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
Malek, Antoine; Obrist, Cristina; Wenzinger, Silvana; von Mandach, Ursula
A sensitive and specific method is presented to simultaneously quantify methadone, heroin, cocaine and metabolites in sweat. Drugs were eluted from sweat patches with sodium acetate buffer, followed by SPE and quantification by GC/MS with electron impact ionization and selected ion monitoring. Daily calibration for anhydroecgonine methyl ester, ecgonine methyl ester, cocaine, benzoylecgonine (BE), codeine, morphine, 6-acetylcodeine, 6-acetylmorphine (6AM), heroin (5–1000 ng/patch) and methadone (10–1000 ng/patch) achieved determination coefficients of >0.995, and calibrators quantified to within ±20% of the target concentrations. Extended calibration curves (1000–10,000 ng/patch) were constructed for methadone, cocaine, BE and 6AM by modifying injection techniques. Within (N=5) and between-run (N=20) imprecisions were calculated at six control levels across the dynamic ranges with coefficients of variation of <6.5%. Accuracies at these concentrations were ±11.9% of target. Heroin hydrolysis during specimen processing was <11%. This novel assay offers effective monitoring of drug exposure during drug treatment, workplace and criminal justice monitoring programs. PMID:18607576
Brunet, Bertrand R.; Barnes, Allan J.; Scheidweiler, Karl B.; Mura, Patrick
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
Stephen M. Gilman; Marc Galanter; Helen Dermatis
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.…
Hirt, Michael; Greenfield, Heywood
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…
Ghitza, Udi E.; Epstein, David H.; Schmittner, John; Vahabzadeh, Massoud; Lin, Jia-Ling; Preston, Kenzie L.
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-1?, IL-6, IL-8, IL-10 and tumor necrosis factor (TNF)-? from a group of heroin addicts (n=34) and healthy controls (n=20). The results show that production of IL-1?, IL-6 and IL-8 was significantly higher in the group of methadone-maintained patients than in the healthy control group. Plasma TNF-? and IL-6 levels were significantly correlated with the dairy methadone dosage administered, and the IL-1? 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. PMID:25660662
Chan, Yuan-Yu; Yang, Szu-Nian; Lin, Jyh-Chyang; Chang, Junn-Liang; Lin, Jaung-Geng; Lo, Wan-Yu
Cocaine use is associated with injecting and sexual HIV risk behaviors. This study was a randomized controlled trial of behavioral interventions for cocaine dependence and HIV risk behaviors among dually (cocaine and heroin) dependent outpatients. Methadone maintenance was augmented with cognitive-behavioral therapy (CBT), contingency management (CM), both (CBT+CM), or neither. The study sample (n=81) was 52% female, 70% African American,
Jennifer R. Schroeder; David H. Epstein; Annie Umbricht; Kenzie L. Preston
Significant proportions of opiate-dependent persons entering methadone treatment are also addicted to cocaine and continue to use cocaine during treatment. One standard response to cocaine use has been inpatient detoxification. This study examined the effectiveness of this procedure by comparing pre- and posttreatment urine toxicologies for methadone patients who had been hospitalized for cocaine withdrawal. The results showed a negligible
Andrew Rosenblum; Jeffrey Foote; Stephen Magura; Victor Sturiano; Neil Xu; Barry Stimmel
STUDY OBJECTIVE: Although the total number of self poisonings in England and Wales has dropped by 32%, the number involving methadone and\\/or heroin rose by 900% in 1974-92. Because of concern about the role of methadone in this increase, the part played by methadone and heroin in poisoning deaths in England and Wales in 1974-92 was investigated. DESIGN: A proportional
J Neeleman; M Farrell
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. PMID:23770647
Phillips, Karran A.; Epstein, David H.; Preston, Kenzie L.
Both heroin-addicted individuals and methadone maintenance patients are likely to face untreated opioid withdrawal while incarcerated. Limited research exists concerning the withdrawal experiences of addicted inmates and their impact on individuals' attitudes and plans concerning drug abuse treatment. In the present study, 53 opioid dependent adults (32 in methadone treatment and 21 out of treatment) were interviewed in an ethnographic
Shannon Gwin Mitchell; Sharon M. Kelly; Barry S. Brown; Heather Schacht Reisinger; James A. Peterson; Adrienne Ruhf; Michael H. Agar; Robert P. Schwartz
In recent years, there has been an increase in cocaine-related deaths at the Department of Legal Medicine and Public Health of Pavia, probably reflecting the rising trend in cocaine use in Western Europe. Deaths from cocaine alone have increased from 6 cases in 1979–1991 (1.5% of drug-of-abuse deaths) to 13 in 1992–2002 (3.2%) and comparing the same periods, heroin-related deaths
Aldo Polettini; Vala Poloni; Angelo Groppi; Cristiana Stramesi; Claudia Vignali; Lucia Politi; Maria Montagna
Significant proportions of opiate-dependent persons entering methadone treatment are also addicted to cocaine and continue to use cocaine during treatment. One standard response to cocaine use has been inpatient detoxification. This study examined the effectiveness of this procedure by comparing pre- and posttreatment urine toxicologies for methadone patients who had been hospitalized for cocaine withdrawal. The results showed a negligible effect on cocaine abstinence (less than 1 out of 10 patients abstinent 12 weeks after detox) and a modest reduction in the frequency of cocaine use (one-quarter decline in urine tests positive after 12 weeks). These findings raise serious doubts about the cost-effectiveness of inpatient cocaine detoxification. Better strategies need to be implemented to enhance the chances of remaining abstinent once detoxified. PMID:9219143
Rosenblum, A; Foote, J; Magura, S; Sturiano, V; Xu, N; Stimmel, B
Both heroin-addicted individuals and methadone maintenance patients are likely to face untreated opioid withdrawal while incarcerated. Limited research exists concerning the withdrawal experiences of addicted inmates and their impact on individuals' attitudes and plans concerning drug abuse treatment. In the present study, 53 opioid dependent adults (32 in methadone treatment and 21 out of treatment) were interviewed in an ethnographic investigation of withdrawal experiences during incarceration. When treatment for opioid withdrawal was unavailable, detoxification experiences were usually described as negative and were often associated with a variety of unhealthy behaviors designed to relieve withdrawal symptoms. Negative methadone withdrawal experiences also negatively influenced participants' receptivity to seeking methadone treatment upon release. A minority of participants took a positive view of their withdrawal experience and saw it as an opportunity to detox from heroin or discontinue methadone. Findings support the importance of providing appropriate opioid detoxification and/or maintenance therapy to opioid-dependent inmates. PMID:19705676
Mitchell, Shannon Gwin; Kelly, Sharon M; Brown, Barry S; Reisinger, Heather Schacht; Peterson, James A; Ruhf, Adrienne; Agar, Michael H; Schwartz, Robert P
Background Studies of sex differences have shown that men and women with drug-use disorders differ in course and outcome and in cue-induced activation of putative brain “control network” areas. We evaluated sex differences in daily functioning and subjective events related to drug use with Ecological Momentary Assessment (EMA). Methods EMA data were collected from cocaine- and heroin-using outpatients (72 men; 42 women) in methadone maintenance in 2–5 randomly prompted (RP) entries per day and in participant-initiated entries for heroin or cocaine use or craving, for up to 25 weeks. Urine drug screens were conducted three times weekly. Data were analyzed via repeated-measures logistic regression, using sex as a predictor of responses. Results In RP reports, women and men reported significantly different patterns of drug-cue exposure, with women significantly more likely to report having seen cocaine or been tempted to use in the past hour. Women also had higher craving after past-hour exposure to drug cues. In reports of drug use, women, compared to men, were more likely to report that they had used more cocaine than they had meant to, tended to feel guilty more often after drug use, and to have used despite trying not to use. Conclusions These findings provide real-time behavioral evidence that women respond differently than men to exposure to drug cues and to drug use, consistent with laboratory and brain-imaging findings. This information may be useful for development of sex-specific treatment strategies. PMID:23357742
Kennedy, Ashley P.; Epstein, David H.; Phillips, Karran A.; Preston, Kenzie L.
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.
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. PMID:23822738
D'Egidio, Pietro Fausto; Bignamini, Emanuele; De Vivo, Enrico; Leonardi, Claudio; Pieri, Maria Chiara; González-Saiz, Francisco; Lucchini, Alfio
All heroin addicts who registered for methadone treatment in Albuquerque in 1969–1971, 1019 in all, were the subjects of this follow-up study, conducted in 1991–1993. The cohort was almost entirely of Hispanic (Chicano) ethnicity, 86% male, with median age 27 at entry. We located 776, dead or alive, and we were able to interview 243 concerning many aspects of their
Avram Goldstein; James Herrera
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. PMID:19192858
Ghitza, Udi E; Epstein, David H; Schmittner, John; Vahabzadeh, Massoud; Lin, Jia-Ling; Preston, Kenzie L
Objective To investigate whether methadone maintenance treatment (MMT) is correlated with sexual dysfunction in heroin-dependent men and to determine the prevalence and risk factors of sexual dysfunction among men on MMT. Methods The study included a retrospective survey and a cross-sectional survey which contained interviews of 293 men who are currently engaged in MMT. The results of the two surveys were compared. For a subset of 43 participants, radioimmunoassay was additionally conducted using retrospective and prospective blood samples to test the levels of plasma testosterone and luteinizing hormone. Other study evaluations were the International Index of Erectile Function (IIEF-15), and Self-rating Depression Scale. Results Sexual dysfunction in all five IIEF-15 domains (erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction) was strongly associated with long-term use of heroin. A decrease in the severity of sexual dysfunction was associated with MMT initiation. Erectile dysfunction, lack of sexual desire, inability to orgasm, and lack of intercourse satisfaction were significantly correlated with increasing age of the participants. Methadone dose and duration of methadone treatment were not found to be associated with sexual dysfunction. The level of plasma testosterone significantly declined during methadone treatment, but results from multivariate analysis indicated low levels of testosterone were not the main cause of sexual dysfunction. No correlation between reported depression status and sexual function was found. Conclusions While high levels of sexual dysfunction were reported by heroin-dependent men in our study before and after MMT initiation, MMT appears to be correlated with improved sexual function in the population of the study. PMID:24520361
Zhang, Minying; Zhang, Huifang; Shi, Cynthia X.; McGoogan, Jennifer M.; Zhang, Baohua; Zhao, Linglong; Zhang, Mianzhi; Rou, Keming; Wu, Zunyou
Background Patterns of heroin and cocaine use vary and may be associated with unique risk factors for bloodborne infections. Methods Latent class analysis identified sub-populations of 552 heroin and cocaine users in Baltimore, Maryland. Using latent class regression, these classes were analyzed for associations with demographic characteristics, risky behaviors, Hepatitis C, and HIV. Results Three classes were found: Crack / Nasal-Heroin users (43.5%), Polysubstance users (34.8%), and Heroin Injectors (21.8%). Compared to Polysubstance users, Crack / Nasal-Heroin users were almost 7 times more likely to identify as Black (OR = 6.97, 95% CI = 4.35-11.2). Sharing needles was over 2.5 times more likely among Polysubstance users than among Heroin Injectors (OR = 2.66, 95% CI = 1.49-4.75). Crack/Nasal-Heroin users were 2.5 times more likely than Polysubstance users to exchange drugs for sex (OR = 2.50, 95% CI = 1.22-5.13). Crack/Nasal-Heroin users were less likely than Heroin Injectors to have Hepatitis C (OR = 0.10, 95% CI = 0.06-0.18), but no significant differences were found for HIV. Conclusions Subpopulations of cocaine and heroin users differed in demographic classifications, HIV-risk behaviors, and Hepatitis C infection. All subpopulations included substantial numbers of HIV-positive individuals. Findings provide further evidence that non-injection drug users face significant infectious disease risk. PMID:22030276
Harrell, PT; Mancha, B; Petras, H; Trenz, R; Latimer, WW
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…
Petry, Nancy M.; Martin, Bonnie; Simcic, Francis
The hypothesis that separate neural systems mediate the reinforcing properties of opiate and psychomotor stimulant drugs was tested in rats trained to lever-press for IV injections of either cocaine or heroin during daily 3-h sessions. Pretreatment with the opiate receptor antagonist drug naltrexone produced dose-dependent increases in heroin self-administration, but had no effect on the rate or pattern of cocaine
Aaron Ettenberg; Hugh O. Pettit; Floyd E. Bloom; George F. Koob
Background and Objectives In heroin dependent individuals, the HIV epidemic has been controlled in countries where access to opioid maintenance treatment (OMT) and needle exchange programs (NEP) have been implemented. However, despite similar routes of contamination for both viruses, the prevalence of hepatitis C (HCV) infection remains high in drug users. The objective of this analysis was to identify the prevalence of HCV and the correlates of being HCV-positive in a sample of out-of-treatment heroin-dependent individuals. Methods Data were collected from five inpatient studies (n = 120 participants) conducted at the New York State Psychiatric Institute. A logistic regression was used to identify correlates of being HCV-positive at baseline. Results Among the 120 heroin-dependent volunteers, 42 were HCV-positive. Participants who had heavier alcohol use, a longer duration of heroin use, or who reported using heroin by injection were more likely to be HCV-positive. Interestingly, participants who had injected cocaine during the previous month had a ninefold greater risk of being HCV-positive compared to non-cocaine users and those who used cocaine by a non-injecting route. Conclusions and Scientific Significance These findings confirm the risk of being HCV-infected through intravenous drug use, especially with cocaine use. These results underscore the importance of rethinking interventions to prevent HCV infection with combined strategies using pharmacological approaches for cocaine dependence and tailored prevention for cocaine users. PMID:24131170
Roux, P.; Fugon, L.; Jones, J.D.; Comer, S.D.
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] 3?-(4-iodophenyl)tropan-2?-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. PMID:24916769
Pattison, Lindsey P; McIntosh, Scot; Sexton, Tammy; Childers, Steven R; Hemby, Scott E
This study investigated association between post-traumatic stress disorder (PTSD) and a 1-year follow-up heroin use among female clients in methadone clinics in Israel. Participants were 104 Israeli female clients from four methadone clinics (Mean age = 39.09, SD = 8.61) who reported victimization to childhood sexual abuse. We tested traces in urine of these female clients for heroin a year
Miriam Schiff; Shabtay Levit; Rinat Cohen-Moreno
Hair of young subjects (N=36) suspected for drug abuse was analysed for morphine, codeine, heroin, 6-acetylmorphine, cocaine, methadone, amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), and 3,4-methylenedioxyethylamphetamine (MDEA). The analysis of morphine, codeine, heroin, 6-acetylmorphine, cocaine, and methadone in hair included incubation in methanol, solid-phase extraction, derivatisation by the mixture of propionic acid anhydride and pyridine, and gas chromatography\\/mass spectrometry (GC\\/MS).
L Skender; V Kara?i?; I Br?i?; A Bagari?
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. PMID:24798661
Zilkha, Noga; Feigin, Eugene; Barnea-Ygael, Noam; Zangen, Abraham
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…
Petry, Nancy M.; Alessi, Sheila M.; Hanson, Tressa; Sierra, Sean
PURPOSE: Buprenorphine is an alternative to methadone for the maintenance treatment of heroine dependence and may be effective on a thrice weekly basis. Our objective was to evaluate the effect of thrice weekly buprenorphine maintenance for the treatment of heroin dependence in a primary care clinic on retention in treatment and illicit opioid use.SUBJECTS AND METHODS: Opioid-dependent patients were randomly
PatrickG O’Connor; AlisonH Oliveto; JuliaM Shi; ElisaG Triffleman; KathleenM Carroll; ThomasR Kosten; BruceJ Rounsaville; JulianaA Pakes; RichardS Schottenfeld
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
Concheiro, Marta; Shakleya, Diaa M.
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. PMID:25217552
Marinetti, Laureen J; Ehlers, Brooke J
The earliest stages of involvement with illicit drugs have been understudied. In a recent report, we examined initial opportunities to try marijuana and transitions from first opportunity to first use of that drug. This report extends that work by investigating early involvement with cocaine, heroin, and hallucinogens as well. We examine sex and race–ethnicity differences in estimates of having a
M. L Van Etten; J. C Anthony
The purpose of the present study was to investigate the occurrence in hair, of some drugs of abuse in deaths caused by heroin overdose, in comparison to findings in blood. Blood, urine and hair samples were obtained during routine post mortem examinations. Samples were analysed for amphetamines, opiates, and cocaine. Immunometric drug screening was performed in urine and positive results
Robert Kronstrand; Robert Grundin; John Jonsson
This study investigated conditions under which methadone patients with urinalysis evidence of persistent multiple drug abuse would respond to take-home incentive procedures. Study subjects submitted > or = 80% opiate and/or cocaine positive urines during a 5-week baseline period (M, W, F urine testing) while maintained on 60 mg methadone. Doses were raised to 80-100 mg methadone under blind conditions and subjects were randomly assigned to receive methadone take-home doses under one of three conditions: (a) earn a 1-day take-home privilege for each opiate and cocaine-free test delivered (daily contingent condition), (b) three negative test results required for the first take-home privilege, with each subsequent negative test earning one take-home dose; a positive test reset the contingency back to three again (weekly contingent condition), or (c) a control group that did not receive take-home privileges (no take-home control). Five of 21 subjects (24%) assigned to a contingent take-home intervention (2 from condition a, 3 from condition b) showed marked reductions in drug use and delivered 4 or more consecutive weeks of drug-free urines during a 16-week intervention. No subject in the control group met these criteria. Percent positive urines decreased by 14% and 18% from baseline in daily and weekly contingency groups, respectively, compared to a decline of 2% in the no take-home control group (planned contrast of means p < .07 and .05, respectively). Thus, the study demonstrated that take-home incentives can be effective for reducing during-treatment use of opiates and cocaine in methadone patients with a poor prognosis related to their persistent multiple drug use. PMID:9888118
Chutuape, M A; Silverman, K; Stitzer, M L
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 abstinence (CA) versus one of four behaviors (CA, treatment attendance, group CM attendance, and methadone compliance) selected randomly at each drawing. Two groups were formed with 22 cocaine-dependent community-based methadone patients and exposed to both CA and multiple behavior (MB) conditions in a reversal design counterbalanced across groups for exposure order. The group CM intervention proved feasible and safe. The MB condition improved group CM meeting attendance relative to the CA condition. PMID:19192861
Kirby, Kimberly C; Kerwin, Marylouise E; Carpenedo, Carolyn M; Rosenwasser, Beth J; Gardner, Robert S
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…
Donlin, Wendy D.; Knealing, Todd W.; Needham, Mick; Wong, Conrad J.; Silverman, Kenneth
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…
Silverman, Kenneth; Robles, Elias; Mudric, Timothy; Bigelow, George E.; Stitzer, Maxine L.
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 24hours 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. 297ng/mL, p=0.03) and peak S-methadone (285 vs. 339ng/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. PMID:25480096
Tetrault, Jeanette M; McCance-Katz, Elinore F; Moody, David E; Fiellin, David A; Lruie, Bonnie S; DInh, An T; Fiellin, Lynn E
The illicit transportation of cocaine and heroin either swallowed or inserted into the rectum and\\/or vagina of individuals, defined as “body-packers”, is becoming increasingly common. Assessment of smuggling by urinalysis from body-packers has been sparsely reported and on-site rapid screening methods are essentially lacking.We screened the presence of cocaine and heroin metabolites in urine from suspected body-packers by an on-site
E. Marchei; P. Colone; G. G. Nastasi; C. Calabrò; M. Pellegrini; R. Pacifici; P. Zuccaro; S. Pichini
The hypothesis that separate neural systems mediate the reinforcing properties of opioid and psychomotor stimulant drugs was tested by examining the role of mesolimbic dopamine (DA) neurons in maintaining intravenous heroin and cocaine self-administration. After local destruction of the DA terminals in the nucleus accumbens (NAcc) with 6-hydroxydopamine (6-OHDA), rats trained to self-administer cocaine and heroin on alternate days were
Hugh O. Pettit; Aaron Ettenberg; Floyd E. Bloom; George F. Koob
Field ion spectrometry, also known as transverse field compensation ion mobility spectrometry, is a new technique for trace gas analysis that can be applied to the detection of cocaine and heroin. Its principle is based on filtering ion species according to the functional dependence of their mobilities with electric field strength. Field ion spectrometry eliminates the gating electrodes needed in conventional IMS to pulse ions into the spectrometer; instead, ions are injected in to the spectrometer and reach the detector continuously, resulting in improved sensitivity. The technique enables analyses that are difficult with conventional constant field strength ion mobility spectrometers. We have shown that a filed ion spectrometer can selectively detect the vapors from cocaine and heroin emitted from both their base and hydrochloride forms. The estimated volumetric limits of detection are in the low pptv range, based on testing with standardized drug vapor generation systems. The spectrometer can detect cocaine base in the vapor phase, at concentrations well below its estimated 100 pptv vapor pressure equivalent at 20 degrees C. This paper describes the underlying principles of field ion spectrometry in relation to narcotic drug detection, and recent results obtained for cocaine and heroin. The work has been sponsored in part by the United States Advanced Research Projects Agency under contract DAAB10-95C-0004, for the DOD Counterdrug Technology Development Program.
Carnahan, Byron L.; Day, Stephen; Kouznetsov, Viktor; Tarassov, Alexandre
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 topiramate's cognitive effects in individuals dually dependent on cocaine and opioids as part of a double-blind, randomized, controlled trial of topiramate for cocaine dependence treatment. After 5 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 2 time points: study weeks 4 through 5 to assess baseline performance and 10 to 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 2 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 opioid and cocaine use disorders, among whom preexisting cognitive impairments are common. (PsycINFO Database Record (c) 2014 APA, all rights reserved). PMID:25365653
Rass, Olga; Umbricht, Annie; Bigelow, George E; Strain, Eric C; Johnson, Matthew W; Mintzer, Miriam Z
Rationale: Despite numerous reports that male and female animals differ in behavioral responses to drugs, few studies have investigated\\u000a sex differences in drug-reinforced behavior. Objectives: Acquisition of IV cocaine and heroin self-administration was compared in 20 female and 22 male Wistar rats. Methods: An autoshaping procedure was used to train rats to press a lever that resulted in either a
Wendy J. Lynch; Marilyn E. Carroll
ACQUISITION OF COCAINE AND HEROIN SELF-ADMINISTRATION IN RATS DEVELOPMENTALLY EXPOSED TO LEAD A Thesis by ANGELICA ROCHA Submitted to the Office of Graduate Studies of Texas A&M University in partial... by ANGELICA ROCHA Submitted to the Office of Graduate Studies of Texas A&M University in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE Approved as to the style and content by...
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
Barrio, G.; De la Fuente, L.; Royuela, L.; Diaz, A.; Rodriguez-Artalej..., F.
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. Method: Cocaine-dependent methadone patients (N = 240) were randomized to 1 of 4 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 3 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 1 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. (PsycINFO Database Record (c) 2014 APA, all rights reserved). PMID:25198284
Petry, Nancy M; Alessi, Sheila M; Barry, Danielle; Carroll, Kathleen M
This study aims to (1) describe rates of lifetime and current partner abuse among women on methadone; (2) examine the relationship between partner violence and demographics, substance abuse, and drug risk behaviors; and (3) explore the association between a victim's current use of crack\\/cocaine, heroin, marijuana, and drug risk behavior after controlling for demographics, household composition, history of victimization and
Nabila El-Bassel; Louisa Gilbert; Robert Schilling; Takeshi Wada
Aims This study aimed to determine the relative effectiveness of 12-months of Interim Methadone (IM; supervised methadone with emergency counseling only for the first 4 months of treatment), Standard Methadone treatment (SM; with routine counseling) and Restored Methadone treatment (RM: routine counseling with smaller caseloads). Design A randomized controlled trial was conducted comparing: IM, SM, and RM treatment. IM lasted for 4 months after which participants were transferred to SM. Setting The study was conducted in two methadone treatment programs in Baltimore, MD, USA. Participants The study included 230 adult methadone patients newly-admitted through waiting lists. Measurements We administered the Addiction Severity Index and a supplemental questionnaire at baseline, 4-, and 12-months post- baseline. Measurements included retention in treatment, self-reported days of heroin and cocaine use, criminal behavior and arrests, and urine tests for heroin and cocaine metabolites. Findings At 12 months, on an intent-to-treat basis, there were no significant differences in retention in treatment among the IM, SM and RM groups (60.6%, 54.8% and 37.8%, respectively). Positive urine tests for the three groups declined significantly from baseline (ps<0.001 and 0.003, for heroin and cocaine metabolistes respectively) but there were no significant Group x Time interactions for these measures. Thirty-one percent of the sample reported at least one arrest during the year, but there were no significant between-group effects. Conclusions Limited availability of drug counseling services should not be a barrier to providing supervised methadone to adults dependent on heroin - at least for the first 4 months of treatment. PMID:22029398
Schwartz, Robert P.; Kelly, Sharon M.; O'Grady, Kevin E.; Gandhi, Devang; Jaffe, Jerome H.
Objective The aim of this study was to evaluate the risk factors associated with dropout from Methadone Maintenance Treatment (MMT) clinics within a 1 year follow-up cohort study in China. Methods A data analysis is to explore the adherence of MMT during one year from three hundred and twenty patients with heroin dependence at five clinics (3 in Shanghai, 2 in Kunming) in China. All participants were from the part of China-United States cooperation project entitled “Research about improving the compliance and efficacy of methadone maintenance treatment in China”. Our data analysis includes the patients’ attendance in the 6 months clinical study and the data in another 6 months afterward. The data of patients at baseline were collected with the Addiction Severity Index (ASI) which is a semi-structured questionnaire covering socio-demographic characteristics and drug use history. The one year attendance after recruitment at the clinics and daily dose were abstracted from the MMT clinic register system. The Cox proportional hazards model were used to explore the risk factor of dropout, defined as seven consecutive days without methadone. Results By the end of 1 year of treatment 86 patients still remained in MMT without dropout (87% in Shanghai and 13% patients in Kunming). Over the entire 1-year period the median days of remaining in the program were 84 days (in Shanghai and Kunming were 317 days and 22 days).The factors associated with retention included age (HR?=?0.98, 95%C.I.:0.96-0.99, P?=?0.0062) and ASI alcohol scores (HR?=?5.72, 95%C.I.:1.49-21.92, P?=?0.0109) at baseline. Conclusion One year retention of newly recruited patients with heroin dependence was related to age and ASI alcohol scores at baseline. The adherence is poorer for the patients who are young and having more serious alcohol problems. PMID:24565169
Background In China, the Compulsory Detoxification Centres are the main response for people who use illegal drugs. Due to high relapse rates among people released from the Compulsory Detoxification Centres, it is likely that they may seek medical help, including Methadone Maintenance Treatment (MMT) services, at some point. Therefore, better understanding of the attitudes and beliefs of people in the Compulsory Detoxification Centres can help to provide more adequate response to opioid dependence. Methods In total, 329 detained heroin users and 112 active MMT clients were recruited from a local Compulsory Detoxification Centre and MMT clinic, respectively. The survey contained specific questions relating to attitudes and beliefs regarding MMT. Results Participants at the Compulsory Detoxification Centre and the MMT clinic expressed different opinions, regarding positive and negative attitudes and beliefs towards MMT. In addition, participants from both sites hold certain negative attitudes and beliefs about methadone despite their acknowledgement of the positive effects of MMT. Finally, participants at the Compulsory Detoxification Centre and the MMT clinic reported distinctive treatment preferences, with the former preferring community-based treatment and the latter MMT. Conclusions Developing targeted education about MMT for people at the Compulsory Detoxification Centres could help improve access to accurate and evidence-based health and treatment information. The study may also help providers understand and adjust services needed for target population in the future. PMID:23915360
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.
Patrick, Julie C.; Orzechowska, Grazyna E.; Poziomek, Edward J.
n The weight of heroin detections at the Australian border in 2005–06 was at its lowest point in 10 years. However, the number of detections was the highest on record. n Despite attempts to establish supply routes for Afghan heroin, South East Asia remained the predominant source for heroin in Australia. n The number of heroin arrests continued to decline and accounted for less than three percent of all drug arrests in Australia. Main Forms Heroin (diacetylmorphine) is a highly addictive morphine derivative obtained from the opium poppy Papaver somniferum. Heroin is a central nervous system depressant that slows nervous system functioning and has strong pain killing characteristics (AIC, 2005; NSW Department of Health, 2003). Opium, morphine and codeine are natural derivatives of the opium poppy. Heroin is commonly administered through intravenous injection, however, it can be snorted or smoked. The purest form of heroin (No. 4 grade) is a white powder which is readily dissolved and injected. This form is typically seized in Australia. Less pure grades include ‘brown rock ’ or
Rationale Heroin is rapidly metabolized to morphine that in turn is transformed in morphine-3-glucuronide (M3G), an inactive metabolite,\\u000a and morphine-6-glucuronide (M6G), a potent mu-opioid receptor (MOR) agonist. We have found that heroin addicts exhibit higher\\u000a M6G\\/M3G ratios relative to morphine-treated control subjects. We have also shown that heroin-treated rats exhibit measurable\\u000a levels of M6G (which is usually undetectable in this species)
Letizia Antonilli; Emma Petecchia; Daniele Caprioli; Aldo Badiani; Paolo Nencini
Drugs of abuse activate the mesolimbic dopaminergic pathway. Genetic variations in the dopaminergic system may contribute to drug addiction. Several processes are shared between cocaine and heroin addictions but some neurobiological mechanisms may be specific. This study examined the association of 98 single nucleotide polymorphisms in 13 dopamine-related genes with heroin addiction (OD) and/or cocaine addiction (CD) in a sample of 801 African Americans (315 subjects with OD ± CD, 279 subjects with CD, and 207 controls). Single-marker analyses provided nominally significant evidence for associations of 24 SNPs) in DRD1, ANKK1/DRD2, DRD3, DRD5, DBH, DDC, COMT and CSNK1E. A DRD2 7-SNPs haplotype that includes SNPs rs1075650 and rs2283265, which were shown to alter D2S/D2L splicing, was indicated in both addictions. The Met allele of the functional COMT Val158Met was associated with protection from OD. None of the signals remained significant after correction for multiple testing. The study results are in accordance with the results of previous studies, including our report of association of DRD1 SNP rs5326 with OD. The findings suggest the presence of an overlap in genetic susceptibility for OD and CD, as well as shared and distinct susceptibility for OD in subjects of African and European descent. PMID:25875614
Levran, Orna; Randesi, Matthew; da Rosa, Joel Correa; Ott, Jurg; Rotrosen, John; Adelson, Miriam; Kreek, Mary Jeanne
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…
Severtson, Stevan G.; Hedden, Sarra L.; Martins, Silvia S.; Latimer, William W.
Context Cocaine dependence, which affects 2.5 million Americans annually, has no FDA approved pharmacotherapy. Objective To evaluate the immunogenicity, safety, and efficacy of a novel cocaine vaccine to treat cocaine dependence. Design 24 week Phase IIb randomized double-blind placebo-controlled trial with efficacy assessed during weeks 8 to 20 and follow-up to week 24. Setting Cocaine and opioid dependent persons recruited from 2003–2005 from greater New Haven, CT. Participants 115 methadone maintained subjects (67% male, 87% Caucasian, aged 18–46) were randomized to vaccine or placebo and 82% completed the trial. Most smoked crack cocaine along with using marijuana (18%), alcohol (10%), and non-prescription opioids (44%). Intervention Over 12 weeks 109/115 subjects received five vaccinations of placebo or succinylnorcocaine linked to cholera B protein. Main Outcome Measure Semi-quantitative urinary cocaine metabolite levels measured thrice weekly with positive cutoff of 300 ng/ml. Results The 38% of vaccinated subjects who attained serum IgG anti-cocaine levels ? 43 µg/mL (high IgG) had significantly more cocaine-free urines than those with < 43 µg/mL (low IgG) and the placebo subjects during weeks 9 to 16 (45% vs 35%). The proportion of subjects having a 50% reduction in cocaine use was significantly greater in the high IgG than low IgG subjects (0.53 vs. 0.23) (P<0.04). The most common side effects were injection site induration and tenderness. There were no treatment related serious adverse events, withdrawals, or deaths. Conclusions Attaining high (? 43 µg/mL) IgG anti-cocaine antibody levels was associated with significantly reduced cocaine use, but only 38% of the vaccinated attained these IgG levels and they had only 2 months of adequate cocaine blockade. Thus, we need improved vaccines and boosters. PMID:19805702
Martell, Bridget A.; Orson, Frank M.; Poling, James; Mitchell, Ellen; Rossen, Roger D.; Gardner, Tracie; Kosten, Thomas R.
Objective To determine whether supervised medical prescription of heroin can successfully treat addicts who do not sufficiently benefit from methadone maintenance treatment. Design Two open label randomised controlled trials. Setting Methadone maintenance programmes in six cities in the Netherlands. Participants 549 heroin addicts. Interventions Inhalable heroin (n = 375) or injectable heroin (n = 174) prescribed over 12 months. Heroin
Wim van den Brink; Vincent M Hendriks; Peter Blanken; Maarten W J Koeter; Zwieten van B. J; Ree van J. M
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
Donlin, Wendy D; Knealing, Todd W; Needham, Mick; Wong, Conrad J; Silverman, Kenneth
In the present study, we examined the effect of an acute administration of the selective suicide inhibitor of ?-aminobutyric acid (GABA)-transaminase, gamma-vinyl GABA on increases in nucleus accumbens dopamine produced by a cocaine\\/heroin challenge in freely moving animals. Cocaine (20 mg\\/kg, i.p.) produced an elevation in extracellular nucleus accumbens dopamine of approximately 380% above baseline, while heroin produced only a
Madina R Gerasimov; Stephen L Dewey
Knowledge about the meanings and consequences of behaviors associated with drug use among diverse populations is essential for developing effective public health and clinical strategies. In this study we identify racial/ethnic variations in patterns of drug use, Addiction Severity Index (ASI) scores, response to intervention, concordance between self-report of drug use and biochemical confirmation, and treatment system contacts in a sample of 1175 out-of-treatment cocaine and heroin users drawn from a trial of brief motivation in the outpatient clinics of an inner-city academic hospital. Key differences were identified in drug of choice, in all of the ASI domains except medical, in validity of self-report of use, and in rate of treatment contact. Differences related to race and ethnicity should be evaluated to determine needs for a variety of substance abuse treatment modalities, assure timely access to culturally competent care, and develop policies that are tailored to real conditions. PMID:16368656
Bernstein, Edward; Bernstein, Judith; Tassiopoulos, Katherine; Valentine, Anne; Heeren, Timothy; Levenson, Suzette; Hingson, Ralph
Studies examining differences in mortality among long-term drug users have been limited. In this paper, we introduce a Bayesian framework that jointly models survival data using a Weibull proportional hazard model with frailty, and substance and alcohol data using mixed-effects models, to examine differences in mortality among heroin, cocaine, and methamphetamine users from five long-term follow-up studies. The traditional approach to analyzing combined survival data from numerous studies assumes that the studies are homogeneous, thus the estimates may be biased due to unobserved heterogeneity among studies. Our approach allows us to structurally combine the data from different studies while accounting for correlation among subjects within each study. Markov chain Monte Carlo facilitates the implementation of Bayesian analyses. Despite the complexity of the model, our approach is relatively straightforward to implement using WinBUGS. We demonstrate our joint modeling approach to the combined data and discuss the results from both approaches. PMID:21052518
Liang, Li-Jung; Huang, David; Brecht, Mary-Lynn; Hser, Yih-Ing
A validated method for quantifying methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine, cocaine, benzoylecgonine, 6-acetylmorphine, morphine, and codeine in human placenta by liquid chromatography–ion trap mass spectrometry is described. Specimens (1 g) were homogenized and subjected to solid-phase extraction. Chromatographic separation was performed on a Synergi Polar RP column with a gradient of 0.1% formic acid and acetonitrile. The method was linear from 10 to 2000 ng/g for methadone and 2.5 to 500 ng/g for other analytes. Limits of detection were 0.25–2.5 ng/g, imprecisions < 9.1%CV, analytical recoveries 84.4–113.3%, extraction efficiencies > 46%, matrix effects ?8.0–129.9%, and process efficiencies 24.2–201.0%. Method applicability was demonstrated by analysis of five placenta specimens from opioid-dependent women receiving methadone pharmacotherapy, with methadone doses ranging from 65 to 95 mg on the day of delivery. These are the first data on placenta concentrations of methadone and metabolites after controlled drug administration. Detection of other common drugs of abuse in placenta will also improve our knowledge of the usefulness of this matrix for detecting in utero drug exposure and studying disposition of drugs in the maternal-fetal dyad. PMID:19671243
de Castro, Ana; Concheiro, Marta; Shakleya, Diaa M.; Huestis, Marilyn A.
