabolism through enzymatic hydrolysis at cocaine benzoyl ester is recognized as a promising therapeutic approach for cocaine abuse treatment. Our more recently designed A199S/F227A/S287G/A328W/Y332G mutant of human BChE, denoted as cocaine hydrolase-3 (CocH3), has a considerably improved catalytic efficiency against cocaine and has been proven active in blocking cocaine-induced toxicity and physiological effects. In the present study, we have further characterized the effects of CocH3 on the detailed metabolic profile of cocaine in rats administrated intravenously (IV) with 5 mg/kg cocaine, demonstrating that IV administration of 0.15 mg/kg CocH3 dramatically changed the metabolic profile of cocaine. Without CocH3 administration, the dominant cocaine-metabolizing pathway in rats was cocaine methyl ester hydrolysis to benzoylecgonine (BZE). With the CocH3 administration, the dominant cocaine-metabolizing pathway in rats became cocaine benzoyl ester hydrolysis to ecgonine methyl ester (EME), and the other two metabolic pathways (i.e. cocaine methyl ester hydrolysis to BZE and cocaine oxidation to norcocaine) became insignificant. The CocH3-catalyzed cocaine benzoyl ester hydrolysis to EME was so efficient such that the measured maximum blood cocaine concentration (∼38 ng/ml) was significantly lower than the threshold blood cocaine concentration (∼72 ng/ml) required to produce any measurable physiological effects.

  2. Intravenous Cocaine Priming Reinstates Cocaine-Induced Conditioned Place Preference

    ERIC Educational Resources Information Center

    Lombas, Andres S.; Freeman, Kevin B.; Roma, Peter G.; Riley, Anthony L.

    2007-01-01

    Separate groups of rats underwent an unbiased conditioned place preference (CPP) procedure involving alternate pairings of distinct environments with intravenous (IV) injections of cocaine (0.75 mg/kg) or saline immediately or 15 min after injection. A subsequent extinction phase consisted of exposure to both conditioning environments preceded by…

  3. Factors Associated with Relapse among Heroin Addicts: Evidence from a Two-Year Community-Based Follow-Up Study in China

    PubMed Central

    Rong, Chao; Jiang, Hai-Feng; Zhang, Rui-Wen; Zhang, Li-Juan; Zhang, Jian-Chen; Zhang, Jing; Feng, Xue-Shan

    2016-01-01

    Background: Many countries including China are facing a serious opiate dependence problem. Anti-drug work effectiveness was affected by the high relapse rate all over the world. This study aims to analyze the factors influencing heroin addict relapse, and to provide evidence for generating relapse prevention strategies. Methods: A community-based follow-up study was conducted in China between October 2010 and September 2012. A total of 554 heroin addicts in accordance with the inclusion criteria from 81 streets in 12 districts of Shanghai, China were divided into 4 groups: group 1—daily dosage taken orally of 60 mL of methadone or under combined with psychological counseling and social supports (n = 130); group 2—daily dosage taken orally of over 60 mL of methadone combined with psychological counseling and social supports (n = 50); group 3—JTT (Jitai tablets) combined with psychological counseling and social supports (n = 206); group 4—JTT combined with social supports (n = 168). Results: Log-rank test results showed that the cumulative relapse rate differences among four groups during the two-year follow-up period were not statistically significant (χ2 = 5.889, p = 0.117). Multivariate Cox regression analysis results showed that only three independent variables were still statistically significant, including compliance with participation in psychological counseling (OR = 3.563, p = 0.000), the years of drug use (OR = 1.078, p = 0.001)and intervention model. Conclusions: Using the detoxification medications combined with appropriate psychological counseling and social support measures will help improve the effectiveness of relapse prevention, which is a kind of alternative community detoxification pattern. Appropriate and standard psychological counseling is very important for anti-drug treatment. The longer the drug addiction lasts, the longer the anti-drug treatment takes. PMID:26828510

