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A gas chromatographic?mass spectrometric (GC?MS) method for the determination of methadone, heroin, cocaine, and their metabolites in urine using Selected Ion Monitoring (SIM) was developed. Following a liquid?liquid extraction with Toxitubes A and using their deuterated analogs as internal standards, the analytes were derivatized with 99:1 (v\\/v) N,O?bis?trimethylsilyl?trifluoroacetamide\\/trimethylchlorosilane and injected by hand, in the splitless mode, at 240°C and a purging
I. Álvarez; F. Palos; A. M. Bermejo; P. Fernández; M. J. Tabernero
Concurrent abuse of cocaine and heroin is a common problem. Methadone is effective for opioid dependence. The question arises as to whether combining agonist-like or antagonist-like medication for cocaine with methadone for opioid dependence might be efficacious. Two parallel studies were conducted. One examined sustained release d-amphetamine and the other risperidone for cocaine dependence, each in combination with methadone. In
John Grabowski; Howard Rhoades; Angela Stotts; Katherine Cowan; Charles Kopecky; Anne Dougherty; F Gerard Moeller; Sohela Hassan; Joy Schmitz
One month before (T-1) and 12 months after (T12) controlled i.v. administration of pharmaceutical heroin–HCl (10–100 mg\\/day)\\u000a in the context of a heroin maintenance program (HMP), concentrations of opiates and cocaine as well as its metabolites were\\u000a determined in head hair (n?=?46) using a validated gas chromatographic–mass spectrometric method. In addition, a patient collective of a methadone maintenance\\u000a program (MMP, daily doses
Frank Musshoff; Katrin Lachenmeier; Dirk Lichtermann; Burkhard Madea
The success of methadone in treating opiate addiction has suggested that long-acting agonist therapies may be similarly useful for treating cocaine addiction. Here, we examined this hypothesis, using the slow-onset long-acting monoamine reuptake inhibitor 31,345, a trans-aminotetralin analog, in a variety of addiction-related animal models, and compared it with methadone's effects on heroin's actions in the same animal models. Systemic
Xiao-Qing Peng; Zheng-Xiong Xi; Xia Li; Krista Spiller; Jie Li; Lauren Chun; Kuo-Ming Wu; Mark Froimowitz; Eliot L Gardner
One month before (T-1) and 12 months after (T12) controlled i.v. administration of pharmaceutical heroin-HCl (10-100 mg/day) in the context of a heroin maintenance program (HMP), concentrations of opiates and cocaine as well as its metabolites were determined in head hair (n = 46) using a validated gas chromatographic-mass spectrometric method. In addition, a patient collective of a methadone maintenance program (MMP, daily doses 15-260 mg) was examined (n = 35). The incidence of additional cocaine consumption decreased in both groups during the study period (T-1 to T12): in HMP from 64.6% to 45.8% and in MMP from 71.4% to 60.0%. A significant reduction of cocaine consumption was defined as an at least 30% reduction of analyte concentrations in hair (Deltac > 30%). Accordingly, in HMP, a decrease in 45.8% of initially (T-1) cocaine-positive patients was determined; in MMP, the reduction was 48.6%. In 22.9% of HMP and 37.1% of MMP, an increase of cocaine concentrations was detected. Codeine and acetylcodeine were found in 50.0% and 43.5% (T-1) and 13.0% and 10.9% (T12) of the samples of the HMP, as well as in 45.7% and 25.7% (T-1) and 17.1% and 5.7% (T12) in MMP, respectively. The missing of acetylcodeine, in particular at T-1, questions its applicability as a characteristic marker of a preceding consumption of illicit heroin in hair analysis. PMID:18661141
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.
Brunet, Bertrand R.; Barnes, Allan J.; Scheidweiler, Karl B.; Mura, Patrick
Although it is well established that methadone can be an effective treatment for opiate addiction, it is not clear how methadone maintenance affects cocaine use and cravings in individuals who self-administer both opiates and cocaine. In our attempt to explore the effect of methadone maintenance on the effects of cocaine, we first assessed the locomotor stimulatory effects of cocaine in
Francesco Leri; Annie Tremblay; Robert E Sorge; Jane Stewart
Urine samples of patients from a heroin maintenance program (HMP) and a methadone maintenance program (MMP) were chromatographically\\u000a analyzed 1 month before and 6 and 12 months into treatment for the presence of classical markers of heroin use as well as\\u000a for the presence of markers for illicit heroin abuse. Furthermore, the samples were immunochemically tested for cannabinoids,\\u000a cocaine metabolites, amphetamine, methylendioxyamphetamines
Frank Musshoff; Jens Trafkowski; Dirk Lichtermann; Burkhard Madea
For a pharmacokinetic–pharmacodynamic study in opioid tolerant patients, who were treated with heroin in combination with methadone, a liquid chromatographic assay with tandem mass spectrometry detection (LC–MS\\/MS) was developed for the simultaneous determination of heroin, methadone, heroin metabolites 6-monoacetylmorphine, morphine, and morphine-6 and 3-glucuronide and methadone metabolite EMDP. To detect any abuse of substances besides the prescribed opioids the assay
Elisabeth J. Rook; Michel J. X. Hillebrand; Hilde Rosing; Jan M. van Ree; Jos H. Beijnen
Summary A review of methadone-related issues and the approach to heroin addicted patients is presented with the aim to clarify what is prac- ticed by the establishment of anti-craving treatment and what is expected within a history of addiction. A series of clinical situations occurring throughout pregnancy to early child development are described, and the etiological hypothesis discussed. Moreover, some
Alcohol and cocaine abuse result in unsatisfactory treatment outcomes for heroin and illicit opioid addicts engaged in Methadone Maintenance Treatment Programs (MMTPs). This study aims to clarify the impact of MMT, which focuses on cessation of opioid abuse and diminishing psychopathology to acceptable levels (stabilization) on alcohol and cocaine abuse. Of specific interest was whether reduction of polysubstance abuse and
Icro Maremmani; Pier Paolo Pani; Anna Mellini; Matteo Pacini; Giada Marini; Mercedes Lovrecic; Giulio Perugi; Marc Shinderman
Background Personality traits such as impulsivity and sensation seeking may contribute to the initiation and maintenance of illicit drug use. Since studies have reported higher impulsivity and sensation seeking traits in cocaine dependent subjects, we were interested in determining whether former heroin addicts in methadone pharmacotherapy with comorbid cocaine addiction have greater impulsivity than those without. Methods Instruments to assess impulsivity (Barratt Impulsiveness Scale version 11) and sensation seeking (Sensation Seeking Scale version V) were administered to former severe heroin addicts meeting Federal criteria for methadone maintenance pharmacotherapy with (n = 71) or without cocaine dependence (n = 31) and to 145 normal healthy (non-methadone-maintained) volunteers. Results The methadone-maintained without cocaine dependence and the methadone-maintained with cocaine dependence groups, both scored higher than did the normal volunteer group on the Barratt Impulsiveness Scale total score (p < 0.001). On the Barratt Impulsiveness Scale Attentional, Nonplanning, and Motor subscales, the methadone-maintained and methadone-maintained with cocaine dependence groups scored higher than did normal volunteers with no history of drug abuse or dependence (p < 0.001). There was no difference among groups on total score or any subscale of the Sensation Seeking Scale. However, males in all groups overall scored higher than did females on Disinhibition and Thrill and Adventure seeking subscales of the Sensation Seeking Scale version V (p < 0.001). Conclusions This study demonstrates higher impulsivity in former severe heroin addicts meeting criteria for or currently in stable methadone maintenance pharmacotherapy, irrespective of a positive or negative history of cocaine dependence.
Nielsen, David A.; Ho, Ann; Bahl, Ajay; Varma, Priya; Kellogg, Scott; Borg, Lisa; Kreek, Mary Jeanne
Methadon is a synthetic morphin used as a substitution therapy for heroin addicts. 21 patients were selected according the usual swiss indications and observed over 1 year. Treatment: daily methadon, weekly psychotherapy and unexpected urine controls. Problems: side effects, lack of medical care and control and the fact that it is a long term treatment for years, troublesome and often merely palliative. PMID:6666360
|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.
The objectives of this study were to determine: 1) the feasibility of expanding interim methadone treatment (IM); (2) the impact of IM on heroin and cocaine use; and (3) the effect of charging a modest fee for IM. Six clinics provided daily methadone plus emergency counseling only (IM) to heroin addicts on a waiting list for treatment. IM was provided for up to 120 days before transfer to regular methadone treatment. Drug testing was conducted at admission to IM and at transfer to MTP. Half the patients were charged $10/week for IM. Logistic regression analysis was utilized to determine the effect of fee status and other variables on transfer. Of 1,000 patients enrolled in IM, 762 patients (76.2%) were admitted to a regular MTP. For those who transferred (n = 762), opioid positive tests decreased from 89.6% to 38.4%; cocaine, from 49.9% to 44.9% from admission to transfer. Logistic regression analysis indicated that fee status at baseline was not significantly associated with transfer. When limited public resources create waiting lists, IM can allow additional patients to sharply reduce heroin use while waiting for admission to MTP.