A validated method for quantifying methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine, cocaine, benzoylecgonine, 6-acetylmorphine, morphine, and codeine in human placenta by liquid chromatography-ion trap mass spectrometry is described. Specimens (1 g) were homogenized and subjected to solid-phase extraction. Chromatographic separation was performed on a Synergi Polar RP column with a gradient of 0.1% formic acid and acetonitrile. The method was linear from 10 to 2000 ng/g for methadone and 2.5 to 500 ng/g for other analytes. Limits of detection were 0.25-2.5 ng/g, imprecisions < 9.1%CV, analytical recoveries 84.4-113.3%, extraction efficiencies > 46%, matrix effects -8.0-129.9%, and process efficiencies 24.2-201.0%. Method applicability was demonstrated by analysis of five placenta specimens from opioid-dependent women receiving methadone pharmacotherapy, with methadone doses ranging from 65 to 95 mg on the day of delivery. These are the first data on placenta concentrations of methadone and metabolites after controlled drug administration. Detection of other common drugs of abuse in placenta will also improve our knowledge of the usefulness of this matrix for detecting in utero drug exposure and studying disposition of drugs in the maternal-fetal dyad. PMID:19671243
de Castro, Ana; Concheiro, Marta; Shakleya, Diaa M; Huestis, Marilyn A
Rats were trained to lever press for intravenous cocaine (1.0 mg\\/kg\\/injection) and then switched to bromocriptine (0.3, 1.0, or 3.0 mg\\/kg\\/injection) on a FR-1 reinforcement schedule. Bromocriptine sustained responding at all three doses; hourly drug intake increased linearly with log-dose. In a second experiment, animals were trained to respond for cocaine (1.0 mg\\/kg\\/injection) or heroin (0.1 mg\\/kg\\/injection) reinforcement; drug was
R. A. Wise; A. Murray; M. A. Bozarth
Crack cocaine use is more associated with impulsivity and a propensity to take risks than heroin use, yet no studies have examined this relationship in the absence of acute drug effects. The current study examined impulsivity (using the Delay Discounting Task) and risk-taking propensity (using the Balloon Analogue Risk Task) across independent groups of primary crack cocaine users with minimal
Marina A. Bornovalova; Stacey B. Daughters; Gustavo Daniel Hernandez; Jerry B. Richards; C. W. Lejuez
Abstract Background This study examined racial differences in the prevalence of sexual risk behaviors and their associations with sexually transmitted diseases (STDs) among recent heroin-using and cocaine-using women. Methods Participants were 214 women (59% black, 41% white) who were recruited during 2002–2010 using targeted sampling to participate in a study in Baltimore, Maryland, and reported using heroin, cocaine, or crack during the previous 6 months. Participants completed self-report questionnaires about their drug use, sexual risk behaviors, and lifetime history of one of six STDs, including gonorrhea, syphilis, chlamydia, genital herpes, genital warts, or trichomoniasis. Results More black women (50%) than white women (28%) reported a lifetime STD. Although there were no racial differences in the lifetime prevalence of sexual risk behaviors assessed, there were racial differences in the sexual behaviors associated with ever having a lifetime STD. Simple logistic regressions revealed that ever having a casual sex partner or anal sex were correlates of having a lifetime STD among black women but not among white women. Multiple logistic regression analyses revealed that ever having a casual sex partner was significantly associated with having a lifetime STD among black women, and ever trading sex for money was significantly associated with having a lifetime STD among white women. Conclusions Findings are consistent with national studies and elucidate racial disparities in STDs and associated sexual behaviors among recent heroin-using and cocaine-using women. Findings underscore the need to tailor STD prevention interventions differently for black and white recent heroin-using and cocaine-using women. PMID:21314446
Floyd, Leah J.; Penniman, Typhanye V.; Hulbert, Alicia; Gaydos, Charlotte; Latimer, William W.
Opiates, cocaine, and metabolites were quantified by liquid chromatography–mass spectrometry (LC–MS) in 284 urine specimens, collected thrice weekly, to monitor possible drug relapse in 15 pregnant heroin-dependent women. Opiates were detected in 149 urine specimens (52%) with limits of quantification (LOQ) of 10–50 ?g/L. Morphine, morphine-3-glucuronide, and/or morphine-6-glucuronide were positive in 121 specimens; 6-acetylmorphine, a biomarker of heroin ingestion, was quantifiable in only 7. No heroin, 6-acetylcodeine, papaverine, or noscapine were detected. One hundred and sixty-five urine specimens (58%) from all 15 participants were positive for one or more cocaine analytes (LOQ 10–100 ?g/L). Ecgonine methylester (EME) and/or benzoylecgonine were the major cocaine biomarkers in 142. Anhydroecgonine methylester, a biomarker of smoked cocaine, was positive in six; cocaethylene and/or ecgonine ethylester, biomarkers of cocaine and ethanol co-ingestion, were found in 25. At the current Substance Abuse Mental Health Services Administration cutoffs for total morphine (2000 ?g/L), codeine (2000 ?g/L), 6-acetylmorphine (10 ?g/L), and benzoylecgonine (100 ?g/L), 16 opiate- and 29 cocaine-positive specimens were identified. Considering 100 ?g/L EME as an additional urinary cocaine biomarker would identify 51 more positive cocaine specimens. Of interest is the differential pattern of opiate and cocaine biomarkers observed after LC–MS as compared to gas chromatography–mass spectrometry analysis. PMID:20109298
Shakleya, Diaa M.; Dams, Riet; Choo, Robin E.; Jones, Hendree; Huestis, Marilyn A.
Opiates, cocaine, and metabolites were quantified by liquid chromatography-mass spectrometry (LC-MS) in 284 urine specimens, collected thrice weekly, to monitor possible drug relapse in 15 pregnant heroin-dependent women. Opiates were detected in 149 urine specimens (52%) with limits of quantification (LOQ) of 10-50 microg/L. Morphine, morphine-3-glucuronide, and/or morphine-6-glucuronide were positive in 121 specimens; 6-acetylmorphine, a biomarker of heroin ingestion, was quantifiable in only 7. No heroin, 6-acetylcodeine, papaverine, or noscapine were detected. One hundred and sixty-five urine specimens (58%) from all 15 participants were positive for one or more cocaine analytes (LOQ 10-100 microg/L). Ecgonine methylester (EME) and/or benzoylecgonine were the major cocaine biomarkers in 142. Anhydroecgonine methylester, a biomarker of smoked cocaine, was positive in six; cocaethylene and/or ecgonine ethylester, biomarkers of cocaine and ethanol co-ingestion, were found in 25. At the current Substance Abuse Mental Health Services Administration cutoffs for total morphine (2000 microg/L), codeine (2000 microg/L), 6-acetylmorphine (10 microg/L), and benzoylecgonine (100 microg/L), 16 opiate- and 29 cocaine-positive specimens were identified. Considering 100 microg/L EME as an additional urinary cocaine biomarker would identify 51 more positive cocaine specimens. Of interest is the differential pattern of opiate and cocaine biomarkers observed after LC-MS as compared to gas chromatography-mass spectrometry analysis. PMID:20109298
Shakleya, Diaa M; Dams, Riet; Choo, Robin E; Jones, Hendree; Huestis, Marilyn A
Cholinergic input to the ventral tegmental area (VTA) is known to contribute to reward. Although it is known that the pedunculopontine tegmental nucleus (PPTg) provides an important source of excitatory input to the dopamine system, the specific role of PPTg cholinergic input to the VTA in cocaine reward has not been previously determined. We used a diphtheria toxin conjugated to urotensin-II (Dtx::UII), the endogenous ligand for urotensin-II receptors expressed by PPTg cholinergic but not glutamatergic or GABAergic cells, to lesion cholinergic PPTg neurons. Dtx::UII toxin infusion resulted in the loss of 95.78 (±0.65)% of PPTg cholinergic cells but did not significantly alter either cocaine or heroin self-administration or the development of cocaine or heroin conditioned place preferences. Thus, cholinergic cells originating in PPTg do not appear to be critical for the rewarding effects of cocaine or of heroin. PMID:24465410
Steidl, Stephan; Wang, Huiling; Wise, Roy A.
Interim methadone (with emergency counseling only) (IM), is an effective, but highly restricted alternative to Methadone Treatment Program (MTP) waiting lists. However, it is not known whether IM disadvantages patients as compared to standard methadone treatment (SM). In this clinical trial, conducted in two MTPs, 230 newly-admitted patients were randomly assigned to: IM, SM and “Restored” Methadone treatment (SM with a counselor with a reduced case load) (RM). Data were analyzed using generalized estimating equations and generalized linear modeling. There were no significant differences among Conditions in: days in treatment or of heroin or cocaine use and heroin or cocaine positive urine drug tests. The IM as compared to the SM group had significantly fewer self-reported days of criminal activity and lower amounts of money spent on drugs and illegal income. These findings suggest that when SM is unavailable, IM should be more widely used and less restricted. These findings suggest that when SM is unavailable IM should be more widely utilized and less restricted. PMID:21353445
Schwartz, Robert P.; Kelly, Sharon M.; O’Grady, Kevin E.; Gandhi, Devang; Jaffe, Jerome H.
A pattern-clustering method for longitudinal data - heroin users receiving methadone CHIEN-JU LIN for supporting me spiritually throughout my life. iii #12;Abstract Methadone is used as a substitute of heroin
Jones, Peter JS
This article describes how the drug type injected at the first injection event is related to characteristics of the initiate, risk behaviors at initiation, and future drug-using trajectories. A diverse sample (n=222) of young injection drug users (IDUs) were recruited from public settings in New York, New Orleans, and Los Angeles during 2004 and 2005. The sample was between 16 and 29 years old, and had injected ketamine at least once in the preceding two years. Interview data was analyzed both quantitatively and qualitatively. Young IDUs initiated with four primary drug types: heroin (48.6%), methamphetamine (20.3%), ketamine (17.1%), and cocaine (14%). Several variables evidenced statistically significant relationships with drug type: age at injection initiation, level of education, region of initiation, setting, mode of administration, patterns of self-injection, number of drugs ever injected, current housing status, and their hepatitis C virus (HCV) status. Qualitative analyses revealed that rationale for injection initiation and subjective experiences at first injection differed by drug type. PMID:21423792
Lankenau, Stephen E.; Wagner, Karla D.; Jackson Bloom, Jennifer; Sanders, Bill; Hathazi, Dodi; Shin, Charles
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)
Bazell, Robert J.
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)
Lennard, Henry L.; And Others
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. PMID:25484035
Anderson, Albert M; Higgins, Melinda K; Ownby, Raymond L; Waldrop-Valverde, Drenna
Summary Psychiatric comorbidity and sex trade were tested as correlates of sexually transmitted infections (STIs) among 76 pregnant heroin or cocaine dependent women. Participants were recruited from a drug treatment program and attended a clinician-administered assessment including the Structured Clinical Interview for DSM-IV (SCID-IV-TR) and self report questionnaires about lifetime histories of sex trade and STIs (i.e. gonorrhea, syphilis, chlamydia, herpes, genital warts, or trichomonas). Lifetime and six month rates of STIs were 53.9% and 18.4% respectively. The majority of women also had lifetime histories of psychiatric comorbidity (61.8%) and/or sex trade (60.5%). Participants with psychiatric comorbidity (AOR 3.9; 95% CI 1.3–11.6) and/or sex trade (AOR 3.2; 95% CI 1.1–9.5) were more likely to report STIs during their lifetime compared to those without such histories while controlling for age, education, and race/ethnicity. Results suggest that as many as one-in-five pregnant heroin or cocaine dependent women in treatment have one or more STIs that are concurrent with their pregnancy and may contribute to risk for contracting HIV and pregnancy complications; psychiatric comorbidity and/or sex trade were associated with greater STI risk. Findings underscore the importance of identifying and addressing comorbid psychiatric disorders and sex trade behavior in this population. PMID:20090001
Cavanaugh, Courtenay E.; Hedden, Sarra L.; Latimer, William W.
Hair specimens were collected from 322 subjects and analyzed as part of an experimental study administering household surveys during 1997 to a high-risk community sample of adults from Chicago, Illinois. Toxicologic results were compared with survey responses about recent and lifetime drug use. About 35% of the sample tested positive for cocaine, and 4% tested positive for heroin. Sample prevalence
Michael Fendrich; Timothy P. Johnson; Seymour Sudman; Joseph S. Wislar; Vina Spiehler
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. PMID:20218800
Wedekind, Dirk; Jacobs, Stefan; Karg, Iris; Luedecke, Christel; Schneider, Udo; Cimander, Konrad; Baumann, Pierre; Ruether, Eckart; Poser, Wolfgang; Havemann-Reinecke, Ursula
Objectives A previous pilot trial evaluating computer-based cognitive behavioral therapy (CBT4CBT) among 77 heterogeneous substance users (alcohol, marijuana, cocaine, opioids) provided preliminary support for its efficacy in the context of a community-based outpatient clinic. Aims of the present trial were to conduct a more definitive trial in a larger, more homogeneous sample. Methods Randomized clinical trial in which 101 cocaine-dependent methadone maintained individuals were randomized to standard methadone maintenance or methadone maintenance with weekly access to CBT4CBT, with 7 modules delivered within an 8 week trial. Results Treatment retention and data availability were high and comparable across the treatment conditions. Participants assigned to the CBT4CBT condition were significantly more likely to attain three or more consecutive weeks of abstinence from cocaine (36 versus 17%, p<.05, OR=.36). The group assigned to CBT4CBT also had better outcomes on most dimensions, including urine specimens negative for all drugs, but these reached statistical significance only for the completer sample (N=69). Follow-up data collected 6 months after treatment termination were available from 93% of the randomized sample; these indicated continued improvement for those assigned to the CBT4CBTgroup, replicating previous findings regarding its durability. Conclusions This trial replicates earlier findings indicating CBT4CBT is an effective adjunct to addiction treatment with durable effects. CBT4CBT is an easily disseminable strategy for broadening the availability of CBT, even in challenging populations such as cocaine-dependent individuals enrolled in methadone maintenance programs. Clinical trials.gov ID number NCT00350610 PMID:24577287
Carroll, Kathleen M.; Kiluk, Brian D.; Nich, Charla; Gordon, Melissa A.; Portnoy, Galina A.; Marino, Daniel R.; Ball, Samuel A.
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 draw for each urine negative for opiates or cocaine, four draws if negative for both, N ?=? 38). There were no group differences in cocaine abstinence during CM or post-CM and no differences in opiate abstinence during CM. Opiate abstinence was greater in the opiate-cocaine group post-CM, and heroin craving was reduced in this group during and post-CM. Draws earned per cocaine-negative urine (four vs. one) did not affect cocaine use. PMID:19192859
Preston, Kenzie L; Ghitza, Udi E; Schmittner, John P; Schroeder, Jennifer R; Epstein, David H
Aims To determine whether cannabinoid-positive urine specimens in heroin-dependent outpatients predict other drug use or impairments in psychosocial functioning, and whether such outcomes are better predicted by cannabis-use disorders than by cannabis use itself. Design Retrospective analyses of three clinical trials; each included a behavioral intervention (contingency management) for cocaine or heroin use during methadone maintenance. Trials lasted 25–29 weeks; follow-up evaluations occurred 3, 6, and 12 months posttreatment. For the present analyses, data were pooled across trials where appropriate. Setting Urban outpatient methadone clinic. Participants 408 polydrug abusers meeting methadone-maintenance criteria. Measurements Participants were categorized as nonusers, occasional users, or frequent users of cannabis based on thrice-weekly qualitative urinalyses. Cannabis-use disorders were assessed with the Diagnostic Interview Schedule III-R. Outcome measures included proportion of cocaine- and opiate-positive urines and the Addiction Severity Index (at intake and follow-ups). Findings Cannabis use was not associated with retention, use of cocaine or heroin, or any other outcome measure during or after treatment. Our analyses had a power of .95 to detect an r2 of .11 between cannabis use and heroin or cocaine use; the r2 we detected was less than .03 and nonsignificant. A previous finding that cannabis use predicted lapse to heroin use in heroin-abstinent patients did not replicate in our sample. However, cannabis-use disorders were weakly associated with psychosocial problems at posttreatment follow-up. Conclusions Cannabinoid-positive urines need not be a major focus of clinical attention during treatment for opiate dependence, unless patients report symptoms of cannabis-use disorders. PMID:12603227
Epstein, D.H.; Preston, K.L.
Few well-controlled studies have examined psychomotor and cognitive performance in methadone maintenance patients (MMP). In the present study, performance of 18 opioid-dependent MMP was evaluated relative to that of 21 control participants without substance abuse histories. The MMP and control groups were balanced with respect to gender, race, age, years of education, current employment status, current reading level, and estimated IQ score. Recent drug abstinence was verified by urine testing. Participants with a urine screen positive for benzodiazepines or a breathalyzer test positive for alcohol prior to performance testing were excluded. To avoid testing under conditions of acute heroin or cocaine intoxication, but without testing under conditions of acute withdrawal, participants with current use of heroin or cocaine were only required to abstain for 24 h prior to performance testing. MMP exhibited impairment relative to controls in psychomotor speed (digit symbol substitution and trail-making tests), working memory (two-back task), decision making (gambling task), and metamemory (confidence ratings on a recognition memory test); results also suggested possible impairment in inhibitory mechanisms (Stroop color-word paradigm). MMP did not exhibit impairment in time estimation, conceptual flexibility or long-term memory. The wide range of impaired functions is striking, and may have important implications for daily functioning in MMP. Further research is necessary to determine the clinical significance of the impairments in laboratory-based tests for daily performance in the natural environment, as well as to differentiate impairments due to acute methadone dosing, chronic methadone maintenance, chronic poly-drug abuse, and other factors. PMID:12062778
Mintzer, Miriam Z; Stitzer, Maxine L
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…
Kirby, Kimberly C.; Kerwin, MaryLouise E.; Carpenedo, Carolyn M.; Rosenwasser, Beth J.; Gardner, Robert S.
LC-MS/MS methods for the quantification of morphine, morphine-3-glucuronide, morphine-6-glucuronide, codeine, 6-acetylmorphine, cocaine, benzoylecgonine, ecgonine methyl ester, hydroxybenzoylecgonine, cocaethylene, amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine (MDMA), methadone, and 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine in human placenta and umbilical cord were developed and validated. Specimens (1 ± 0.02 g) were homogenized with the Ultra-Turrax T8 disperser and centrifuged, and the supernatant was submitted to solid-phase extraction with Oasis MCX cartridges. Chromatographic separation was performed using an Atlantis T3 analytical column (100 × 2.1 mm, 3 ?m) and a gradient of 0.1 % formic acid and acetonitrile. Selectivity was verified in 10 different blank specimens. The method was linear from 1-5 to 100-500 ng/g, depending on the analyte. Limits of detection and quantification ranged from 0.5 to 2.5 ng/g and 1 to 5 ng/g, respectively. Method imprecision was ?15.3 %, except for MDMA at low quality control (18.1 %); accuracy, 87.1 to 114 %; extraction efficiency, 16.3 to 154.0 % (%CV = 1.8-39.4 %); matrix effect, -75.7 to 449.9 % (%CV = 3.5-50 %); and process efficiency, 8.7 to 316.0 %. The method was applied to authentic placenta and umbilical cord specimens from drug-user pregnant women. PMID:23397092
de Castro, Ana; Díaz, Ariana; Piñeiro, Beatriz; Lendoiro, Elena; Cruz, Angelines; López-Rivadulla, Manuel; Concheiro, Marta
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
María Teresa Contreras; Antonio F. Hernández; Marisa González; Susana González; Rosa Ventura; Antonio Pla; Juan Luis Valverde; Jordi Segura; Rafael de la Torre
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
Moreno-López, Laura; Stamatakis, Emmanuel A.; Fernández-Serrano, Maria José; Gómez-Río, Manuel; Rodríguez-Fernández, Antonio; Pérez-García, Miguel; Verdejo-García, Antonio
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 (58.8%), and high GIF/intact EF profile (10.4%). Using a multinomial logistic regression, it was determined that individuals who reported being diagnosed with either a learning disability (LD) and/or attention-deficit/hyperactivity disorder (ADHD) were more likely to be in the impaired GIF and EF profile than other profiles. Results from a logistic regression indicated that the impaired GIF and EF profile was associated with a greater prevalence of past hepatitis B and/or C infection. Implication for harm reduction and treatment programs and the need to take into account individuals with LD and ADHD are discussed. PMID:20574063
Severtson, Stevan G; Hedden, Sarra L; Martins, Silvia S; Latimer, William W
This article investigates behaviours that may be associated HIV infection among users and sellers of crack, powder cocaine and heroin in central Harlem. Chain referral sampling and other strategies were combined to acquire a sample of 637 (Users = 546; Sellers = 91) who provided urine specimens that were tested for the presence of drugs and HIV. Nearly a quarter (23.9%) of all respondents were HIV positive. Drug injectors were more than 2.5 times more likely to have HIV infections than other respondents (OR = 2.66; 95% CI 1.66–4.26). Those involved in frauds/cons were almost as likely to be HIV positive (OR = 2.58; 95% CI 1.64–4.06). Those with a marital status of being separated, divorced or widowed were twice as likely to be HIV infected (OR 2.16; 95% CI 1.43–3.25). Respondents currently having multiple partner sex (OR = 1.66; 95% CI 1.1–2.51) or who were female (OR = 1.66; 95% CI 1.12–2.45) were more than 1.5 times more likely to be HIV positive. Thus, controlling for lifetime drug injection and current multiple partner sex, other factors, such as participating in frauds/cons, as well as relationship status and being female, were also associated with HIV infection. PMID:16338774
DAVIS, W. REES; JOHNSON, B. D.; RANDOLPH, D.; LIBERTY, H. J.
Changes in sleep architecture and continuity are frequent side effects of drugs of abuse, and complaints of poor sleep are often reported by recovering drug abusers. As part of a Phase 1 assessment of the safety and efficacy of 4 and 8 mg\\/day of buprenorphine treatment, the sleep patterns of 20 male opiate-and cocaine-dependent patients were quantified by using standard
Scott E. Lukas; Cynthia M. Dorsey; Nancy K. Mello; Jack H. Mendelson; Leslie H. Lundahl; Michelle Sholar; Steven L. Cunningham
BACKGROUND Previous research has suggested possible sex-related differences in executive functioning among cocaine users; however, no studies specifically explain sex-related differences in neurocognitive impairment (NCI) among cocaine users receiving clinical care. Knowledge about this association can aid in the development of targeted prevention strategies to reduce adverse health outcomes. This study was designed to examine the sex-related differences in NCI among high-risk cocaine users receiving substance-abuse treatment. METHODS The Neuropsychological Impairment Scale (NIS) was administered to 199 cocaine users (98 men; 101 women), receiving methadone maintainance treatment, to assess self-reported NCI by identifying the patients’ awareness of neuropsychological symptoms. We used T-test comparison to find differences in NCI between men and women and multiple regression analysis to explore the relative contribution of sex to NCI. RESULTS Consistent with prior work, high NCI was evident within this sample, as indicated by high scores on most of the NIS subscales. Women reported greater impairment than men, as evidenced by significantly higher scores on several NIS subscales, after controlling for demographic and other confounding variables. Interestingly, cocaine craving significantly predicted NCI among men but not among women, as suggested by the significant association between cocaine craving and all except one of the NIS subscales. CONCLUSIONS These findings suggest that cocaine users enter into treatment with a range of NCI – with women having significantly more neurocognitive deficits than men – that may contribute to differential treatment outcomes. This highlights the need to include additional services such as neuropsychological screening and sex-specific treatment programs to optimally reduce adverse health outcomes in these high-risk, cognitively impaired patients.
Shrestha, Roman; Huedo-Medina, Tania B; Copenhaver, Michael M
Objective This secondary data analysis examined the association between criminal justice (CJ) status and outcomes over 12 months of methadone maintenance treatment. Methods In the parent study, 230 newly-admitted patients were randomly assigned to methadone either with or without counseling for 4 months followed by standard methadone with counseling. Participants completed the ASI and urine drug testing at baseline and 4- and 12-month follow-up and the Treatment Readiness (TR) scale at baseline. The relationship between baseline CJ status (whether participants were on probation or parole), CJ status by study counseling condition, and CJ status by TR with heroin and cocaine use, illegal activity, days in treatment and treatment retention, arrests, and number of days incarcerated or hospitalized during follow-up was examined. Results Compared to participants not on probation/parole, probationers/parolees showed significant reductions in cocaine-positive tests from baseline to 12 months (p<.001). Probationers/parolees additionally reported significantly fewer days of illegal activity than non-probationers/parolees at 12 months (p=.02). There was no relationship between CJ status and counseling condition for any outcomes. The relationship between CJ status and TR was significant only for cocaine-positive tests assessed over time (p=.017). Conclusions Findings suggest that methadone patients on probation/parole showed improvements in outcomes comparable to patients not on probation/parole, regardless of whether they received counseling during the first 4 months of treatment. PMID:23455877
Kelly, Sharon M.; O’Grady, Kevin E.; Jaffe, Jerome H.; Gandhi, Devang; Schwartz, Robert P.
Adipose tissue is a complex biological matrix that necessitates several pre-analytical preparation steps to separate drugs and metabolites from the lipophilic matrix. A novel, sensitive, and specific gas chromatographic-mass spectrometric (GC-MS) method for the determination of cocaine (metabolites), methadone, and morphine in postmortem adipose tissue was developed, optimized, and validated. The method involves the aqueous acid extraction of analytes, alkalinization of the extract, solid-phase extraction with chloroform, and derivatization with BSTFA before GC-MS analysis. Deuterated compounds were used as internal standards for determination and quantification of analytes. Limits of detection were 0.005 microg/g for cocaine and cocaethylene, 0.02 microg/g for benzoylecgonine, 0.01 microg/g for ecgoninemethylester, 0.005 microg/g for methadone, and 0.01 microg/g for morphine. Linearity ranged from 0.1 to 1.000 microg/g for all analytes. Intra- and interday accuracy ranged from 70.6 to 105%, and intra- and interday precisions were less than 8.2% and 8.6%, respectively, for all analytes. The method showed a good recovery. PMID:20663287
Colucci, A P; Aventaggiato, L; Centrone, M; Gagliano-Candela, R
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…
Piazza, Nick J.; Yeager, Rebecca D.
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 ? 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 ?<= 0.01.
Avci, Recep; Maccagnano, Sara; Bohannan, Gary; Gresham, Gary; Groenewold, Gary
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)
Objective To compare HCV and HIV infection among heroin addicts in MMT and not in MMT in two large cities in central China. Methods A total of 541 heroin addicts were recruited from MMT clinics and voluntary detoxification centers in Changsha and Wuhan, China. Structured questionnaires collected data on their socio-demographics, clinical status, risk behaviors, and their knowledge of HIV. Their HIV serostatus and Hepatitis C virus (HCV) serostatus were determined by testing antibodies in blood serum. Results We observed a higher prevalence of HCV infection among MMT heroin addicts (82.3%) than that in the non-MMT group (50.6%). However, our findings indicated that the heroin addicts in MMT had less drug or sexual HIV/HCV risk behaviors and more knowledge about HIV than non-MMT addicts. The heroin addicts in MMT had a significantly higher percentage of individuals who always used condoms (44.9%) compared with patients in the non-MMT group (14.6%, p?=?0.039), and they had more knowledge about HIV than non-MMT individuals (p<.001). The percentage of HIV-positive addicts in the MMT group (0.7%) and non-MMT group (0.8%) were almost same. Conclusion Our study indicated that the rate of HCV infection among heroin addicts among MMT or non-MMT settings in central China is very high. The non-MMT heroin addicts have higher risk of becoming infected with HCV in the future, while at present they have lower rates of HCV infection than MMT heroin addicts. Although rates of HIV infection among MMT and non-MMT heroin addicts are low now, they are all at great risk of becoming infected with HIV in the future, especially for non-MMT heroin addicts. We should use the MMT sites as a platform to improve the control of HCV and HIV infection in heroin addicts. PMID:23029149
Wang, Xuyi; Tan, Linxiang; Li, Yi; Zhang, Yao; Zhou, Dongyi; Liu, Tieqiao; Hao, Wei
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 implications. (NQ)
This study explored the association between readiness to enter treatment and performance on the Wisconsin Card Sorting Test (WCST), a measure of problem solving ability and executive functioning. Data for this analysis was collected on 258 current regular users of heroin and/or cocaine as part of an epidemiologic study on executive function and drug use. A structural equation model was used to test the hypotheses that poorer performance on the WCST would predict lower scores on two latent constructs measuring motivation to change drug use. Specifically, poorer performance on the WCST was associated with lower recognition of problem use. Associations between treatment enrollment within the past six months and regular use of more than one drug were also observed. Findings highlight the importance of considering cognitive impairment in programs targeting active drug users and promoting treatment participation. PMID:20226598
Severtson, Stevan Geoffrey; von Thomsen, Sarah; Hedden, Sarra L; Latimer, William
Background. Sudden sensorineural hearing loss (SSHL) caused by opiate abuse or overuse has been well documented in the medical literature. Most documented case reports have involved either heroin or hydrocodone/acetaminophen. Recently, case reposts of methadone induced SSHL have been published. Case Report. We present the case of a 31-year-old man who developed SSHL after a methadone overdose induced stupor. He was subsequently restarted on methadone at his regular dose. On follow-up audiometry exams, he displayed persistent moderately severe sensorineural hearing loss bilaterally. Discussion. This case is notable because unlike all but one previously reported case, the patient—who was restated on methadone—did not make a complete recovery. Conclusion. Methadone overuse in rare cases causes SSHL. PMID:23983704
Saifan, Chadi; Barakat, Iskandar; El-Sayegh, Suzanne
This study examined the impact of prison-initiated methadone maintenance at 12 months postrelease. Males with preincarceration heroin dependence (N = 204) were randomly assigned to (a) Counseling Only: counseling in prison, with passive referral to treatment upon release; (b) Counseling + Transfer: counseling in prison with transfer to methadone maintenance treatment upon release; and (c) Counseling + Methadone: counseling and
Timothy W. Kinlock; Michael S. Gordon; Robert P. Schwartz; Terrence T. Fitzgerald; Kevin E. O'Grady
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…
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…
Stotts, Angela L.; Masuda, Akihiko; Wilson, Kelly
Two hundred community-based methadone patients (CM); 200 prison inmates enrolled in prison methadone programs (PM); and 150 prison inmates with no history of heroin use (PNH) were interviewed to obtain diagnoses of antisocial personality disorder (ASPD) and Psychopathy Checklist-defined psychopathy. Large proportions of subjects in all three groups met the criteria for a diagnosis of ASPD (CM 44%, PM 65%,
Shane Darke; Sharlene Kaye; Robert Finlay-Jones
Amongst the illicit drugs cocaine, amphetamines and cannabis have been studied and documented well to cause myocardial infarction by different mechanisms but there is very sparse data available on myocardial involvement after heroin abuse. We report a young man who developed acute myocardial injury after heroin inhalation and alcohol binge drinking. Heroin induced cardio toxic effect and vasospasm compounded by alcohol were suspected to be the cause of this. PMID:23129970
Karoli, Ritu; Fatima, J.; Singh, Pushker; Kazmi, Khursheed I.
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…
Join Together, Boston, MA.
It may be argued that seizing large quantities of heroin being imported into the country should decrease its supply and hence increase its price, resulting in a reduction in the quantity of the drug being purchased or consumed. To date, however, there has been no empirical evidence that heroin seizures in Australia have any effect on the price of heroin at street level. This article describes a 2-year research study during which the price and purity of street-level heroin were regularly monitored. It was found that heroin seizures had no effect on the price, purity or perceived availability of heroin at street level. It was further found that admissions to methadone treatment were not affected by the price or perceived availability of heroin or by local arrests for heroin use/possession, nor was any relationship found between these arrests and the price of street-level heroin. Nevertheless, two-thirds of those who sought entry to local methadone programmes indicated the price as a reason for stopping using heroin. This paper argues that supply-side law enforcement should only be used as a strategy for maintaining high heroin prices if the demand for heroin can be shown to be price-elastic and, further, that the costs of such a strategy need to be weighted against the benefits. PMID:9219378
Weatherburn, D; Lind, B
A wide range of commonly abused drugs have effects on the noradrenergic neurotransmitter system, including alterations during acute intoxication and chronic use of these drugs. It is not established, however, that individual differences in noradrenergic signaling, which may be present prior to use of drugs, predispose certain persons to substance abuse. This paper puts forth the novel hypothesis that elevated noradrenergic signaling, which may be raised largely due to genetics but also due to environmental factors, is an etiological factor in the abuse of a wide range of substances, including alcohol, nicotine, marijuana, heroin, cocaine, and caffeine. Data are reviewed for each of these drugs comprising their interaction with norepinephrine during acute intoxication, long-term use, subsequent withdrawal, and stress-induced relapse. In general, the data suggest that these drugs acutely boost noradrenergic signaling, whereas long-term use also affects this neurotransmitter system, possibly suppressing it. During acute withdrawal after chronic drug use, noradrenergic signaling tends to be elevated, consistent with the observation that norepinephrine lowering drugs such as clonidine reduce withdrawal symptoms. Since psychological stress can promote relapse of drug seeking in susceptible individuals and stress produces elevated norepinephrine release, this suggests that these drugs may be suppressing noradrenergic signaling during chronic use or instead elevating it only in reward circuits of the brain. If elevated noradrenergic signaling is an etiological factor in the abuse of a broad range of substances, then chronic use of pharmacological agents that reduce noradrenergic signaling, such as clonidine, guanfacine, lofexidine, propranolol, or prazosin, may help prevent or treat drug abuse in general. PMID:24151426
Fitzgerald, Paul J.