  4. Acetylcodeine as a urinary marker to differentiate the use of street heroin and pharmaceutical heroin.

    PubMed

    Brenneisen, Rudolf; Hasler, Felix; Würsch, Daniel

    2002-01-01

    Acetylcodeine (ACOD) is a synthesis byproduct present in street heroin but not in pharmaceutical diacetylmorphine (DAM) as used in the Swiss program Heroin-Assisted Treatment for Opiate Dependent Drug Users (HAT). ACOD was evaluated and validated as an urine marker to detect the consumption of street heroin by HAT participants. A gas chromatography-mass spectrometry method allowing the quantitation of ACOD concentrations as low as 0.2 ng/mL urine has been developed. In opiate-naïve subjects, intravenous (i.v.) ACOD showed a plasma elimination half-life of 237 +/- 18 min, urine peak concentrations 2 h after administration, and a detection window of 8 h. Only 0.4 +/- 0.1% was excreted unchanged, with codeine (COD) as the main metabolite. ACOD may be formed by transacetylation when i.v. DAM and oral codeine are co-administered. To avoid false-positive results, the calculation of COD/ACOD ratios is recommended. In a study with 105 HAT participants, 14% of the tested urines were ACOD positive. Only a low correlation was found between the anonymously self-declared consumption of street heroin and the ACOD positive rate.

  5. Managing Heroin Addiction in an Outpatient Setting: A Case Study.

    PubMed

    Malliarakis, Kate Driscoll

    2015-12-01

    Heroin use may be under-recognized among older adults. Baby Boomers are the largest age as well as the largest drug-using cohort in modern history. Although some drug users age out of their addiction, others do not. Nurses caring for older adults may come into contact with heroin users due to associated conditions or sequelae of their drug use that cause them to seek care. Few nurses are prepared to provide the care needed when heroin use accompanies other health problems. Using an individual example, the current article provides guidance for identifying heroin addiction, essential information about heroin use, and resources for guiding patients to experts for the comprehensive care needed for recovery.

  6. Personality Differences among Black, White, and Hispanic-American Male Heroin Addicts on MMPI Content Scales.

    ERIC Educational Resources Information Center

    Dolan, M. P.; And Others

    1983-01-01

    Assessed personality differences among Black, White, and Hispanic-American heroin addicts (N=423). Results confirmed the hypotheses that minority group heroin addicts (Blacks and Hispanics) would show better adjustment than White heroin addicts and that Hispanic-American heroin addicts would evidence personality characteristics unlike those of…

  7. Supply of a nondrug substitute reduces escalated heroin consumption.

    PubMed

    Lenoir, Magalie; Ahmed, Serge H

    2008-08-01

    Escalation of drug consumption-a hallmark of addiction-has been hypothesized to be associated with a relative devaluation of alternative nondrug rewards and thus with a decrease in their ability to compete with or to substitute for the drug. In a behavioral economic framework, decreased substitutability of nondrug rewards for drug would explain why drug consumption is behaviorally dominant and relatively resistant to change (eg price-inelastic) in drug-addicted individuals. The goal of the present study was to test this hypothesis using a validated rat model of heroin intake escalation. Escalation was precipitated by long (6 h, long access (LgA)), but not short (1 h, short access (ShA)), daily access to i.v. heroin self-administration. After escalation, the effects of price (ie fixed-ratio value) on heroin consumption were assessed under two alternative reward conditions: in the presence or absence of a nondrug substitute for heroin (ie four freely available chow pellets). As expected, escalated heroin consumption by LgA rats was less sensitive to price than heroin consumption by ShA rats, showing that heroin had acquired greater reinforcing strength during escalation. However, supplying a substitute during access to heroin was sufficient to reverse this post-escalation increase in the reinforcing effectiveness of heroin. Thus, escalated heroin consumption is not associated with a decreased sensitivity to competing nondrug rewards. Escalated drug use may therefore persist, not so much because of a relative devaluation of nondrug substitutes, but because of a loss or reduction of their availability.

  8. Escalation patterns of varying periods of heroin access.

    PubMed

    Vendruscolo, Leandro F; Schlosburg, Joel E; Misra, Kaushik K; Chen, Scott A; Greenwell, Thomas N; Koob, George F

    2011-06-01

    The prevalence of opioid abuse and dependence has been on the rise in just the past few years. Animal studies indicate that extended access to heroin produces escalation of intake over time, whereas stable intake is observed under limited-access conditions. Escalation of drug intake has been suggested to model the transition from controlled drug use to compulsive drug seeking and taking. Here, we directly compared the pattern of heroin intake in animals with varying periods of heroin access. Food intake was also monitored over the course of escalation. Rats were allowed to lever press on a fixed-ratio 1 schedule of reinforcement to receive intravenous infusions of heroin for 1, 6, 12, or 23h per day for 14 sessions. The results showed that heroin intake in the 12 and 23h groups markedly increased over time, whereas heroin intake in the 1h group was stable. The 6h group showed a significant but modest escalation of intake. Total heroin intake was similar in the 12 and 23h groups, but the rate of heroin self-administration was two-fold higher in the 12h group compared with the 23h group. Food intake decreased over sessions only in the 12h group. The 12 and 23h groups showed marked physical signs of naloxone-precipitated withdrawal. These findings suggest that 12h heroin access per day may be the optimal access time for producing escalation of heroin intake. The advantages of this model and the potential relevance for studying drug addiction are discussed.