Schwartz, Robert P.; Jaffe, Jerome H.; O'Grady, Kevin E.; Das, Babita; Highfield, David A.; Wilson, Monique E.
The first X-ray structure of human carboxylesterase 1 (hCE1) and the structures of hCE1 with drug analogs bound reveal important molecular details of how the drugs cocaine, heroin, and tacrine are metabolized and cleared.
Despite agreement that methadone maintenance treatment (MMT) is an effective and safe option for treatment of heroin dependence, there have been controversies about its effect on heroin craving. A systematic literature review of the PubMed database was used to find studies eligible for inclusion in the study. The authors present the results of 16 articles that met all inclusion criteria. Overall, 7 studies reported that methadone could reduce heroin craving, 4 studies reported that patients in MMT are still at risk of having heroin craving, 1 study reported that methadone could increase heroin craving, and 4 studies reported that methadone has a neutral effect on heroin craving. One may speculate from these data that methadone may help with heroin craving, but patients in MMT may still be at risk of cue-induced heroin cravings. Methadone provides a helpful tool for reducing some components of craving and risk of relapse for patient receiving MMT. PMID:21218308
Fareed, Ayman; Vayalapalli, Sreedevi; Stout, Steven; Casarella, Jennifer; Drexler, Karen; Bailey, Stephen P
This is an exploratory study of 18 inner-city methadone patients who reported on their hourly activities across nine consecutive days. Subjects were 56% male, unemployed, 89% used crack, 28% used intranasal cocaine, and 22% injected cocaine. The most frequent daily activities were: sleeping, watching TV, substance and\\/or alcohol use, socializing, food preparation\\/eating, and attending the methadone program. On days cocaine
Methods have been developed to analyze for cocaine, heroin and their metabolites in human saliva and the results compared to urinalysis. Analysis of 26 samples showed that 14 positive by urinalysis and 16 positive by saliva analysis. Thus, saliva testing ...
Escalating reinforcement for sustained abstinence has been effective in treating cocaine abuse. Under this schedule, patients receive vouchers for cocaine-free urine samples; vouchers have monetary values that increase with the number of consecutive cocaine-free urine samples. Cocaine-abusing methadone patients were randomly assigned to receive vouchers for 12 weeks under (a) an escalating schedule (n = 20), (b) an escalating schedule
Kenneth Silverman; Conrad J. Wong; Annie Umbricht-Schneiter; Ivan D. Montoya; Charles R. Schuster; Kenzie L. Preston
This study examined the methadone maintenance therapy (MMT) retention rates of heroin users in Taiwan and the predictors for dropout in the 18-month period after starting MMT. We consecutively recruited 368 intravenous heroin users receiving MMT in 2007-2008 and applied Cox proportional hazards regression analysis to determine the predictive effect of pre- and in-treatment variables on early discontinuation of MMT. The retention rate at 18 months was 32.3%. High heroin expenses, more severe harm caused by heroin use, perceived lower family support, and lower methadone dosage at 3 months after starting MMT increased the risk of dropout in the follow-up period. PMID:23368704
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
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.
Ghitza, Udi E; Epstein, David H; Schmittner, John; Vahabzadeh, Massoud; Lin, Jia-Ling; Preston, Kenzie L
Summary The main goals of opioid treatment in heroin addiction are to eliminate or reduce the use of heroin and other substances of abuse, to promote patients' social rehabilitation and to improve their quality of life. The purpose of this study is to evaluate the efficacy of buprenorphine and methadone on the quality of life of patients. These subjects were
Icro Maremmani; Pier Paolo Pani; Dina Popovic; Matteo Pacini; Joseph Deltito; Giulio Perugi
This study tested contingent access to methadone treatment as an incentive. Forty-four mixed opiate–cocaine abusers participated in a 90-day premaintenance probationary program. They were stabilized on 50 mg of methadone and assigned to 1 of 2 treatment groups. Contingent treatment patients were required to submit 2 consecutive weeks of cocaine-free urines during their first 7 weeks of treatment to gain
Injection drug users engage in behaviors that increase the spread of human immunodeficiency virus (HIV) and other infectious diseases. Although methadone maintenance (MM) is highly effective in decreasing heroin use and the spread of HIV, polydrug use, especially the combined use of cocaine and alcohol, is common in MM patients. Alcohol use is independently associated with HIV risk behaviors, and the effects of alcohol use on risk behaviors may vary by gender. This study evaluated the effects of recent heavy alcohol use and gender with respect to HIV risk behaviors in 118 cocaine-abusing methadone patients. Both lifetime and past month injection and sexual risk behaviors were examined. Recent heavy drinkers (n = 46) were more likely to be male than nonheavy drinkers (n = 72). Recent heavy drinkers reported more risky sexual behaviors over their lifetimes than nonheavy drinkers. Gender effects were also present for lifetime risk behaviors, with females demonstrating more sexual and injection risk behaviors than men. In terms of recent injection risk behaviors, there was a significant alcohol use by gender effect. Heavy drinking females reported significantly more drug-sharing behaviors and less frequent needle cleaning than nonheavy drinking females. Recent sexual behaviors did not differ based on alcohol use status or gender. These findings may inform HIV prevention strategies in cocaine-abusing MM patients, and they suggest that cocaine-abusing women who drink heavily are a particularly high risk group who should be counseled about risky injection drug use practices.
Pulmonary oedema lasting six days occurred in a 68 year old man after sniffing cocaine. He also had evidence of parenteral self-administration of heroin. Pulmonary microvascular filtration pressure and permeability were normal. Delayed resolution of the pulmonary oedema may have been caused by a cocaine-induced impairment of sodium and thus fluid transport across alveolar epithelium. Recognition may be important, since lowering filtration pressure with diuretics may not hasten resolution of oedema. Images
Raijmakers, P G; Groeneveld, A B; de Groot, M C; Teule, G J; Thijs, L G
Previously, the authors reported that progesterone treatment attenuated reports of cocaine-induced high in male and female cocaine users. In this pilot clinical trial, the authors tested the safety and efficacy of oral progesterone as a treatment for cocaine dependence in methadone-stabilized male cocaine users. This was a 10-week, randomized, double-blind, placebo-controlled trial. Forty-five male methadone-stabilized cocaine users were randomized to
Mehmet Sofuoglu; James Poling; Gerardo Gonzalez; Kishorchandra Gonsai; Alison Oliveto; Thomas R. Kosten
This paper investigates factors affecting the demand for marijuana, cocaine and heroin in Australia using micro-unit data from a national survey. Accounting for cross-commodity correlation potentially induced by unobserved personal characteristics such as tastes and addictive personalities, we estimate a trivariate probit model where the participation decisions for all drugs are jointly modelled as a system with correlated error terms.
Widespread use of cocaine by methadone clients is undermining the effectiveness of methadone treatment programs in reducing illicit drug use, decreasing criminal behavior, and slowing the spread of the human immunodeficiency virus (HIV). In response, methadone programs are implementing a range of behavioral interventions to manage this growing problem. Many of these interventions, however, have yet to be evaluated for effectiveness for reducing cocaine use among methadone clients. Interventions that are effective for cocaine use in the general population may not be as effective with cocaine users in methadone programs because these clients differ from other cocaine users in ways that are likely to affect how they respond to the interventions. This paper reviews the literature on the significance and scope of the problem of cocaine use by methadone clients and on the behavioral interventions that have been evaluated for these clients. PMID:1787544
Condelli, W S; Fairbank, J A; Dennis, M L; Rachal, J V
Objectives To explore methadone and 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) umbilical cord disposition, correlate with maternal methadone dose and neonatal outcomes, and evaluate the window of drug detection in umbilical cord of in utero illicit drug exposure. Methods Subjects, 19 opioid-dependent pregnant women from two clinical studies, one comparing methadone and buprenorphine pharmacotherapy for opioid-dependence treatment, and the second examining monetary reinforcement schedules to maintain drug abstinence. Correlations were calculated for methadone and EDDP umbilical cord concentrations and maternal methadone dose, and neonatal outcomes. Cocaine- and opiate-positive umbilical cord concentrations were compared to those in placenta and meconium, and urine specimens collected throughout gestation. Results Significant positive correlations were found for umbilical cord methadone concentrations and methadone mean daily dose, mean dose during the 3rd trimester and methadone cumulative daily dose. Umbilical cord EDDP concentrations and EDDP/methadone concentration ratios were positively correlated to newborn length, peak neonatal abstinence syndrome (NAS) score and time-to-peak NAS score. Methadone concentrations and EDDP/methadone ratios in umbilical cord and placenta were positively correlated. Meconium identified many more cocaine and opiate positive specimens than umbilical cord. Conclusion Umbilical cord methadone concentrations were correlated to methadone doses. Also, our results indicate that methadone and EDDP concentrations might help to predict NAS severity. Meconium proved to be more suitable than umbilical cord to detect in utero exposure to cocaine and opiates; however, umbilical cord could be useful when meconium is unavailable due to in utero or delayed expulsion.
de Castro, Ana; Jones, Hendree E.; Johnson, Rolley E.; Gray, Teresa R; Shakleya, Diaa M; Huestis, Marilyn A
A consensus panel convened by the National Institutes of Health (NIH) today strongly recommended a broader access to methadone maintenance treatment programs for people who are addicted to heroin or other opiate drugs and that the Federal and State regulations and other barriers impeding this access be eliminated.