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
O’Brien, Charles P.
Aims Methadone is standard pharmacotherapy for opioid-dependent pregnant women, yet the relationship between maternal methadone dose and neonatal abstinence syndrome (NAS) severity is still unclear. This research evaluated whether quantification of fetal methadone and drug exposure via meconium would reflect maternal dose and predict neonatal outcomes. Design Prospective clinical study Setting An urban drug treatment facility treating pregnant and post-partum women and their children Participants Forty-nine opioid-dependent pregnant women received 30–110 mg methadone daily. Measurements Maternal methadone dose, infant birth parameters and NAS assessments were extracted from medical records. Thrice-weekly urine specimens were screened for opioids and cocaine. Newborn meconium specimens were quantified for methadone, opioid, cocaine and tobacco biomarkers. Findings There was no relationship between meconium methadone concentrations, presence of opioids, cocaine and/or tobacco in meconium, maternal methadone dose or NAS severity. Opioid, cocaine and tobacco biomarkers also were found in 36.7, 38.7 and 81.1% of meconium specimens, respectively, and were associated with positive urine specimens in the third trimester. The presence of opioids other than methadone in meconium correlated with increased rates of preterm birth, longer infant hospital stays and decreased maternal time in drug treatment. Conclusions Methadone and its metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) concentrations in meconium did not predict infant birth parameters or NAS severity. Prospective urine testing defined meconium drug detection windows for opiates and cocaine as three months, rather than the currently accepted six months. The presence of opioids in meconium could be used as a biomarker for infants at elevated risk in the newborn period. PMID:20854338
Gray, Teresa R.; Choo, Robin E.; Concheiro, Marta; Williams, Erica; Elko, Andrea; Jansson, Lauren M.; Jones, Hendrée E.; Huestis, Marilyn A.
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 parent drug of both methadone and drugs of abuse and provide a means for drug testing. Compared with blood which has a widow of detection of several hours, urine has a wider window of detection, approximately 1 to 3 days, and is therefore considered more useful than blood for drug testing. Because of this, and the fact that obtaining a urine specimen is relatively easy, urine drug screening is considered the criterion measure (gold standard) for methadone maintenance monitoring. However, 2 main concerns exist with urine specimens: the possibility of sample tampering by the patient and the necessity for observed urine collection. Urine specimens may be tampered with in 3 ways: dilution, adulteration (contamination) with chemicals, and substitution (patient submits another persons urine specimen). To circumvent sample tampering the supervised collection of urine specimens is a common and recommended practice. However, it has been suggested that this practice may have negative effects including humiliation experienced by patient and staff, and may discourage patients from staying in treatment. Supervised urine specimen collection may also present an operational problem as staff must be available to provide same-sex supervision. Oral fluid testing has been proposed as a replacement for urine because it can be collected easily under direct supervision without infringement of privacy and reduces the likelihood of sample tampering. Generally, the results of oral fluid drug testing are similar to urine drug testing but there are some differences, such as lower concentrations of substances in oral fluid than urine, and some drugs remain detectable for longer periods of time in urine than oral fluid. The Technology Being Reviewed The Intercept Oral Specimen Collection Device (Ora-Sure Technologies, Bethlehem, PA) consists of an absorbent pad mounted on a plastic stick. The pad is coated with common salts. The absorbent pad is inserted into the mouth and placed between the cheek and gums for 3 minutes on average. The pad absorbs the oral fluid. After 3 minutes (range 2min-5
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 (mean = $60/day) if: (1) they encountered a 33% decrease in income (DPA = $34), (2) family/friends no longer paid their living expenses (DPA = $32), or (3) 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, i.e., live closer to their primary dealer, 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 purchasing 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. PMID:21443296
Roddy, Juliette; Steinmiller, Caren L.; Greenwald, Mark K.
Background: Client characteristics provide useful information for designing programs that target individuals with risk factors for substance use and for determining client retention. Therefore, this study examined the profiles of clients attending a methadone clinic. Methods: A cross-sectional analysis of clients of a methadone clinic was conducted through a survey to obtain a profile of methadone clients. Results: Of the 51 patients who responded (response rate: 66.2%), the mean (SD) age at which they started substance use was 19.8 (5.1) years. Friends were cited as the most regular source of drugs (82.4%), and heroin was the most commonly used drug (98%). Daily substance use was reported by 72.5% of the respondents; 23.5% admitted to having stolen money to purchase drugs; 92.2% tried quitting substance use on their own and 98% stated that the main reason for registering at the clinic was that they wanted to stop their drug dependence. Approximately 60% of clients were receiving methadone doses of less than 60 mg/day. Conclusion: Heroin is still the most popular drug of abuse and most clients still receive methadone doses below the recommended level, despite evidence of poor patient retention rates associated with these low doses.
JACOB, Sabrina Anne; MOHAMMED, Fauziah; HASSALI, Mohamed Azmi Ahmad
Research suggests that buprenorphine may possess antidepressant activity. The Beck Depression Inventory was completed at baseline and 3 months by heroin dependent subjects receiving either buprenorphine or methadone maintenance as part of a larger, pre-existing, double blind trial conducted by NDARC (Australia). Depressive symptoms improved in all subjects, with no difference between methadone and buprenorphine groups, suggesting no differential benefit on
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)
Hser, Yih-Ing; And Others
Research suggests that buprenorphine may possess antidepressant activity. The Beck Depression Inventory was completed at baseline and 3 months by heroin dependent subjects receiving either buprenorphine or methadone maintenance as part of a larger, pre-existing, double blind trial conducted by NDARC (Australia). Depressive symptoms improved in all subjects, with no difference between methadone and buprenorphine groups, suggesting no differential benefit on depressive symptoms for buprenorphine compared to methadone. PMID:15589713
Dean, Angela J; Bell, James; Christie, Macdonald J; Mattick, Richard P
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.
Kaye, B.R.; Fainstat, M.
BACKGROUND: In the United Kingdom (UK), there is an extensive market for the class 'A' drug heroin and many heroin users spend time in prison. People addicted to heroin often require prescribed medication when attempting to cease their drug use. The most commonly used detoxification agents in UK prisons are currently buprenorphine and methadone, both are recommended by national clinical
Laura Sheard; Nat MJ Wright; Clive E Adams; Nicole Bound; Bruno Rushforth; Roger Hart; Charlotte NE Tompkins
Background:After prison release, offenders with heroin use problems are at high risk of relapse and overdose death. There is a particular need for treatments that can be initiated in prison and continued after release into the community. Methadone maintenance treatment has been shown to reduce heroin use, criminality and mortality. Naltrexone implant treatment has not previously been evaluated in prison
Philipp P. Lobmaier; Nikolaj Kunøe; Michael Gossop; Tormod Katevoll; Helge Waal
This article describes profiles of heroin addicts in three types of treatment (methadone, detox and therapeutic community) and those not in treatment in the local community. The profiles are based on data at item-level of the revised Addiction Severity Index. In total, 310 heroin addicts were interviewed. The results show that on the one hand the community group and the
M. Anne Eland-Goossensen; Annemieke J. Benschop; Henk F. L. Garretsen
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)
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. PMID:19137479
Joe, George W; Simpson, D Dwayne; Rowan-Szal, Grace A
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
Yuferov, Vadim; Levran, Orna; Proudnikov, Dmitri; Nielsen, David A.; Kreek, Mary Jeanne
Rationale Effects of an intervention cannot be understood without precise knowledge of the baseline behavior on which the intervention is superimposed. For misusers of illicit drugs, patterns of daily activities and moods have not been studied in a way that is amenable to statistical aggregation. Objective To compare hour-by-hour daily activities in cocaine-dependent outpatients during urine-verified periods of use and abstinence. Methods In a cohort design, a volunteer sample of 112 methadone-maintained cocaine- and heroin-abusing outpatients provided ecological momentary assessment (EMA) data on handheld computers for 10,781 person-days. EMA responses to questions about current location, activities, companions, moods, and recent exposure to putative drug-use triggers were compared across periods of use and abstinence using SAS Proc Glimmix (for binary outcomes) and Proc Mixed (for continuous outcomes). Results Periods of cocaine use were associated with idle, solitary, affectively negative afternoons, but, unexpectedly, were also associated with a greater likelihood of early-morning or late-evening work. The whole-day concomitants of cocaine use were often distinct from the acute predecessors of use seen in prior analyses from the same sample. Several measures of negative mood increased during abstinence. Conclusions Weeks of cocaine use and abstinence in outpatients are associated with distinct patterns of mood and behavior; the detailed hourly data reported here should help inform treatment interventions aimed at changing daily activities. The findings also argue against the contention that cocaine abstinence symptoms decrease monotonically from the day of cessation. PMID:20532873
Epstein, David H.; Preston, Kenzie L.
BACKGROUND Methadone is a synthetic opioid, which has been successfully used in treating heroin addiction and chronic pain syndrome in palliative care for more than 30 years. This drug is a potent blocker of the delayed rectifier potassium ion channel, which may result in corrected QT (QTc) interval prolongation and increased risk of torsades de pointes (TdP) in susceptible individuals. CASE REPORT We describe here a case of methadone-induced TdP that deteriorated into ventricular fibrillation, which was resolved after treatment with IV magnesium, potassium, and Lidocaine. Our purpose in this case review was to highlight the risk of cardiac arrhythmias, in particular QTc interval prolongation leading to TdP in a heroin-dependent patient receiving methadone substitution therapy, and then to present a perspective on treatment and prevention strategies of methadone induced prolonged QTc. CONCLUSION Methadone-induced TdP is a potentially fatal complication of methadone therapy. As the popularity of methadone use grows, clinicians will encounter more cases of methadone induced TdP, especially in our region, Iran. Hence, a thorough patient history and electrocardiogram monitoring are essential for patients treated with this agent, and alterations in treatment options may be necessary.
Khalesi, Somayeh; Shemirani, Hassan; Dehghani-Tafti, Faezeh
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…
Do It Now Foundation, Phoenix, AZ.
Previous studies suggest that fatal poisoning deaths involving methadone occur more frequently on the weekends. We assessed changes in the daily pattern of mortality because of methadone poisoning following a review of drug misuse services in 1996 and publication of revised clinical guidelines in 1999. We also compared this to the daily pattern of deaths involving heroin/morphine. The Office for National Statistics provided data on all deaths in England and Wales between 1993 and 2003 for which methadone and heroin/morphine were mentioned on the coroner's certificate of death registration after inquest, with or without alcohol or other drugs. There were 3098 deaths involving methadone. The death rate increased up to 1997 and then declined. Initially, there was a marked excess of deaths occurring on Saturdays. The rate of decline was greatest for deaths occurring on Saturdays. As a result, the Saturday peak disappeared (P = 0.006). There were 6328 deaths involving heroin/morphine. No change in the daily pattern of heroin/morphine deaths was observed during the study period. Although the marked change in the epidemiology of methadone deaths coincided with recommendations for service redevelopment and clinical management of methadone treatment, the contribution of improved prescribing practice or treatment services is unclear. PMID:17060353
Morgan, O W; Johnson, H; Rooney, C; Seagroatt, V; Griffiths, C
Relapse to cocaine use necessitates remodeling excitatory synapses in the nucleus accumbens and synaptic reorganization requires matrix metalloproteinase (MMP) degradation of the extracellular matrix proteins. We found enduring increases in MMP-2 activity in rats after withdrawal from self-administered cocaine and transient increases in MMP-9 during cue-induced cocaine relapse. Cue-induced heroin and nicotine relapse increased MMP activity, and increased MMP activity was required for both cocaine relapse and relapse-associated synaptic plasticity. PMID:25326689
Smith, Alexander C W; Kupchik, Yonatan M; Scofield, Michael D; Gipson, Cassandra D; Wiggins, Armina; Thomas, Charles A; Kalivas, Peter W
Methadone, a synthetic opioid, has been used for more than 35 years to treat heroin addiction. It is also an effective therapy for chronic pain. An increase in the mean dose used nationally to treat these patients has been reported. There is an ongoing debate over whether it is necessary to screen patients with an ECG before and during therapy with methadone. We present a patient who developed QT prolongation and sustained ventricular arrhythmias after her methadone dose was increased. Previous literature, as well as the mechanism and risk factors, will be reviewed in this article. Recommendations will be given as to when an ECG is preferably to be performed. PMID:17378505
Iskandar, Said B; Abi-Saleh, Bernard S; Mechleb, Bassam K; Fahrig, Stephen A
Background Opioid use is associated with increased incidence of infectious diseases. Although experimental studies have shown that opioids affect various functions of immune cells, only limited data are available from human studies. Drug use is an important risk factor for HIV transmission; however no data are available whether heroin and/or methadone modulate immune response. Therefore, we examined the effect of heroin and methadone use among HIV-infected individuals on the production of cytokines after ex vivo stimulation with various pathogens. Methods Treatment naïve HIV-infected individuals from Indonesia were recruited. Several cohorts of individuals were recruited: 1) using heroin 2) receiving methadone opioid substitution 3) using heroin over 1 year ago and 4) controls (never used opioids). Whole blood was stimulated with Mycobacterium tuberculosis, Candida albicans and LPS for 24 to 48 hours. Cytokine production (IL-1 ?, IL-6, IL-10, IFN-?, IFN-? and TNF-?) was determined using multiplex beads assay. Results Among 82 individuals, the cytokine levels in unstimulated samples did not differ between groups. Overall, heroin users had significantly lower cytokine response after exposure to LPS (p<0.05). After stimulation with either M. tuberculosis or C. albicans the cytokine production of all groups were comparable. Conclusion The cytokine production after exposure to LPS is significantly down-regulated in HIV-infected heroin users. Interesting, methadone use did not suppress cytokine response, which could have implications guidelines of opioid substitution. PMID:25830312
Meijerink, Hinta; Indrati, Agnes; Utami, Fitri; Soedarmo, Suharyani; Alisjahbana, Bachti; Netea, Mihai G.; van Crevel, Reinout; Wisaksana, Rudi; van der Ven, Andre Jam
Background: Among substance users, health seeking remains a major challenge for which few data are available. Objectives: We sought to investigate the perceptions of methadone-maintained heroin users who are also problem or heavy drinkers, their barriers and facilitators to seeking help for substance and general and chronic care treatment. Methods: A qualitative design using a semistructured focus group approach was
Adeline. Nyamathi; Donna McNeese. Smith; Steven. Shoptaw; Malaika. Mutere; Allan. Cohen; Louis Morales; Viviane de Castro
Previous studies have shown that the use of behavior modification techniques, specifically the use of token reinforcement systems, can produce positive changes in the behavior of heroin addicts within a hospital setting. A token economy program was assessed to determine the effectiveness of such a program with patients in an outpatient methadone…
Kelly, John S.; Gambatese, Richard J.
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…
This article describes profiles of heroin addicts in three types of treatment (methadone, detox and therapeutic community) and those not in treatment in the local community. The profiles are based on data at item-level of the revised Addiction Severity Index. In total, 310 heroin addicts were interviewed. The results show that on the one hand the community group and the methadone group are roughly comparable, and on the other hand the detox and therapeutic community groups have similar characteristics. The latter groups report significantly more psychological and social problems. The community group mentions the fewest problems with drug use and more illegal activities in the past month. The results indicate that large differences exist between the groups in psychosocial problems. Furthermore, they indicate that the methadone group has no specific pattern of problems. Two important groups outside treatment are identified with respect to matching: addicts under 25 years old and addicts with a non-Dutch cultural background. PMID:9565204
Eland-Goossensen, M A; van de Goor, I A; Benschop, A J; Garretsen, H F
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…
Preston, Kenzie L.; Ghitza, Udi E.; Schmittner, John P.; Schroeder, Jennifer R.; Epstein, David H.
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
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
The featured molecules this month come from the article "The Conversion of Carboxylic Acids to Ketones: A Repeated Discovery" by John W. Nicholson and Alan D. Wilson. The authors describe the repeated discovery of this reaction and illustrate its central role in Woodward's total synthesis of strychnine. Strychnine is a member of a large class of nitrogen heterocycles known as alkaloids, a name derived from the fact that all produce basic solutions in water. Other well-known members of this class of compounds, all of which are pharmacologically active, are nicotine, atropine (deadly nightshade), quinine, lysergic acid, cocaine, and the three structurally similar compounds codeine, heroin, and morphine.
In nine experienced users of cocaine, we examined the urge to use cocaine or other drugs following a 40 mg dose of intravenous (IV) cocaine with and without oral pretreatment with 2.5 mg bromocriptine. The urge to use cocaine was assessed with a questionnaire constructed to assess both “wanting” and “craving” for cocaine or other drugs. Fifteen minutes after the
Jerome H. Jaffe; Nicola G. Cascella; Karen M. Kumor; Michael A. Sherer
Introduction: Magnesium influences the nervous system via its actions on the release and metabolism of neurotransmitters, and abnormal magnesium metabolism has been implicated in several neuropsychiatric disorders with prominent mood symptoms. The aim of this study was to compare the serum levels of magnesium of cocaine addicts to those of heroin addicts and normal controls. We also attempted to clarify
F. Tonioni; G. Martinotti; A. Barra; D. Martinelli; G. Autullo; C. Rinaldi; D. Tedeschi; L. Janiri; P. Bria
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…
Bradvik, Louise; Frank, Arne; Hulenvik, Per; Medvedeo, Alvaro; Berglund, Mats
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…
Gordon, Michael S.; Kinlock, Timothy W.; Couvillion, Kathryn A.; Schwartz, Robert P.; O'Grady, Kevin
In this study we evaluated, by means of the "cocaine rush visual analog scale," the impact of ropinirole on the expected rush induced by cocaine in a group of heroin addicts abusing cocaine; the self-reported reaction to the rush blockade (if any) on cocaine consumption, and the correlations between this self-reported reaction and individual, clinical, and therapeutic parameters. Nineteen cocaine abuser heroin-dependent patients entered the study. Their experienced cocaine rush was 61.31?±?32.1% of the maximum effect previously experienced. Compared with their previous rush intensity 16 patients experienced significantly lower intensity, 3 the same intensity, and none a higher intensity. In particular, two patients experienced a complete blockade of rush and reported a reduced use of cocaine. Fourteen patients experienced a partial blockade of cocaine rush; of these, nine reported they had reduced their use of cocaine. Ropinirole does diminish the subjective intensity of an expected cocaine rush, so interfering with the dynamics of reward, while supporting its possible use in the treatment of cocaine dependence. PMID:21852977
Maremmani, Angelo Giovanni Icro; Pacini, Matteo; Rovai, Luca; Rugani, Fabio; Dell'osso, Liliana; Maremmani, Icro
The number of heroin border detections in 2006–07 is the highest on record. The weight of heroin detections at the border increased by 65 percent compared with 2005–06. However, it remains the third lowest weight in the last decade. ‘Scatter ’ importations through the postal and air cargo streams continue to account for the largest number of heroin detections. South-East Asia remains the primary embarkation point of heroin into Australia. India has become a key embarkation point. In 2006–07, the weight of national heroin seizures increased by 192 percent. 48 ILLICIT DRUG DATA REPORT 2006–07Main Forms Heroin (diacetylmorphine) is derived from the opium poppy, Papaver somniferum. It is a highly addictive opiate which acts as a depressant on the central nervous system and has strong pain killing characteristics (AIC, 2007). Opium, morphine and codeine are all natural derivatives of the opium poppy. Heroin is harvested from hardened opium gum, which is collected from scored opium seed pods. The gum is then processed with other chemicals, such as ammonium chloride, acetic anhydride and hydrochloric acid, to produce heroin (Interpol, 2007).
Aims: Within the guidelines of the research programme on medical prescription of narcotics for opioid addicts (PROVE), heroin, morphine, and methadone were prescribed to heavily opioid addicted individuals in Switzerland since 1994. This contribution analyses the course of dose levels during the treatment period. Design: Naturalistic description of consumed dosages per day and month. Setting and Participants: The study describes
Patrick Gschwend; Jürgen Rehm; Richard Blättler; Thomas Steffen; André Seidenberg; Stephan Christen; Christoph Bürki; Felix Gutzwiller
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…
Greenfield, Lawrence; Tang, Beth Archibald
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 ?-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-6?-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. PMID:23467779
Faskowitz, Andrew J; Kramskiy, Vladimir N; Pasternak, Gavril W
A sensitive and selective ultra performance liquid chromatographic-tandem mass spectrometric method was developed and fully validated for the simultaneous determination of (in order of chromatographic elution) methylecgonine, pholcodine, morphine, hydromorphone, oxymorphone, norcodeine, codeine, dihydrocodeine, oxycodone, 6-Monoacetylmorphine (6-MAM), hydrocodone, ethylmorphine, norfentanyl, benzoylecgonine, tramadol, normeperidine, meperidine, cocaine, pentazocine, cocaethylene, fentanyl, norbuprenorphine, 2-ethylidine-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), buprenorphine, propoxyphene, and methadone in blood. The matrixes analyzed during the validation experiments were as follows: citrated blank plasma for calibrators, fluoride blank plasma for internal quality control (QC), lyophilized serum for external QC, fluoride plasma and whole blood for authentic samples, and lyophilized serum and whole blood for proficiency testing schemes. Samples were extracted with cation exchange solid-phase extraction cartridges. The target drugs were separated and quantified in a chromatographic run of 8.1 minutes using 0.1% formic acid in water and methanol (with 0.1% formic acid) as mobile phase. The limit of quantification ranged from 0.5 to 2.5 ng/mL depending on the compound and the therapeutic concentration. The intra- and interassay precision was less than 15% for all the compounds (except for pentazocine and EDDP, which was <20%) determined with 2 internal and 2 external QC samples, and the bias was within ±15% (except for methylecgonine, which was <20%). Extraction efficiency was greater than 70% for all the compounds except for EDDP. Matrix effects were evaluated with authentic blood samples (n = 10), and they ranged from 47 to 95%, but they were compensated for most analytes using deuterated analogs as internal standards. Prepared samples were stable for 62 hours in the autosampler. This method was successfully applied to authentic samples (n = 120), involving the use of heroin, cocaine, tramadol, and methadone, and to proficiency testing schemes. PMID:23783166
Fernández, María del Mar Ramírez; Wille, Sarah M R; Kummer, Nathalie; Di Fazio, Vincent; Ruyssinckx, Evi; Samyn, Nele
Background Recent policy initiatives in Baltimore City, MD significantly reduced access disparities between methadone and buprenorphine in the publicly-funded treatment sector. Objectives This study examines reasons for choosing buprenorphine over methadone among patients with access to both medications. Methods This study was embedded within a larger clinical trial conducted at two outpatient substance abuse treatment programs offering buprenorphine. Qualitative and quantitative data on treatment choice were collected for new patients starting buprenorphine treatment (n=80). The sample consisted of predominantly urban African American (94%) heroin users who had prior experience with non-prescribed street buprenorphine (85%) and opioid agonist treatment (68%). Qualitative data were transcribed and coded for themes, while quantitative data were analyzed using descriptive and bivariate statistics. Results Participants typically conveyed their choice of buprenorphine treatment as a decision against methadone. Buprenorphine was perceived as a helpful medication while methadone was perceived as a harmful narcotic with multiple unwanted physical effects. Positive experiences with non-prescribed “street buprenorphine” were a central factor in participants’ decisions to seek buprenorphine treatment. Conclusions Differences in service structure between methadone and buprenorphine did not strongly influence treatment-seeking decisions in this sample. Personal experiences with medications and the street narrative surrounding them play an important role in treatment selection decisions. Scientific Significance This study characterizes important decision factors that underlie patients’ selection of buprenorphine over methadone treatment. PMID:23617873
Gryczynski, Jan; Jaffe, Jerome H.; Schwartz, Robert P.; Dušek, Kristi A.; Gugsa, Nishan; Monroe, Cristin L.; O'Grady, Kevin E.; Olsen, Yngvild K.; Mitchell, Shannon Gwin
Because the outcome of methadone and buprenorphine substitution treatment in adolescents is unclear, we completed a retrospective cohort study of 100 consecutive heroin-dependent adolescents who sought these treatments over an 8-year recruitment period. The participants' average age was 16.6 years, and 54 were female. Half of the patient group remained in treatment for over 1 year. Among those still in
Bobby P. Smyth; John Fagan; Kathy Kernan
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. PMID:24035957
Moghadam, Mohsen Saber; Alavinia, Mohammad
Fourteen body packers carrying 2-112 heroin packages are reported. Nine people swallowed the packets, and five inserted them rectally. The ingested packages were large and radio-opaque; they consisted of hard lumps of concentrated heroin usually covered with glove latex, white adhesive tape, and a toy balloon. There were two complications in the 14 patients. One patient developed a bowel obstruction; at laparotomy 8 packages were found in the stomach and 27 at the ileo-cecal valve. Another patient, with heroin wrapped only with black electrician's tape and no latex inner or outer wrappings, developed heroin intoxication, noncardiogenic pulmonary edema, and a bowel obstruction. Eighteen packages were surgically removed from his stomach and 26 from his bowel. We recommend bisacodyl suppositories, activated charcoal mixed with a 3% sodium sulfate cathartic, and phosphosoda enemas for package removal; close observation for heroin toxicity or bowel obstruction; and surgical intervention for continuing toxicity, retention of packages in the stomach, or bowel obstruction. PMID:8445184
Utecht, M J; Stone, A F; McCarron, M M
The current paper examines critically the literature on deaths attributed to heroin overdose, and examines the characteristics and circumstances of such deaths. In particular, the dominance of the widely held belief that heroin-related fatalities are a consequence of overdose is challenged. Deaths attributed to overdose represented in the literature are typically older, heroin-dependent males not in drug treatment at the
SHANE DARKE; DEBORAH ZADOR
Methadone maintenance treatment (MMT) is the standard of care during pregnancy for opioid-dependency, showing efficacy in improving prenatal care and reducing risk of relapse. By design, however, MMT is only intended to prevent withdrawal thus facilitating cognitive behavioural interventions. In order to maximize the benefits of MMT, it is essential that methadone is both properly prescribed and that additional addiction treatment is concurrently administered. This study aims to determine the effectiveness of MMT engagement in high-risk pregnant women in reducing polydrug use by objective laboratory examination of neonatal meconium. Patients and Methods Over a 29-month period, the Motherisk Laboratory at the Hospital for Sick Children in Toronto analyzed meconium samples as per request by social services and hospitals for drugs of abuse. Results Of the 904 meconium samples received, 273 were tested for methadone with 164 positive and 109 negative for methadone. Almost half of the methadone positive samples (46.34%) were also positive for at least one other opioid compound, which did not differ statistically from the methadone-negative control samples (46.79%; Chi square test, p=0.94). No differences were found between the methadone positive and negative groups in rates of concurrent amphetamines, cocaine, cannabis, and alcohol use indicating a similar risk of polydrug use between pregnant women taking or not taking methadone in this population. Discussion The high rates of additional opioid and other drug use in the MMT group, suggest that MMT is failing this population of patients. It is possible that methadone doses during pregnancy are not appropriately adjusted for changes in pharmacokinetic parameters (e.g. blood volume, renal function) during the second and third trimesters. This may result in sub-therapeutic dosing creating withdrawal symptoms leading to additional substance use. Alternatively, these results may be demonstrating a substantial lack in delivery of addiction support services in this vulnerable population. PMID:24312668
Delano, Kaitlyn; Gareri, Joey; Koren, Gideon
Previous reports have shown antisocial personality disorder (ASPD) to be strongly associated with injection equipment sharing and increased rates of human immunodeficiency virus (HIV) infection in a sample of heroin injectors. Another report has shown ASPD to be associated with injection drug use, needle sharing, sexual promiscuity, and prostitution in a sample of methadone maintenance clients. The current study extends
Wilson M. Compton; Linda B. Cottler; Audrey M. Shillington; Rumi K. Price
(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. PMID:25556261
Hendrikson, Hollie; Hansen, Melissa
The aim of this work was to automate a sample preparation procedure extracting morphine, hydromorphone, oxymorphone, norcodeine, codeine, dihydrocodeine, oxycodone, 6-monoacetyl-morphine, hydrocodone, ethylmorphine, benzoylecgonine, cocaine, cocaethylene, tramadol, meperidine, pentazocine, fentanyl, norfentanyl, buprenorphine, norbuprenorphine, propoxyphene, methadone and 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine from urine samples. Samples were extracted by solid-phase extraction (SPE) with cation exchange cartridges using a TECAN Freedom Evo 100 base robotic system, including a hydrolysis step previous extraction when required. Block modules were carefully selected in order to use the same consumable material as in manual procedures to reduce cost and/or manual sample transfers. Moreover, the present configuration included pressure monitoring pipetting increasing pipetting accuracy and detecting sampling errors. The compounds were then separated in a chromatographic run of 9 min using a BEH Phenyl analytical column on a ultra-performance liquid chromatography-tandem mass spectrometry system. Optimization of the SPE was performed with different wash conditions and elution solvents. Intra- and inter-day relative standard deviations (RSDs) were within ±15% and bias was within ±15% for most of the compounds. Recovery was >69% (RSD < 11%) and matrix effects ranged from 1 to 26% when compensated with the internal standard. The limits of quantification ranged from 3 to 25 ng/mL depending on the compound. No cross-contamination in the automated SPE system was observed. The extracted samples were stable for 72 h in the autosampler (4°C). This method was applied to authentic samples (from forensic and toxicology cases) and to proficiency testing schemes containing cocaine, heroin, buprenorphine and methadone, offering fast and reliable results. Automation resulted in improved precision and accuracy, and a minimum operator intervention, leading to safer sample handling and less time-consuming procedures. PMID:24790061
Ramírez Fernández, María del Mar; Van Durme, Filip; Wille, Sarah M R; di Fazio, Vincent; Kummer, Natalie; Samyn, Nele
Background Problem alcohol use is associated with adverse health outcomes among current or former heroin users and primary care is providing methadone treatment for increasing numbers of this population. This study aimed todetermine the prevalence of problem alcohol use among current or former heroin users attending primary care for methadone treatment and to describe the socio-demographic characteristics and health service utilisation characteristics associated with problem alcohol uses. Methods We conducted a cross sectional survey of patients sampled from a national database of patients attending general practice for methadone treatment. Participants were recruited by their general practitioner and data was collected using an interviewer-administered questionnaire, which included the Alcohol Use Disorders Identification Test ('AUDIT'), with a score of >7 considered abnormal (ie 'AUDIT positive cases') and socio-demographic, medical and substance use characteristics. Results We interviewed 196 patients (71% of those invited, 31% of those sampled, 11% of the national database). The median age was 32 years, 55% were hepatitis C positive, 79% had used illicit drugs in the previous month and 68% were male. Sixty-eight 'AUDIT positive' cases were identified (prevalence of 35%, 95% CI = 28–41%) and these were more likely to have attended a local Emergency Department in the previous year (p < 0.05) and less likely to have attended a hospital clinic in the previous year (p < 0.05). Twenty-seven (14%) scored 20 or higher indicating possible alcohol dependence. Conclusion Problem alcohol use has a high prevalence among current or former heroin users attending primary care for methadone treatment and interventions that address this issue should be explored as a priority. Interventions that address problem alcohol use in this population should be considered as a priority, although the complex medical and psychological needs of this population may make this challenging. PMID:19519882
Ryder, Niamh; Cullen, Walter; Barry, Joseph; Bury, Gerard; Keenan, Eamon; Smyth, Bobby P
The connections between prostitution and drug use have long been a topic of social research. Much of this work has focused on the use of opiates, especially heroin. With the increasing availability of a smokable form of cocaine commonly called “crack,” new questions have emerged about the basic relation between drugs and prostitution.Drawing on interviews with 39 crack?using female prostitutes,
Thomas E. Feucht
Exposure to addictive drugs has been associated with disrupted brain white matter integrity. A few studies have examined the white matter deficits in heroin users; however, the results were influenced by the use of substitution drugs such as methadone and buprenorphine. The present study assessed the alteration in white matter integrity and heroin-related neuropathology in heroin dependents who had not received any replacement therapy using quantitative diffusion tensor imaging (DTI). The study comprised 17 heroin-dependent (HD) subjects and 15 matched healthy controls (HC). Fractional anisotropy (FA) and eigenvalues (??, ?||) of white matter in the whole brain were measured and compared using a voxel-based analysis. The correlation between DTI measurements in identified regions and history of heroin exposure was tested by partial correlation analysis. Compared with HCs, HD subjects displayed decreased FA in the bilateral frontal lobe sub-gyrus, cingulate gyrus, medial frontal gyrus, extra-nuclear, left temporal lobe sub-gyrus and right superior frontal gyrus. Among these regions, the HD group had significantly increased ?? in the bilateral frontal lobe sub-gyrus, cingulate gyrus and extra-nuclear relative to the HC group. There were no group differences in ?||. In addition, there were no significant correlations between duration of heroin use or accumulated dosage and FA or ?? values. In conclusion, chronic heroin-dependent subjects had widespread disruption of white matter structural connectivity located mainly in anterior and superior regions of the brain. Damage to myelin other than axons was the primary pathological feature in the brain of the heroin user. PMID:23895765
Li, Wei; Li, Qiang; Zhu, Jia; Qin, Yue; Zheng, Ying; Chang, Haifeng; Zhang, Dongsheng; Wang, Hanyue; Wang, Lina; Wang, Yarong; Wang, Wei
Fifty-one Asian heroin addicts in Laos were matched for sex, ethnicity, and age with 51 opium addicts. All subjects were voluntary patients at a treatment facility for addicts. The two groups were compared for demographic characteristics, past narcotic history, current narcotic use, and readmission within 1 year following discharge from treatment. Heroin addicts took more doses of drug per day, spent more money per day on narcotic drugs, required higher detoxification doses of methadone, and sought treatment much sooner than did opium addicts. The two groups did not differ for duration of narcotic use prior to becoming addicted, or for rate of readmission following treatment. Demographic differences in occupation and employment reflected the urban distribution of heroin addicts, and the mixed urban-rural residence of opium addicts. These data suggest that heroin is not per se more or less apt to produce addiction (i.e., is not more "addictogenic") as compared to opium. The type of narcotic drug also does not appear to be an important factor in determining treatment outcome. However, heroin does appear to be more "pathogenic" than opium, since heroin addicts sought treatment much sooner than did opium addicts. This may have been due to economic factors (i. e., heroin addicts took more doses per day, spent more time in phases of intoxication and withdrawal, and spent less time in the middle phase with work and other coping behaviors). Opium addiction is not a "benign" or "social" form of addiction. In comparison to heroin, however, opium does cost less, requires fewer doses per day, and has a less toxic withdrawal (at least in the initial phase). Moreover, opium apparently takes longer to produce life crises that motivate the addict to seek treatment. PMID:864449
Westermeyer, J; Peng, G
Background Illicit use of methadone and buprenorphine has been described as a growing problem in Sweden in recent years, and has been associated with an increased drug-related mortality. Critics claim that the substances have become popular among adolescents and that they function as a gateway to heroin use. The aim of this study is to investigate, firstly, the extent to which illicit use of methadone and buprenorphine occurs among adolescents and young adults in Sweden, and secondly, at what stage in a user’s drug career these substances tend to appear. Methods The study is based on surveys and structured interviews on drug use among various populations of young people, in addition to qualitative interviews with 86 informants who, in their professional capacity, encounter adolescents or young adults who are using illicit drugs. Results Illicit use of methadone and buprenorphine is rare among young people in Sweden. According to high school surveys, less than 0.1% have tried these substances. Among young drug users in general, few have tried the substances, and there is nothing to indicate that they act as gateway drugs. Among adolescents and young adults with severe drug problems, however, the illicit use of methadone and buprenorphine is more common (54% in a compulsory care sample). These substances normally enter the drug career late, and few use them as their main drug of choice. Other prescription drugs, like benzodiazepines and tramadol, are used by adolescents to a far greater extent. Diversion and illicit use of methadone and buprenorphine is not seen as a serious problem by the professionals interviewed. A general view is that the substances are mainly used by people with a heroin or polydrug addiction, often for “self-medication” purposes. However, several informants express concern that methadone and buprenorphine may cause fatalities among young drug users without an opioid tolerance. Conclusions Illicit use of methadone and buprenorphine among young drug users is not a widespread problem in Sweden. Harm-reduction measures should target drug users with more severe problems, among whom illicit use of methadone and buprenorphine is more common and pose a medical risk. Illicit use of other prescription drugs, which are less controlled and more widely used by young people, is an important issue for further research. PMID:24139199
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 progression to sniffing and subsequently to injecting heroin. Historically and structurally these users found themselves caught at the intersection of two major developments in the opiate supply: (1) an over 500% increase in opiate pill prescription from 1997 to 2005 resulting in easy access to diverted supplies of less stigmatized opiates than heroin and (2) a heroin supply glut, following the US entry of Colombian-sourced, heroin in the early 1990s, that decreased cost and increased purity at the retail level. A nationwide up-cycle of heroin use may be occurring among young inner city, suburban and rural youth fueled by widespread prescription opioid pill use. PMID:24238956
Mars, Sarah G; Bourgois, Philippe; Karandinos, George; Montero, Fernando; Ciccarone, Daniel
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
Michael S. Gordon; Timothy W. Kinlock; Kathryn A. Couvillion; Robert P. Schwartz; Kevin OGrady
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.