  9. The First American Cocaine Epidemic.

    ERIC Educational Resources Information Center

    Courtwright, David T.

    1991-01-01

    Discusses the wave of cocaine abuse that followed the drug's recommendation by the late nineteenth-century medical community as a cure all. Details drug addiction among ethnic and social groups at the turn of the century. Warns that drug epidemics have important social and legal consequences. Suggests legal pressure may alter the form of drug…

  10. Plasma catecholamines during an ultrarapid heroin detoxification.

    PubMed

    Macedo, T R; Relvas, J; Fontes Ribeiro CA; Pacheco, F; Morgadinho, M T; Pinto, C M; Gomes, P C; Ventura, M; Henriques, V; Nunes, S V; Ruis, G R; Ramalheira, C; Boto, I; Vale, L L

    2000-09-01

    The adrenergic system has long been known to be activated in a situation of stress and thus during opiate withdrawal. A method for detoxification that decreases the stimulation of the sympathetic nervous system will prevent changes of catecholamine levels. Some of such methods have been developed. One of them uses direct transition from heroin to oral naltrexone after deep sedation with midazolam in conjunction with naloxone, droperidol, ondansetron, and clonidine treatment for 24 hours. Can such method prevent adrenergic changes? Moreover, 5-HT has been related to mood disorders. This study aims to determine plasma catecholamines and 5-HT before heroin withdrawal, during the day of the withdrawal, and at the ends of the first day, the first week, and the first 6 months. Forty-three patients with more than 6 years of drug abuse volunteered to seek help to detoxify. After clinical evaluation, blood samples were taken. Plasma catecholamines were isolated by standard alumina procedures and measured by high-performance liquid chromatography with electrochemical detection. Only for NE was there a significant decrease in the day of heroin withdrawal with deep sedation, followed the next day by an increase. During the following days, NE plasma concentrations returned slowly to basal levels. Epinephrine and dopamine plasma levels did not significantly change. Platelet 5-HT levels progressively decreased from the day before detoxification until the last period of observation. We also found that there were no abrupt changes in cardiovascular functions. In conclusion, our results suggest that this type of ultrarapid opiate detoxification prevents the dramatic activation of the autonomic nervous system.

  11. Humoral Dysregulation Associated with Increased Systemic Inflammation among Injection Heroin Users

    PubMed Central

    Piepenbrink, Michael S.; Samuel, Memorie; Zheng, Bo; Carter, Brittany; Fucile, Christopher; Bunce, Catherine; Kiebala, Michelle; Khan, Atif A.; Thakar, Juilee; Maggirwar, Sanjay B.; Morse, Diane; Rosenberg, Alexander F.; Haughey, Norman J.; Valenti, William; Keefer, Michael C.; Kobie, James J.

    2016-01-01

    Background Injection drug use is a growing major public health concern. Injection drug users (IDUs) have a higher incidence of co-morbidities including HIV, Hepatitis, and other infections. An effective humoral response is critical for optimal homeostasis and protection from infection; however, the impact of injection heroin use on humoral immunity is poorly understood. We hypothesized that IDUs have altered B cell and antibody profiles. Methods and Findings A comprehensive systems biology-based cross-sectional assessment of 130 peripheral blood B cell flow cytometry- and plasma- based features was performed on HIV-/Hepatitis C-, active heroin IDUs who participated in a syringe exchange program (n = 19) and healthy control subjects (n = 19). The IDU group had substantial polydrug use, with 89% reporting cocaine injection within the preceding month. IDUs exhibited a significant, 2-fold increase in total B cells compared to healthy subjects, which was associated with increased activated B cell subsets. Although plasma total IgG titers were similar between groups, IDUs had significantly higher IgG3 and IgG4, suggestive of chronic B cell activation. Total IgM was also increased in IDUs, as well as HIV Envelope-specific IgM, suggestive of increased HIV exposure. IDUs exhibited numerous features suggestive of systemic inflammation, including significantly increased plasma sCD40L, TNF-α, TGF-α, IL-8, and ceramide metabolites. Machine learning multivariate analysis distilled a set of 10 features that classified samples based on group with absolute accuracy. Conclusions These results demonstrate broad alterations in the steady-state humoral profile of IDUs that are associated with increased systemic inflammation. Such dysregulation may impact the ability of IDUs to generate optimal responses to vaccination and infection, or lead to increased risk for inflammation-related co-morbidities, and should be considered when developing immune-based interventions for this growing