A liquid chromatography tandem mass spectrometry method for buprenorphine (BUP), norbuprenorphine (NBUP), methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine\\u000a (EDDP), cocaine, benzoylecgonine, ecgonine methyl ester (EME), morphine, codeine, 6-acetylmorphine, heroin, 6-acetylcodeine,\\u000a cotinine, and trans-3?-hydroxycotinine quantification in sweat was developed and comprehensively validated. Sweat patches\\u000a were mixed with 6 mL acetate buffer at pH 4.5, and supernatant extracted with Strata-XC-cartridges. Reverse-phase separation\\u000a was achieved with a gradient mobile
Marta Concheiro; Diaa M. Shakleya; Marilyn A. Huestis
Background Health-related quality of life (HRQoL) remains poor among heroin users, even after being treated with methadone. Evidence regarding self-reported psychopathology and HRQoL in heroin users is also limited. The present study aimed to investigate the association between self-reported psychopathology and HRQoL in Asian heroin users treated with methadone. Methods Thirty-nine heroin users treated with methadone and 39 healthy controls were recruited. Both groups self-reported on demographic data, the Brief Symptom Rating Scale, EuroQoL-5D, and World Health Organization Questionnaire on Quality of Life: Short Form. We compared clinical characteristics, psychopathology, and HRQoL between the two study groups. Correlation and regression analyses were conducted to explore the association between psychopathology and HRQoL in the heroin user group. Results Heroin users had more psychopathology and worse HRQoL than healthy controls. The HRQoL of heroin users had significant correlations with Brief Symptom Rating Scale scores. HRQoL could be predicted by depression, anxiety, paranoia, and additional symptoms (ie, poor appetite and sleep difficulties) independently. Conclusion Self-reported psychopathology, depression, anxiety, paranoia, poor appetite, and sleep difficulties had a negative impact on each domain of HRQoL among heroin users treated with methadone. The importance of the environmental domain of HRQoL is discussed. Clinicians should recognize comorbid psychiatric symptoms early on to improve HRQoL in heroin users.
Aims of the present investigation were: (i) to assess the prevalence of current smokers and relative smoking status among a large number of heroin addicts attending opioid-substitution therapy prevalence; (ii) to evaluate the relationship between the type (methadone, buprenorphine) and dosage of opioid substitution therapy and nicotine dependence. Three hundred and five (305) heroin addicts under opioid-substitution therapy were recruited at five Addiction Units. All participants completed a questionnaire assessing sociodemographic information, type and dose of opioid-substitution therapy, smoking history and status, Fagerström Test for Nicotine Dependence (FTND), and the Zung Self-Rating Depression scale (SDS). 298 subjects, out of 305 (97.2%) were smokers, with an average of 20.5 cigarette/day and a median FTND of 6. Our data confirmed the high prevalence of smokers among heroin addicts, the highest described in the literature to date among heroin addicts under substitution therapies, without any significant difference between methadone vs. buprenorphine therapy groups. There was no correlation between dose of methadone or buprenorphine and average number of cigarettes/day. Patients in substance abuse treatment very frequently smoke cigarettes and often die of tobacco-related diseases. Substance abuse treatment programs too often ignore tobacco use. We hope that these findings will help to incorporate smoking cessation in substance abuse treatments. PMID:22690174
Up to 1999 more opioid dependent patients in Germany were substituted with codeine or dihydrocodeine (summarised as codeine) than with methadone. The current retrospective study compares the differences in detoxification treatment outcome for codeine-substituted patients, methadone-substituted patients and patients injecting illicit heroin. The study is based on the medical records of 1070 patients admitted consecutively for opioid and polytox detoxification
Markus Backmund; Kirsten Meyer; Dieter Eichenlaub; Christian G. Schütz
It has been documented that methadone maintenance treatment is effective in reducing drug craving and relevant risk behaviors in heroin users. However, it is not understood whether methadone maintenance treatment impairs the dopamine transporter in the striatum. To establish whether chronic opiate use might impair brain dopamine neurons in humans, we assessed dopamine transporter (DAT) uptake function in the striatum
Jie Shi; Li-Yan Zhao; Marc L. Copersino; Yu-Xia Fang; Yingmao Chen; Jiahe Tian; Yanping Deng; Yinliang Shuai; Jun Jin; Lin Lu
BackgroundMultiple substance use is a common problem among heroin users. This study aims to describe patterns of multiple substance use one year before and during attendance at methadone maintenance treatment (MMT) programs and associated variables of continued heroin use in MMT clinics in Yunnan, China.
Lei Li; Rassamee Sangthong; Virasakdi Chongsuvivatwong; Edward McNeil; Jianhua Li
Drug abuse is associated with epigenetic changes, such as histone modifications and DNA methylation. The purpose of the present study was to examine the effect of chronic cocaine and heroin administration on global DNA methylation in brain and liver. Male, 8 week old, C57BL/6J mice received heroin in a chronic 'intermittent' escalating dose paradigm, or cocaine in a chronic escalating dose 'binge' paradigm, which mimic the human pattern of opioid or cocaine abuse respectively. Following sacrifice, livers and brains were removed and DNA was extracted from them. The extracted DNA was hydrolyzed and 2'-deoxycytidine and 5-methyl-2'-deoxycytidine were determined by HPLC-UV. The % 5-methyl-2'-deoxycytidine content of DNA was significantly higher in the brain compared to the liver. There were no differences between the control animals and the cocaine or heroin treated animals in neither of the tissues examined, which is surprising since cocaine administration induced gross morphological changes in the liver. Moreover, there was no difference in the % 5-methyl-2'-deoxycytidine content of DNA between the cocaine and the heroin treated animals. The global DNA methylation status in the brain and liver of mice chronically treated with cocaine or heroin remains unaffected, but this finding cannot exclude the existence of anatomical region or gene-specific methylation differences. This is the first time that global DNA methylation in the liver and whole brain has been studied following chronic cocaine or heroin treatment. PMID:23454526
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.
Whilst unsupervised injectable methadone and diamorphine treatment has been part of the British treatment system for decades, the numbers receiving injectable opioid treatment (IOT) has been steadily diminishing in recent years. In contrast, there has been a recent expansion of supervised injectable diamorphine programs under trial conditions in a number of European and North American cities, although the evidence regarding the safety, efficacy and cost effectiveness of this treatment approach remains equivocal. Recent British clinical guidance indicates that IOT should be a second-line treatment for those patients in high-quality oral methadone treatment who continue to regularly inject heroin, and that treatment be initiated in newly-developed supervised injecting clinics. The Randomised Injectable Opioid Treatment Trial (RIOTT) is a multisite, prospective open-label randomised controlled trial (RCT) examining the role of treatment with injected opioids (methadone and heroin) for the management of heroin dependence in patients not responding to conventional substitution treatment. Specifically, the study examines whether efforts should be made to optimise methadone treatment for such patients (e.g. regular attendance, supervised dosing, high oral doses, access to psychosocial services), or whether such patients should be treated with injected methadone or heroin. Eligible patients (in oral substitution treatment and injecting illicit heroin on a regular basis) are randomised to one of three conditions: (1) optimized oral methadone treatment (Control group); (2) injected methadone treatment; or (3) injected heroin treatment (with access to oral methadone doses). Subjects are followed up for 6-months, with between-group comparisons on an intention-to-treat basis across a range of outcome measures. The primary outcome is the proportion of patients who discontinue regular illicit heroin use (operationalised as providing >50% urine drug screens negative for markers of illicit heroin in months 4 to 6). Secondary outcomes include measures of other drug use, injecting practices, health and psychosocial functioning, criminal activity, patient satisfaction and incremental cost effectiveness. The study aims to recruit 150 subjects, with 50 patients per group, and is to be conducted in supervised injecting clinics across England.