Goel, Narender; Pullman, James M.; Coco, Maria
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
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.
in cocaine patients with pretreatment marijuana use. Drug Alcohol Depend. 2011. (Pubmed ID 21440999) Agrawal:1063-1071. (Pubmed ID 1527386) Byrne SA, Petry NM. Concurrent alcohol dependence among methadone-maintained cocaine as a treatment for cancer-related fatigue: a randomized controlled study. Support Care Cancer. 2011. [Epub ahead
Oliver, Douglas L.
Urinalysis (UA) tests for opiates and cocaine were obtained over a 12-month period for a total of 155 long-term clients who participated in treatment in one of three urban methadone centers. At admission, clients were randomly assigned to “node-link mapping” (n = 82) or “standard” (n = 73) counseling treatment. Node-link mapping is a strategy for visually representing interrelationships between
Sandra M. Dees; Donald F. Dansereau; D. Dwayne Simpson
This study examined under naturalistic assessment conditions the validity of self-reported opiate and cocaine use among 175 veterans enrolled in methadone treatment, and factors related to self-report validity, such as stage in treatment and drug of abuse. Veterans were interviewed by clinical staff about past 30-day drug use with the addiction severity index (ASI), and urinalysis results were obtained for
Stephen T Chermack; John Roll; Mark Reilly; Leonard Davis; Usha Kilaru; John Grabowski
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.
Liu, S.J.; Wang, R.I.H.
Background In methadone maintenance treatment programs (MMTPs), 80–90% of participants smoke cigarettes. Patients in MMTPs are at particular risk for life stress, and nicotine, as well as other substances like alcohol, benzodiazepines, cocaine, marijuana, and opiates have been shown to reduce the effects of stress. Use of these addictive substances to cope with stress may precipitate illicit opiate relapse in MMTP patients. In the current study, we examined the relationship between perceived stress and substance abuse. Methods Participants were 315 cigarette smokers recruited from nine MMTPs for a smoking cessation study. Logistic regression was used to evaluate the adjusted association of perceived stress with dichotomous indicators of hazardous alcohol use and recent substance use at baseline. Results After controlling for demographic and smoking-related variables, perceived stress was associated positively and significantly with the likelihood of screening positive for hazardous drinking or alcohol-related problems (OR = 1.13, 95%CI 1.02; 1.25), with the likelihood of recent cocaine use (OR = 1.18, 95%CI 1.02; 1.37), and with the likelihood of recent benzodiazepine use (OR = 1.24, 95%CI 1.07). Conclusions Perceived stress may be a marker of patients’ risk for illicit substance use, a known risk factor for illicit opiate relapse. These findings indicate that cigarette use might not be sufficient in managing stress and methadone-maintained persons turn to other substances for relief. PMID:24011853
Moitra, Ethan; Anderson, Bradley J.; Stein, Michael D.
This study compared the efficacy of 2 approaches for the treatment of cocaine dependence among methadone-maintained patients with and without antisocial personality disorder (ASPD). Patients were randomly assigned to 4 study conditions: cognitive-behavioral treatment (CBT), contingency management (CM), CBT with CM, or methadone maintenance. The Structural Clinical Interview for Mental Disorders-IV was administered to 108 patients to assess ASPD. A
Nena Messina; David Farabee; Richard Rawson
Casually exposing adolescents to prescription opioid agents may escalate to daily use. A trend exists for adolescents using prescription opioid agents to substitute heroin because it is significantly cheaper than pills (approximately half of the cost) and is often more readily available. Additionally, it is more potent than most prescription opioid agents and carries increased risks of overdose and death. Although treatment for substance use disorders has traditionally centered on total abstinence, opioid replacement therapy (ORT) is an option that saves lives and prevents overdose deaths. In the United States, ORT is based on two medicines: methadone and buprenorphine. These drugs can be substituted for other opiate agents and have much lower overdose risks. Nursing implications and web-based resources for teaching are presented. [Journal of Psychosocial Nursing and Mental Health Services, 53(2), 27-30.]. PMID:25654572
Fogger, Susanne; McGuinness, Teena M
Effective treatment for patients with opioid use problems is as critical as ever given the upsurge in heroin and prescription opioid abuse. Yet, results from prior studies show that the majority of methadone maintenance treatment (MMT) programs in the US have not provided dose levels that meet evidence-based standards. Thus, this paper examines the extent to which US MMT programs have made changes in the past 23 years to provide adequate methadone doses; we also identify factors associated with variation in program performance. Program directors and clinical supervisors of nationally-representative methadone treatment programs were surveyed in 1988 (n=172), 1990 (n=140), 1995 (n=116), 2000 (n=150), 2005 (n=146), and 2011 (n=140). Results show that the proportion of patients who received doses below 60 mg/day-the minimum recommended-declined from 79.5 to 22.8% in a 23-year span. Results from random effects models show that programs that serve a higher proportion of African-American or Hispanic patients were more likely to report low-dose care. Programs with Joint Commission accreditation were more likely to provide higher doses, as were a program that serves a higher proportion of unemployed and older patients. Efforts to improve methadone treatment practices have made substantial progress, but 23% of patients across the nation are still receiving doses that are too low to be effective. PMID:25012549
D'Aunno, Thomas; Pollack, Harold A; Frimpong, Jemima A; Wuchiett, David
This article examined the extent to which methadone maintenance (MM) is considered a treatment alternative for drug-dependent parents, as reflected in the social work and child welfare literature and in child welfare policies. Findings were derived from a review of 15 social work journals published from 1996 through 2002 and from a review of child welfare policies in 27 states in regard to treatment recommendations for substance-abusing parents. These reviews found that 23 articles focused on child welfare-substance abuse issues; no article specifically discussed MM as a treatment option for heroin-using parents; and of the 27 states, only three included methadone as a treatment option in their child welfare policy recommendations. Practice and policy recommendations are discussed. PMID:15688680
Lundgren, Lena M; Schilling, Robert F; Peloquin, Susan D
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 was 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 (> or =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
Nyamathi, Adeline; Cohen, Allan; Marfisee, Mary; Shoptaw, Steven; Greengold, Barbara; de Castro, Viviane; George, Daniel; Leake, Barbara
Background: Although methadone maintenance is effective in reducing injection drug use, needle sharing, and the overall mortal- ity associated with opiate abuse, many health plans offer little or no access to methadone, and many methadone providers do not comply with treatment guidelines regarding dose, duration of treatment, or provision of ancillary services. Moral and politica l judgments have helped shape
PAUL G. BARNETT; SALLY S. HUI
This cross-sectional study examines predictors of heavy smoking among 256 male and female methadone maintenance therapy (MMT) clients from five MMT clinics in the Los Angeles area. The authors find that women report lower rates of heavy smoking than men (47% vs. 54%, respectively), in concordance with current literature pointing to gender differences in smoking behaviors. In particular, men who report heavy drinking, fair or poor health, and recent heroin use are more likely to report heavy smoking compared with men not reporting these factors. Women who report recent heroin use, a lifetime history of sex trade, and who have been ill enough to require a blood transfusion also have greater odds of reporting heavy cigarette smoking. Findings from this study may aid not only in designing gender-based smoking cessation programs for MMT clients but also in addressing the gender-based issues related to smoking in such a population. PMID:19597186
Nyamathi, Adeline M; Sinha, Karabi; Marfisee, Mary; Cohen, Allan; Greengold, Barbara; Leake, Barbara
BACKGROUND: A sharp reduction in heroin supply in Australia in 2001 was followed by a large but transient increase in cocaine use among injecting drug users (IDU) in Sydney. This paper assesses whether the increase in cocaine use among IDU was accompanied by increased rates of violent crime as occurred in the United States in the 1980s. Specifically, the paper
Louisa Degenhardt; Carolyn Day; Wayne Hall; Elizabeth Conroy; Stuart Gilmour
Acupuncture at Baihui (GV20) and Dazhui (GV14) reduces neuronal loss and attenuates ultrastructural damage in cerebral ischemic rats. However, whether acupuncture can treat addiction and prevent readdiction through changes to brain cell ultrastructure remains unknown. In this study, cell apoptosis was observed in the hippocampus and frontal lobe of heroin readdicted rats by electron microscopy. Immunohistochemical staining displayed a reduction in Bcl-2 expression and an increase in Bax expression in the hippocampus and frontal lobe. After rats were given acupuncture at Baihui and Dazhui, the pathological damage in the hippocampus and frontal lobe was significantly reduced, Bcl-2 expression was upregulated and Bax expression was downregulated. Acupuncture exerted a similar effect with methadone, a commonly used drug for clinical treatment of drug addiction. Experimental findings suggest that acupuncture at Dazhui and Baihui can prevent brain cell apoptosis in heroin readdicted rats. PMID:25206797
Hou, Xiaorong; Zhang, Rongjun; Lv, Hang; Cai, Xinghui; Xie, Guangchuan; Song, Xiaoge
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. PMID:8801682
Andersen, H S; Sestoft, D M; Lillebaek, T; Gabrielsen, G
Over the last few decades, cocaine and morphine (heroin) have been among the primary causes of deaths related to drug abuse. Cocaine is frequently altered by dilution, substitution, contamination, and adulteration. Trimethoprim has never been identified in the powders of cocaine, making this the first post-mortem case report in which the presence of this compound is described. The case reported here is that of a 46-year-old woman with a history of cocaine and morphine abuse who was found dead inside her bathroom. The police found the corpse next to a syringe, with a telephone card containing trace of cocaine on the sink. Toxicological analysis was performed, and drug levels were measured by means of gas chromatography/mass spectrometry. In addition to the presence of cocaine and smaller alkaloids, trimethoprim was also detected on the syringe and telephone card and in the woman's nasal mucosa. Trimethoprim analysis is very quick and easy and can be added to the routine analysis of drugs of abuse seized on the illicit market to obtain more information. PMID:25361939
Fucci, Nadia; Pascali, Vincenzo L
Background With up to 40% of opioid injectors infected with HIV, Ukraine has one of the most concentrated HIV epidemics in the world, mainly due to unsterile injection practices and a historical absence of effective prevention services. Harm reduction programs, including syringe exchange and a small buprenorphine treatment program, were introduced in 2004 and methadone maintenance was allowed in 2007. Despite an initial expansion, by 2009, only 3221 injectors were receiving methadone treatment. A growing body of research on methadone maintenance has found high retention rates with reduction in opioid use and HIV risk behaviors. We report on the acceptability and initial outcome of methadone treatment as a function of HIV status, an issue that has not yet been reported for injectors in Ukraine. Methods Longitudinal observational study of a 12-week course of methadone treatment in 25 HIV+ and 25 HIV? opioid addicted individuals recruited from a harm reduction program and the city AIDS Center. Drug use and HIV risk were assessed at baseline and weeks 4, 8, 12 and 20; all patients were offered continued methadone maintenance in the Kyiv city program at the end of 12 weeks. Results Fifty-four individuals were asked if they were interested in the study and 50, demographically similar to other samples of opioid addicted Ukrainians, agreed to participate. Two died of non-study related causes; the other 48 completed assessments at weeks 4, 8 and 12, and 47 completed followups at week 20. Significant reductions were seen in use of heroin (p<. 0001), other opiates/analgesics (p< 0.0001), and HIV risk behaviors (drug, sex, total; all p <0.0001). All 48 patients chose to continue methadone after the 12-weeks of study medication ended. Unlike most opioid treatment studies, sexual risk was somewhat higher than injecting risk at study intake. Conclusions Methadone maintenance was well accepted by HIV+ and HIV? opioid dependent individuals and has the potential for significant public health impact if made more widely available with sustained access and support. PMID:24548802
Dvoriak, Sergii; Karachevsky, Andrey; Chhatre, Sumedha; Booth, Robert; Metzger, David; Schumacher, Joseph; Chychula, Nina; Pecoraro, Anna; Woody, George
We administered for 2 weeks intramuscular buprenorphine 0.3 mg/kg per day (and in a separate series, its vehicle) to each of 7 male, group-living Macaca fuscata (Japanese Snow Monkeys). Animals received one injection of cocaine 0.75 mg/kg and one of saline (about Days 9 and 14) in each series; after each of these doses ethologic observers recorded for 3 h the frequency of occurrence of 64 separate social, self-care, position and other behaviors. Cocaine alone changed the frequency of many behaviors. Buprenorphine alone only reduced the frequency of eating, yawning and ejaculation. The drugs had no interactive effects on behavior. In a dose reported to suppress monkeys' heroin and cocaine self-administration, buprenorphine showed remarkably few disruptions of normal group behavior. But it neither reversed nor enhanced cocaine's behavioral effects. PMID:8462413
Crowley, T J; Williams, E A; Mikulich, S K; Ingersoll, N C
In order to determine the role played by heroin purity in fatal heroin overdoses, time series analyses were conducted on the purity of street heroin seizures in south western Sydney and overdose fatalities in that region. A total of 322 heroin samples were analysed in fortnightly periods between February 1993 to January 1995. A total of 61 overdose deaths occurred
Shane Darke; Wayne Hall; Don Weatherburn; Bronwyn Lind
Microdialysis during i.v. drug self-administration (SA) have implicated nucleus accumbens (NAc) shell DA in cocaine and heroin reinforcement. However, this correlative evidence has not been yet substantiated by experimental evidence obtained by studying the effect of selective manipulation of NAc shell DA transmission on cocaine and heroin SA. In order to investigate this issue, DA D1a receptor (D1aR) expression was impaired in the NAc shell and core by locally infusing lentiviral vectors (LV) expressing specific D1aR-siRNAs (LV-siRNAs). Control rats were infused in the same areas with LV expressing GFP. Fifteen days later, rats were trained to acquire i.v. cocaine or heroin self-administration (SA). At the end of behavioral experiments, in order to evaluate the effect of LV-siRNA on D1aR expression, rats were challenged with amphetamine and the brains were processed for immunohistochemical detection of c-Fos and D1aR. Control rats acquired i.v. cocaine and heroin SA. Infusion of LV-siRNAs in the medial NAc shell reduced D1aR density and the number of c-Fos positive nuclei in the NAc shell, while sparing the core, and prevented the acquisition of cocaine, but not heroin SA. In turn, LV-siRNAs infusion in the core reduced D1aR density and the number of c-Fos positive nuclei in the same area, while sparing the shell, and failed to affect acquisition of cocaine. The differential effect of LV impairment of NAc shell D1aR on cocaine and heroin SA indicates that NAc shell DA acting on D1aR specifically mediates cocaine reinforcement. PMID:25446574
Pisanu, Augusta; Lecca, Daniele; Valentini, Valentina; Bahi, Amine; Dreyer, Jean-Luc; Cacciapaglia, Fabio; Scifo, Andrea; Piras, Giovanna; Cadoni, Cristina; Di Chiara, Gaetano
Background This study examined long-term improvement of quality of life amongst heroin users enrolled in methadone maintenance treatment (MMT). Methods The sample contained 553 heroin-dependent individuals from 4 hospitals in northern Taiwan who enrolled in MMT for an average of 184 days. Each patient signed a consent form and was assessed prospectively 3 times semi-annually. Quality of life was measured using the WHOQOL-BREF questionnaire, 26 items of which were scored by the participants. The WHOQOL-BREF consists of four domains: physical, psychological, social, and environmental. 285 and 155 participants completed 6-month and 12-month follow-ups respectively. Results After controlling for demographic and clinical characteristics, there were statistically significant improvements in the psychological and environmental domains between baseline and 6 months. Significant improvements were found in psychological and social domains between baseline and 12 months. Conclusions It is concluded that methadone maintenance treatment improves heroin users’ long-term quality of life in the psychological and social relationship domains. PMID:23865898
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
Nguyen, Tam T. M.; Nguyen, Long T.; Pham, Manh D.; Vu, Hoang H.; Mulvey, Kevin P.
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)
DuPont, Robert L.; Greene, Mark H.
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
Raleigh, Michael D.; Pentel, Paul R.; LeSage, Mark G.
Background Substance misuse is associated with cognitive dysfunction. We used a stop signal task to examine deficits in cognitive control in individuals with opioid dependence (OD). We examined how response inhibition and post-error slowing are compromised and whether methadone maintenance treatment (MMT), abstinence duration, and psychiatric comorbidity are related to these measures in individuals with OD. Methods Two-hundred-and-sixty-four men with OD who were incarcerated at a detention center and abstinent for up to 2 months (n?=?108) or at a correctional facility and abstinent for approximately 6 months (n?=?156), 65 OD men under MMT at a psychiatric clinic, and 64 age and education matched healthy control (HC) participants were assessed. We computed the stop signal reaction time (SSRT) to index the capacity of response inhibition and post-error slowing (PES) to represent error-related behavioral adjustment, as in our previous work. We examined group effects with analyses of variance and covariance analyses, followed by planned comparisons. Specifically, we compared OD and HC participants to examine the effects of opioid dependence and MMT and compared OD sub-groups to examine the effects of abstinence duration and psychiatric comorbidity. Results The SSRT was significantly prolonged in OD but not MMT individuals, as compared to HC. The extent of post-error slowing diminished in OD and MMT, as compared to HC (trend; p?=?0.061), and there was no difference between the OD and MMT groups. Individuals in longer abstinence were no less impaired in these measures. Furthermore, these results remained when psychiatric comorbidities including misuse of other substances were accounted for. Conclusions Methadone treatment appears to be associated with relatively intact cognitive control in opioid dependent individuals. MMT may facilitate public health by augmenting cognitive control and thereby mitigating risky behaviors in heroin addicts. PMID:24727743
Liao, Ding-Lieh; Huang, Cheng-Yi; Hu, Sien; Fang, Su-Chen; Wu, Chi-Shin; Chen, Wei-Ti; Lee, Tony Szu-Hsien; Chen, Pau-Chung; Li, Chiang-shan R.
The relationship between heroin use and street crime has been studied for the better part of this century, but the findings have been inconclusive. Research in this area has been limited to analyses of criminality in terms of arrest data, and samples have been drawn only from officially known populations of drug users. The present study focuses on a sample
James A. Inciardi
A 30-year-old male died in Thailand after a scuffle. The corpse was embalmed and repatriated to France where an autopsy was performed. As usual in cases of embalmment, fluids such as blood and urine were unavailable and the toxicological analyses was performed on the bile and the liver. An overdose of heroin was determined as the cause of death. A
V. Alunni-Perret; P. Kintz; B. Ludes; P. Ohayon; G. Quatrehomme
Long-term drug-induced alterations in gene expression underlying neuroplasticity in the nucleus accumbens (NAc) may play a crucial role in relapse behavior in abstinent drug addicts. In this respect, stimulus-induced relapse behavior is considered as the retrieval of stored drug-related information. Because the NAc shell may determine the impact of external and internal stimuli on goal-directed behavior, we compared long-term gene expression in this brain region after active and passive administration of different drugs of abuse. We made use of a preselected set of transcripts that were down-regulated 3 wk after active i.v. heroin self-administration. We found that most of these transcripts were not down-regulated long after passive exposure to the opiate. Most of the active heroin administration-regulated transcripts were also down-regulated in the NAc shell following active cocaine administration (common denominators). As observed with passive administration of heroin, passive exposure to cocaine was found to be relatively ineffective in reducing the expression of these transcripts. This work reveals that active drug consumption during self-administration (instrumental learning) is a crucial psychological factor directing long-term genomic responses in the brain. PMID:12397092
Jacobs, Edwin H; Spijker, Sabine; Verhoog, Clarine W; Kamprath, Konny; de Vries, Taco J; Smit, August B; Schoffelmeer, Anton N M
Cigarette smoking prevalence is very high, and cessation rates are very low, among people in methadone treatment. This may in part be due to interactions between methadone administration and cigarette smoking. The present study explores relationships between methadone dose timing and smoking rates. Twenty methadone patients, over a period of 19 days, used electronic cigarette packs to record their smoking
Kimber P. Richter; Ashley K. Hamilton; Sandra Hall; Delwyn Catley; Lisa S. Cox; James Grobe
Background Opioid dependence treatment traditionally involves methadone clinics, for which dispensing schedules can be cumbersome. Buprenorphine, a partial agonist of the mu receptor and antagonist of the kappa receptor, is a potential outpatient alternative to methadone. Funded by a grant from the State of Maryland's Community Health Resources Commission (CHRC), the Buprenorphine Outpatient Outcomes Project (BOOP) evaluates the outcome of Suboxone (buprenorphine/naloxone) treatment on abstinence from heroin use, rates of emergency room visits and hospitalizations, legal issues, and quality of life. Methods Active heroin users were recruited between June 2007 and June 2010 and induction therapy with Suboxone was instituted during hospitalization. Once discharged, patients were followed as outpatients for maintenance treatment and counseling. Data were collected from electronic medical records, Maryland state legal records, and SF-36® Health Surveys regarding several parameters and patients were categorized according to duration of treatment with Suboxone into one of three groups: <1 month, 1–3 months, and >3 months. Results A total of 220 participants were included in the study. The age range of participants was 18–67 years with most being African American males. Eighty-three (38%) remained in the study for at least 1 month, with 37 of the 83 (45%) remaining in treatment for >3 months. Ten of the 37 (27%) never relapsed after their longest period of abstinence from heroin. During the first year after initiating treatment with Suboxone, hospitalization and emergency room visit rates for all 220 participants decreased by 45 and 23%, respectively, as compared to the year prior to starting treatment. The number of legal charges for drug possession decreased from 70 to 62. Anecdotally, the quality of life seemed to improve in those who were treated with Suboxone for longer periods of time and received regular counseling. Conclusion Overall, Suboxone is an effective treatment method for heroin addiction and is a viable outpatient therapy option. Individualized treatment plans and counseling must be implemented for maximum benefits to be seen. Retention of patients for a long duration of therapy was difficult, but for those who did remain, benefits were seen in overall health, abstinence from heroin use, cognition, and quality of life. PMID:24765257
Sittambalam, Charmian D.; Vij, Radhika; Ferguson, Robert P.
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…
Kohn, Paul M.; And Others
Because the outcome of methadone and buprenorphine substitution treatment in adolescents is unclear, we completed a retrospective cohort study of 100 consecutive heroin-dependent adolescents who sought these treatments over an 8-year recruitment period. The participants' average age was 16.6 years, and 54 were female. Half of the patient group remained in treatment for over 1 year. Among those still in treatment at 12 months, 39% demonstrated abstinence from heroin. The final route of departure from the treatment program was via planned detox for 22%, dropout for 32%, and imprisonment for 8%. The remaining 39% were transferred elsewhere for ongoing opiate substitution treatment after a median period of 23 months of treatment. Males were more likely to exit via imprisonment (p < .05), but other outcomes were not predicted by gender. There were no deaths during treatment among these 100 patients who had a cumulative period of 129 person years at risk. Our findings suggest that this treatment delivers reductions in heroin use and that one fifth of patients will exit treatment following detox completion within a 1- to 2-year time frame. PMID:21940134
Smyth, Bobby P; Fagan, John; Kernan, Kathy
Exposure to 10 min of footshock stress (1 mA; 0.5 s on, with a mean off period of 40 s) reinstated heroin-seeking behavior in heroin-experienced, drug-free rats after many sessions of extinction and up to 6 weeks after last exposure to heroin. In reinstating the behavior, the footshock mimicked the effect of a non-contingent priming infusion of heroin (50 µg\\/kg).
Yavin Shaham; J. Stewart
...positive test result for marijuana, cocaine, amphetamines...presents a legitimate medical explanation for the...that has a legitimate medical use. Use of a drug... heroin, PCP, marijuana) or any other substance...having a legitimate medical use can never be...
The number of drugs targeted may have an important influence on the ability of drug abusers to abstain during motivational incentive procedures. The authors investigated outcomes in methadone maintenance patients (n = 58), who had evidence of both opiate and cocaine use, when continuous abstinence from cocaine only (single target) or from both cocaine and heroin (dual target) was required
Christopher J. Correia; Jesse Dallery; Elizabeth C. Katz; Kenneth Silverman; George Bigelow; Maxine L. Stitzer
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. The current 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 and 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, while 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. While 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. PMID:18295434
Dunn, Kelly E.; Sigmon, Stacey C.; McGee, Mark R.; Heil, Sarah H; Higgins, Stephen T.
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%). Some factors possibly affecting the yields of photodegradation in hair and partially explaining the differences observed between the in vivo and the in vitro studies were also investigated, such as the colour of hair (the role of melanin) and the integrity of the keratin matrix. PMID:24817052
Favretto, Donata; Tucci, Marianna; Monaldi, Alice; Ferrara, Santo Davide; Miolo, Giorgia
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; the unique requirements and conditions of getting a site, and the study, approved; working with the media; recruitment into the study; a brief status report on the study; and a brief conclusion from the authors' perspectives. Trail Registration ClinicalTrials.gov registration number: NCT00175357 PMID:19159475
Gartry, Candice C; Oviedo-Joekes, Eugenia; Laliberté, Nancy; Schechter, Martin T
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…
Gordon, Susan M.
This article discusses various ethical and philosophical aspects of heroin addiction. It arose as a result of the plan by the Amsterdam city council to supply free heroin to drug addicts. The objective of treatment of heroin addicts is ambivalent because what is in fact a socio-cultural problem is transformed into a medical problem. The characteristics of this treatment are made explicit through a philosophical analysis which sees the medical intervention as part of a strategy aimed at achieving social normalisation. The reason why such a social control function is practised by physicians is discussed, as well as the reason why heroin users in particular are the object of such a process. In this paper, heroin addiction is considered primarily as a cultural problem. The consequences of this for treatment and ethics form the conclusion. PMID:4078854
ten Have, H; Sporken, P
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 methods approaches to investigating newly-introduced interventions. PMID:25748417
Rhodes, Tim; Guise, Andy; Ndimbii, James; Strathdee, Steffanie; Ngugi, Elizabeth; Platt, Lucy; Kurth, Ann; Cleland, Charles; Vickerman, Peter
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)
King, Charles H.
...DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology Test Systems § 862.3620 Methadone test system. (a) Identification. A methadone...