  12. A vitamin profile of heroin addiction.

    PubMed

    el-Nakah, A; Frank, O; Louria, D B; Quinones, M A; Baker, H

    1979-10-01

    Circulating thiamine, riboflavin, nicotinates, folates, vitamin B12, B6, A, and carotenes of 149 heroin addicts aged 17-60 years were compared to 204 healthy subjects not using drugs or vitamins. Only 24 per cent of the addicts had no evidence of hypovitaminemia; 45 per cent and 37 per cent had vitamin B6 and folate deficit respectively, whereas deficits of thiamine, vitamin B12, riboflavin, and nicotinate were recorded for 13-19 per cent of the addict population; impaired liver function in addicts did not influence these results.

  13. 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

  14. 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.

  15. First case of stress cardiomyopathy as a result of methadone withdrawal secondary to drug-drug interaction.

    PubMed

    Lemesle, Frédéric; Lemesle, Florence; Nicola, Walid; Pierre Jonville-Béra, Annie

    2010-03-01

    We describe the first case of stress cardiomyopathy secondary to a drug-drug interaction. A 44-year-old man was admitted for acute agitation, hallucinations, tachycardia, and fever within 2 hours of ingestion of naltrexone prescribed to stop alcohol consumption. He had been receiving methadone (120 mg/d) for several months for a history of heroin use; thus, acute opiate withdrawal syndrome secondary to naltrexone treatment was diagnosed. Because electrocardiography showed diffuse ST-segment elevation, a transthoracic echocardiography was performed. It revealed apical akinesia of the left ventricle with a reduction in systolic function. The echocardiogram showed an ejection fraction of 35%, apical and midventricular wall motion abnormalities of the left ventricle, and a cardiac output of 4 L/min without coronary stenosis. The patient was transferred to the cardiologic intensive care unit with a diagnosis of transient left ventricular apical ballooning syndrome secondary to acute opiate withdrawal syndrome. It is likely that opioid withdrawal, inducing a marked increase in catecholamine plasma concentrations, contributed to the development of stress cardiomyopathy. To our knowledge, this is the first case of stress cardiomyopathy described after abrupt opiate withdrawal secondary to a drug-drug interaction.

  16. Multiple faces of BDNF in cocaine addiction

    PubMed Central

    Li, Xuan; Wolf, Marina E.

    2014-01-01

    Brain-derived neurotrophic factor (BDNF) has been found to play roles in many types of plasticity including drug addiction. Here we focus on rodent studies over the past two decades that have demonstrated diverse roles of BDNF in models of cocaine addiction. First, we will provide an overview of studies showing that cocaine exposure alters (and generally increases) BDNF levels in reward-related regions including the ventral tegmental area, nucleus accumbens, prefrontal cortex, and amygdala. Then we will review evidence that BDNF contributes to behavioral changes in animal models of cocaine addiction, focusing on conditioned place preference, behavioral sensitization, maintenance and reinstatement of self-administration, and incubation of cocaine craving. Last, we will review the role of BDNF in synaptic plasticity, particularly as it relates to plasticity of AMPA receptor transmission after cocaine exposure. We conclude that BDNF regulates cocaine-induced behaviors in a highly complex manner that varies depending on the brain region (and even among different cell types within the same brain region), the nature of cocaine exposure, and the “addiction phase” examined (e.g., acquisition vs maintenance; early vs late withdrawal). These complexities make BDNF a daunting therapeutic target for treating cocaine addiction. However, recent clinical evidence suggests that the serum BDNF level may serve as a biomarker in cocaine addicts to predict future relapse, providing an alternative direction for exploring BDNF’s potential relevance to treating cocaine addiction. PMID:25449839

  17. 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