Methadone maintenance treatment (MMT) has elevated rates of co-morbid memory deficit and depression that are associated with higher relapse rates for substance abuse. White matter (WM) disruption in MMT patients have been reported but their impact on these co-morbidities is unknown. This study aimed to investigate changes in WM integrity of MMT subjects using diffusion tensor image (DTI), and their relationship with history of heroin and methadone use in treated opiate-dependent individuals. The association between WM integrity changes from direct group comparisons and the severity of memory deficit and depression was also investigated. Differences in WM integrity between 35 MMT patients and 23 healthy controls were evaluated using DTI with tract-based spatial statistical analysis. Differences in DTI indices correlated with diminished memory function, Beck Depression Inventory, duration of heroin use and MMT, and dose of heroin and methadone administration. Changes in WM integrity were found in several WM regions, including the temporal and frontal lobes, pons, cerebellum, and cingulum bundles. The duration of MMT was associated with declining DTI indices in the superior longitudinal fasciculus and para-hippocampus. MMT patients had more memory and emotional deficits than healthy subjects. Worse scores in both depression and memory functions were associated with altered WM integrity in the superior longitudinal fasciculus, para-hippocampus, and middle cerebellar peduncle in MMT. Patients on MMT also had significant WM differences in the reward circuit and in depression- and memory-associated regions. Correlations among decreased DTI indices, disease severity, and accumulation effects of methadone suggest that WM alterations may be involved in the psychopathology and pathophysiology of co-morbidities in MMT. PMID:22496768
The disposition of methadone, its metabolites, and other illicit drugs of abuse was investigated in head hair samples collected from heroin users (N = 20) enrolled in an outpatient detoxification study. Hair samples were assayed for methadone, methadone primary metabolite (2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine, EDDP), methadone secondary metabolite (2-ethyl-5-methyl-3,3-diphenylpyrroline, EMDP), cocaine, phencyclidine, heroin, and 6-acetylmorphine. Hair samples were cut, washed, and incubated in methanol. The methanolic hair wash and incubation fractions were purified with solid-phase extraction and assayed by gas chromatography-mass spectrometry. Methadone, methadone metabolites, cocaine, and phencyclidine were assayed quantitatively, and other drugs were measured qualitatively. The number of positive results and the corresponding concentration ranges were as follows: methadone, 0-15.0 ng/mg (N = 18); EDDP, trace (N = 13); EMDP, trace (N = 1); cocaine, 0->40 ng/mg (N = 14); phencyclidine, 0-1.5 ng/mg (N = 2); heroin, positive (N = 3); and 6-acetylmorphine, positive (N = 4). These data suggest that testing hair for methadone, methadone metabolites, and other illicit drugs of abuse may be useful to drug-treatment specialists as a means of verifying drug-use history, monitoring compliance, and providing a broad measure of drug exposure. PMID:9788529
Goldberger, B A; Darraj, A G; Caplan, Y H; Cone, E J
Opioid overdose, which is commonly associated with opioid induced respiratory depression, is a problem with both therapeutic and illicit opioid use. While the central mechanisms involved in the effects of opioids are well described, it has also been suggested that a peripheral component may contribute to the effects observed. This study aimed to further characterise the effects of the peripherally acting naloxone methiodide on the respiratory, analgesic and withdrawal effects produced by various opioid agonists. A comparison of the respiratory and analgesic effects of morphine, methadone and heroin in male Swiss-Albino mice was conducted and respiratory depressive ED(80) doses of each opioid determined. These doses (morphine 9 mg/kg i.p., methadone 7 mg/kg i.p., and heroin 17 mg/kg i.p.) were then used to show that both naloxone (3 mg/kg i.p.) and naloxone methiodide (30-100 mg/kg i.p.) could reverse the respiratory and analgesic effects of these opioid agonists, but only naloxone precipitated withdrawal. Further investigation in female C57BL/6J mice using barometric plethysmography found that both opioid antagonists could reverse methadone induced decreases in respiratory rate and increases in tidal volume. Its effects do not appear to be strain or sex dependent. It was concluded that naloxone methiodide can reverse the respiratory and analgesic actions of a variety of opioid agonists, without inducing opioid withdrawal. PMID:16102783
Lewanowitsch, Tanya; Miller, John H; Irvine, Rodney J
ObjectiveTo identify ethnic differences in HIV risk behaviors among cocaine using women receiving methadone maintenance for opioid dependence, and to evaluate the efficacy of contingency management (CM) for cocaine use disorders in reducing HIV risk behaviors.
Danielle Barry; Jeremiah Weinstock; Nancy M. Petry
|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…
Methadone maintenance treatment (MMT) might cause the impairments of neuropsychological and neurotransmitter function in opioid addicts. Whether long-term MMT could lead to the impairment of white matter (WM) in heroin addiction brain is unclear. This study compared the WM integrity in the bilateral frontal lobe, temporal lobe, splenium and genu of corpus collasum (CC) between MMT patients (n=13), former heroin addicts (n=11) in prolonged abstinence (PA), and healthy control subjects (n=15) using diffusion tensor imaging (DTI). Fractional anisotropy (FA), apparent diffusion coefficient (ADC) and eigenvalues (?(?), ?(||)) were measured. The correlation between DTI measures and accumulated former heroin dose, total methadone consumption, and PA duration were determined. Although the PA subjects showed no difference in DTI measures relative to the controls, the extensive correlations between the former heroin consumption and the DTI measures were noted. The MMT subjects showed a decreased FA values in the left genu, as well as the increased ADC and ?(?) values in the left splenium of CC in comparison to the controls. Compared with the PA, the MMT subjects had a significantly increased ADC value in the bilateral splenium of CC. Importantly, the methadone dosage used in the MMT group was correlated with the FA value in the left splenium of CC and in the right frontal lobe. Our preliminary results suggest that methadone plays a role in the impairment of WM integrity in heroin users on long-term MMT and the normalization of WM injury may occur during abstinence. PMID:21362458
Contingency management (CM) is an efficacious intervention for cocaine abusing methadone patients, but typically only about half of patients respond. By investigating time to onset of cocaine abstinence and factors associated with abstinence, we may be able to more efficiently direct CM approaches to patients most likely to benefit. Onset of cocaine abstinence was evaluated in cocaine abusing methadone maintenance patients (N = 193) enrolled in one of three randomized clinical trials of CM. Participants received standard treatment with frequent urine toxicology monitoring or standard treatment plus CM during the trials. Slightly more than half the sample obtained at least one week of cocaine abstinence, and approximately a third of the sample obtained at least four weeks of cocaine abstinence. Discrete-time survival and hazard analyses found Weeks 1 and 2 of the intervention period had the greatest probability for the initiation of abstinence, and few participants initiated any period of abstinence after Week 4. Patients randomized to CM, those with more years of cocaine use, and those with less recent cocaine use were more likely to achieve abstinence. Overall, these results indicate onset of cocaine abstinence is likely to occur early in treatment and in individuals with less severe cocaine use. Practical implications of these results for designing and implementing CM interventions in methadone maintenance clinics are discussed.
Weinstock, Jeremiah; Rash, Carla J.; Petry, Nancy M.
Rationale Exposure to intermittent episodes of social defeat stress can increase drug seeking and leads to intense drug taking in rats. Objectives This study investigated the consequences of repeated, intermittent social defeat stress on patterns of drug self-administration in rats with access to heroin, cocaine, or a heroin-cocaine combination (“speedball”). Methods Male Long-Evans rats were either handled (controls) or subjected to 25 min social defeat stress episodes on days 1, 4, 7 and 10 during confrontations with an aggressive resident. Ten days following the last defeat, rats were assessed for locomotor cross-sensitization in response to heroin or cocaine. Animals were then prepared with intrajugular catheters for drug self-administration. Separate groups of controls and defeated rats were examined for self-administration of heroin (Experiment 1), a heroin-cocaine combination (Experiment 2), or cocaine (Experiment 3). Drug self-administration patterns were evaluated using fixed or progressive ratio schedules (FR, PR respectively) of reinforcement during limited access sessions or a 24-h unlimited access binge. Results Rats with a history of intermittent social defeat stress showed sensitized locomotor behavior when challenged with heroin or cocaine relative to controls. During the 24-h binge session, defeated rats escalated cocaine taking behavior (ca. 110 mg/kg vs. 66 mg/kg in controls), persisted in self-administering cocaine or the heroin-cocaine mixture for more hours, and showed a tendency for increased heroin-cocaine intake, but no effects on heroin taking. Conclusions A history of social defeat stress seems to preferentially promote escalated intake of cocaine but not heroin, unless a heroin-cocaine combination is available.
Cruz, Fabio C.; Quadros, Isabel M.; Hogenelst, Koen; Planeta, Cleopatra S.; Miczek, Klaus A.