This pilot study explores somatic, psychological, and urogenital menopause symptoms associated with HIV drug and sexual risk among midlife women with substance abuse histories in methadone maintenance treatment. The Menopause Rating Scale (MRS) assessed menopause symptoms and severity. The Risk Behavior Assessment assessed demographic characteristics, drug, and sexual risk behaviors. Menopause symptom associations of HIV drug and sexual risk findings indicated that high school graduates and women not having sex with a regular partner scored significantly higher on the MRS somatic symptom subscale. HIV negative women had higher total MRS scores compared with HIV positive women. Forty-six percent of the sample was sexually active with almost half engaged in unprotected sex. Significant associations with sexual risk were high MRS somatic subscale scores with inconsistent condom use for vaginal sex, HIV negative with inconsistent protected vaginal sex, heroin use with having sex while high with HIV negative status. Preliminary data provide a basis for further exploration and designing intervention approaches to reduce HIV risk and further transmission among midlife women in methadone treatment. PMID:23607674
Tuchman, Ellen; Pennington, Laurie E; Kull, Ryan M; Daneshyar, Saba
Opioid substitution treatment (OST) is still controversial, despite positive results. The issue of diversion to the illicit drug market is a cornerstone in the criticism typically voiced against the treatment. Little research is available concerning how professionals who work in OST view the issue of diversion. In this article, we discuss existing ideas and attitudes toward diversion of methadone and buprenorphine among OST staff in Sweden. The article is based on semi-structured interviews with 25 professionals working in eight OST-programs in southern Sweden. Diversion was seen as a deleterious phenomenon by the interviewees. Three problematic aspects were highlighted: medical risks in the form of overdose fatalities and the recruitment of new opiate/opioid users; negative consequences for the legitimacy of OST; and moral objections, since diversion means that the patients remain in a criminal environment. However, positive aspects were also highlighted. Illicit methadone or buprenorphine is perceived as safer than heroin. In this way, diversion can fulfill a positive function; for instance, if there is a shortage of access to regular treatment. Patients who share their medication with opioid-dependent friends are seen as less culpable than those who sell to anyone for money. PMID:25364995
Johnson, Björn; Richert, Torkel
Laudanosine, reticuline, codamine, and laudanine are members of the tetrahydrobenzylisoquinoline family of natural products. These alkaloids are present in the opium poppy, Papaver somniferum, and are subsequently found as impurities in clandestinely processed morphine. Morphine is then synthesized to heroin using hot acetic anhydride. During the course of this study, it was determined that these four tetrahydrobenzylisoquinolines undergo degradation to a series of 18 neutral impurities when subjected to hot acetic anhydride. Based on the degradation pathway, these new impurities were categorized into two sets of impurities called the C1-acetates compounds and the stilbene compounds. Synthesis, isolation, and structural elucidation information is provided for the tetrahydrobenzylisoquinoline alkaloids, and the new neutral impurities have been studied. Several hundred authentic heroin samples were analyzed using an established heroin signature program method. This methodology features the detection of trace neutral impurities present in heroin samples. It was determined that all 18 new impurities were detected in various quantities in four different types of heroin samples. Analytical results featuring these new impurities are reported for South American-, Southwest Asian-, Mexican-, and Southeast Asian-type heroin samples. These new impurities, coupled with other established forensic markers, enhance the ability to classify illicit heroin samples. PMID:16566764
Toske, Steven G; Cooper, Samuel D; Morello, David R; Hays, Patrick A; Casale, John F; Casale, Ellen
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…
Yankowitz, Robert; Randell, Joan
While methadone maintenance treatment (MMT) is beneficial for heroin dependence, there is little information regarding the reductions in monetary cost and gains in productivity following MMT. The aim of this study was to evaluate the changes in the monetary cost of heroin addiction and productivity after one year of MMT. Twenty-nine participants from an MMT clinic were included. The monetary cost, productivity, quality of life (QOL) and mental health status were assessed at both baseline and one year follow-up. The average annual total cost was approximately US$26,485 (1.43 GDP per capita in 2010) at baseline, and decreased by 59.3% to US$10,784 (0.58 GDP) at follow-up. The mean number of months of unemployment dropped from 6.03 to 2.79, the mean income increased to exceed the basic salary, but only reached 45.3% of the national average monthly earnings. The participants? mental health improved, but their QOL scores did not increase significantly. After one year of MMT, the monetary cost of heroin addiction fell, both the productivity and mental health of the participants? improved, but limited gains were seen with regard to their QOL. PMID:25500321
Hsiao, Chih Yin; Chen, Kao Chin; Lee, Lan-Ting; Tsai, Hsin Chun; Chang, Wei Hung; Lee, I Hui; Chen, Po See; Lu, Ru-Band; Yang, Yen Kuang
The purpose of this cross-sectional study was to examine predictors of heavy smoking among 256 male and female methadone maintenance therapy (MMT) clients from five MMT clinics in the Los Angeles area. We found that females reported lower rates of heavy smoking than males (47% vs 54%, respectively), in concordance with current literature pointing to gender-differences in smoking behaviors. In particular, males who reported heavy drinking, fair/poor health, and recent heroin use were more likely to report heavy smoking compared to males not reporting these factors. On the other hand, females who reported recent heroin use, a lifetime history of sex trade, and who had been ill enough to require a blood transfusion also had greater odds of reporting heavy cigarette-smoking. Findings from this study may direct us to not only design gender-based smoking cessation program for MMT clients but also to address the gender-based issues related to smoking in such a population. PMID:19597186
Nyamathi, Adeline M.; Sinha, Karabi; Marfisee, Mary; Cohen, Allan; Greengold, Barbara; Leake, Barbara
Dopaminergic activity in the mesocorticolimbic system is associated with reinforcing properties of psychostimulant drugs. We previously demonstrated that increased ?-aminobutyric acid (GABA)-ergic activity produced by ?-vinyl GABA [d,l-4-amino-hex-5-enoic acid (Vigabatrin®)], an irreversible inhibitor of GABA-transaminase, attenuated cocaine, nicotine, heroin, alcohol, and methamphetamine-induced increases in extracellular nucleus accumbens dopamine as well as behaviors associated with these biochemical changes. In the present
Madina R Gerasimov; Wynne K Schiffer; Jonathan D Brodie; Ian C Lennon; Stephen J. C Taylor; Stephen L Dewey
Cocaine has actions in the peripheral nervous system that reliably precede—and thus predict—its soon-to-follow central rewarding effects. In cocaine-experienced animals, the peripheral cocaine signal is relayed to the central nervous system, triggering excitatory input to the ventral tegmental origin of the mesocorticolimbic dopamine system, the system that mediates the rewarding effects of the drug. We used cocaine methiodide, a cocaine analog that does not cross the blood–brain barrier, to isolate the peripheral actions of cocaine and determine their central and behavioral effects in animals first trained to lever-press for cocaine hydrochloride (the centrally acting and abused form of the drug). We first confirmed with fast-scan cyclic voltammetry that cocaine methiodide causes rapid dopamine release from dopamine terminals in cocaine hydrochloride-trained rats. We then compared the ability of cocaine hydrochloride and cocaine methiodide to establish conditioned place preferences in rats with self-administration experience. While cocaine hydrochloride established stronger place preferences, cocaine methiodide was also effective and its effectiveness increased (incubated) over weeks of cocaine abstinence. Cocaine self-administration was extinguished when cocaine methiodide or saline was substituted for cocaine hydrochloride in the intravenous self-administration paradigm, but cocaine hydrochloride and cocaine methiodide each reinstated non-rewarded lever-pressing after extinction. Rats extinguished by cocaine methiodide substitution showed weaker cocaine-induced reinstatement than rats extinguished by saline substitution. These findings suggest that the conditioned peripheral effects of cocaine can contribute significantly to cocaine-induced (but not stress-induced) cocaine craving, and also suggest the cocaine cue as an important target for cue-exposure therapies for cocaine addiction. PMID:23535778
Wang, Bin; You, Zhi-Bing; Oleson, Erik B; Cheer, Joseph F; Myal, Stephanie; Wise, Roy A
Six human participants with recent histories of cocaine use were trained to discriminate 200 mg oral cocaine hydrochloride. A range of doses of oral cocaine (50–300 mg), methylphenidate (15–90 mg), triazolam (0.125–0.75 mg), and placebo were then tested to determine whether they shared discriminative-stimulus and participant-rated effects with 200 mg cocaine. Cocaine and methylphenidate dose-dependently increased cocaine-appropriate responding, produced prototypical
Craig R. Rush; Robert W. Baker
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…
Schilling, Robert; Dornig, Katrina; Lungren, Lena
China faces the challenge of dual epidemics of drug use and HIV/AIDS. Despite the high relapse rate among heroin addicts released from compulsory rehabilitation facilities, there are few programs available in China to assist these addicts in the community. We pilot-tested in China a Recovery Management Intervention (RMI) program designed to facilitate early detection of relapse and prompt linkage from compulsory rehabilitation to the community and, if participants relapse, to community-based methadone maintenance treatment (MMT) programs. One hundred heroin addicts were randomly assigned to either the Standard Care group (n = 50) or the RMI group (n = 50). At the end of the 3-month trial, participants in the RMI group, relative to the standard care group, demonstrated positive outcomes in recidivism due to relapse (0 vs. 6%, p = .08; d = 0.354), MMT participation (8% vs. 0, p = 0.06; d = 0.417), and employment (33% vs. 2%, p < .001; d = 0.876), although no difference was found in urine testing results (8.5% vs. 8.7%; d = 0.013) among interviewed participants. These pilot study results were based on a small sample size and short-term observation, suggesting the need for more research to further improve and test RMI effectiveness with larger samples over a longer period of time in order to provide evidence in support of RMI as an effective strategy for community reintegration among addicts released from rehabilitation facilities in China. PMID:22520276
Hser, Yih-Ing; Fu, Liming; Wu, Fei; Du, Jiang; Zhao, Min
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 ?-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
Farid, W.O; Dunlop, S.A; Tait, R.J; Hulse, G.K
There is evidence that the use of MDMA (methylenedioxymethamphetamine), colloquially known as "ecstasy" particularly among late adolescents and young adults is increasing in Australia. Despite recent government-sponsored public education programs, there is a perception that recreational use of MDMA is much less harmful than other illicit substances like heroin. Recent seizures by police in Australia underline the extent of the demand for MDMA and how lucrative trafficking in MDMA has become. In two recent Australian cases, appellate courts considered the legislative intent of both State and Commonwealth legislation and held that a quantity-based penalty regime applied which distinguished between "traffickable" and "commercial" quantities of illicit drugs and that no distinction turned on the relative "harmfulness" of MDMA. In examining the question of harmfulness, this column summarises the pharmacology and morbidity of MDMA and considers the links between MDMA and other substances of abuse and the implications for further prevention programs. PMID:20169795
Heroin addiction, a chronic relapsing disorder characterized by excessive drug taking and seeking, requires constant psychotherapeutic and pharmacotherapeutic interventions to minimize the potential for further abuse. Vaccine strategies against many drugs of abuse are being developed that generate antibodies that bind drug in the bloodstream, preventing entry into the brain and nullifying psychoactivity. However, this strategy is complicated by heroin’s rapid metabolism to 6-acetylmorphine and morphine. We recently developed a “dynamic” vaccine that creates antibodies against heroin and its psychoactive metabolites by presenting multihaptenic structures to the immune system that match heroin’s metabolism. The current study presents evidence of effective and continuous sequestration of brain-permeable constituents of heroin in the bloodstream following vaccination. The result is efficient blockade of heroin activity in treated rats, preventing various features of drugs of abuse: heroin reward, drug-induced reinstatement of drug seeking, and reescalation of compulsive heroin self-administration following abstinence in dependent rats. The dynamic vaccine shows the capability to significantly devalue the reinforcing and motivating properties of heroin, even in subjects with a history of dependence. In addition, targeting a less brain-permeable downstream metabolite, morphine, is insufficient to prevent heroin-induced activity in these models, suggesting that heroin and 6-acetylmorphine are critical players in heroin’s psychoactivity. Because the heroin vaccine does not target opioid receptors or common opioid pharmacotherapeutics, it can be used in conjunction with available treatment options. Thus, our vaccine represents a promising adjunct therapy for heroin addiction, providing continuous heroin antagonism, requiring minimal medical monitoring and patient compliance. PMID:23650354
Schlosburg, Joel E.; Vendruscolo, Leandro F.; Bremer, Paul T.; Lockner, Jonathan W.; Wade, Carrie L.; Nunes, Ashlee A. K.; Stowe, G. Neil; Edwards, Scott; Janda, Kim D.; Koob, George F.
Rationale: Benzodiazepines are used as anti anxiety drugs, as well as in adjunct treatment for a range of neurological and psychiatric disorders. Abusive patterns of use were increasingly reported and building evidence points to prevalence of benzodiazepines abuse, on one hand as well as to their common abuse in combination with other drugs such as opioids, most frequently. Objective: The main objective of this research is to conduct a systematic study on the behavior profile of a patient admitted to a prison hospital, who is a benzodiazepines user consecutive to admission into a methadone administration program. Methods and results: Statistic values have been taken into account describing the distribution and the distribution form of the various variables studied to find the normality degree of distributions, regarding three measurements at the three moments: before the administration of methadone, immediately after its completion and two months after completion. Conclusions and discussions: The statistic results obtained speak of a strong positive correlation, allowing the support of the fact that persons diagnosed with prescribed/ unprescribed benzodiazepine, use the display association with the admission into a methadone administration program, based on the assumption which concerns a significant positive association between the use of reported benzodiazepine and the administration of methadone in the questioned patients on admission. As far as the second premise regarding the administration of methadone is concerned it brings about an improvement in the level of benzodiazepines used in research patients, which one may assert that, according to the results obtained, the initiation of methadone therapy in the detoxification program is conducive to the reduction of benzodiazepines use.
Popescu, G; Negrei, C; B?l?l?u, D; Ciobanu, AM; Baconi, D; B?l?l?u, C
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. PMID:24720731
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
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
Spellicy, Catherine J.; Kosten, Thomas R.; Hamon, Sara C.; Harding, Mark J.; Nielsen, David A.
High-magnitude and long-duration abstinence reinforcement can promote drug abstinence but can be difficult to finance. Employment may be a vehicle for arranging high-magnitude and long-duration abstinence reinforcement. This study determined if employment-based abstinence reinforcement could increase cocaine abstinence in adults who inject drugs and use cocaine during methadone treatment. Participants could work 4?hr every weekday in a workplace where they could earn about $10.00 per hour in vouchers; they were required to provide routine urine samples. Participants who attended the workplace and provided cocaine-positive urine samples during the initial 4?weeks were invited to work 26?weeks and were randomly assigned to an abstinence-and-work (n ?=? 28) or work-only (n ?=? 28) group. Abstinence-and-work participants had to provide urine samples showing cocaine abstinence to work and maintain maximum pay. Work-only participants could work independent of their urinalysis results. Abstinence-and-work participants provided more (p ?=? .004; OR ?=? 5.80, 95% CI ?=? 2.03–16.56) cocaine-negative urine samples (29%) than did work-only participants (10%). Employment-based abstinence reinforcement can increase cocaine abstinence. PMID:17970256
Silverman, Kenneth; Wong, Conrad J; Needham, Mick; Diemer, Karly N; Knealing, Todd; Crone-Todd, Darlene; Fingerhood, Michael; Nuzzo, Paul; Kolodner, Kenneth
The Neuropsychology of Cocaine Addiction: Recent Cocaine Use Masks Impairment Patricia A Woicik*,1 in individuals addicted to cocaine. Neuropsychopharmacology (2009) 34, 1112Â1122; doi:10.1038/npp.2008.60; published online 21 May 2008 Keywords: cocaine addiction; neuropsychological function; alcohol; dysphoria
Homes, Christopher C.
The Neuropsychology of Cocaine Addiction: Recent Cocaine Use Masks Impairment Patricia A Woicik*,1 in individuals addicted to cocaine. Neuropsychopharmacology advance online publication, 21 May 2008; doi:10.1038/npp.2008.60 Keywords: cocaine addiction; neuropsychological function; alcohol; dysphoria; cigarette
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)
Lerner, Steven E.; Linder, Ronald L.
Despite the seriousness of acute medical and psychological consequences of cocaine abuse, little knowledge exists about the chronic effects of the drug. Investigation of a sample of abstinent freebase (crack) abusers in the Bahamas provides the first research evidence that prolonged cocaine abuse may result in persistent short-term memory disturbances. PMID:2387150
Manschreck, T C; Schneyer, M L; Weisstein, C C; Laughery, J; Rosenthal, J; Celada, T; Berner, J
Background: The pharmacokinetics of methadone is altered during pregnancy, but the most appropriate dosing and monitoring regimen has yet to be identified. Objective: To review dosing and monitoring of methadone therapy in pregnancy. Methods: A literature search was performed in several databases (PubMed, MEDLINE, Embase, International Pharmaceutical Abstracts, and the Cochrane Database of Systematic Reviews) from inception to May 2012. The search terms were “methadone”, “pregnancy”, “pharmacokinetic”, “clearance”, “metabolism”, “therapeutic drug monitoring”, and “methadone dosing”. Additional papers were identified by searching the bibliographies of primary and review articles. All English-language primary articles related to methadone pharmacokinetics in pregnancy were included. Articles not related to maternal outcomes were excluded. Results: The literature search yielded 1 case report and 10 studies discussing use of methadone by pregnant women. Methadone pharmacokinetics in pregnancy has been studied in 3 pharmacokinetic trials, and split dosing of methadone in pregnant women has been described in 1 case report and 3 dosing trials. Only 4 trials evaluated monitoring of methadone concentration in pregnancy. The studies included in this review confirm that methadone pharmacokinetics is altered in pregnancy and is potentially correlated with increases in maternal withdrawal symptoms. Insufficient evidence is available to warrant routine monitoring of serum methadone concentrations in pregnant women with opioid dependence. Conclusions: Few studies of methadone pharmacokinetics and therapeutic drug monitoring are available for pregnant women with opioid dependence. Although it is known that methadone pharmacokinetics is altered in pregnancy, there is insufficient evidence to guide dosage adjustments and serum concentration monitoring. Until further studies are available, regular follow-up of maternal withdrawal symptoms and empiric dosage adjustments throughout pregnancy are still recommended. PMID:23129867
Shiu, Jennifer R; Ensom, Mary H H
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)
Bloch, Harriet I.; And Others
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)
Schwartzman, John; Bokos, Peter
With repeated cocaine use, cocaine conditioned behavior develops to associated stimuli, and in addition, sensitization can occur to the unconditioned stimulant effects of cocaine. To investigate the relationship between the conditioned and unconditioned behavioral effects of repeated cocaine use, two groups of rats (n=7) were given five daily paired cocaine treatments (10 mg\\/kg i.p.) immediately before a 20-min placement in
Robert J Carey; Junmin Gui
Addiction changes prefrontal cortex regulation of the nucleus accumbens, including reduced ability to induce long-term potentiation (LTP) and long-term depression (LTD). This important potential mechanism of impaired prefrontal regulation of behavior has been shown only for cocaine. Here we show that animals trained to self-administer heroin demonstrate impaired LTP and LTD in the core of the nucleus accumbens following in vivo stimulation of the prelimbic prefrontal cortex. These data indicate that compromised synaptic plasticity in prefrontal to accumbens projections is a common feature of at least two distinct classes of addictive drug. PMID:23110855
Shen, Haowei; Kalivas, Peter W
OBJECTIVES: This study deter- mined human immunodeficiency virus (HIV) seroprevalence and factors associated with HIV infection among street-recruited injection drug users and crack cocaine smokers. METHODS: An analysis was performed on HIV serologies and risk behaviors of 6402 injection drug users and 3383 crack smokers in 16 US municipalities in 1992 and 1993. RESULTS: HIV seroprevalence was 12.7% among injection drug users and 7.5% among crack smokers. Most high-seroprevalence municipalities (>25%) were located along the eastern seaboard of the United States. In high-seroprevalence municipalities, but not in others, HIV seroprevalence was higher for injection drug users than for crack smokers. Among injection drug users, cocaine injection, use of speedballs (cocaine or amphetamines with heroin), and sexual risk behaviors were independently associated with HIV infection. Among crack smokers, sexual risk behaviors were associated with HIV infection. CONCLUSIONS: Injection drug users and crack smokers are at high risk for HIV infection. PMID:9584014
Kral, A H; Bluthenthal, R N; Booth, R E; Watters, J K
The rapid metabolism of heroin to 6-acetylmorphine and its slower conversion to morphine has led many to believe that heroin and morphine act through the same receptors and that the differences between them are due to their pharmacokinetics. We now present evidence strongly implying that heroin and two potent mu drugs, fentanyl and etonitazine, act through a unique receptor mechanism
Grace C. Rossi; George P. Brown; Liza Leventhal; Ke Yang; Gavril W. Pasternak
BEHAVIORAL NEUROSCIENCE Orexin / hypocretin 1 receptor antagonist reduces heroin self-administration and cue-induced heroin seeking Rachel J. Smith and Gary Aston-Jones Department of Neurosciences, Medical experiments, we examined the involvement of orexin in heroin reinforcement and relapse by administering
Global Stability for a Heroin Model with Two Distributed Delays Bin Fang1,2 , Xue-Zhi Li1 , Maia, we consider global stability for a heroin model with two distributed de- lays. The basic reproduction number of the heroin spread is obtained, which completely determine the stability of equilibria. Using
Psychosis was present in 29 percent of cocaine-disordered patients hospitalized in 1985 during an epidemic of freebase cocaine abuse in the Bahamas. Record reviews revealed that a variety of psychotic phenomenologic patterns were present. Prior major mental disorders and increased dosage of cocaine were more common among psychotic than non-psychotic patients. Violent behavior was common among cocaine patients, especially those with psychosis. We conclude that freebase cocaine psychosis is neither rare nor benign. PMID:3407210
Manschreck, T C; Laughery, J A; Weisstein, C C; Allen, D; Humblestone, B; Neville, M; Podlewski, H; Mitra, N
Blood toxicology results for deaths attributed to heroin overdose during 1995 in the South Western Sydney (SWS) region (n=39) were compared with those of a sample of 100 current SWS heroin users who had injected within the preceding 24 h. Heroin-related deaths had a higher median concentration of morphine than current heroin users (0.35 versus 0.09 mg\\/l). However, there was
Shane Darke; Sandra Sunjic; Deborah Zador; Tania Prolov
While prison-initiated methadone maintenance treatment is effective, it is largely unknown as to what patient and program factors are related to outcomes. These issues were studied in a secondary analysis of data from 67 male prerelease prison inmates with preincarceration heroin addiction. Three outcomes are examined: completed prison treatment; completed 1 year of community treatment; and number of days in community treatment. Being employed (p = .045) during the three years prior to index incarceration was significantly and positively related to community treatment completion. Increased frequency of urine tests taken was significantly associated with a greater number of days in community treatment (p < .001). Limitations, policy implications, and directions for future research are discussed. PMID:25580067
KINLOCK, TIMOTHY W.; GORDON, MICHAEL S.; SCHWARTZ, ROBERT P.; O’GRADY, KEVIN E.
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. Orv. Hetil., 2015, 156(9), 352-357. PMID:25702255
Pap, Ágota; Heged?s, Katalin
Heroin addiction, a chronic relapsing disorder characterized by excessive drug taking and seeking, requires constant psychotherapeutic and pharmacotherapeutic interventions to minimize the potential for further abuse. Vaccine strategies against many drugs of abuse are being developed that generate antibodies that bind drug in the bloodstream, preventing entry into the brain and nullifying psychoactivity. However, this strategy is complicated by heroin's rapid metabolism to 6-acetylmorphine and morphine. We recently developed a "dynamic" vaccine that creates antibodies against heroin and its psychoactive metabolites by presenting multihaptenic structures to the immune system that match heroin's metabolism. The current study presents evidence of effective and continuous sequestration of brain-permeable constituents of heroin in the bloodstream following vaccination. The result is efficient blockade of heroin activity in treated rats, preventing various features of drugs of abuse: heroin reward, drug-induced reinstatement of drug seeking, and reescalation of compulsive heroin self-administration following abstinence in dependent rats. The dynamic vaccine shows the capability to significantly devalue the reinforcing and motivating properties of heroin, even in subjects with a history of dependence. In addition, targeting a less brain-permeable downstream metabolite, morphine, is insufficient to prevent heroin-induced activity in these models, suggesting that heroin and 6-acetylmorphine are critical players in heroin's psychoactivity. Because the heroin vaccine does not target opioid receptors or common opioid pharmacotherapeutics, it can be used in conjunction with available treatment options. Thus, our vaccine represents a promising adjunct therapy for heroin addiction, providing continuous heroin antagonism, requiring minimal medical monitoring and patient compliance. PMID:23650354
Schlosburg, Joel E; Vendruscolo, Leandro F; Bremer, Paul T; Lockner, Jonathan W; Wade, Carrie L; Nunes, Ashlee A K; Stowe, G Neil; Edwards, Scott; Janda, Kim D; Koob, George F
This study evaluated whether cocaine use patterns changed following investigational intravenous cocaine administration to intravenous-naive cocaine users. Subjects were respondents to a follow-up survey who had participated in one to three intravenous double-blind cocaine (0.2 or 0.4 mg\\/kg) administration studies. The group included healthy men (n=17) and women (n=8) with histories of occasional cocaine use (lifetime self-reported use of 12±12
Marc J. Kaufman; Jonathan M. Levin; Thellea J. Kukes; Rosemond A. Villafuerte; John Hennen; Scott E. Lukas; Jack H. Mendelson; Perry F. Renshaw
Methadone is largely used for the substitution management of opiate-dependent individuals but can also be easily found on the black market. The first cases involving repetitive sedation linked to the use of methadone and subsequent death of 2 babies are reported. At the autopsy, no particular morphologic changes were noted except for pulmonary and visceral congestion. There was no evidence of violence, and the pathologist in both cases found no needle marks. Toxicological analyses, as achieved by GC/MS, demonstrated both recent and repetitive methadone exposure. In case 1, a 14-month-old girl was found dead at home. Blood concentrations were 1071 and 148 ng/mL for methadone and EDDP, respectively. Hair (6 cm) tested positive at 1.91 and 0.82 ng/mg for methadone and EDDP, respectively. In case 2, a 5-month-old girl was taken to hospital in a pediatric unit for coma. Antemortem blood analysis demonstrated methadone exposure (142 ng/mL), and the baby was declared dead 12 days after admission. Hair analysis (5 cm) by segmentation was positive for methadone in the range 1.0 (root) to 21.3 ng/mg (end). The death of the babies was attributed to accidental asphyxia ina situation where methadone was considered as a chemical weapon. The mothers, who were the perpetrators in both cases, did not deny the use of methadone as a sedative drug. PMID:16404812
Kintz, Pascal; Villain, Marion; Dumestre-Toulet, Véronique; Capolaghi, Bernard; Cirimele, Vincent
The Rikers Island Key Extended Entry Program (KEEP) has offered methadone treatment for opioid dependent inmates incarcerated in New York City's jails since 1986. In response to a trend toward low-dose methadone maintenance prescribing, a quality improvement (QI) protocol trained KEEP counselors, physicians, and pharmacists in the evidence base supporting moderate-to-high methadone maintenance doses in order to maximize therapeutic effects
Andiea Harris; Daniel Selling; Charles Luther; Jason Hershberger; Joan Brittain; Sam Dickenson; Alvin Glick; Joshua D. Lee
The Rikers Island Key Extended Entry Program (KEEP) has offered methadone treatment for opioid dependent inmates incarcerated in New York City's jails since 1986. In response to a trend toward low-dose methadone maintenance prescribing, a quality improvement (QI) protocol trained KEEP counselors, physicians, and pharmacists in the evidence base supporting moderate-to-high methadone maintenance doses in order to maximize therapeutic effects
Andiea Harris; Daniel Selling; Charles Luther; Jason Hershberger; Joan Brittain; Samuel Dickman; Alvin Glick; Joshua D. Lee
Background Cocaine is a cause of intracerebral hemorrhage (ICH), but there are no large studies that have characterized the location, pathology, and outcome of patients with cocaine-associated ICH. Methods We performed a retrospective analysis of all patients admitted to our stroke service from 2004 to 2007 who had non-traumatic ICH and urine drug screens positive for cocaine and compared them with similar patients who had a negative drug screen for cocaine. Results We identified 45 patients with cocaine-associated ICH and 105 patients with cocaine-negative ICH. There were no significant differences in age or gender but there was a significantly higher incidence of African-American patients in the cocaine positive group. Cocaine-associated ICH patients had higher admission blood pressures, significantly more subcortical hemorrhages, and higher rates of intraventricular hemorrhage (IVH) compared to patients with cocaine-negative ICH. Cocaine-positive patients had worse functional outcome, defined as an mRS>3 at the time of discharge (OR 4.90, 95% CI 2.19–10.97), and were less likely to be discharged home or to inpatient rehab. Patients with cocaine-associated ICH were nearly 3 times more likely to die during their acute hospitalization when compared to cocaine-negative patients. Conclusion Recent cocaine ingestion is associated with hemorrhages that occur more frequently in subcortical locations, have a higher risk of IVH, and carry a poor prognosis compared to patients with cocaine-negative, spontaneous ICH. PMID:20185779
Martin-Schild, Sheryl; Albright, Karen C.; Hallevi, Hen; Barreto, Andrew D.; Philip, Maria; Misra, Vivek; Grotta, James C.; Savitz, Sean I.
As U.S. general internists play an increasing role in providing opioid maintenance therapy in practice offices, they are having to face the challenge of identifying patients who need specialized services especially at the outset of treatment. In methadone maintenance treatment, prognostic studies have failed to find robust predictors on the basis of single predictive variables. We hypothesize that a multivariable staging system will predict treatment outcome more accurately than single variables. We reviewed baseline and treatment data regarding 226 consecutive patients admitted to a methadone maintenance program in New Haven, Connecticut, from January 1, 1993 to March 28, 1994, and followed until December 1, 1996. The staging system was developed from the data on the first 112 patients, confirmed in the remaining 114 patients, and then applied to the entire cohort of 226 patients. Retention was the main outcome measure used in developing the staging system. The staging system was also validated as a predictor of illicit drug use during treatment and adverse discharge. In the staging system one point is scored for each of the following: use of more than two bags of heroin daily, previous prison term, previous period in reform school, and a history of diseases related to substance use, e.g., endocarditis, hepatitis, abscesses, and overdose. The total score classifies patients as Stage I (0 and 1 points), Stage II (2 points), or Stage III (3 and 4 points). This staging system was significantly associated with retention in a proportional-hazards model, and no other variable added any additional predictive influence. The specific stage was also found to be a significant predictor of adverse discharge. Although additional validation is necessary in other populations, we found the staging system to be a useful and simple way of identifying patients at risk for early attrition and adverse discharge. PMID:12438836
Favrat, Bernard; Rao, Surita; O'Connor, Patrick G; Schottenfeld, Richard
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
Kreek, Mary Jeanne; Borg, Lisa; Ducat, Elizabeth; Ray, Brenda
The use of phenytoin (PHT) as a cocaine adulterant was reported decades ago; that practice is still current. Ironically PHT has also been used for the treatment of cocaine dependence. A drug smuggler developed PHT toxicity after swallowing several rocks of crack. We investigated the current trends of PHT as a cocaine adulterant and its toxicological implications. We also reviewed the clinical use of PTH in relation to cocaine. The use of PHT as cocaine cut is a current practice. This may affect the clinical manifestations and the management of the cocaine-related visits to the emergency department. PMID:24672596
Roldan, Carlos J.
The use of phenytoin (PHT) as a cocaine adulterant was reported decades ago; that practice is still current. Ironically PHT has also been used for the treatment of cocaine dependence. A drug smuggler developed PHT toxicity after swallowing several rocks of crack. We investigated the current trends of PHT as a cocaine adulterant and its toxicological implications. We also reviewed the clinical use of PTH in relation to cocaine. The use of PHT as cocaine cut is a current practice. This may affect the clinical manifestations and the management of the cocaine-related visits to the emergency department. PMID:24672596
Roldan, Carlos J
Opioid abuse and addiction have increased in frequency in the United States over the past 20 years. In 2009, an estimated 5.3 million persons used opioid medications nonmedically within the past month, 200 000 used heroin, and approximately 9.6% of African Americans used an illicit drug. Racial and ethnic minorities experience disparities in availability and access to mental health care, including substance use disorders. Primary care practitioners are often called upon to differentiate between appropriate, medically indicated opioid use in pain management vs inappropriate abuse or addiction. Racial and ethnic minority populations tend to favor primary care treatment settings over specialty mental health settings. Recent therapeutic advances allow patients requiring specialized treatment for opioid abuse and addiction to be managed in primary care settings. The Drug Addiction Treatment Act of 2000 enables qualified physicians with readily available short-term training to treat opioid-dependent patients with buprenorphine in an office-based setting, potentially making primary care physicians active partners in the diagnosis and treatment of opioid use disorders. Methadone and buprenorphine are effective opioid replacement agents for maintenance and/or detoxification of opioid-addicted individuals. However, restrictive federal regulations and stigmatization of opioid addiction and treatment have limited the availability of methadone. The opioid partial agonist-antagonist buprenorphine/naloxone combination has proven an effective alternative. This article reviews the literature on differences between buprenorphine and methadone regarding availability, efficacy, safety, side-effects, and dosing, identifying resources for enhancing the effectiveness of medication-assisted recovery through coordination with behavioral/psychological counseling, embedded in the context of recovery-oriented systems of care. PMID:23092049
Bonhomme, Jean; Shim, Ruth S.; Gooden, Richard; Tyus, Dawn; Rust, George
Both noncontingent cocaine and the presentation of cocaine-paired external stimuli will reinstate cocaine-appropriate operant responding. However, the interaction of noncontingent cocaine and cocaine-paired stimuli in producing reinstatement has not been extensively examined. In the present study, the ability of noncontingent cocaine alone, the combination of noncontingent cocaine+contingent cocaine-paired lights+tone and contingent lights+tone alone to produce reinstatement were examined. No cocaine
Keith L Shelton; Elizabeth Hendrick; Patrick M Beardsley
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. PMID:25520464
Phillips, John R
Drug use histories and treatment outcomes were compared for age, race and gender-matched samples of intravenous (IV; n = 28) versus intranasal (IN; n = 28) opiate abusers entering a 3-day inpatient detoxification unit. Data were derived from the Addiction Severity Index (ASI) interview. Both groups reported daily heroin use prior to detoxification, but IV users reported more days of alcohol and multiple drug use during the past 30 days. Despite age matching, IV users also started using alcohol at an earlier age and accumulated more lifetime months of regular alcohol, cocaine and multidrug use. IV users were more likely to enter treatment following the detox, but no significant outcome differences were noted at 1 and 3 months post-detoxification. The results show that intravenous, as compared to intranasal, opiate users have both a more severe pattern and a more extensive history of the use of non-opiate drugs. PMID:10933336
Carpenter, M J; Chutuape, M A; Stitzer, M L
The abuse of alcohol is associated with chronic cardiomyopathy, hypertension, and arrhythmia. Abstinence or using alcohol in moderation can reverse these cardiovascular problems. Alcohol is also distinguished among the substances of abuse by having possible protective effects against coronary artery disease and stroke when used in moderate amounts. Amphetamines (eg, speed, ice, ecstasy) have many of the cardiovascular toxicities seen with cocaine, including acute and chronic cardiovascular diseases. Heroin and other opiates can cause arrhythmias and noncardiac pulmonary edema, and may reduce cardiac output. Cardiovascular problems are less common with cannabis (marijuana) than with opiates, but major cognitive disorders may be seen with its chronic use. It is still controversial whether caffeine can cause hypertension and coronary artery disease, and questions have been raised about its safety in patients with heart failure and arrhythmia. PMID:12877759
Frishman, William H; Del Vecchio, Alexander; Sanal, Shirin; Ismail, Anjum
Opioid dependence is one of the most severe drug dependencies. Naltrexone is a medication that completely blocks the subjective and other effects of opioids and, when administered to detoxified opioid addicts and taken as directed, prevents relapse and helps maintain abstinence. The major problem with naltrexone is poor compliance, particularly in countries in which there is a treatment alternative based on substitution of illicit opioids such as heroin with orally administered opioid agonists (methadone) or partial agonist/antagonists (buprenorphine). In Russia, substitution therapy is forbidden by law, and naltrexone is the only available pharmacotherapy for heroin dependence. Due to the lack of alternatives to naltrexone and stronger family control of compliance (adherence), naltrexone is more effective for relapse prevention and abstinence stabilization in Russia than in Western countries. Long-acting, sustained-release formulations (injectable and implantable) seem particularly effective compared with oral formulations. This article summarizes the results of studies conducted in Russia during the past 10 years that demonstrate these points. PMID:20640538
Zvartau, Edwin; Woody, George
A fast gas chromatography (GC)-MS method has been developed and validated for the simultaneous screening of different classes\\u000a of drugs of abuse in urine. Tetrahydrocannabinol metabolite, cocaine, opiates such as morphine, O-6-monoacetylmorphine (O-6-MAM), codeine, opioids such as buprenorphine, methadone, pentazocine, fentanyl and analogues and their main metabolites\\u000a can be detected and quantified after a simple liquid–liquid extraction in alkaline conditions
Sabina Strano-Rossi; Ana Maria Bermejo; Xavier de la Torre; Francesco Botrè
Little is known about the effects of cocaine on cognitive tasks. Event-related potentials (ERP) were recorded in 7 cocaine abusers during the performance of the auditory oddball task before and after the intravenous injections of saline and cocaine (60–80 mg). The P3B and slow wave components of the ERP were significantly larger 60–210 min after the cocaine than after the
Ronald I. Herning; Barbara J. Glover; Xiaoyan Guo
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
Virginia Delaney-Black; Lisa M. Chiodo; John H. Hannigan; Mark K. Greenwald; James Janisse; Grace Patterson; Marilyn A. Huestis; Robert T. Partridge; Joel Ager; Robert J. Sokol
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
Wang, A-L; Elman, I; Lowen, S B; Blady, S J; Lynch, K G; Hyatt, J M; O'Brien, C P; Langleben, D D
Injectable extended-release naltrexone (XRNTX) presents an effective therapeutic strategy for opioid addiction, however its use is 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.
Wang, A-L; Elman, I; Lowen, S B; Blady, S J; Lynch, K G; Hyatt, J M; O'Brien, C P; Langleben, D D
Although studies on the beliefs of persons with chronic nonmalignant pain (CNMP) are still scarce, methadone is increasingly prescribed for the treatment of CNMP. This qualitative case study uses semistructured interviews to explore the beliefs of 11 patients with CNMP and the challenges they faced coming to terms with and integrating methadone treatment into their lives. The study identifies a two-phase process of acceptance and integration. In the first phase, during acceptance of the prescribed methadone treatment, initial beliefs were mostly determined by the societal stigma that "methadone is for junkies." Different influencing factors such as knowledge about methadone for pain management, family support, and trust in physicians changed behavior in a positive way. In the second phase, patients dealt with the degree of disclosure about their treatment. Full disclosers have no problem in telling others that they were being treated with methadone, whereas partial disclosers were more selective. They were confronted with various barriers: negative encounters with family, friends, and the public; past addict experiences; safety issues; and obstacles within the health care system. As a result of these challenges, their beliefs were summarized as: "others think I'm an addict," and "methadone can harm me and/or my family."This study highlights the important role nurses have in the education of patients on the use of methadone in pain management, and in assisting patients with CNMP to gain confidence and a greater sense of control to cope with the challenging issues related to disclosing information. PMID:16490733
Arnaert, Antonia; Ciccotosto, Gina
The Treatment Evaluation Project was established to evaluate the feasibility of using behavioral treatment in conjunction with methadone maintenance to improve the effectiveness of methadone treatment. Over 100 outpatients were accepted into treatment and randomly assigned to one of four behavioral treatment modalities in addition to the usual…
Bigelow, George; And Others
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 was heavy
Adeline Nyamathi; Allan Cohen; Mary Marfisee; Steven Shoptaw; Barbara Greengold; Viviane de Castro; Daniel George; Barbara Leake
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.…
Kushner, Marlene; And Others
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)
Brill, Leon; Chambers, Carl D.