Voucher-based reinforcement of cocaine abstinence has been one of the most effective means of treating cocaine abuse in methadone\\u000a patients, but it has not been effective in all patients. This study was designed to determine if we could promote cocaine\\u000a abstinence in a population of treatment-resistant cocaine abusing methadone patients by increasing the magnitude of voucher-based\\u000a abstinence reinforcement. Participants were
Kenneth Silverman; Mary Ann Chutuape; George E. Bigelow; Maxine L. Stitzer
Introduction Acute intoxication with drugs of abuse in children is often only the tip of the iceberg, actually hiding chronic exposure. Analysis using non-conventional matrices such as hair can provide long-term information about exposure to recreational drugs. Case presentation We report the case of a one-month-old Caucasian boy admitted to our pediatric emergency unit with respiratory distress and neurological abnormalities. A routine urine test was positive for opiates, suggesting an acute opiate ingestion. No other drugs of misuse, such as cocaine, cannabis, amphetamines or derivatives, were detected in the baby's urine. Subsequently, hair samples from the baby and the parents were collected to evaluate the possibility of chronic exposure to drug misuse by segmental analysis. Opiates and cocaine metabolites were detected in hair samples from the baby boy and his parents. Conclusions In light of these and previous results, we recommend hair analysis in babies and children from risky environments to detect exposure to heroin and other drug misuse, which could provide the basis for specific social and health interventions.
Interviews were conducted with a sample of jailed intravenous opioid users who were not in treatment at the time of their arrest and who were admitted to an in-jail methadone maintenance program. At release, subjects were to be referred to dedicated slots in participating community methadone programs. Virtually all subjects were daily injectors of heroin and cocaine. Although the majority
We present the first crystal structures of a human protein bound to analogs of cocaine and heroin. Human carboxylesterase 1 (hCE1) is a broad-spectrum bioscavenger that catalyzes the hydrolysis of heroin and cocaine, and the detoxification of organophosphate chemical weapons, such as sarin, soman and tabun. Crystal structures of the hCE1 glycoprotein in complex with the cocaine analog homatropine and the heroin analog naloxone provide explicit details about narcotic metabolism in humans. The hCE1 active site contains both specific and promiscuous compartments, which enable the enzyme to act on structurally distinct chemicals. A selective surface ligand-binding site regulates the trimer-hexamer equilibrium of hCE1 and allows each hCE1 monomer to bind two narcotic molecules simultaneously. The bioscavenger properties of hCE1 can likely be used to treat both narcotic overdose and chemical weapon exposure. PMID:12679808
Bencharit, Sompop; Morton, Christopher L; Xue, Yu; Potter, Philip M; Redinbo, Matthew R
To examine dynamic changes in drug-use trajectories over time we analyzed episode types and predictors of quitting use over the 10 years following drug-use initiation for 1797 heroin, cocaine, and methamphetamine (meth) users. Most episodes reflected high use and incarceration, however these events occurred more frequently among heroin and meth users. Quitting was predicted by current treatment and self-help participation among
Yih-Ing Hser; Elizabeth Evans; David Huang; Mary-Lynn Brecht; Libo Li
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 abstinence-reinforcement groups could earn take-home methadone doses for providing opiate- and cocaine-free
Kenneth Silverman; Elias Robles; Timothy Mudric; George E. Bigelow; Maxine L. Stitzer
This study examined benefits of methadone maintenance among prerelease prison inmates. Incarcerated males with preincarceration heroin dependence (n = 197) were randomly assigned to (a) group educational counseling (counseling only); (b) counseling, with opportunity to begin methadone maintenance on release (counseling + transfer); or (c) counseling and methadone maintenance in prison, with opportunity to continue methadone maintenance on release (counseling + methadone). At 90-day follow-up, counseling + methadone participants were significantly more likely than counseling-only and counseling + transfer participants to attend drug treatment (p = .0001) and less likely to be reincarcerated (p = .019). Counseling + methadone and counseling + transfer participants were significantly less likely (all ps < .05) to report heroin use, cocaine use, and criminal involvement than counseling-only participants. Follow-up is needed to determine whether these findings hold over a longer period.
Kinlock, Timothy W.; Gordon, Michael S.; Schwartz, Robert P.; O'Grady, Kevin E.
... Civil Commitment,” which essentially placed heroin addicts in prison camps. After use of heroin (and other drugs) ... for example, that methadone maintenance treatment, begun in prison and continued in the community post-release, can ...
Researchers have identified the association between the use of cocaine and sexual behavior as an important risk factor for HIV infection and have attempted to elucidate the nature of this association. Several lines of research have suggested that facilitation of sexual behavior during intoxication with cocaine may be due to the direct pharmacological effects of the drug (e.g., increase in sexual desire), whereas others have pointed to the importance of factors related to the context of drug use (e.g., opportunities for sexual behavior, expectations about the effects of the drug, social norms). The present study explored the perceived effects of cocaine and heroin on sexual behavior, as well as the social context of drug use as a function of drug type (cocaine versus heroin), among 46 inner-city drug users who reported a history of regular use of both crack cocaine and heroin. Results indicated that compared to heroin, cocaine had deleterious effects on participants’ perceived sexual desire and performance. Despite such deleterious effects on sexual behavior, cocaine was more frequently used with an intimate partner than heroin. Furthermore, participants did not differ in the extent to which they used the two drugs in other social contexts (e.g. with friends, family or neighbors). These preliminary results suggest that the relationship between cocaine and sexual behavior, especially among long-term cocaine users, may be facilitated by opportunities for sex that exist in the context of cocaine use, rather than by the pharmacological effects of the drug.
Kopetz, Catalina E.; Reynolds, Elizabeth K.; Hart, Carl L.; Kruglanski, Arie W.; Lejuez, C.W.
Researchers have identified the association between the use of cocaine and sexual behavior as an important risk factor for HIV infection and have attempted to elucidate the nature of this association. Several lines of research have suggested that facilitation of sexual behavior during intoxication with cocaine may be because of the direct pharmacological effects of the drug (e.g., increase in sexual desire), whereas others have pointed to the importance of factors related to the context of drug use (e.g., opportunities for sexual behavior, expectations about the effects of the drug, social norms). The present study explored the perceived effects of cocaine and heroin on sexual behavior, as well as the social context of drug use as a function of drug type (cocaine vs. heroin), among 46 inner-city drug users who reported a history of regular use of both crack cocaine and heroin. Results indicated that compared to heroin, cocaine had deleterious effects on participants' perceived sexual desire and performance. Despite such deleterious effects on sexual behavior, cocaine was more frequently used with an intimate partner than heroin. Furthermore, participants did not differ in the extent to which they used the two drugs in other social contexts (e.g., with friends, family, or neighbors). These preliminary results suggest that the relationship between cocaine and sexual behavior, especially among long-term cocaine users, may be facilitated by opportunities for sex that exist in the context of cocaine use, rather than by the pharmacological effects of the drug. PMID:20545385
Kopetz, Catalina E; Reynolds, Elizabeth K; Hart, Carl L; Kruglanski, Arie W; Lejuez, C W
Concurrent alcohol dependence (AD) among polysubstance abusers has been associated with negative consequences, although it may not necessarily lead to poor treatment outcomes. One of the most efficacious treatments for cocaine abuse is contingency management (CM), but little research has explored the impact of AD on abstinence outcomes, particularly among patients in methadone maintenance. Using data from three trials of
This article investigates factors affecting the participation in marijuana, cocaine and heroin using micro-unit data from an Australian national survey on recreational drugs. Accounting for cross-drug correlation potentially induced by unobserved personal characteristics such as individual tastes and addictive personalities, we estimate a trivariate probit model, where the participation decisions are jointly modelled as a system with correlated error terms.
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
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
Byron L. Carnahan; Stephen Day; Viktor Kouznetsov; Alexandre Tarassov
Background This study examines 30-year trajectories of heroin and other drug use among men and women who were in methadone maintenance treatment in California in the late1970s and interviewed in 1978–1981. Methods Nearly half (n = 428; 46.8%) of the original study sample (N = 914) was deceased. Of the remaining 486 subjects, 343 (44.3% female) completed a follow-up interview in 2005-09 (70.6% of those not deceased). Average age at follow-up was 58.3 (SD = 4.9) years for males and 55.0 (SD = 4.1) years for females. Longitudinal data was obtained on their drug use, treatment participation, and criminal justice status over the follow-up period. Trajectory group modeling was used to identify distinctive trajectory groups based on monthly averages of heroin and other drug use per year; group differences were examined. Results Four heroin and five alcohol and other drug (AOD) trajectory groups were identified. A greater proportion of women (60%) were in the “rapid decrease” heroin group (odds of use less than 10% by 10 years following initiation of use) as compared with the other groups. More rapid decrease of heroin use was associated with increases in AOD use, whereas a gradual decrease in heroin use was associated with a gradual decrease in AOD use. More school problems and earlier age at onset of heroin use and first arrest were associated with more persistent heroin use. Conclusion Heroin-use trajectories were linked with changes in AOD use. Childhood antecedents of heroin-use trajectories were identified as well as gender differences.
BACKGROUND AND OBJETIVE: Methadone is largely used as the primary opioid substitution therapy for the treatment of heroin addiction; the objective of the study was to describe the clinical characteristics of heroin abusers admitted into a methadone maintenance program (MMP) in metropolitan Barcelona. METHOD: Cross-sectional study in patients enrolled in MMP since its introduction in 1992 through December 2010. Socio-demographic data, drug use characteristics, prevalence of blood-borne infections (human immunodeficiency virus [HIV], and hepatitis B [HBV] and C [HCV]) and psychiatric co-morbidity were assessed at entry. RESULTS: One thousand and six hundred seventy eight patients (82.8% male). A total of 608 (36.2%) patients were admitted during 1992-1996, 566 (33.7%) between 1997-2001, 305 (18.2%) between 2002-2006 and 199 (11.9%) in the last period. Age at admission to methadone increased significantly (28 years in period 1992-1996 vs. 37 years in the last period [P<.005]). The percentage of patients with a history of intravenous drug use decreased significantly (89.5% in first period vs. 56.4% in period 2007-2010 [P<.05]). Prevalence of HIV, HCV and HBV (HBcAb+) was 53.7, 73.6 and 61.3%, respectively. The prevalence of HIV decreased over time from 66.2% in first period to 43.5% in 2007-2010 (P<.05); the prevalence of HCV decreased significantly from 82.8% in 1992-1996 to 69.8% in last period (P<.05). Twenty five percent of patients had psychiatric co-morbidity at admission and the prevalence of psychiatric co-morbidity increased over time (21% in 1992-1996 and 32% in 2007-2010; P<.05). CONCLUSION: Age at first opioid substitution therapy is increasing over time, as well as the proportion of patients with psychiatric co-morbidity. There were significant reductions in blood-borne infections. PMID:23337454
This article analyzes hidden status among crack, powder cocaine, and heroin users and setters, in contrast to more accessible users/sellers. Several sampling strategies acquired 657 users (N=559) and sellers (N=98). Indicators of hidden status were those who (1) paid rent in full in the last 30 days, (2) used nonstreet drug procurement. (3) had legal jobs, and (4) earned $1,000 or more in legal income in the last 30 days. Nearly half had at least one indicator: approximately 16% of users/sellers had two to four indicators. In logistic regression analyses, those who had not panhandled in the last 30 days, those who had used powder cocaine in the last 30 days, and those never arrested were the most likely to have hidden status, whether the analysis predicted those having any indicators or those having two to four indicators. The four indicators begin to operationally define hidden status among users of cocaine and heroin.
Davis, W. Rees; Johnson, Bruce D.; Liberty, Hilary James; Randolph, Doris D.
This 18-month follow-up study examined the predictors of the severity of depressive symptoms among intravenous heroin users receiving methadone maintenance treatment (MMT) in Taiwan. The severity of depressive symptoms in 368 intravenous heroin users receiving MMT in southern Taiwan was assessed using the Center for Epidemiological Studies Depression scale at baseline and at 3, 6, 9, 12, 15, and 18 months of treatment. Demographic and substance-using characteristics, severity of heroin use, HIV serostatus, criminal record, and family function were collected during baseline interviews. Data on methadone dosage at each follow-up interview and the duration of retention in the MMT program were also collected. A generalized estimating equation was used to determine independent predictors of depressive symptoms during the 18-month period of MMT. Female gender, lack of fixed employment, severe heroin use, concurrent methamphetamine use, low family function at baseline, heroin use during the MMT, low methadone dosage, and short duration of participation in MMT predicted more severe depressive symptoms during the 18-month MMT. This study found that sociodemographic and substance-using characteristics at baseline predicted the severity of depressive symptoms among heroin users receiving MMT. Methadone dosage and MMT duration were also predictive of depression severity. The predictors found in this study can be used to identify heroin users who are at risk for depressive symptoms in the MMT program. PMID:21859169
To examine dynamic changes in drug-use trajectories over time we analyzed episode types and predictors of quitting use over the 10 years following drug-use initiation for 1797 heroin, cocaine, and methamphetamine (meth) users. Most episodes reflected high use and incarceration, however these events occurred more frequently among heroin and meth users. Quitting was predicted by current treatment and self-help participation among meth (RR 2.57, 1.79–3.70; 2.57, 1.80–3.67) and cocaine (RR 2.00, 1.42–2.81; 2.10, 1.63–2.72) users, and by a history of quitting for meth users (RR 1.11, 1.06–1.17). Quitting was less likely among all users under legal supervision (RR 0.55–0.69) and among heroin (RR 0.66, 0.45–0.97) and meth users (RR 0.73, 0.60–0.89) with an early drug-use onset. Relative to cocaine or meth use, heroin use was characterized by persistent use at a high-level which was often only interrupted by incarceration. While quitting drug use can be facilitated by treatment and/or self-help participation, few people had these experiences in the 10 years following first use.
The objective of this review is to describe self-administration procedures for modeling addiction to cocaine, cannabis and heroin in the human laboratory, the benefits and pitfalls of the approach, and the methodological issues unique to each drug. In addition, the predictive validity of the model for testing treatment medications will be addressed. The results show that all three drugs of abuse are reliably and robustly self-administered by non-treatment-seeking research volunteers. In terms of pharmacotherapies, cocaine use is extraordinarily difficult to disrupt either in the laboratory or in the clinic. A range of medications has been shown to significantly decrease cocaine's subjective effects and craving without decreasing either cocaine self-administration or cocaine abuse by patients. These negative data combined with recent positive findings with modafinil suggest that self-administration procedures are an important intermediary step between pre-clinical and clinical studies. In terms of cannabis, a recent study suggests that medications that improve sleep and mood during cannabis withdrawal decrease the resumption of marijuana self-administration in abstinent volunteers. Clinical data on patients seeking treatment for their marijuana use are needed to validate these laboratory findings. Finally, in contrast to cannabis or cocaine dependence, there are three efficacious Food and Drug Administration-approved medications to treat opioid dependence, all of which decrease both heroin self-administration and subjective effects in the human laboratory. In summary, self-administration procedures provide meaningful behavioral data in a small number of individuals. These studies contribute to our understanding of the variables maintaining cocaine, marijuana and heroin intake, and are important in guiding the development of more effective drug treatment programs. PMID:18855806
The simultaneous i.v. administration of heroin and cocaine, called a ‘speedball,’ is often reported clinically, and identification of effective pharmacotherapies is a continuing challenge. We hypothesized that treatment with combinations of a monoamine releaser d-amphetamine, and a mu partial agonist, buprenorphine, might reduce speedball self-administration by rhesus monkeys. Speedballs (0.01 mg\\/kg\\/inj cocaine+0.0032 mg\\/kg\\/inj heroin) and food (1 g banana-flavored pellets)
This article discusses drug purity, frequency of appearance and concentration ranges of adulterants of 471 illicit cocaine and 962 illicit heroin samples seized in Luxembourg from January 2005 to December 2010. For cocaine samples the mean concentration was lowest in 2009 (43.2%) and highest in 2005 (54.7%) but no clear trend could be observed during the last 6 years. 14 different adulterants have been detected in cocaine samples, from which phenacetin has been the most abundant in terms of frequency of appearance and concentration until 2009. In 2010 the veterinary antihelminthic drug levamisole has become the most abundant adulterant detected in cocaine samples, its concentrations however remained low (1.5-4.1%). The mean heroin concentration was 26.6% in 2005, a decline has been observed in 2006 and the concentrations have been relatively stable since then (15.8-17.4%). Paracetamol and caffeine were by far the most abundant adulterants detected in heroin samples. PMID:21767923
In the present investigation we tried to answer the question whether differences between heroin-dependent patients (n = 26, age: M = 24.96, SD = 6.30 years), a methadone substitution group (n = 20, age: M = 30.92, SD = 8.21 years) and a morphine substitution group (n = 20, age: M = 33.25, SD = 4.59 years) and healthy normals (n = 31, age: M = 25.07, SD = 4.62 years) could be found by means of measurement of electrodermal activity (SC, SCR, habituation of the SCR). Concerning "basal" skin conductance reflecting sympathetic activity, no significant differences were obtained. The methadone substitution group showed slight shortened onset latencies (information processing). In the morphine substitution group as compared to the other groups a small increase of the amplitude was observed indicating a slight increase in cognitive emotional intensity of appraisal after presentation of an acoustic stimulus. This small changes could be mediated by adaptation processes of the vegetative nervous system to the opioid, which occur "below" of those neuronal networks connected directly with the emotional stimuli processing. Concerning the speed of habituation no significant differences between the groups could be obtained. This indicates that no psychovegetative attenuation could be observed. The morphine substitution group as compared to the other groups was characterized by a longer persistence and a small increase of the intensity of excitement. However these variables ranged within normal limits and did not reach the level of statistical significance. This could be mediated by the effects of the opioid on the vegetative nervous system. PMID:12658967
This pilot trial explored the effectiveness of an adjunctive single session of motivational interviewing (MI) to reduce crack cocaine use in a methadone maintenance treatment population. Twenty-nine participants were cluster randomised by clinician to MI or a crack information control condition as part of treatment as usual. The intervention had a modest impact on one crack cocaine measure but was
|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.