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…
Inciardi, James A.
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…
Sex hormones may have a role in the pathophysiology of substance use disorders, as demonstrated by the association between testosterone and addictive behaviour in opioid dependence. Although opioid use has been found to suppress testosterone levels in men and women, the extent of this effect and how it relates to methadone treatment for opioid dependence is unclear. The present multi-centre cross-sectional study consecutively recruited 231 patients with opioid dependence from methadone clinics across Ontario, Canada between June and December of 2011. We obtained demographic details, substance use, psychiatric history, and blood and urine samples from enrolled subjects. The control group included 783 non-opioid using adults recruited from a primary care setting in Ontario, Canada. Average testosterone level in men receiving methadone treatment was significantly lower than controls. No effect of opioids including methadone on testosterone level in women was found and testosterone did not fluctuate significantly between menstrual cycle phases. In methadone patients, testosterone level was significantly associated with methadone dose in men only. We recommend that testosterone levels be checked in men prior and during methadone and other opioid therapy, in order to detect and treat testosterone deficiency associated with opioids and lead to successful methadone treatment outcomes. PMID:25155550
Bawor, Monica; Dennis, Brittany B.; Samaan, M. Constantine; Plater, Carolyn; Worster, Andrew; Varenbut, Michael; Daiter, Jeff; Marsh, David C.; Desai, Dipika; Steiner, Meir; Anglin, Rebecca; Coote, Margaret; Pare, Guillaume; Thabane, Lehana; Samaan, Zainab
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…
Spiga, Ralph; Maxwell, R. Stockton; Meisch, Richard A.; Grabowski, John
Individuals with current cocaine use disorders (CUD) form a heterogeneous group, making sensitive neuropsychological (NP) comparisons with healthy individuals difficult. The current study examined the effects on NP functioning of four factors that commonly vary among CUD: urine status for cocaine (positive vs negative on study day), cigarette smoking, alcohol consumption, and dysphoria. Sixty-four cocaine abusers were matched to healthy
Patricia A Woicik; Scott J Moeller; Nelly Alia-Klein; Thomas Maloney; Tanya M Lukasik; Olga Yeliosof; Gene-Jack Wang; Nora D Volkow; Rita Z Goldstein; PA Woicik
Despite a wealth of information on cocaine-like compounds, there is no information on cocaine analogs with substitutions at C-1. Here, we report on (R)-(?)-cocaine analogs with various C-1 substituents: methyl (2), ethyl (3), n-propyl (4), n-pentyl (5), and phenyl (6). Analog 2 was equipotent to cocaine as an inhibitor of the dopamine transporter (DAT), whereas 3 and 6 were 3- and 10-fold more potent, respectively. None of the analogs, however, stimulated mouse locomotor activity, in contrast to cocaine. Pharmacokinetic assays showed compound 2 occupied mouse brain rapidly, as cocaine itself; moreover, 2 and 6 were behaviorally active in mice in the forced-swim test model of depression and the conditioned place preference test. Analog 2 was a weaker inhibitor of voltage-dependent Na+ channels than cocaine, although 6 was more potent than cocaine, highlighting the need to assay future C-1 analogs for this activity. Receptorome screening indicated few significant binding targets other than the monoamine transporters. Benztropine-like “atypical” DAT inhibitors are known to display reduced cocaine-like locomotor stimulation, presumably by their propensity to interact with an inward-facing transporter conformation. However, 2 and 6, like cocaine, but unlike benztropine, exhibited preferential interaction with an outward-facing conformation upon docking in our DAT homology model. In summary, C-1 cocaine analogs are not cocaine-like in that they are not stimulatory in vivo. However, they are not benztropine-like in binding mechanism and seem to interact with the DAT similarly to cocaine. The present data warrant further consideration of these novel cocaine analogs for antidepressant or cocaine substitution potential. PMID:22895898
Ali, Solav; Hashim, Audrey; Sheikh, Imran S.; Theddu, Naresh; Gaddiraju, Narendra V.; Mehrotra, Suneet; Schmitt, Kyle C.; Murray, Thomas F.; Sershen, Henry; Unterwald, Ellen M.; Davis, Franklin A.
Sweat patches (N=350) were collected throughout gestation from 29 opioid-dependent pregnant women participating in an outpatient methadone assisted therapy program. Volunteers provided informed consent to participate in Institutional Review Board-approved protocols. Methadone was eluted from sweat patches with sodium acetate buffer, followed by solid-phase extraction and quantification by GCMS (LOQ ?10 ng/patch). Methadone was present in all weekly patches (N=311) in concentrations ranging from 10.2 to 12,129.7 ng/patch and in 92.3% of short-term patches (N=39, worn for 12 or 24 h) in concentrations up to 3303.9 ng/patch. Correlation between patch concentrations and total amount of drug administered (r=0.224), and concentrations and duration of patch wear (r=0.129) were both weak. Although there were large intra- and inter-subject variation in sweat drug concentrations, sweat testing was an effective alternative technique to qualitatively monitor illicit drug use and simultaneously document methadone medication assisted treatment. PMID:20592651
Barnes, Allan J.; Brunet, Bertrand R.; Choo, Robin E.; Mura, Patrick; Johnson, Rolley E.; Jones, Hendrée E.; Huestis, Marilyn A.
Objective Deficits in cognitive functioning have been well-documented in persons with substance use disorders. In addition, some evidence suggests that poorer cognitive functioning predicts poorer engagement in substance abuse treatment and worse treatment outcomes. TRIAL DESIGN Non-blind, randomized clinical trial with parallel design. Methods Clients were recruited from a local methadone maintenance clinic within the first 30 days of treatment. All participants completed a comprehensive, computerized neuropsychological assessment (MicroCog) at the time they entered the clinical trial. Participants were randomized to receive 12 months of either standard methadone maintenance treatment, or methadone maintenance treatment with an integrated web-based intervention as part of treatment. The aims of the current study were to (1) characterize the cognitive functioning of clients entering methadone maintenance treatment; (2) evaluate the impact of cognitive functioning on the primary outcomes of treatment retention and opioid abstinence; and (3) determine whether cognitive functioning had a differential impact on these outcomes across treatment conditions. Randomization was non-blind and participants were stratified on past month cocaine use, prior history of methadone, LAAM or buprenorphine treatment, and counselor. Results Eighty participants were randomized to each condition (total n=160). Mean scores on MicroCog scales fell in the average and low average ranges and there were no differences in scores between treatment groups. Lower scores on General Cognitive Proficiency predicted longer study retention (?2=5.03, p < .05), though this effect was quite small. Generalized linear modeling showed that scores on all MicroCog scales except for Spatial Processing significantly predicted opioid abstinence (defined as percent of total weeks and percent of tested weeks with continuous abstinence), with lower scores predicting smaller percentages of continuous weeks of abstinence. This pattern was not evident in regression analyses in which abstinence was defined as number of total weeks of abstinence. An interaction effect was observed, whereby lower cognitive scores predicted lower levels of abstinence for participants in standard methadone maintenance treatment, but not for those who received the web-based intervention as part of methadone maintenance treatment. Conclusions Technology-based interventions may hold promise for minimizing the impact of poorer cognitive functioning on treatment outcomes. PMID:23671409
Acosta, Michelle C.; Marsch, Lisa A.; Xie, Haiyi; Guarino, Honoria; Aponte-Melendez, Yesenia
...Drugs 8 2013-04-01 2013-04-01 false Cocaine and cocaine metabolite test system. 862.3250 Section 862... Clinical Toxicology Test Systems § 862.3250 Cocaine and cocaine metabolite test system. (a)...
Detecting Cocaine Use with Wearable Electrocardiogram Sensors Detecting Cocaine Use with Wearable;Detecting Cocaine Use with Wearable Electrocardiogram Sensors Introduction Physiological Sensing personalized interventions In this paper: We study the problem of detecting cocaine use based on physiological
Massachusetts at Amherst, University of
...Drugs 8 2010-04-01 2010-04-01 false Cocaine and cocaine metabolite test system. 862.3250 Section 862... Clinical Toxicology Test Systems § 862.3250 Cocaine and cocaine metabolite test system. (a)...
...Drugs 8 2012-04-01 2012-04-01 false Cocaine and cocaine metabolite test system. 862.3250 Section 862... Clinical Toxicology Test Systems § 862.3250 Cocaine and cocaine metabolite test system. (a)...
...Drugs 8 2014-04-01 2014-04-01 false Cocaine and cocaine metabolite test system. 862.3250 Section 862... Clinical Toxicology Test Systems § 862.3250 Cocaine and cocaine metabolite test system. (a)...
...Drugs 8 2011-04-01 2011-04-01 false Cocaine and cocaine metabolite test system. 862.3250 Section 862... Clinical Toxicology Test Systems § 862.3250 Cocaine and cocaine metabolite test system. (a)...
Methylphenidate Attenuates Limbic Brain Inhibition after Cocaine-Cues Exposure in Cocaine Abusers Abstract Dopamine (phasic release) is implicated in conditioned responses. Imaging studies in cocaine of increasing tonic dopamine levels (using oral methylphenidate) on brain activation induced by cocaine
Homes, Christopher C.
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 approaches tailored to couples are also urgently needed and could decrease HCV-risk in this population. The trial is registered with the French Agency of Pharmaceutical Products (ANSM) under the number 2008-A0277-48, the European Union Drug Regulating Authorities Clinical Trials. Number Eudract 2008-001338-28, the ClinicalTrials.gov Identifier: NCT00657397 and the International Standard Randomised Controlled Trial Number Register ISRCTN31125511. PMID:25209306
Non-contingent, ‘priming’ IV drug injections led to reinstatement of heroin-reinforced responding after a period of extinction. Rats implanted with IV catheters were trained to self-administer heroin (100 µg\\/kg\\/infusion diacetylmorphine HCl) and were given test sessions consisting of a period of self-administration followed by extinction conditions. ‘Priming’ infusions of heroin and other drugs were presented during extinction and lever pressing following
Harriet de Wit; Jane Stewart
Drug overdose is a major cause of premature death and morbidity among heroin users. This article examines recent research\\u000a into heroin overdose to inform interventions that will reduce the rate of overdose death. The demographic characteristics\\u000a of overdose cases are discussed, including factors associated with overdose: polydrug use, drug purity, drug tolerance, routes\\u000a of administration, and suicide. Responses by heroin
Shane Darke; Wayne Hall
Cocaine is a white crystalline powder that is prepared from the leaf of the Erythroxylon coca bush, which is grown in Peru and Bolivia. It was first identified by a German chemist named Albert Niemann in the mid-19th century, when it was initiated as a tonic/elixir in medicines to treat real or envisioned illnesses. The mechanism of action of cocaine is to block the reuptake of dopamine, an important neurotransmitter. Cocaine was used medically as a local anesthetic to perform eye, ear, nose, or throat surgery, although it has long since been replaced. Now, it is generally sold on the streets as a powder to be snorted in order to increase alertness and temporary feelings of pleasure.
This study describes the characteristics of 67 young heroin users, interviewed using a semistructured qualitative questionnaire (QQ) as part of a larger study of 18- to 25-year-old heroin users seeking detoxification with buprenorphine at a drug treatment center in Baltimore. This new generation of heroin users has a different demographic profile compared to older heroin users in this area. Our data, supported by data from another clinic and from the Maryland State Alcohol and Drug Abuse Administration, seem to indicate that the younger heroin users in treatment settings are predominantly White, with a high proportion of women, often living in the suburbs. Based on responses to the QQ, all subjects initiated heroin use intranasally, usually in a group setting; 75% had subsequently gone on to use intravenously. The typical young heroin user in Baltimore Metropolitan area appears to be a young White man or woman from a middle/working-class background, with exposure to drug use among close contacts while growing up, experimenting with gateway drugs with peers before proceeding first to intranasal, and then intravenous heroin use, engaging in criminal activities to support the habit, repeatedly seeking help with assistance from family, but failing to sustain abstinence due to continued exposure to drug using peers and a poorly implemented plan of aftercare. Further research should focus on efforts to engage peer groups and families in order to improve treatment outcomes in young heroin users. PMID:16595322
Gandhi, Devang H; Kavanagh, Greg J; Jaffe, Jerome H
This case study looks at cocaine, including its addictive properties and the chemistry involved in the synthesis of the drug in its different forms. The lesson can be used to teach nucleophilic addition reactions, nucleophilic acyl substitution, and cocaine metabolism. The material was designed for use in an undergraduate organic chemistry course but could also be used in medicinal chemistry coursework. The case study and teaching notes may be downloaded in PDF format. The site also includes a section for instructor feedback where general comments may be read and contributed.
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.
Srijanto, Bernadeta; Cheney, Christine P.; Hedden, David L.; Gehl, Anthony; Ferrell, Thomas L.
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. PMID:3757767
Higgins, S T; Stitzer, M L; Bigelow, G E; Liebson, I A
As reported in the 2011 World Drug Report, cocaine is likely to be the most problematic drug worldwide in terms of trafficking-related violence and second only to heroin in terms of negative health consequences and drug deaths. Over a period of 60 years, cocaine evolved from the celebrated panacea of the 1860s to outlawed street drug of the 1920s. As demonstrated by the evolution of cocaine use and abuse in the United Kingdom and United States during this time period, cultural attitudes influenced both the acceptance of cocaine into the medical field and the reaction to the harmful effects of cocaine. Our review of articles on cocaine use in the United Kingdom and the United States from 1860 to 1920 reveals an attitude of caution in the United Kingdom compared with an attitude of progressivism in the United States. When the trends in medical literature are viewed in the context of the development of drug regulations, our analysis provides insight into the relationship between cultural attitudes and drug policy, supporting the premise that it is cultural and social factors which shape drug policy, rather than drug regulations changing culture. PMID:23772315
Wielenga, Vicki; Gilchrist, Dawna
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 and Social Knowledge Structure theories can perhaps provide a more plausible theoretical background. Further work is required to clarify which factors underlie this testing technique’s functioning. Reappraisal is advised before further forensic use of the instrument to ensure that general associations not related to autobiographical memory do not confound results. PMID:23767665
Background Prisoners have extremely high rates of smoking with rates 3–4 times higher than the general community. Many prisoners have used heroin. The aims of this study were to investigate the impact of heroin use on smoking cessation and the social determinants of health among prisoners. Methods Secondary analysis of data from a randomised controlled trial of a multi-component smoking cessation intervention involving 425 Australian male prisoners. Inmates who, prior to imprisonment, used heroin regularly were compared to those who did not use heroin regularly. Self-reported smoking status was validated at baseline and each follow-up by measuring carbon monoxide levels. Readings exceeding 10 ppm were defined as indicating current smoking. Results Over half (56.5%) of the participants had ever used heroin while 37.7% regularly (daily or almost daily) used heroin in the year prior to entering prison. Prisoners who regularly used heroin had significantly worse social determinants of health and smoking behaviours, including lower educational attainment, more frequent incarceration and earlier initiation into smoking. Prisoners who regularly used heroin also used and injected other drugs significantly more frequently. At 12-month follow-up, the smoking cessation of prisoners who had regularly used heroin was also significantly lower than prisoners who did not regularly use heroin, a finding confirmed by logistic regression. Conclusions Regular heroin use prior to imprisonment is an important risk factor for unsuccessful attempts to quit smoking among prisoners and is also associated with worse social determinants of health, higher drug use, and worse smoking behaviours. More effective and earlier smoking cessation interventions are required for particularly disadvantaged groups. Trial registration This trial is registered with the Australian New Zealand Clinical Trials Registry 12606000229572. PMID:24354968
Recreational use of cocaine dates back to the Incas in South America 5000 years ago. Cocaine is derived from the leaves of Erythroxylon coca, a shrub native to South America. In the late 1800s, Sigmund Freud popularized the drug in Europe. He used cocaine to treat depression, asthma, cachexia, and for overcoming morphine addiction. Also in this period cocaine rapidly gained acceptance in surgical procedures as a local anesthetic and vasoconstrictor. Cocaine reached the United States in the early 1900s, and its popularity led President Taft to declare it public enemy number one in 1910. Cocaine became popular again in the 1980s. Currently cocaine use is responsible for more ED visits then any of the other illicit drugs. Because most cocaine users are young, they are at a lower risk for coronary artery atherosclerotic disease. An estimated 25 million people between the ages of 26 and 34 years have used cocaine at least once, 20% were women and 30% men. Habitual users of cocaine are estimated to number 1.5 million. Most cocaine-induced chest pains do not progress to MI, and in fact many originate in the chest wall. The chest pains due to cocaine, however, are induced by myocardial ischemia, a result of vasospasm and not a thrombotic occlusion of a coronary artery that has a ruptured atheromatous plaque. ECG findings can be misleading in the diagnosis because the early repolarization syndrome, a normal variant, is a frequent finding in young African American men. Measurement of cardiac troponin levels is the most reliable diagnostic test. Percutaneous coronary intervention and angioplasty, rather than thrombolysis, is the treatment of choice because intense coronary vasospasm is the primary pathophysiology in cocaine-induced MI. PMID:14619364
Keller, Kathryn Buchanan; Lemberg, Louis
is accompanied by a similar trend of quitting, perhaps, indicating a relatively short heroin use career. A sharp, be used to extract historical (dynamic) trends of certain important variables. 2 #12;1 Introduction analysis which would identify the population trends among heroin users, and in turn help policy makers
Heroin is an illicit narcotic abused by millions of people worldwide. In the present work, we estimated peroxyl radical-trapping capacity (PRTC), oxidative stress markers – malondialdehyde and protein carbonyl groups, as well as antioxidant enzymes – superoxide dismutase and catalase, in different regions of brain. Studies conducted on nine brains from heroin abusers and eight from control subjects revealed a
Marzena Gutowicz; Bo?enna Sadurska; Ma?gorzata Cho?ojczyk; Maria Pokorska-Lis; Agnieszka Siwi?ska-Zió?kowska; Anna Bara?czyk-Ku?ma
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.
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.
Alcohol has been reported to modulate the reinforcing and aversive properties of cocaine. Given these effects, the present study examined whether this interaction could be extended to cocaine seeking using the conditioned place preference (CPP) procedure. Specifically, 31 drug-naive, male Sprague–Dawley rats were injected every other day (for 8 days) with either 20 mg\\/kg cocaine or vehicle in an alternating
Gregory D. Busse; Anthony L. Riley
Summary Use of cocaine, by inhalation, is currently increasing in Western Countries and its use is superseding heroin in the rising generation. Young people of the third millennium use narcotics to avoid the negative conditions of daily life and to escape on “unreal” trips, as happened in the ’60s and ’70s for the heroin-addicted. Today, on the contrary, people addicted to cocaine want to be more competitive and “winners” and believe that cocaine can help them to reach this goal. A series of 104 patients (75 male, 29 female), aged between 16 and 54 yrs, all habitual inhaling cocaine users (? 10 times per month) have been observed for 2 years. Among them, 11 (10.5%) had nasal septal perforation, which is frequently related to cocaine use. Of these 11 patients, 8 (72.7%) had nasal septal perforation of the quadrangular cartilage, while in the other 3 (27.3%) the perforation involved also the bony tract (vomer-perpendicular ethmoidal lamina). Psychological analysis of these 104 patients is reported: 62 patients (59.6%) answered that they inhaled cocaine to improve endurance and to feel stronger and less tired; 34 patients (32.7%) in order to enjoy themselves more during parties and to communicate more effectively with other people; 5 patients (4.8%) to gain confidence and to overcome their shyness, 2 patients (1.9%) to improve their sexual performance and 1 patient (1%) to drink more alcoholic drinks for a longer time without feeling sleepy. All the patients underwent psychotherapeutic treatment, but the lack of compliance and constantly missing the scheduled follow-up visits resulted in complete therapy being performed in only 16 patients (15.3%). All the patients with nasal septal perforation underwent rhino-endoscopy, at T0, with 0°, 45° endoscopes, computed tomography scan of nose and paranasal sinuses and biopsy. At the time of the observational period, none of the 11 patients who presented nasal septal perforation agreed to stop cocaine abuse; therefore, a temporary solution has been offered to all the patients (accepted by 3 of them), i.e., the positioning of a silicone button to close the perforation and, thus, improve the air flow in the nose and reduce progression of local necrosis. Together with the button, the positioning is described, under local anaesthesia, of two layers per septal side of hyaluronic acid, at different levels of esterification, kept in site by the button as a “sandwich” in order to obtain better re-growth of the mucosa and fewer scabs and bleeding PMID:19186454
Di Rienzo Businco, L; Lauriello, M; Marsico, C; Corbisiero, A; Cipriani, O; Coen Tirelli, G
Use of cocaine, by inhalation, is currently increasing in Western Countries and its use is superseding heroin in the rising generation. Young people of the third millennium use narcotics to avoid the negative conditions of daily life and to escape on "unreal" trips, as happened in the '60s and '70s for the heroin-addicted. Today, on the contrary, people addicted to cocaine want to be more competitive and "winners" and believe that cocaine can help them to reach this goal. A series of 104 patients (75 male, 29 female), aged between 16 and 54 yrs, all habitual inhaling cocaine users (> or = 10 times per month) have been observed for 2 years. Among them, 11 (10.5%) had nasal septal perforation, which is frequently related to cocaine use. Of these 11 patients, 8 (72.7%) had nasal septal perforation of the quadrangular cartilage, while in the other 3 (27.3%) the perforation involved also the bony tract (vomer-perpendicular ethmoidal lamina). Psychological analysis of these 104 patients is reported: 62 patients (59.6%) answered that they inhaled cocaine to improve endurance and to feel stronger and less tired; 34 patients (32.7%) in order to enjoy themselves more during parties and to communicate more effectively with other people; 5 patients (4.8%) to gain confidence and to overcome their shyness, 2 patients (1.9%) to improve their sexual performance and 1 patient (1%) to drink more alcoholic drinks for a longer time without feeling sleepy. All the patients underwent psychotherapeutic treatment, but the lack of compliance and constantly missing the scheduled follow-up visits resulted in complete therapy being performed in only 16 patients (15.3%). All the patients with nasal septal perforation underwent rhino-endoscopy, at T0, with 0 degrees, 45 degrees endoscopes, computed tomography scan of nose and paranasal sinuses and biopsy. At the time of the observational period, none of the 11 patients who presented nasal septal perforation agreed to stop cocaine abuse; therefore, a temporary solution has been offered to all the patients (accepted by 3 of them), i.e., the positioning of a silicone button to close the perforation and, thus, improve the air flow in the nose and reduce progression of local necrosis. Together with the button, the positioning is described, under local anaesthesia, of two layers per septal side of hyaluronic acid, at different levels of esterification, kept in site by the button as a "sandwich" in order to obtain better re-growth of the mucosa and fewer scabs and bleeding. PMID:19186454
Businco, L Di Rienzo; Lauriello, M; Marsico, C; Corbisiero, A; Cipriani, O; Tirelli, G Coen
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
Objectives To estimate the cost of providing methadone maintenance treatment in Ontario, Canada, from the perspective of the public payer. Methods We analyzed a database of all patient clinic visits, laboratory tests for urine toxicology screening, and methadone scripts from a group of methadone clinics in Ontario. The database consisted of patient visits and visit information from January 1, 2003 to December 31, 2009. We estimated the cost of providing methadone maintenance treatment as the sum of physician costs, laboratory costs for urine samples (toxicology screens), methadone costs and pharmacy costs. Pharmacy costs include dispensing fees and markups. All costs are expressed in 2010 CAD. Results The database consisted of 9479 unique patients. The average age on the date of the first recorded visit was 34.3 and 62.3% were male. There were 6,425,937 patient-days of treatment and the total cost of all treatment-related services was approximately $99,491,000. The total cost was comprised of physician billing (9.8%), pharmacy costs (39.8%), methadone (3.8%), and performing urine toxicology screens (46.7%). The average cost per day in treatment was $15.48, corresponding to $5651 per year if patients were to remain in treatment continuously. Conclusions The cost of providing methadone maintenance treatment in Ontario is comparable to estimates from the United States and Australia. Scientific Significance This information is important to policy makers for planning and budgeting purposes and as part of a full cost-benefit or cost-effectiveness analysis of methadone treatment. PMID:22783917
Zaric, Gregory S.; Brennan, Andrew W.; Varenbut, Michael; Daiter, Jeff M.
. N-Demethylation of metha- done in vitro is predominantly mediated by cytochrome P450 CYP3A4 and CYP2 interactions were not stereoselective with CYP2C19 or CYP3A4. For all three cytochromes P450, methadone N- rameters for methadone N-demethylation by recombinant CYP2B6, CYP3A4, and CYP2C19, and the potential
Steinbach, Joe Henry
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
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…
Dolan, M. P.; And Others
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
Weimer, Melissa B.; Korthuis, P. Todd; Behonick, George S.; Wunsch, Martha J.
Cocaine has high abuse liability but only a subset of individuals who experiment with it develop dependence. The DSM-IV (APA. Diagnostic and Statistical Manual of Mental Disorders DSM-IV-R. American Psychiatric Association, Washington, DC, 2000) provides criteria for diagnosing cocaine abuse and cocaine dependence as distinct disorders- the latter characterized by additional symptoms related to loss of control over drug use.
Sharon L. Walsh; Eric C. Donny; Paul A. Nuzzo; Annie Umbricht; George E. Bigelow
Imagine that the circles, called vesicles, at the top of the images are filled with molecules of dopamine, such as the arrow labeled as "1". The vesicles fuse with the axonal membrane to release the dopamine into the area called the synaptic gap. Dopamine can then activate the next axon ("6") or be recycled into the previous axon (through "5"). Cocaine blocks the channel that takes dopamine up again ("5"), so dopamine activates the next axon continuously. This can cause extreme mood swings.
N/A N/A (None; )
Drug abuse with alcohol consumption have been on the rise in Split-Dalmatian County for a while now. This article reports two separate cases with three deaths due to fatal combinations of heroin and alcohol. The first case of poisoning is related to a young couple, a 30-year-old man and a 28-year-old woman, who were found dead in a car, surrounded by cans of a variety alcoholic drinks. Two needles were found beside the bodies as well. The victims were registered drug abusers who had been in withdrawal programs. The second case was a 29-year-old man who was found dead in a house. Three fresh injection marks were visible on his right arm, and two needles were near his body. He was not known as a drug addict, but he had tried to commit suicide recently. Carboxyhaemoglobin was found in blood samples of both victims from the first case. The concentration was 25% and that could contribute to their death. In both described cases blood alcohol concentration was higher then 1.60 g kg(-1). Toxicology tests were positive for heroin, meconin, acetaminophen, 6-acetylmorphine, codeine, noscapine and papaverine. Ethanol, being a respiratory depressant, combined with morphine drastically increases the risk of rapid death due to respiration failure. PMID:17913687
Sutlovi?, Davorka; Definis-Gojanovi?, Marija
Nationally, death rates from prescription opioid pain reliever (OPR) overdoses quadrupled during 1999-2010, whereas rates from heroin overdoses increased by <50%. Individual states and cities have reported substantial increases in deaths from heroin overdose since 2010. CDC analyzed recent mortality data from 28 states to determine the scope of the heroin overdose death increase and to determine whether increases were associated with changes in OPR overdose death rates since 2010. This report summarizes the results of that analysis, which found that, from 2010 to 2012, the death rate from heroin overdose for the 28 states increased from 1.0 to 2.1 per 100,000, whereas the death rate from OPR overdose declined from 6.0 per 100,000 in 2010 to 5.6 per 100,000 in 2012. Heroin overdose death rates increased significantly for both sexes, all age groups, all census regions, and all racial/ethnic groups other than American Indians/Alaska Natives. OPR overdose mortality declined significantly among males, persons aged <45 years, persons in the South, and non-Hispanic whites. Five states had increases in the OPR death rate, seven states had decreases, and 16 states had no change. Of the 18 states with statistically reliable heroin overdose death rates (i.e., rates based on at least 20 deaths), 15 states reported increases. Decreases in OPR death rates were not associated with increases in heroin death rates. The findings indicate a need for intensified prevention efforts aimed at reducing overdose deaths from all types of opioids while recognizing the demographic differences between the heroin and OPR-using populations. Efforts to prevent expansion of the number of OPR users who might use heroin when it is available should continue. PMID:25275328
Rudd, Rose A; Paulozzi, Len J; Bauer, Michael J; Burleson, Richard W; Carlson, Rick E; Dao, Dan; Davis, James W; Dudek, Jennifer; Eichler, Beth Ann; Fernandes, Jessie C; Fondario, Anna; Gabella, Barbara; Hume, Beth; Huntamer, Theron; Kariisa, Mbabazi; Largo, Thomas W; Miles, JoAnne; Newmyer, Ashley; Nitcheva, Daniela; Perez, Beatriz E; Proescholdbell, Scott K; Sabel, Jennifer C; Skiba, Jessica; Slavova, Svetla; Stone, Kathy; Tharp, John M; Wendling, Tracy; Wright, Dagan; Zehner, Anne M
The present study describes complex drug and sexual risk in a group of male sex workers (n=79) who were recruited in the context of a larger study of young heroin users in Hanoi, Vietnam (n=1270). Male sex workers were significantly more likely than male non-sex workers to be migrants (P<0.001) and to have unstable housing (P<0.001), to have lifetime exposure to marijuana (P<0.001), 3,4 methylenedioxymethamphetamine (MDMA, ecstasy) (P<0.01), amphetamines (P<0.05), cocaine (P<0.01) and morphine (P<0.001). Male sex workers are more likely to currently use MDMA (P<0.05), amphetamines (P<0.001), morphine (P<0.05) and to ‘smoke’ as their most frequent mode of heroin administration (P<0.01). Male sex workers are more likely to have both male and female concurrent sex partners (P<0.001), to have a history of sexual victimisation (P<0.001), to have had more than three different sex partners in the past 30 days (P<0.001), and to have had partners who injected drugs before sex (P<0.001) or who used drugs during sex (P<0.01). In their last sexual encounter with a client partner, approximately one-third (31.1%) reported having had receptive anal sex. In nearly three-quarters of these exchanges (71.4%), no condom was used. Similarly, in their last sexual encounter with a client partner, 42.2% reported having had insertive anal sex and in nearly half (47.4%) of these encounters no condom was used. Consistent with recent data from elsewhere in the region, there is an urgent need for additional research on male sex work in South-east Asia in order to properly situate behavioural interventions for male sex workers in this region. PMID:18082070
Clatts, Michael C.; Giang, Le M.; Goldsamt, Lloyd A.; Yi, Huso
Cocaine use results in anhedonia during withdrawal, but it is not clear how this emotional state interacts with an individual's vulnerability for addiction. Rats selectively bred for high (HiS) or low (LoS) saccharin intake are a well-established model of drug abuse vulnerability, with HiS rats being more likely to consume sweets and drugs of abuse such as cocaine and heroin (Carroll et al., 2002) than LoS rats. This study examined whether the motivational consequences of cocaine withdrawal are differentially expressed in HiS and LoS rats. HiS and LoS rats were trained to respond for a sucrose reward on a progressive ratio (PR) schedule of reinforcement and breakpoints were measured during and after chronic, continuous exposure to cocaine (30 mg/kg/day). Cocaine, but not saline, treatment resulted in lower breakpoints for sucrose during withdrawal in LoS rats only. These results suggest anhedonia during withdrawal is more pronounced in the less vulnerable LoS rats. Fewer motivational deficits during withdrawal may contribute to greater drug vulnerability in the HiS line. PMID:25482327
Radke, Anna K; Zlebnik, Natalie E; Carroll, Marilyn E
In the absence of any effective pharmacotherapy for cocaine addiction, immunotherapy is being actively pursued as a therapeutic intervention. While several different cocaine haptens have been explored to develop anticocaine antibodies, none of the hapten was successfully designed, which had a protonated tropane nitrogen as is found in native cocaine under physiological conditions, including the succinyl norcocaine (SNC) hapten that has been tested in phase II clinical trials. Herein, we discuss three different cocaine haptens: hexyl norcocaine (HNC), bromoacetamido butyl norcocaine (BNC), and succinyl butyl norcocaine (SBNC), each with a tertiary nitrogen structure mimicking that of native cocaine which could optimize the specificity of anticocaine antibodies for better cocaine recognition. Mice immunized with these haptens conjugated to immunogenic proteins produced high titre anticocaine antibodies. However, during chemical conjugation of HNC and BNC haptens to carrier proteins, the 2? methyl ester group is hydrolyzed, and immunizing mice with these conjugate vaccines in mice produced antibodies that bound both cocaine and the inactive benzoylecgonine metabolite. While in the case of the SBNC conjugate, vaccine hydrolysis of the methyl ester did not appear to occur, leading to antibodies with high specificity to cocaine over BE. Although we observed similar specificity with a SNC hapten, the striking difference is that SBNC carries a positive charge on the tropane nitrogen atom, and therefore, it is expected to have better binding of cocaine. The 50% cocaine inhibitory concentration (IC50 ) value for SBNC antibodies (2.8 ?m) was significantly better than the SNC antibodies (9.4 ?m) when respective hapten-BSA was used as a substrate. In addition, antibodies from both sera had no inhibitory effect from BE. In contrast to BNC and HNC, the SBNC conjugate was also found to be highly stable without any noticeable hydrolysis for several months at 4 °C and 2-3 days in pH 10 buffer at 37 °C. PMID:24803171
Ramakrishnan, Muthu; Kinsey, Berma M; Singh, Rana A; Kosten, Thomas R; Orson, Frank M
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. PMID:20190634
Letsky, Michael C; Zumwalt, Ross E; Seifert, Steven A; Benson, Blaine E
Genetic deletion of the neurokinin 1 receptor (NK1R) has been shown to decrease the reinforcing properties of opioids, but it is unknown whether pharmacological NK1R blockade has the same effect. Here, we examined the effect of L822429, a rat-specific NK1R antagonist, on the reinforcing properties of heroin in rats on short (1?h: ShA) or long (12?h: LgA) access to intravenous heroin self-administration. ShA produces heroin self-administration rates that are stable over time, whereas LgA leads to an escalation of heroin intake thought to model important dependence-related aspects of addiction. L822429 reduced heroin self-administration and the motivation to consume heroin, measured using a progressive-ratio schedule, in both ShA and LgA rats. L822429 also decreased anxiety-like behavior in both groups, measured on the elevated plus maze, but did not affect mechanical hypersensitivity observed in LgA rats. Expression of TacR1 (the gene encoding NK1R) was decreased in reward- and stress-related brain areas both in ShA and LgA rats compared with heroin-naïve rats, but did not differ between the two heroin-experienced groups. In contrast, passive exposure to heroin produced increases in TacR1 expression in the prefrontal cortex and nucleus accumbens. Taken together, these results show that pharmacological NK1R blockade attenuates heroin reinforcement. The observation that animals with ShA and LgA to heroin were similarly affected by L822429 indicates that the SP/NK1R system is not specifically involved in neuroadaptations that underlie escalation resulting from LgA self-administration. Instead, the NK1R antagonist appears to attenuate acute, positively reinforcing properties of heroin and may be useful as an adjunct to relapse prevention in detoxified opioid-dependent subjects. PMID:23303056
Barbier, Estelle; Vendruscolo, Leandro F; Schlosburg, Joel E; Edwards, Scott; Juergens, Nathan; Park, Paula E; Misra, Kaushik K; Cheng, Kejun; Rice, Kenner C; Schank, Jesse; Schulteis, Gery; Koob, George F; Heilig, Markus
Cocaine abuse is associated with a variety of severe acute neurologic complications typically occurring in the abusers themselves. These include ischemic stroke, subarachnoid and intraparenchymal hemorrhage, headaches, syncope, seizures, and death. Sixteen pediatric patients with presumed cocaine-related seizures secondary to maternal consumption are reported. They were evaluated only because of requests for neurologic consultation. All were seen during the 1987
Lynn D. Kramer; George E. Locke; Abayomi Ogunyemi; Lowell Nelson
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. 74.8days, 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
Kidorf, Michael; King, Van L; Peirce, Jessica; Gandotra, Neeraj; Ghazarian, Sharon; Brooner, Robert K
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 implementation. PMID:23251580
Tran, Bach Xuan; Ohinmaa, Arto; Mills, Steve; Duong, Anh Thuy; Nguyen, Long Thanh; Jacobs, Philip; Houston, Stan
Heroin overdose deaths have increased alarmingly in Chicago over the past decade. Naloxone, an opioid antagonist with no abuse potential, has been used to reverse opiate overdose in emergency medical settings for decades. We describe here a program to educate opiate users in the prevention of opiate overdose and its reversal with intramuscular naloxone. Participant education and naloxone prescription are accomplished within a large comprehensive harm reduction program network. Since institution of the program in January 2001, more than 3,500 10 ml (0.4 mg/ml) vials of naloxone have been prescribed and 319 reports of peer reversals received. The Medical Examiner of Cook County reported a steady increase in heroin overdose deaths since 1991, with a four-fold increase between 1996 and 2000. This trend reversed in 2001, with a 20% decrease in 2001 and 10% decreases in 2002 and 2003. PMID:16956873
Maxwell, Sarz; Bigg, Dan; Stanczykiewicz, Karen; Carlberg-Racich, Suzanne
Immunization with a phosphonate monoester transition-state analog of cocaine provided monoclonal antibodies capable of catalyzing the hydrolysis of the cocaine benzoyl ester group. An assay for the degradation of radiolabeled cocaine identified active enzymes. Benzoyl esterolysis yields ecgonine methyl ester and benzoic acid, fragments devoid of cocaine's stimulant activity. Passive immunization with such an artificial enzyme could provide a treatment
Donald W. Landry; Kang Zhao; Ginger X.-Q. Yang; Michael Glickman; Taxiarchis M. Georgiadis
This article uses cross-country data to estimate the potential effect of drastic reductions in the price of cocaine on the share of the population that consumes this drug. In order to identify movements along the cocaine consumption\\/demand function, this article instruments for cocaine prices with variables that affect the supply of cocaine. Liberalization of drug policies would produce an increase
Norman V. Loayza; Naotaka Sugawara
abuse treatment, medical care, and AIDS medications may beMedication coaching Voucher administration Long-term methadone Detoxi?cation methadone Residential substance abuseMedication coach visits Voucher dispensing visits Long-term methadone (days) Detoxi?cation methadone (days) Residential substance abuse
Barnett, Paul G; Sorensen, James L; Wong, Wynnie; Haug, Nancy A; Hall, Sharon M
Cocaine covalently modifies proteins through a reaction in which the methyl ester of cocaine acylates the -amino group of lysine residues. This reaction is highly specific in vitro, because no other amino acid reacts with cocaine, and only cocaine's methyl ester reacts with the lysine side chain. Covalently modified proteins were present in the plasma of rats and human subjects chronically exposed to cocaine. Modified endogenous proteins are immunogenic, and specific antibodies were elicited in mouse and detected in the plasma of human subjects. Covalent modification of proteins could explain cocaine's autoimmune effects and provide a new biochemical approach to cocaine's long-term actions.