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.
Kirby, Kimberly C; Kerwin, MaryLouise E; Carpenedo, Carolyn M; Rosenwasser, Beth J; Gardner, Robert S
This article analyzes hidden status among crack, powder cocaine, and heroin users and sellers, in contrast to more accessible users\\/sellers. Several sampling strategies acquired 657 users (N=559) and sellers (N=98). Indicators of hidden status were those who (1) paid rent in full in the last 30 days, (2) used nonstreet drug procurement, (3) had legal jobs, and (4) earned $1,000
W. Rees Davis; Bruce D. Johnson; Hilary James Liberty; Doris D. Randolph
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 average maximum of $300 in contingent prizes for 12 weeks. CM participants achieved longer
Nancy M. Petry; Sheila M. Alessi; Tressa Hanson; Sean Sierra
The risk of relapse into frequent heroin use was studied among 732 participants of the Amsterdam Cohort Study (ACS) on HIV\\/AIDS among drug users, who experienced an episode of abstinence from or occasional use of heroin. Participants of the ACS were recruited primarily from easy access (“low-threshold”) methadone programs. The duration of abstinence\\/occasional use and relative risks (RR) of relapse
Fabian Termorshuizen; Anneke Krol; Maria Prins; Ronald Geskus; Wim van den Brink; Erik J. C. van Ameijden
OBJECTIVE To evaluate the effect of rooming-in (rather than standard nursery care) on the incidence and severity of neonatal abstinence syndrome among opioid-exposed newborns and on the proportion of mothers who retain custody of their babies at hospital discharge. DESIGN Retrospective cohort study. SETTING Lower mainland in southwestern British Columbia. PARTICIPANTS We selected 32 women in the city of Vancouver known to have used heroin or methadone during pregnancy between October 2001 and December 2002. Comparison groups were a historical cohort of 38 women in Vancouver and a concurrent cohort of 36 women cared for in a neighbouring community hospital. MAIN OUTCOME MEASURES Need for treatment with morphine, number of days of treatment with morphine, and whether babies were discharged in the custody of their mothers. RESULTS Rooming-in was associated with a significant decrease in need for treatment of neonatal abstinence syndrome compared with the historical cohort (adjusted relative risk [RR] 0.40, 95% confidence interval [CI] 0.20 to 0.78) and the concurrent cohort (adjusted RR 0.39, 95% CI 0.20 to 0.75). Rooming-in was also associated with shorter newborn length of stay in hospital compared with both comparison groups. Newborns who roomed in at BC Women’s Hospital were significantly more likely to be discharged in the custody of their mothers than babies in the historical cohort (RR 2.23, 95% CI 1.43 to 3.98) or the concurrent cohort (RR 1.52, 95% CI 1.15 to 2.53) were. CONCLUSION Rooming-in might ease opioid-exposed newborns’ transition to extrauterine life and promote more effective mothering.
Abrahams, Ronald R.; Kelly, S. Ann; Payne, Sarah; Thiessen, Paul N.; Mackintosh, Jessica; Janssen, Patricia A.
In a previous study, steady-state methadone treatment was found to prevent associative cocaine learning, as well as related decreases in mRNA expression of preprohypocretin/preproorexin (ppHcrt) in the lateral hypothalamus (LH) and dopamine D2 receptor (DR2) in the caudate-putamen (CP), and increases in mu-opioid receptor in the ventral striatum of rats. To investigate whether the same regimen of methadone exposure could prevent the incubation of cocaine sensitization and related alterations in gene expression, male Sprague–Dawley rats received 45 mg/kg/day steadydose “binge” cocaine administration (IP) for 14 days followed by mini-pumps releasing 30 mg/kg/day methadone (SC). After 14 days of methadone, and a subsequent 10-day drug-free period, all rats were tested for sensitization (cocaine test dose: 15 mg/kg) and brain tissue was collected to quantify mRNA expression. Rats exposed to cocaine displayed cocaine-induced stereotypy at test, as well as enhanced ppHcrt mRNA in the LH and reduced DR2 mRNA in the CP. Importantly, these alterations were significantly reduced in rats treated with methadone following cocaine. These results suggest that steady-state methadone can interfere with the incubation of neuroadaptations underlying changes in behavioral responses to cocaine and cocaine-associated stimuli, and that these effects can be observed even after withdrawal from methadone.
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.
Schwartz, Robert P.; Kelly, Sharon M.; O'Grady, Kevin E.; Gandhi, Devang; Jaffe, Jerome H.
Cigarette smoking is ubiquitous among illicit drug users. Some have speculated that this may be partially due to similarities in the route of administration. However, research examining the relationship between cigarette smoking and routes of administration of illicit drugs is limited. To address this gap, we investigated sociodemographic and drug use factors associated with cigarette smoking among cocaine and heroin users in the Baltimore, Maryland community (N=576). Regular and heavy cigarette smokers were more likely to be White, have a history of a prior marriage, and have a lower education level. Regular smoking of marijuana and crack was associated with cigarette smoking, but not heavy cigarette smoking. Injection use was more common among heavy cigarette smokers. In particular, regular cigarette smokers were more likely to have a lifetime history of regularly injecting heroin. Optimal prevention and treatment outcomes can only occur through a comprehensive understanding of the interrelations between different substances of abuse.
Harrell, PT; Trenz, RC; Scherer, M; Ropelewski, LR; Latimer, WW
The diffusion and trends in use of each substance is a basic information in policy planning of strategies aiming at deterrence of drug abuse or in the organization of the fight against drug trafficking. The actual diffusion of illicit drugs in a population is hardly measurable, but, among the various measures available, the analysis of waste water plants represents one of the most reliable source of data. We analyzed waste water in order to monitor illicit drug use by local population. We investigated the use of cocaine and heroin in the city of Florence, Italy, over a 1-year (July 2006-June 2007) period using state-of-the-art measuring techniques from waste water samples. Cocaine, benzoylecgonine, and morphine were determined in water samples by gas chromatography-mass spectrometer, and the amount of illicit substance was estimated. Data indicate for cocaine a bimodal distribution (December and March), while heroin showed a main peak in April. The heroin-to-cocaine use ratio in terms of estimated doses per month ranged from 0.11 to 0.76, representing new evidence of wider distribution of cocaine than heroin in Florence. Waste water analysis can become a valuable tool in monitoring use of illicit drugs over time. In particular, it can highlight changes in the magnitude and relative use of illicit drug at a population level thereby becoming useful to develop strategies against drug trafficking and abuse. If routinely performed, it can be part of Epidemiologic Surveillance Programmes on drug abuse. PMID:19467810
Background Methadone treatment was introduced in Taiwan in 2006 as a harm-reduction program in response to the human immunodeficiency virus (HIV), which is endemic among Taiwanese heroin users. The present study was aimed at examining the clinical and behavioral characteristics of methadone patients in northern Taiwan according to their HIV status. Methods The study was conducted at four methadone clinics. Participants were patients who had undergone methadone treatment at the clinics and who voluntarily signed a consent form. Between August and November 2008, each participant completed a face-to-face interview that included questions on demographics, risk behavior, quality of life, and psychiatric symptoms. Data on HIV and hepatitis C virus (HCV) infections, methadone dosage, and morphine in the urine were retrieved from patient files on the clinical premises, with permission of the participants. Results Of 576 participants, 71 were HIV positive, and 514 had hepatitis C. There were significant differences between the HIV-positive and HIV-negative groups on source of treatment payment, HCV infection, urine test results, methadone dosage, and treatment duration. The results indicate that HIV-negative heroin users were more likely to have sexual intercourse and not use condoms during the 6 months prior to the study. A substantial percent of the sample reported anxiety (21.0%), depression (27.2%), memory loss (32.7%), attempted suicide (32.7%), and administration of psychiatric medications (16.1%). There were no significant differences between the HIV-positive and HIV-negative patients on psychiatric symptoms or quality of life. Conclusions HIV-positive IDUs were comorbid with HCV, indicating the need to refer both HIV- and HCV-infected individuals for treatment in methadone clinics. Currently, there is a gap between psychiatric/psychosocial services and patient symptoms, and more integrated medical services should be provided to heroin-using populations.