Deng, Shi-Xian; Bharat, Narine; Fischman, Marian C.; Landry, Donald W.
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 ?6months. The primary outcome of BMI was assessed at intake and a subsequent physical examination approximately 1.8±0.95years 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±7.7kg/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. 1.7kg/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. PMID:25441923
Fenn, Jennifer M; Laurent, Jennifer S; Sigmon, Stacey C
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 $1,470 (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. PMID:24239030
Schwartz, Robert P.; Alexandre, Pierre K.; Kelly, Sharon M.; O’Grady, Kevin E.; Gryczynski, Jan; Jaffe, Jerome H.
? Abstract There is increasing interest in the use of oral fluids for detection of drugs of abuse in the workplace and as a possible substitute for blood in driving under the influence cases. Oral fluids often have higher concentrations of parent drugs that are detectable for longer periods of time than in urine and blood. This increased window of
Dean F. Fritch; Keith Kardos; R. Sam Niedbala; Greg Newland; Nadine Koenig; Paul Davis; Joann Sell
Studies in humans suggest that exposure to stress increases the probability of relapse to drug use, but until recently there has been no animal model to study the mechanisms that mediate this effect. We have developed a reinstatement procedure that allows us to study the effect of stress on relapse to drug seeking in rats. Using this procedure, we have
Yavin Shaham; Suzanne Erb; Jane Stewart
Profound thrombocytopenia developed in a 22-year-old man after intravenous use of heroin. A high-titer, quinine-dependent, platelet-specific antibody was detected in his serum using lysis of normal platelets labeled with chromium 51 and an electroimmunoassay for measurement of platelet-associated IgG. The antibody was specific for quinine and failed to react with platelets in the presence of quinidine hydrochloride or two structural analogues of heroin. Quinine, a common adulterant found in heroin, was detected in the patient's blood and urine. On the basis of these observations, the patient was judged to have quinine-induced immunologic thrombocytopenia. To our knowledge, this report is the first to confirm that quinine used as an adulterant can induce immunologic thrombocytopenia following an injection of heroin.
Christie, D.J.; Walker, R.H.; Kolins, M.D.; Wilner, F.M.; Aster, R.H.
Abstract A painful petechial rash developed in a patient after the subcutaneous or intravenous injection of reported black tar heroin. Additional history and the appearance of the skin lesion suggested otherwise. PMID:25597468
Hendrickson, R G
This study documents the costs of heroin addiction in the United States, both to the addict and society at large. Using a cost-of-illness approach, costs were estimated in four broad areas: medical care, lost productivity, crime, and social welfare. We estimate that the cost of heroin addiction in the United States was US$21.9 billion in 1996. Of these costs, productivity
Tami L Mark; George E Woody; Tim Juday; Herbert D Kleber
Aims To determine death rates from methadone over time, to characterize methadone-related death and to discuss public health surveillance of methadone-related death. Design We analyzed medical examiner data for all unintentional drug over- dose deaths in New Mexico, USA, between 1998 and 2002. Measurements Age-adjusted death rates for methadone-related death, logis- tic regression models for likelihood of methadone-related death among
Nina Shah; Sarah L. Lathrop; Michael G. Landen
The consumption of psychoactive substances during pregnancy has a negative impact on fetal growth. Heroin, methadone, and heavy alcohol consumption during pregnancy are associated with lower birth weight and central nervous system (C NS) dysfunction. Recent evidence suggests that marijuana use also may be associated with lower birth weight No information documents the impact of cocaine use on fetal outcome.
Increasingly invertebrates are being used to investigate the molecular and cellular effects of drugs of abuse to explore basic mechanisms of addiction. However, in mammals the principle factors contributing to addiction are long-term adaptive responses to repeated drug use. Here we examined whether adaptive responses to cocaine are also seen in invertebrates using the honey bee model system. Repeated topical treatment with a low dose of cocaine rendered bees resistant to the deleterious motor effects of a higher cocaine dose, indicating the development of physiological tolerance to cocaine in bees. Cocaine inhibits biogenic amine reuptake transporters, but neither acute nor repeated cocaine treatments caused measurable changes in levels of biogenic amines measured in whole bee brains. Our data show clear short and long-term behavioural responses of bees to cocaine administration, but caution that, despite the small size of the bee brain, measures of biogenic amines conducted at the whole-brain level may not reveal neurochemical effects of the drug. PMID:23741423
Søvik, Eirik; Cornish, Jennifer L.; Barron, Andrew B.
The subjective and objective sleep patterns of patients with opioid dependence have been previously reported, but the sleep characteristics of patients in early methadone treatment, especially the objective sleep patterns, remain largely unexamined. This study was designed to explore the nocturnal sleep structure of patients on early methadone treatment. Twenty male methadone treatment (MT) patients and 20 male age- and body mass index-matched controls were assessed with overnight limited polysomnography. Subjective sleep was assessed using the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS). Compared with healthy controls, MT patients had lower sleep efficiency, shorter total sleep time, more awakenings and shorter slow wave sleep (SWS). The PSQI and ESS scores in MT patients were significantly higher than in the controls. ESS scores of the patients were significantly associated with the SWS. The findings indicate that patients in early MT have poor sleep quality and abnormal sleep architecture. PMID:20483171
Xiao, Le; Tang, Yi-lang; Smith, Alicia K; Xiang, Yu-tao; Sheng, Li-xia; Chi, Yong; Du, Wan-jun; Guo, Song; Jiang, Zuo-ning; Zhang, Guo-fu; Luo, Xiao-nian
The aim of this qualitative study was to examine the narratives of people who experience chronic pain (lasting 6 months or more) and were receiving methadone for the treatment of their opiate addiction through a major methadone clinic. This paper featured the pathway of how the participants developed chronic pain and addiction, and their beliefs of how prescription opioids would impact their addiction in the future. Thirty-four participants who experienced chronic pain and received methadone for treatment of opiate addiction were willing to tell the story of their experiences. The findings in three areas are presented: (a) whether participants experienced addiction first or pain first and how their exposures to addictive substances influenced their experiences, (b) the significance of recreational drug use and patterns of abuse behaviors leading to chronic pain, and (c) participants’ experiences and beliefs about the potential for abuse of prescription opioid used for treatment of pain. PMID:23858068
St. Marie, Barbara
At a Detroit research program from 2004 to 2005, out-of-treatment chronic daily heroin users (N = 100) were interviewed to evaluate relationships between past 30-day income and factors influencing heroin price, expenditures, and consumption. Weekly heroin purchasing frequency was positively related to income and number of suppliers, and negatively related to time cost (min) from primary supplier. Daily heroin consumption was positively related to income and injection heroin use, and negatively related to unit cost of heroin. Implications and limitations are noted. Simulations are underway to assess within-subject changes in drug demand. PMID:19938929
Roddy, Juliette; Greenwald, Mark
and Cocaine: Fatal Attraction? Cristina Gonzales, PharmD PGY1 Pharmacy. Discuss the historic use of -blockade in cocaine toxicity 2. List the adverse effects related to cocaine use 3. Discuss the management of cocaine-associated chest
Abstract Recently, Willuhn et al. reported that cocaine use and even non-substance-related addictive behavior increases as dopaminergic function is reduced. Chronic cocaine exposure has been associated with decreases in D2/D3 receptors and was also associated with lower activation of cues in occipital cortex and cerebellum, in a recent PET study by Volkow's et al. Therefore, treatment strategies, like dopamine agonist therapy, that might conserve dopamine function may be an interesting approach to relapse prevention in psychoactive drug and behavioral addictions. To this aim, we evaluated the effect of KB220Z™ on reward circuitry of 10 heroin addicts undergoing protracted abstinence (average 16.9 months). In a randomized placebo-controlled crossover study of KB220Z, five subjects completed a triple-blinded experiment in which the subject, the person administering the treatment, and the person evaluating the response to treatment were blinded to the treatment that any particular subject was receiving. In addition, nine subjects were genotyped utilizing the GARSDX™ test. We preliminarily report that KB220Z induced an increase in BOLD activation in caudate-accumbens-dopaminergic pathways compared to placebo following 1-hour acute administration. Furthermore, KB220Z also reduced resting-state activity in the putamen of abstinent heroin addicts. In the second phase of this pilot study of all 10 abstinent heroin-dependent subjects, we observed that three brain regions of interest were significantly activated from resting state by KB220Z compared to placebo (p < 0.05). Increased functional connectivity was observed in a putative network that included the dorsal anterior cingulate, medial frontal gyrus, nucleus accumbens, posterior cingulate, occipital cortical areas, and cerebellum. These results and other quantitative electroencephalogy (qEEG) study results suggest a putative anti-craving/anti-relapse role of KB220Z in addiction by direct or indirect dopaminergic interaction. Due to small sample size, we caution definitive interpretation of these preliminary results, and confirmation with additional research and ongoing rodent and human studies of KB220Z is required. PMID:25526228
Blum, Kenneth; Liu, Yijun; Wang, Wei; Wang, Yarong; Zhang, Yi; Oscar-Berman, Marlene; Smolen, Andrew; Febo, Marcelo; Han, David; Simpatico, Thomas; Cronjé, Frans J; Demetrovics, Zsolt; Gold, Mark S
Stress is considered to be one of the major triggers to drug relapse, even after prolonged periods of abstinence. In rats, the activation of stress-related brain systems, including corticotropin-releasing factor and norepinephrine, is critical for stress-induced reinstatement of extinguished drug seeking, an animal model for drug relapse. In addition, there are strong indications that activation of the endogenous opioid system is important for the effects of stress on drug seeking. More specifically, activation of the dynorphin/kappa opioid receptor (KOR) system is critically involved in the reinstatement of cocaine seeking following exposure to stressors, such as footshock, forced swimming or social stress. However, studies on the role of the dynorphin/KOR system in stress-induced reinstatement of heroin seeking are scarce. Here, rats were trained to self-administer heroin (0.1?mg/kg/infusion) for 10 days. Drug seeking was then extinguished and the rats were tested for acute (21 hours) food deprivation-induced reinstatement of heroin seeking. In two separate experiments, rats were injected with the mu-opioid receptor (MOR) antagonist, naltrexone (0.0, 1.0, 10.0?mg/kg; s.c.) or the KOR antagonist, norBNI (0.0, 1.0, 10.0?mg/kg; i.p.) before the reinstatement test. Naltrexone treatment did not affect stress-induced reinstatement. In contrast, treatment with norBNI dose-dependently attenuated food deprivation-induced reinstatement of heroin seeking. These results support the hypothesis that activation of KOR, but not MOR, is critically involved in stress-induced reinstatement of drug seeking. PMID:24725195
Sedki, Firas; Eigenmann, Karine; Gelinas, Jessica; Schouela, Nicholas; Courchesne, Shannon; Shalev, Uri
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. PMID:17114567
Ko, Mei-Chuan; Bowen, Luvina D; Narasimhan, Diwahar; Berlin, Aaron A; Lukacs, Nicholas W; Sunahara, Roger K; Cooper, Ziva D; Woods, James H
The ability to measure concentrations of cocaine in body fluids can contribute substantially to any investigation of cocaine's pharmacological effects. Design of research which involves the administration of cocaine must take into account current knowledge regarding the drug's pharmacokinetics. Cocaine's very rapid elimination from the body should be considered in attempting to understand patterns of cocaine abuse, and such phenomena as bingeing and acute tolerance. Accurate analysis of cocaine and/or its metabolites is essential to the diagnosis and evaluation of cocaine use whether for medical or forensic purposes. Appropriate selection of methods for analysis of cocaine depends upon the intended purpose of the assay, and correct interpretation of the data obtained upon knowledge of cocaine's kinetics and metabolic disposition. PMID:3043924
Cocaine, a potent addictive substance, is an inhibitor of monoamine transporters, including DAT (dopamine transporter), SERT (serotonin transporter) and NET (norepinephrine transporter). Cocaine administration induces complex behavioral alterations in mammals, but the underlying mechanisms are not well understood. Here, we tested the effect of cocaine on C. elegans behavior. We show for the first time that acute cocaine treatment evokes changes in C. elegans locomotor activity. Interestingly, the neurotransmitter serotonin, rather than dopamine, is required for cocaine response in C. elegans.TheC. elegans SERT MOD-5 is essential for the effect of cocaine, consistent with the role of cocaine in targeting monoamine transporters. We further show that the behavioral response to cocaine is primarily mediated by the ionotropic serotonin receptor MOD-1. Thus, cocaine modulates locomotion behavior in C. elegans primarily by impinging on its serotoninergic system.
Alex Ward; Vyvyca J. Walker; Zhaoyang Feng; X. Z. Shawn Xu
Background The Ministry of Health, Treatment and Medical Education of Iran has recently announced an estimated figure of 200,000 injecting drug users (IDUs). The aim of this study was to pilot a national program using demographics, types of drug abuse and prevalence of blood-borne infections among IDUs. Methods: In order to elicit data on demographics, types of drug abuse and prevalence of blood-borne infections among IDUs, a questionnaire was designed in the Bureau of Mental-Social Health and Addiction in collaboration with Iran’s Drug Control Headquarters of the Police Department. Therapeutical alliance of addiction in Shafagh Center was based on Methadone Maintenance Therapy (MMT). Results: Among 402 reported IDUs most of them were male, single and in age range of 20 to 39 years old with 72.7% history of imprisonment. Most of them had elementary and high school education and a history of addiction treatment. The majority were current users of opioid, heroin and crack. The prevalence of blood-borne infections was 65.9% and 18.8% for HCV and HIV/AIDS infections, respectively. Conclusion: Prevention programs about harm reduction, treatment and counseling should include young IDUs as a core focus of their intervention structure. PMID:23967426
ESKANDARIEH, Sharareh; NIKFARJAM, Ali; TARJOMAN, Termeh; NASEHI, Abassali; JAFARI, Firoozeh; SABERI-ZAFARGHANDI, Mohammad-Bagher
Individuals with current cocaine use disorders (CUD) form a heterogeneous group, making sensitive neuropsychological (NP) comparisons with healthy individuals difficult. The current study examined the effects on NP functioning of four factors that commonly vary among CUD: urine status for cocaine (positive vs negative on study day), cigarette smoking, alcohol consumption, and dysphoria. Sixty-four cocaine abusers were matched to healthy comparison subjects on gender and race; the groups also did not differ in measures of general intellectual functioning. All subjects were administered an extensive NP battery measuring attention, executive function, memory, facial and emotion recognition, and motor function. Compared with healthy control subjects, CUD exhibited performance deficits on tasks of attention, executive function, and verbal memory (within one standard deviation of controls). Although CUD with positive urine status, who had higher frequency and more recent cocaine use, reported greater symptoms of dysphoria, these cognitive deficits were most pronounced in the CUD with negative urine status. Cigarette smoking, frequency of alcohol consumption, and dysphoria did not alter these results. The current findings replicate a previously reported statistically significant, but relatively mild NP impairment in CUD as compared with matched healthy control individuals and further suggest that frequent/recent cocaine may mask underlying cognitive (but not mood) disturbances. These results call for development of pharmacological agents targeted to enhance cognition, without negatively impacting mood in individuals addicted to cocaine. PMID:18496524
Woicik, Patricia A; Moeller, Scott J; Alia-Klein, Nelly; Maloney, Thomas; Lukasik, Tanya M; Yeliosof, Olga; Wang, Gene-Jack; Volkow, Nora D; Goldstein, Rita Z
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.…
Substance Abuse and Mental Health Services Administration, 2005
Up to now, many different methods have been developed for detection of cocaine, but most of these methods are usually time-consuming, tedious and require special or expensive equipment. Therefore, the development of simple, sensitive and rapid detection methods is necessary. In the last decade, aptamers have been used as a new biosensor platform for detection of cocaine in different samples. Aptamers are artificial single-stranded DNA or RNA oligonucleotides capable of binding to specific molecular targets with high affinity and if integrated to nanomaterials, it may lead in precise methods for cocaine detection in the common laboratories. In this review, recent advances and applications of aptamer-based biosensors and nanobiosensors, have been updated, paying attention to the use of fluorescence, colorimetric and electrochemical techniques for the detection and quantitative determination of cocaine. PMID:25562736
Mokhtarzadeh, Ahad; Dolatabadi, Jafar Ezzati Nazhad; Abnous, Khalil; de la Guardia, Miguel; Ramezani, Mohammad
Ninety-eight of 945 patients admitted to Hennepin County Medical Center with acute medical complications of cocaine intoxication presented with seizures within 90 min of cocaine ingestion. Cocaine-related seizures were most frequently single, generalized convulsions, and these individuals all had normal cranial CT and EEG. Of the 945 patients, 18.4% of the women presented with seizures, compared with only 6.2% of the men. All subjects who presented with new onset focal seizures following cocaine ingestion had acute cocaine-related cerebral strokes or hemorrhages. Individuals with a history of cocaine-unrelated seizures, had their typical convulsions precipitated with "recreational" doses of cocaine. All four subjects with status epilepticus had ingested massive doses of cocaine, were resistant to medical treatment, and had significant morbidity and mortality. We were able to characterize four subgroups of subjects at risk for cocaine-related convulsions. First, individuals who had ingested massive doses of cocaine (2-8 gms) in whom cocaine induced seizures by its direct, dose-related convulsant effects. Second, individuals with a history of epilepsy had their typical seizures precipitated by lowering the seizure threshold. Third, females are at greater risk for cocaine-related compared to males. Fourth, years of chronic, habitual cocaine abuse may result in "chemical" kindling of epilepsy. PMID:1745445
Dhuna, A; Pascual-Leone, A; Langendorf, F; Anderson, D C
The Antisocial personality disorder (ASPD), one of the most common co-morbid psychiatric disorders in heroin-dependent patients, is associated with a lack of affective modulation. The present study aimed to compare the affect-modulated startle responses of opioid-maintained heroin-dependent patients with and without ASPD relative to those of healthy controls. Sixty participants (20 heroin-dependent patients with ASPD, 20 heroin-dependent patients without ASPD,
Marc Walter; Bigna Degen; Constanze Treugut; Jürgen Albrich; Monika Oppel; André Schulz; Hartmut Schächinger; Kenneth M. Dürsteler-MacFarland; Gerhard A. Wiesbeck
In humans, exposure to cues previously associated with heroin use often provokes relapse after prolonged withdrawal periods. In rats, cue-induced heroin-seeking progressively increases after withdrawal (incubation of heroin craving). Here, we examined the role of orbitofrontal cortex (OFC) neuronal ensembles in the enhanced response to heroin cues after prolonged withdrawal or the expression of incubation of heroin craving. We trained rats to self-administer heroin (6-h/d for 10 d) and assessed cue-induced heroin-seeking in extinction tests after 1 or 14 withdrawal days. Cue-induced heroin-seeking increased from 1 day to 14 days and was accompanied by increased Fos expression in ~12% of OFC neurons. Non-selective inactivation of OFC neurons with the GABA agonists baclofen+muscimol decreased cue-induced heroin-seeking on withdrawal day 14 but not day 1. We then used the Daun02 inactivation procedure to assess a causal role of the minority of selectively activated Fos-expressing OFC neurons (that presumably form cue-encoding neuronal ensembles) in cue-induced heroin-seeking after 14 withdrawal days. We trained cfos-lacZ transgenic rats to self-administer heroin and 11 days later re-exposed them to heroin-associated cues or novel cues for 15 min (induction day) followed by OFC Daun02 or vehicle injections 90 min later; we then tested the rats in extinction tests 3 days later. Daun02 selectively decreased cue-induced heroin-seeking in rats previously re-exposed to the heroin-associated cues on induction day, but not in rats previously exposed to novel cues. Results suggest that heroin-cue-activated OFC neuronal ensembles contribute to the expression of incubation of heroin craving. PMID:22915104
Fanous, Sanya; Goldart, Evan M.; Theberge, Florence R.M.; Bossert, Jennifer M.; Shaham, Yavin; Hope, Bruce T.
of Statistics The University of Adelaide Australia 5005 Address for correspondence: P. J. Solomon, Department of Statistics, The University of Adelaide, South Australia 5005, Australia email : psolomon the South Australian Methadone Program. Injecting drug users may have several entries to and exits from
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
Kelly E. Dunn; Stacey C. Sigmon; Mark R. McGee; Sarah H. Heil; Stephen T. Higgins
A review of studies on counseling with methadone clients affirmed the importance of counseling services. Support was found for analytic therapy, T-group therapy, behavioral training, reality therapy, and family therapy. There was evidence of client resistance to group therapy. (Author)
Powers, Robert J.; Powers, Henrietta B.
Introduction: Medical associations and licensing bodies face pressure to implement quality assurance programs, but evidence-based models are lacking. To improve the quality of methadone maintenance treatment (MMT), the College of Physicians and Surgeons of Ontario, Canada, conducts an innovative quality assurance program on the basis of peer…
Strike, Carol; Wenghofer, Elizabeth; Gnam, William; Hillier, Wade; Veldhuizen, Scott; Millson, Margaret
A chronic pain patient prescribed 20 mg of methadone per day was seen at the Emergency Department within one hour following a witnessed intentional 200 mg ingestion. In addition, he was taking the serotonin re-uptake inhibitor antidepressant drugs, sertraline and venlafaxine as prescribed. Methadone is also a serotonin re-uptake inhibitor which has been involved in serotonin toxicity reactions. Initially, no symptoms of narcotic overdose (depressed central nervous system, respiration, or blood pressure) could be distinguished, and the standard narcotic urine screen was negative. No decontamination or antagonist therapy was given, and the patient was discharged to a psychiatric unit for observation. At 5 hours post-ingestion he presented in a panic with hallucinations and elevated blood pressure, pulse, and respiration. These symptoms are characteristic of serotonin syndrome which is often described as mental status changes, autonomic hyperactivity, and neuromuscular abnormalities. At 10 hours post-ingestion the patient was found unconscious. He had aspirated stomach contents into his lungs. His respiration, blood pressure, and pulse were all severely depressed. He never regained conciousness, and he died 5 days later. The medical examiner's finding was probable acute methadone intoxication. In this case serotonin syndrome appears to have opposed and delayed typical narcotic symptoms. Methadone has additional pharmacologic and toxicologic properties which may complicate the assessment and treatment in overdose situations. PMID:19544673
Martinez, Terry T; Martinez, Daniel N
This report concerns a case of torsades de pointes (TdP) associated with the concomitant administration of methadone and voriconazole in a patient with comorbid medical conditions. A 57-year-old man, with a medical history of human immunodeficiency virus, infective endocarditis, hepatitis C and orbital Aspergillus infection, was admitted to the intensive care unit following several episodes of TdP. The patient was being treated with methadone for opioid addiction and had started taking voriconazole 2 weeks prior for orbital Aspergillosis. He experienced multiple episodes of TdP with a prolonged QTc interval (>600 ms). The pronounced inhibitory impact of voriconazole on methadone metabolism via the cytochrome P450 (CYP)2B6 isoenzyme was identified as a probable cause of the arrhythmia. Voriconazole was subsequently temporarily withheld and the methadone dose was significantly reduced. The patient received an implantable cardioverter-defibrillator, did not experience additional episodes of TdP during hospitalisation, and was discharged from the hospital on day 13. PMID:22190985
Reinhold, Jennifer A; Sanoski, Cynthia A; Russo, Andrea M; Cooper, Joshua M; Spinler, Sarah A
An innovative employment counseling model, Customized Employment Supports, was developed for methadone-treatment patients, a population with historically low employment rates. The effectiveness of a key component of the model, "vocational fieldwork," the delivery of services in the community rather than only within the clinic, was assessed through…
Blankertz, Laura; Spinelli, Michael; Magura, Stephen; Bali, Priti; Madison, Elizabeth M.; Staines, Graham L.; Horowitz, Emily; Guarino, Honoria; Grandy, Audrey; Fong, Chunki; Gomez, Augustin; Dimun, Amy; Friedman, Ellen
This pretest/posttest study used two samples of injecting drug users (184 from street outreach and 103 from a methadone program) to assess drug use and human immunodeficiency virus risk practices. The improvement in risk behaviors at posttest suggests that intervention programs were agents of change. (SLD)
Wechsberg, Wendee M.; And Others
A cost analysis is presented for developing a training and employment (TEP) program at four methadone treatment centers in a quasi-experimental pilot study. Average annual costs for TEP per client were derived. The methodology can be used in other projects to compare standard and TEP-enhanced substance-abuse treatment. (SLD)
French, Michael T.; And Others
In this paper the nature, scope, and drug relatedness of violent events reported by a sample of methadone maintenance treatment clients is examined and compared with events reported by a sample of drug abusers not in treatment. The drug relatedness of events is ascertained according to a tripartite model of the drugs-violence relationship. Data derive from a study of the
Barry J. Spunt; Paul J. Goldstein; Patricia A. Bellucci; Thomas Miller
Motivated attention to cocaine and emotional cues in abstinent and current cocaine users Â an ERP National Institute on Drug Abuse, Bethesda, MD, USA Keywords: cocaine addiction, emotional processing (LPP) appears to be enhanced following cocaine-related compared with neutral stimuli in human
Homes, Christopher C.
Reduced Metabolism in Brain ``Control Networks'' following Cocaine-Cues Exposure in Female Cocaine States of America Abstract Objective: Gender differences in vulnerability for cocaine addiction have been brain metabolism (using PET and 18 FDG) between female (n = 10) and male (n = 16) active cocaine abusers
Homes, Christopher C.
The effects of cocaine were examined prior to and during bupropion maintenance in nonopioid-dependent cocaine abusers. Prior to bupropion maintenance, subjects underwent an experimental session during which repeated cocaine doses (0, 50, 100 mg\\/70 kg) were administered intranasally. Then subjects were maintained on bupropion (150 and 300 mg per day) and underwent experimental sessions as before. Cocaine, regardless of bupropion,
Alison Oliveto; F. Elinore McCance-Katz; Amrita Singha; Ismene Petrakis; Faiq Hameedi; Thomas R Kosten
Sixteen trace elements found in 309 street heroin samples, piped water and contaminated water were determined using inductively coupled plasma-mass spectrometry. All the street heroin samples were found to contain high levels of sodium, a reflection of the use of sodium bicarbonate during heroin synthesis. Additionally, this element was also found to be one of the potential contaminants acquired from the piped water. Calcium could be derived from lime while iron, aluminum and zinc could have come from the metallic container used in the processing/cutting stage. The levels of these elements remained low in the heroin and it could be due to the dilution effects from the addition of adulterants. Statistical validation was performed with six links of related heroin samples using principal component analysis to find the best pretreatment for sample classification. It was obtained that normalization followed by fourth root showed promising results with 8% errors in the sample clustering. The technique was then applied to the case samples. Finally, the result suggested that the case samples could have originated from at least two major groups respectively showing unique elemental profiles at the street level. PMID:23380066
Chan, Kar-Weng; Tan, Guan-Huat; Wong, Richard C S
Heroin is an illicit narcotic abused by millions of people worldwide. In our earlier studies we have shown that heroin intoxication changes the antioxidant status in human brain. In the present work we continued our studies by estimating the effect of heroin abuse on reduced glutathione (GSH) and enzymes related to this cofactor, such as glutathione S-transferase detoxifying electrophilics (GST)
Marzena Gutowicz; Beata Ka?mierczak; Anna Bara?czyk-Ku?ma
Children born to heroin-dependent mothers (n=83) were compared to 76 children born to heroin-dependent fathers and to 3 control groups with and without environmental deprivation and health problems. Results found that developmental delays and behavioral disorders found among heroin-exposed children resulted primarily from severe environmental…
Ornoy, Asher; And Others
Abstract Problem In Malaysia, human immunodeficiency virus (HIV) infection is highly concentrated among people who inject opioids. For this reason, the country undertook a three-phase roll-out of a methadone maintenance treatment (MMT) programme. In Phase 3, described in this paper, MMT was implemented within prisons and retention in care was assessed. Approach After developing standard operating procedures and agreement between its Prisons Department and Ministry of Health, Malaysia established pilot MMT programmes in two prisons in the states of Kelantan (2008) and Selangor (2009) – those with the highest proportions of HIV-infected prisoners. Community-based MMT programmes were also established in Malaysia to integrate treatment activities after prisoners’ release. Local setting Having failed to reduce the incidence of HIV infection, in 2005 Malaysia embarked on a harm reduction strategy. Relevant changes Standard operating procedures were modified to: (i) escalate the dose of methadone more slowly; (ii) provide ongoing education and training for medical and correctional staff and inmates; (iii) increase the duration of methadone treatment before releasing prisoners; (iv) reinforce linkages with community MMT programmes after prisoners’ release; (v) screen for and treat tuberculosis; (vi) escalate the dose of methadone during treatment for HIV infection and tuberculosis; and (vii) optimize the daily oral dose of methadone (>?80 mg) before releasing prisoners. Lessons learnt Prison-based MMT programmes can be effectively implemented but require adequate dosing and measures are needed to improve communication between prison and police authorities, prevent police harassment of MMT clients after their release, and improve systems for tracking release dates. PMID:23554524
Wickersham, Jeffrey A; Marcus, Ruthanne; Kamarulzaman, Adeeba; Zahari, Muhammad Muhsin
Background In general, information about women who use drugs comes from studies performed in the West. Whether women in countries such as Iran are likely to enter drug treatment or how they will respond is not known. Purpose To examine the short-term impact of methadone maintenance treatment (MMT) on drug use, dependence, social functioning, crime, and human immunodeficiency virus (HIV) and hepatitis C virus (HCV) risk behavior and seroincidence in female drug users in Iran. Methods Women were eligible for inclusion in the study if they were assessed as dependent on opiates according to the International Statistical Classification of Diseases and Related Health Problems, tenth revision (ICD-10). The sample comprised 78 female heroin or opium users who attended the Persepolis women’s drug treatment clinic in Tehran between 2007 and 2008. Participants were followed up in 2009/2010. Heroin and the use of other drugs, social functioning, involvement in crime, and involvement in HIV and HCV risk behavior were measured by self-report. The prevalence and incidence of HIV and HCV were measured by serology and self-report. Findings Of the 78 women recruited, 40 were followed up, and this occurred approximately 7 months later. One in four women reported a history of drug injection. At follow-up there were significant reductions in self-reported heroin use on ICD-10 dependence scores. Subjects with more severe drug dependence at baseline were significantly more likely to be criminally active than less severely dependent subjects. Baseline prevalence for HIV and HCV was 5% and 24%, respectively. At follow-up, no one had acquired HIV infection, but one participant had acquired HCV, giving an incidence rate of 7.1 per 100 person-years. Conclusion This research provides the first evidence that Iranian female drug users can enter MMT and respond well. Within a few months of entering MMT, improvements occurred in heroin use, levels of dependence, social functioning, and HIV risk behavior. While the incidence of blood-borne viral infections was low, there was a serious risk of HIV transmission among this cohort and also to participants’ needle and sexual contacts. In a country with high levels of drug use, the high levels of HCV among female drug users require more women to enter drug treatment if an HIV epidemic is to be avoided. Many participants had a chronic drug problem and had had little or no previous exposure to MMT. The introduction or expansion of women-only drug treatment services is urgently needed in order to engage more women in treatment. PMID:24474875
Dolan, Kate; Salimi, Shabnam; Nassirimanesh, Bijan; Mohsenifar, Setareh; Allsop, David; Mokri, Azarakhsh
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.
Martin, B.R.; Lue, L.P.; Boni, J.P. (Virginia Commonwealth Univ., Richmond (USA))
Immunization with a phosphonate monoester transition-state analog of cocaine provided monoclonal antibodies capable of catalyzing the hydrolysis of the cocaine benzoyl ester group. An assay for the degradation of radiolabeled cocaine identified active enzymes. Benzoyl esterolysis yields ecgonine methyl ester and benzoic acid, fragments devoid of cocaine's stimulant activity. Passive immunization with such an artificial enzyme could provide a treatment for dependence by blunting reinforcement.
Landry, Donald W.; Zhao, Kang; Yang, Ginger X.-Q.; Glickman, Michael; Georgiadis, Taxiarchis M.
A wide range of social indicators turned sharply negative for Blacks in the late 1980s and began to rebound roughly a decade later. We explore whether the rise and fall of crack cocaine can explain these patterns. Absent a direct measure of crack cocaine%u2019s prevalence, we construct an index based on a range of indirect proxies (cocaine arrests, cocaine-related emergency
Roland G. Fryer; Paul S. Heaton; Steven D. Levitt; Kevin M. Murphy
Methodological issues related to the self-administration of cocaine and the effect of the magnitude of alternative reinforcers on cocaine self-administration were examined. Hospitalized male cocaine abusers (N = 12) were involved in an inpatient study in which the between-subjects variable was the monetary value of the alternative reinforcer, and the within-subject variable was 3 dose sizes of cocaine. Ss could
Dorothy K. Hatsukami; Timothy N. Thompson; Paul R. Pentel; Brian K. Flygare; Marilyn E. Carroll
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,…
Eiden, Rina D.; Veira, Yvette; Granger, Douglas A.
Detecting Cocaine Use with Wearable Electrocardiogram Sensors Annamalai Natarajan1 Abhinav Parate1 of cocaine use. The current paper takes the first step in this important direction by posing a simple, but crucial question: Can cocaine use be reliably detected using wearable electro- cardiogram (ECG) sensors
Massachusetts at Amherst, University of
Although approximately 32% of all smoked cocaine (“crack”) users are women, most studies investigating cocaine use have recruited only male subjects. Therefore, this study examined the smoked cocaine self-administration patterns of female crack abusers. A work requirement, where up to five tokens were earned by subjects, was followed by the administration of a sample delivery of one of three dose
S. A. Dudish; Dorothy K. Hatsukami; P. R. Pentel
The pathophysiology of the effects of cocaine on fetal development has been described along 2 major pathways: neurochemical effects and vasoconstrictive effects. Following a summary of these effects, we suggest a ‘third pathophysiology’ in which altered fetal programming affects the acute and long-term adverse effects of in utero cocaine exposure. We describe how cocaine as a stressor alters the expression
Barry M. Lester; James F. Padbury
We report a case of "crack" cocaine abuse in a pregnant patient associated with haematuria, proteinuria, haemolytic anaemia, renal impairment, thrombocytopenia and pulmonary oedema. The case illustrates the problems for clinicians where unrecognized cocaine abuse interferes with the diagnosis and management of a complicated pregnancy. In addition, we discuss the principles for the safe conduct of anaesthesia in the pregnant cocaine abuser. PMID:8942348
Campbell, D; Parr, M J; Shutt, L E
The current state of knowledge about the neurodevel opmental sequelae of prenatal cocaine exposure is reviewed. Mater nal cocaine use is associated with a number of other factors such as poor nutrition, inadequate prenatal care, and exposure to other substances, including alcohol and tobacco, that also affect neurode velopmental outcome. The effects of postnatal maternal cocaine use on the mother's
Linda C. Mayes
Unemployment remains a common problem among methadone patients. This study examined the effectiveness of the Vocational Problem-Solving Skills (VPSS) intervention to help unemployed methadone patients obtain employment. Methods: 109 patients were randomly assigned to receive 10 sessions of either VPSS (n=62) or Interpersonal Problem-Solving (IPS) (n=47). Fourteen counselors from two methadone programs were trained to deliver both the VPSS and
David A. Zanis; Donna Coviello; Arthur I. Alterman; Sharon E. Appling
Background and objectives: Cytochrome P450 (CYP) 3A4 is the main CYP isozyme involved in methadone metabolism. We investigated the influence of grapefruit juice, which contains inhibitors of intestinal CYP3A, on the steady-state pharmacokinetics of methadone.Methods: For 5 days, 8 patients undergoing methadone maintenance treatment received 200 mL water or grapefruit juice 30 minutes before and again together with their daily
Messaoud Benmebarek; Corinne Devaud; Marianne Gex-Fabry; Kerry Powell Golay; Christian Brogli; Pierre Baumann; Bruno Gravier; Chin B. Eap
Narcotic withdrawal is often accompanied by an atypical depression which responds to resumption of narcotics. It was hypothesized that methadone might exert its antidepressant effects through monoamine oxidase (MAO) inhibition. The current study examined /sub 3/H-methadone distribution in rat brain and effects on regional MAO activity with acute doses (2.5 mg/kg) which approximate those found during chronic methadone maintenance in man. Limbic areas (amygdala, basomedial hypothalamus, caudate-putamen, hippocampus, preoptic nucleus), as well as pituitary and liver were assayed for MAO activity and methadone concentration. MAO activities did not differ significantly in acute methadone or saline-treated cage-mates at 1 or 24 hr. The concentrations of methadone at 1 hr ranged between 17 and 223 ng/100 mg wet wt tissue in the preoptic nucleus and pituitary, respectively. No significant correlation was found between change in MAO activity (MAO methadone/MAO saline) and methadone concentration in any region at 1 or 24 hr. This study does not support the hypothesis that methadone acts as an antidepressant through MAO inhibition, at least not following acute administration of this exogenous opioid.
Kaufmann, C.A.; Kreek, M.J.; Raghunath, J.; Arns, P.
A case study is presented where a woman travelling from South America to the Republic of Ireland was detained at Dublin Airport and articles of clothing she had in her luggage were found to be impregnated with cocaine. The study shows that the amount of powder recovered from the garments was approximately 14% of the total weight of the garments. The cocaine was in the form of cocaine hydrochloride and the purity was approximately 80%. An examination of the garments under filtered light highlighted the areas exposed to cocaine and indicated that the method of impregnation was by pouring liquid containing cocaine onto the clothing. PMID:16382839
McDermott, Seán D; Power, John D
Based on prior clinical trials indicating that ?-aminobutyric acid (GABA) based anticonvulsant medications reduce drug craving in cocaine dependent study participants, we tested the effects of valproate treatment on cue-induced cocaine craving. Crack cocaine dependent individuals (N=20) were tested in a randomized, placebo-controlled, within-subjects, crossover study design. Valproate treatment was titrated up to 1500 mg/day by Day 6 of treatment, cue testing was completed on Day 8 of treatment, and all study participants underwent a washout period of 5 days between active and placebo medication treatment periods. Testing included both cocaine and neutral cue exposure sessions, presented in a random and counterbalanced order. Main effects of cue exposure were found for subjective ratings of “desire to use cocaine now”, the cocaine craving index, cocaine-like high, and cocaine withdrawal. Treatment interaction effects were found with “desire to use cocaine now”, which underwent a greater increase following cocaine cue exposure in the valproate condition. Main effects of medication treatment were found, in which lower blood pressure and heart rate, and higher plasma cortisol levels, were associated with valproate treatment. Valproate treatment was also associated, at a trend level, with higher pre-test cocaine craving levels. The results demonstrate that cocaine cue reactivity is a robust phenomena across two assessment sessions, but fail to support the use of valproate as a means of reducing spontaneous and cue-induced cocaine craving. The use of valproate as a treatment for cocaine dependence is not supported. PMID:19375250
Reid, Malcolm S.; Thakkar, Vatsal
Recent studies have shown that post-retrieval extinction training attenuates fear and reward-related memories in both humans and rodents. This noninvasive, behavioral approach has the potential to be used in clinical settings to treat maladaptive memories that underlie several psychiatric disorders, including drug addiction. However, few studies to date have used a post-retrieval extinction approach to attenuate addiction-related memories. In the current study, we attempted to disrupt cocaine-related memories by using the post-retrieval extinction paradigm in male Sprague Dawley rats. Results revealed that starting extinction training 1?h after cocaine contextual memory was retrieved significantly attenuated cocaine-primed reinstatement of conditioned place preference (CPP) and relapse of cocaine CPP (drug-free and cocaine-primed) following 30 days of abstinence. However, animals that did not retrieve the contextual cocaine memory before extinction training, or animals that began extinction training 24?h after retrieval (outside of the reconsolidation window), demonstrated normal cocaine CPP. Conversely, animals that received additional CPP conditioning, rather than extinction training, 1?h after reactivation of cocaine memory showed enhanced cocaine CPP compared with animals that did not reactivate the cocaine memory before conditioning. These results reveal that a behavioral manipulation that takes advantage of reconsolidation and extinction of drug memories may be useful in decreasing preference for, and abuse of, cocaine. PMID:24257156
Sartor, Gregory C; Aston-Jones, Gary
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
Beniczky, Sándor; Tfelt-Hansen, Peer; Fabricius, Martin; Andersen, Kjeld V
Background Rates of relapse among cocaine-dependent patients are high, and new treatment approaches are needed. Clinical data demonstrate that a cocaine vaccine (TA-CD: Celtic Pharmaceutical) produces selective anti-cocaine antibodies, yet the impact of these antibodies on cocaine’s direct effects is unknown. The objective of this human laboratory study was to measure the relationship between antibody titers and the effects of smoked cocaine on ratings of intoxication, craving and cardiovascular effects. Methods Ten cocaine-dependent men not seeking drug treatment spent 2 nights per week for 13 weeks inpatient where the effects of cocaine (0, 25, 50 mg) were determined prior to vaccination and at weekly intervals thereafter. Two doses of TA-CD (82 µg, n=4; 360 µg, n=6) were administered at weeks 1, 3, 5 and 9. Results Peak plasma antibody levels, which were highly variable, significantly predicted cocaine’s effects. Those individuals in the upper half of antibody production had an immediate (within 4 minutes of cocaine smoking) and robust (55–81%) reduction in ratings of Good Drug Effect and Cocaine Quality, while those in the lower half showed only a nonsignificant attenuation (6–26%). Self-reported cocaine use while participants were outpatient tended to decrease as a function of antibody titer (p < 0.12). By contrast, higher antibody levels predicted significantly greater cocaine-induced tachycardia. Conclusions The TA-CD vaccine substantially decreased smoked cocaine’s intoxicating effects in those generating sufficient antibody. These data support further testing of cocaine immunotherapy as a treatment for cocaine dependence. PMID:19846066
Haney, Margaret; Gunderson, Erik W.; Jiang, Huiping; Collins, Eric D.; Foltin, Richard W.
The present study is the first to utilize bacterial cocaine esterase (CocE) to increase elimination of a lethal dose of cocaine and evaluate its cardioprotective effects. Rats received one of 5 treatments: CocE 1 min after saline; CocE 1 min after a lethal i.p. dose of cocaine; saline 1 min after a lethal i.p. dose of cocaine; CocE immediately after observing a cocaine-induced convulsion; and CocE 1 min after observing a cocaine-induced convulsion. Measures were taken of ECG, blood pressure, and cardiac troponin I (cTnI). The specificity of CocE against cocaine was determined by evaluating its actions against the cocaine analogue, WIN-35,065-2, which lacks an ester attack point for CocE. In addition, CocE's effects were compared with those of midazolam, a benzodiazepine often used to manage cocaine overdose. Whereas CocE alone had negligible cardiovascular effects, it blocked or reversed cocaine-induced QRS complex widening, increased QTc interval, ST elevation, bradycardia, and hypertension. When administered 1 min after cocaine, CocE inhibited myocardial damage; however, administered 1 min after a cocaine-induced convulsion (approximately 40s before cocaine-induced death), CocE did not block cTnI release, but did restore cardiac function. Midazolam blocked convulsions, but exhibited inadequate protection against cocaine-induced cardiotoxicity. The majority of rats given cocaine plus midazolam died. CocE did not prevent the lethal cardiovascular effects of WIN-35,065-2. In all likelihood, CocE rapidly and specifically reduced the body burden of cocaine and inhibited or reversed the cardiovascular consequences of high-dose cocaine. These results support CocE as a potential therapeutic avenue in cocaine overdose. PMID:19800183
Wood, Susan K; Narasimhan, Diwahar; Cooper, Ziva; Sunahara, Roger K; Woods, James H
This article examines the behavioral practices and health risks associated with preparing crack cocaine for injection. Using an ethno-epidemiological approach, injection drug users (n=38) were recruited between 1999 and 2000 from public settings in New York City and Bridgeport, Connecticut and responded to a semistructured interview focusing on crack injection initiation and their most recent crack injection. Study findings indicate that methods of preparing crack for injection were impacted by a transforming agent, heat applied to the “cooker,” heroin use, age of the injector, and geographic location of the injector. The findings suggest that crack injectors use a variety of methods to prepare crack, which may carry different risks for the transmission of bloodborne pathogens. In particular, crack injection may be an important factor in the current HIV epidemic. PMID:18079990
Lankenau, Stephen E.; Clatts, Michael C.; Goldsamt, Lloyd A.; Welle, Dorinda L.
Aims To examine patient and medication characteristics associated with retention and continued illicit opioid use in methadone (MET) versus buprenorphine/naloxone (BUP) treatment for opioid dependence. Design/Settings/Participants This secondary analysis included 1,267 opioid-dependent individuals participating in 9 opioid treatment programs between 2006 and 2009 and randomized to receive open-label BUP or MET for 24 weeks. Measurements The analyses included measures of patient characteristics at baseline (demographics; use of alcohol, cigarettes, and illicit drugs; self-rated mental and physical health), medication dose and urine drug screens during treatment, and treatment completion and days in treatment during the 24 week trial. Findings The treatment completion rate was 74% for MET vs. 46% for BUP (p<.01); the rate among MET participants increased to 80% when the maximum MET dose reached or exceeded 60mg/day. With BUP, the completion rate increased linearly with higher doses, reaching 60% with doses of 30–32mg/day. Of those remaining in treatment, positive opioid urine results were significantly lower (OR=0.63, 95%CI=0.52–0.76, p<.01) among BUP relative to MET participants during the first 9 weeks of treatment. Higher medication dose was related to lower opiate use, more so among BUP patients. A Cox proportional hazards model revealed factors associated with dropout: (1) BUP (vs. MET, HR=1.61, CI:1.20–2.15), (2) lower medication dose (<16mg for BUP, <60mg for MET; HR=3.09, CI:2.19–4.37), (3) the interaction of dose and treatment condition (those with higher BUP dose were 1.04 times more likely to drop out than those with lower MET dose, and (4) being younger, Hispanic, and using heroin or other substances during treatment. Conclusions Provision of methadone appears to be associated with better retention in treatment for opioid dependence than buprenorphine, as does use of provision of higher doses of both medications. Provision of buprenorphine is associated with lower continued use of illicit opioids. PMID:23961726
Hser, Yih-Ing; Saxon, Andrew J.; Huang, David; Hasson, Al; Thomas, Christie; Hillhouse, Maureen; Jacobs, Petra; Teruya, Cheryl; McLaughlin, Paul; Wiest, Katharina; Cohen, Allan; Ling, Walter
Several drugs with structural similarities to SKF-525A were tested for their ability to inhibit rat liver aldehyde oxidase using the experimental antitumour agent N-[(2'-dimethylamino)ethyl]acridine-4-carboxamide (AC; NSC 601316; acridine carboxamide) as substrate. The antihistamine D-chlorpheniramine, and the antiarrhythmics disopyramide, procainamide and lignocaine were ineffective in inhibiting this reaction. The antihistamines diphenhydramine, pheniramine, doxylamine, orphenadrine, methapyrilene and pyrilamine, gave IC50 values of 100-500 microM. The narcotic analgesics D-propoxyphene and, in particular, methadone were potent inhibitors of acridine formation with IC50 values of 15.5 and 0.31 microM, respectively. Further analysis indicates mixed non-competitive type inhibition by methadone with inhibition constants (Kis and Kii, respectively) of 0.03 +/- 0.01 (SE) and 0.57 +/- 0.12 microM. PMID:8117328
Robertson, I G; Gamage, R S
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…
Lombas, Andres S.; Freeman, Kevin B.; Roma, Peter G.; Riley, Anthony L.
Changes in a patient’s patterns of cocaine use are generally considered an important outcome measure of treatment efficacy. Other treatment outcome measures are important as well, but if a treatment does not stop or significantly decrease the intensity of a
Reese T. Jones
The prevalence of diagnoses of substance dependence, anxiety disorders and depressive disorders were estimated in a sample of 222 heroin injectors, using the Composite International Diagnostic Interview. Subjects had a median of three lifetime substance diagnoses and two current diagnoses. A total of 60% met the criteria for a lifetime anxiety disorder, and 51% had a current anxiety disorder. A
S. Darke; J. Ross
The HIV risks associated with the sexual behaviour of drug injectors have sometimes been overshadowed by the more obvious risks of injection behaviour. In this study, 408 heroin users were interviewed in the community; SO% were not currently in treatment and 42% had never had any treatment contact. In addition to data on drug use, information was collected on sexual
M. Gossop; P. Griffiths; B. Powis; J. Strang
Groups of subjects whose primary drug of abuse was amphetamine or heroin were compared, together with age- and IQ-matched control subjects. The study consisted of a neuropsychological test battery which included both conventional tests and also computerised tests of recognition memory, spatial working memory, planning, sequence generation, visual discrimination learning, and attentional set-shifting. Many of these tests have previously been
TJ Ornstein; JL Iddon; AM Baldacchino; BJ Sahakian; BJ Everitt; TW Robbins
A severe pulmonary vascular derangement, usually reported in drug addicts, was diagnosed in a 28-year-old asymptomatic ex-heroin user by means of fortuitously performed pulmonary perfusion imaging. Neither physical findings nor pulmonary function tests, aroused suspicion of the diagnosis. A search for asymptomatic pulmonary vascular disease probably should be undertaken in drug addicts.
Antonelli Incalzi, R.; Ludovico Maini, C.; Giuliano Bonetti, M.; Campioni, P.; Pistelli, R.; Fuso, L.
In order to examine risk factors for attempting suicide in heroin dependent patients, a group of 527 abstinent opiate dependent patients had a psychiatric interview and completed the Childhood Trauma Questionnaire. Patients who had or had never attempted suicide were compared on putative suicide risk factors. It was found that 207 of the 527…
... DetTabsSect7peTabs1to45-2011.htm#Tab7.40A . To determine the percentage of people who used heroin among those who abused or were dependent on pain medications the authors conducted an independent analysis of National Survey on Drug Use and Health ( ...
A positive reinforcement contingency increased opioid abstinence during outpatient dose tapering (4, 2, then 0 mg/day during Weeks 1 through 3) in non-treatment-seeking heroin-dependent volunteers who had been maintained on buprenorphine (8 mg/day) during an inpatient research protocol. The control group (n = 12) received $4.00 for completing…
Greenwald, Mark K.
Discusses how a recent fashion trend known as "heroin chic" challenges conventional modes of argumentation. Considers how its popularization of abject, emaciated bodies presents an alternative to a logic of rationalism that grounds traditional argumentation. Discusses how by foregrounding corporeal performativity as a form of argument, the…
Harold, Christine L.
A patient was seen on the palliative care service at our institution who developed serotonin syndrome and mutism associated with methadone use. Serotonin syndrome is often described as a clinical triad of mental status changes, autonomic hyperactivity, and neuromuscular abnormalities, but not all of these findings are consistently present in all patients with the disorder. The incidence of the serotonin syndrome is thought to mirror the increasing number of proserotonergic agents being used in clinical practice. In 2002, the Toxic Exposure Surveillance System, which receives case descriptions from office-based practices, inpatient settings, and emergency departments, reported 26,733 incidences of exposure to selective serotonin-reuptake inhibitors (SSRIs) that caused significant toxic effects in 7349 persons and resulted in 93 deaths. Serotonin syndrome is not an idiopathic drug reaction; it is a predictable consequence of excess serotonergic agonism of central nervous system (CNS) receptors and peripheral serotonergic receptors. The myriad of symptoms with which serotonin syndrome may present is compounded by the fact that more than 85% of physicians are unaware of serotonin syndrome as a clinical diagnosis. Other SSRIs such as fluoxetine and fluvoxamine have been shown to increase methadone plasma concentrations in dependent patients. Although the exact mechanism is unknown, there are several pathways via which a significant interaction could occur. This would include the effects methadone has on N-methyl-D-aspartate (NMDA) in addition to the impact of methadone on the cytochrome P450 enzyme system. The mainstay of treatment of serotonin syndrome is withdrawal of the offending agent and supportive care. These actions resulted in resolution of our patient's symptoms. Serotonin syndrome is becoming more common, and with the utilization of polypharmacy on many palliative care services should be considered as unifying differential diagnosis in the appropriate setting. PMID:17187532
Bush, Eric; Miller, Carol; Friedman, Irwin
Zusammenfassung \\u000a Bei jedem Fünften (19\\/102) der zwischen Februar 1994 und Februar 1998 im Institut für Rechtsmedizin der RWTH Aachen registrierten\\u000a Drogentodesfälle wurde eine Beteiligung des Opioides Methadon festgestellt. Obwohl sich die gesamte Anzahl der opiatsubstituierten\\u000a Patienten in Stadt und Kreis Aachen im genannten Zeitraum etwa verzehnfachte, kam es jährlich gleichbleibend zu 4 bis 6 methadonassoziierten\\u000a Todesfällen, zumeist infolge von Mischintoxikationen.
D. Servais; M. Erkens
This study examines the relationship between age and HIV sexual risk behaviors among a random sample of 372 women in methadone\\u000a treatment in New York City. Logistic regression results indicate that women of all ages are at risk for HIV through inconsistent\\u000a condom use. Exposure to intimate partner violence (IPV), alcohol use, and HIV-negative status are associated with inconsistent\\u000a condom
Malitta Engstrom; Tazuko Shibusawa; Nabila El-Bassel; Louisa Gilbert
This study examined retention rates and associated predictors of methadone maintenance treatment (MMT) duration among 128 newly admitted patients in Taiwan. A semi-structured questionnaire was used to obtain demographic and drug use history. Daily records of methadone taken and test results for HIV, HCV, and morphine toxicology were taken from a computerized medical registry. Cox regression analyses were performed to examine factors associated with MMT duration. MMT retention rates were 80.5%, 68.8%, 53.9%, and 41.4% for 3, 6, 12, and 18 months, respectively. Excluding 38 patients incarcerated during the study period, retention rates were 81.1%, 73.3%, 61.1%, and 48.9% for 3 months, 6 months, 12 months, and 18 months, respectively. No participant seroconverted to HIV and 1 died during the 18-months follow-up. Results showed that being female, imprisonment, a longer distance from house to clinic, having a lower methadone dose after 30 days, being HCV positive, and in the New Taipei city program predicted early patient dropout. The findings suggest favorable MMT outcomes of HIV seroincidence and mortality. Results indicate that the need to minimize travel distance and to provide programs that meet women’s requirements justify expansion of MMT clinics in Taiwan. PMID:25875531
Peng, Ching-Yi; Chao, En; Lee, Tony Szu-Hsien
GABRB3 encoding the ?3 subunit of GABAA receptor has been implicated in multiple neuropsychiatric disorders, including substance abuse. Previous studies reported that SNPs at the 5? regulatory region of GABRB3 could regulate GABRB3 gene expression and associated with childhood absence epilepsy (CAE). The study aimed to investigate whether SNPs at the 5? regulatory region of GABRB3 were associated with heroin dependence in our population. We first re-sequenced 1.5 kb of the 5?regulatory region of GABRB3 gene to examine the SNP profile in the genomic DNA of 365 control subjects. Then, we conducted a case-control association analysis between 576 subjects with heroin dependence (549 males, 27 females) and 886 controls (472 males, 414 females) by genotyping the rs4906902 as a tag SNP. We also conducted a reporter gene assay to assess the promoter activity of two major haplotypes derived from SNPs at this region. We detected 3 common SNPs (rs4906902, rs8179184 and rs20317) at this region that had strong pair-wise linkage disequilibrium. The C allele of rs4906902 was found to be associated with increased risk of heroin dependence (odds ratio:1.27, p?=?0.002). Two major haplotypes (C-A-G and T-G-C) derived from these 3 SNPs accounted for 99% of this sample, and reporter gene activity assay showed that haplotype C-A-G that contained the C allele of the tag SNP rs4906902 had higher activity than haplotype T-G-C. Our data suggest that GABRB3 might be associated with heroin dependence, and increased expression of GABRB3 might contribute to the pathogenesis of heroin dependence. PMID:25025424
Chen, Chia-Hsiang; Huang, Chia-Chun; Liao, Ding-Lieh
Numerous findings suggest that drug seeking and ingestive behaviors share common neurobiological mechanisms, but the relevant pathways are unknown. Dietary manipulations result in changes in endocrine the and\\/or neuropeptide signals, such as the hormones leptin and ghrelin, which are dynamically linked to energy balance and the regulation of feeding behavior. We have recently demonstrated that food deprivation-induced reinstatement of heroin
Tia Maric; Stephanie Tobin; Tammie Quinn; Uri Shalev
Numerous studies have documented cognitive impairments and hypoactivity in the prefrontal and anterior cingulate cortices in drug users. However, the relationships between opiate dependence and brain structure changes in heroin users are largely unknown. In the present study, we measured the density of gray matter (DGM) with voxel-based…
Yuan, Yi; Zhu, Zude; Shi, Jinfu; Zou, Zhiling; Yuan, Fei; Liu, Yijun; Lee, Tatia M. C.; Weng, Xuchu
Brain glutamate has been shown to play an important role in reinstatement to drug seeking, a behavior considered to be of relevance to relapse to drug taking in humans. Therefore, glutamate receptors, in particular metabotropic glutamate (mGlu) receptors, have become important targets for medication development for the treatment of drug dependence. In this review article, we focus on the mGlu7 receptor subtype, and discuss recent findings with AMN082, a selective mGlu7 receptor allosteric agonist, in animal models with relevance to drug dependence. Systemic or local administration of AMN082 into the nucleus accumbens (NAc), a critical brain region involved in reward and drug dependence processes, inhibited the reinforcing and motivational effects of cocaine, heroin and ethanol, as assessed by the intravenous drug self-administration procedure. In addition, AMN082 inhibited the reward-enhancing effects induced by cocaine, as assessed in the intracranial self-stimulation procedure, and cocaine- or cue-induced reinstatement of drug-seeking behavior. In vivo microdialysis studies indicated that systemic or intra-NAc administration of AMN082 significantly decreased extracellular ?-aminobutyric acid (GABA) and elevated extracellular glutamate, but had no effect on extracellular dopamine in the NAc, suggesting that a non-dopaminergic mechanism underlies the effects of AMN082 on the actions of cocaine. Further, data indicated that AMN082-induced changes in glutamate were the net effect of two actions: one is the direct inhibition of glutamate release by activation of mGlu7 receptors on glutamatergic neurons; another is the indirect increases of glutamate release mediated by decreases in GABA transmission. These increases in extracellular glutamate functionally antagonized cocaine-induced inhibition of NAc-ventral pallidum GABAergic neurotransmission, and therefore, the rewarding effects of cocaine. In addition, elevated extracellular glutamate activated presynaptic mGlu2/3 autoreceptors which in turn inhibited cocaine priming- or cue-induced enhancement of glutamate release and reinstatement of drug-seeking behavior. Taken together, these findings suggest that the mGlu7 receptor is an important target for medication development for the treatment of drug dependence. AMN082 or other mGlu7 receptor allosteric agonists may have potential as novel pharmacotherapies for cocaine addiction. PMID:22546614
Li, Xia; Xi, Zheng-Xiong; Markou, Athina
Absence of successful transition to post-detoxification treatment leads to high rates of relapse among detoxified heroin users. The present study evaluated a pilot buprenorphine treatment program (BTP). Heroin dependent individuals were inducted onto buprenorphine/naloxone in detox, maintained while transitioning through an intensive inpatient program (IIP), and gradually tapered off medication over 5 months of outpatient (OP) treatment. Compared to programmatic indicators of treatment engagement in the year prior to BTP implementation, referrals from detox to IIP, entry into and completion of IIP and subsequent OP, and days in OP treatment increased substantially. BTP completers, compared to non-completers, viewed abstinence as more difficult and as requiring more assistance to achieve, were less likely to be current cocaine and alcohol users or to have relapsed during the course of treatment. Although preliminary and in need of replication, initial adjunctive use of buprenorphine in an abstinence-based continuum of care may improve post-detoxification treatment entry, engagement, and completion. PMID:23007109
Donovan, Dennis M; Knox, Patricia C; Skytta, Jenny A F; Blayney, Jessica A; DiCenzo, Jessica
The cellular mechanisms by which opiate addiction develops with repetitive use remain largely unresolved. Intercellular calcium homeostasis is one of the most critical elements to determine neuroadaptive changes and neuronal fate. Heroin, one of the most addictive opiates, may induce neurotoxicity potentially inducing brain impairment, especially for those chronic users who get an overdose. Here we examined changes in intracellular calcium concentration ([Ca2+]i) after repeated exposure to heroin using cultured cerebral cortical neurons. Dynamic changes in [Ca2+]i indicated by fluo-3-AM were monitored using confocal laser scan microscopy, followed by cytotoxicity assessments. It showed that the cells dissociated from heroin-dependent rats had a smaller depolarization-induced [Ca2+]i responses, and a higher elevation in [Ca2+]i when challenged with a high concentration of heroin (500 ?M). The restoration ability to remove calcium after washout of these stimulants was impaired. Calcium channel blocker verapamil inhibited the heroin-induced [Ca2+]i elevations as well as the heroin-induced cell damage. The relative [Ca2+]i of the nerve cells closely correlated with the number of damaged cells induced by heroin. These results demonstrate that nerve cells from heroin-dependent rats manifest abnormal [Ca2+]i homeostasis, as well as vulnerability to heroin overdose, suggesting involvement of [Ca2+]i regulation mechanisms in heroin addiction and neurotoxicity. PMID:24854119
Liu, Xiaoshan; Wang, Guangyong; Pu, Hongwei; Jing, Hualan
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
Li, Xuan; Wolf, Marina E
The model for management of opiate dependence in the United Kingdom includes long term methadone maintenance. A consequence is either long waiting lists for treatment or that treatment capacity is expanded. General practitioners are encouraged to prescribe methadone for opiate dependent patients, but little is known about the differences between patients or outcomes in primary or secondary care settings. This
David Lewis; Mark Bellis
Methadone dosing has been an issue of controversy among clinicians for a long time. Few recent studies reported that doses above 100 mg daily seem promising in better control of illicit opiate use for some patients, but more research is needed to support that notion. A retrospective chart review for patients maintained on methadone at Atlanta Veterans Affairs Medical Center
Ayman Fareed; Jennifer Casarella; Mary Roberts; Mary Sleboda; Richard Amar; Shreedevi Vayalapalli; Karen Drexler
While psychiatric comorbidity has been shown to produce a negative impact on the outcome of opioid use disorders, longitudinal studies carried out in the context of methadone maintenance treatment programs (MMTP) to evaluate outcomes strictly linked to methadone efficacy have not demonstrated a similar negative influence. To verify whether results obtained considering psychopathology in terms of formal psychiatric diagnoses were
Pier Paolo Pani; Icro Maremmani; Matteo Pacini; Francesco Lamanna; Angelo G. I. Maremmani; Liliana dell’Osso
The purpose of this article was to investigate the personal and social barriers experienced by methadone maintained clients when seeking treatment for alcohol abuse along with strategies for engaging such clients in treatment programs. A qualitative design using semi-structured focus groups was used to obtain the perspectives of 41 methadone-maintained clients in Los Angeles, California. Sessions were recorded, transcribed, and
Adeline Nyamathi; Viviane de Castro; Donna McNeese-Smith; Kamala Nyamathi; Steven Shoptaw; Mary Marfisee; Farinaz Khalilifard; Allan Cohen
The purpose of this study was to investigate the influence of the severity of concomitant psychiatric symptomatology on some selected measures of methadone maintenance treatment efficacy in a comprehensive methadone maintenance treatment program (MMTP). The cohort studied included 267 patients who entered a maintenance program in the years 1991–1992. Two groups of patients differing in the severity of psychiatric symptomatology
Pier Paolo Pani; Emanuela Trogu; Paolo Contu; Alessandro Agus; Gian Luigi Gessa
This policy commentary addresses a significant access to care issue that faces methadone maintenance patients seeking residential treatment in the United States. Methadone maintenance therapy (MMT) has demonstrated strong efficacy in the outpatient treatment of opiate dependence. However, many opiate dependent patients are also in need of more…
Hettema, Jennifer E.; Sorensen, James L.
The physical and neurobehavioral findings at 3 years of age for 39 children born to mothers on methadone- maintenance and 23 children born to drug-free comparison mothers are reported. The methadone children had a higher incidence of head circumferences less than the third percentile, nystagmus/strabismus, and otitis media. No differences were…
Johnson, Helen L.; And Others
Compares 17 methadone-exposed and 23 control four-month-old infants in interactions with their mothers. Results indicate that methadone is only one of several risk factors affecting interaction. Mothers rated poor in communication have poor psychosocial and psychological resources, and infants rated poor in communication showed problematic motor…
Jeremy, Rita Jeruchimowicz; Bernstein, Victor J.
Research on vocational services for methadone clients is reviewed, and preliminary results of an evaluation of a training and employment program for 249 methadone treatment clients in 3 community-based programs are presented. Results suggest the usefulness of vocational services in increasing training access and use. (SLD)
Dennis, Michael L.; And Others
Compared the Adjective Check List descriptions of addicts in treatment toward methadone maintenance, multimodality, and therapeutic community clients and program staff. Results indicate client pessimism regarding methadone maintenance. Results suggest addict opinions represent a valuable source for evaluating treatment approaches and identifying…