This study examined gender differences in heroin users who first received MMT. Compared with men, female heroin users were younger and more likely to be unemployed, to have family members using illicit substances, to initiate heroin use at a younger age, to begin MMT earlier after starting heroin use, to have methamphetamine use, to initiate methamphetamine use at a younger age, and to report a child-raising burden and a prior history of traumatic experiences. Men were more likely to have use of betel quid, and to initiate alcohol, nicotine and betel quid use at a younger age than women. PMID:23815421
The law enforcement and treatmentpolicies of the Nixon administration are oftencredited with ending the epidemic of heroinaddiction that rose in America's cities in the1960s. In this article it is argued thatalthough the interventions did in fact cause amajor change in heroin distribution and use,the epidemic did not end in any simple way. Thedecline in heroin and increase in methadonethat resulted
|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…
Severtson, Stevan G.; Hedden, Sarra L.; Martins, Silvia S.; Latimer, William W.
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.
Drug law enforcement aims to reduce the consumption of illicit drugs through reducing supply and increasing prices. Data on cocaine and heroin seizures, prices, and methods of trafficking are presented for 1983—93. Seizures, giving some indirect indicator of trafficking, rose sharply for both drugs in the second half of the the 1980s. Prices of both drugs showed a decline across
As part of an ongoing research program on the development of drug detection methodology, we developed an assay for the simultaneous measurement of cocaine, heroin and metabolites in plasma, saliva, urine and hair by solid-phase extraction (SPE) and gas chromatography-mass spectrometry (GC-MS). The analytes that could be measured by this assay were the following: anhydroecgonine methyl ester; ecgonine methyl ester;. ecgonine ethyl ester; cocaine; cocaethylene; benzoylecgonine; cocaethylene; norcocaethylene; benzoylnorecgonine; codeine; morphine; norcodeine; 6-acetylmorphine; normorphine; and heroin. Liquid specimens were diluted, filtered and then extracted by SPE. Additional handling steps were necessary for the analysis of hair samples. An initial wash procedure was utilized to remove surface contaminants. Washed hair samples were extracted with methanol overnight at 40 degrees C. Both wash and extract fractions were collected, evaporated and purified by SPE. All extracts were evaporated, derivatized with N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) with 1% trimethylchlorosilane (TMCS) and analyzed by GC-MS. The limit of detection (LOD) for cocaine, heroin and metabolites in biological specimens was approximately 1 ng/ml with the exception of norcodeine, normorphine and benzoylnorecgonine (LOD = 5 ng/ml). The LOD for cocaine, heroin and metabolites in hair was approximately 0.1 ng/mg of hair with the exception of norcodeine (LOD = 0.3 ng/mg) and normorphine and benzoylnorecgonine (LOD = 0.5 ng/mg). Coefficients of variation ranged from 3 to 26.5% in the hair assay. This assay has been successfully utilized in research on the disposition of cocaine, heroin and metabolites in hair, plasma, saliva and urine and in treatment studies. PMID:7866518
Animals were trained to traverse a straight alley for drug reinforcement consisting of five IV injections of either 0.75 mg/kg/injection cocaine (n = 6) or 0.06 mg/kg/injection heroin (n = 6). Testing involved single daily trials during which the latency to leave the start box and the time required to traverse the alley were recorded for each animal. In addition, input from 12 pairs of infrared photocell detector/emittors placed along the length of the alley provided information on the precise location of the animal at 0.1-s intervals throughout the course of each trial. This information was recorded by computer and provided the basis for construction of graphic representations of each trial in the form of spatiotemporal records that revealed the precise route the subject took in getting to the goal box. The experiment revealed substantial differences in the runway behavior of heroin and cocaine animals. While the heroin group exhibited typical patterns of operant performance in that both start latency and goal times decreased gradually over the course of the experiment, cocaine animals were reliably slower than heroin subjects to leave the start box and exhibited a progressive increase in goal times over trials. The latter effect appeared to be a consequence of a "stop and retreat" behavior that was observed in all six cocaine subjects and increased in frequency as the experiment progressed. Because the runway behaviors exhibited here were emitted prior to delivery of the drug reinforcer, they suggest that the motivational state underlying drug-seeking behavior is qualitatively different for heroin- and cocaine-reinforced animals. PMID:8430122
Background We hypothesize that the population with borderline personality shows different autonomic response to methadone compared to individuals with other personalities. This study applies heart rate variability (HRV) measurements and the Tridimensional Personality Questionnaire (TPQ) to examine this hypothesis. Methodology/Principal Findings Forty-four male patients with heroin dependence were recruited from a methadone maintenance treatment program. Eight personality patterns were classified according to the TPQ norm used in Taiwan. The borderline pattern (BP, composed of high novelty seeking, high harm avoidance and low reward dependence) and the other personality patterns (OP) were separated into two groups. We compared the HRV profiles between the BP and OP groups. Correlation and regression analysis were performed to clarify relationship between HRV differences and the borderline index (BI, a new concept defined by us, which is calculated as novelty seeking + harm avoidance – reward dependence). The HRV targets investigated included low frequency (LF) power, high frequency (HF) power, total power (TP), normalized LF (LF%), and LF/HF. No baseline HRV parameters showed any inter-group difference. The BP group had a significantly lower ?HF and a higher ?LF/HF than the OP group. The personality dimension, reward dependence, showed a negative correlation with ?LF/HF and ?LF%. BI was negatively correlated with ?HF and positively correlated with ?LF/HF and ?LF%. Conclusions/Significance Borderline personality individuals show increased sympathetic activity and decreased parasympathetic activity compared to other personalities after taking methadone. The results support the hypothesis that there is an interaction between borderline personality and autonomic modulation.
Huang, Wei-Lieh; Lin, Yu-Hsuan; Kuo, Terry B. J.; Chang, Li-Ren; Chen, Ying-Zai; Yang, Cheryl C. H.
Context: Most research on heroin dependence treat- ments assesses short-term changes in patients' self- reported drug use. To our knowledge, long-term sustainability of changes in patients' drug use and associated hospital morbidity posttreatment have not been studied. Objectives: To evaluate drug-related hospital morbid- ity in heroin users at 6 months and 3 1 Ú2 years after re- ceiving naltrexone implant
Alpha-2 adrenoceptor agonists (lofexidine, clonidine) are used to alleviate short-term opioid withdrawal in humans. In rats, acute injections of these agents attenuate stress-induced reinstatement of heroin and cocaine seeking at time points that are beyond the acute drug withdrawal phase. Here, we studied whether exposure to lofexidine would attenuate reinstatement of a heroin-cocaine mixture (speedball) seeking induced by exposure to
How methadone setting, duration of drug career, and dose impact on treatment are assessed. Two hundred fifteen participants were recruited. Analysis revealed significant reductions in drug use at 1 year within all settings, but the pattern varied. Proportions using heroin reduced in all settings, unprescribed benzodiazepines reduced in community, and general practitioner settings and cocaine use reduced in community and
Background Cocaine abuse and dependence continue to be widespread. Currently there are no pharmacotherapies shown to be effective in the treatment of cocaine dependence. Methods A 33-week outpatient clinical trial of fluoxetine (60 mg/day, p.o.) for cocaine dependence was conducted that incorporated abstinence-contingent voucher incentives. Participants (n=145) were both cocaine and opioid dependent and treated with methadone. A stratified randomization procedure assigned subjects to one of four conditions: fluoxetine plus voucher incentives (FV), placebo plus voucher incentives (PV), fluoxetine without vouchers (F), and placebo without vouchers (P). Dosing of fluoxetine/placebo was double blind. Primary outcomes were treatment retention and cocaine use based on thrice-weekly urine testing. Results The PV group had the longest treatment retention (mean of 165 days) and lowest probability of cocaine use. The adjusted predicted probabilities of cocaine use were: 65% in the P group, 60% in the F group, 56% in the FV group, and 31% in the PV group. Conclusions Fluoxetine was not efficacious in reducing cocaine use in patients dually dependent on cocaine and opioids.
Winstanley, Erin L.; Bigelow, George E.; Silverman, Kenneth; Johnson, Rolley E.; Strain, Eric C.
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.
Martell, Bridget A.; Orson, Frank M.; Poling, James; Mitchell, Ellen; Rossen, Roger D.; Gardner, Tracie; Kosten, Thomas R.
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.
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
The purpose of the current study was to assess neuropeptidergic alterations during a phase of the drug addiction cycle associated with drug craving as compared to a time period when the drug had been recently self-administered. Male Wistar rats were allowed to self-administer cocaine, heroin or saline for 6 h for 5 consecutive days. Immediately following the last self-administration session
Susanne L. T Cappendijk; Yasmin L Hurd; Ingrid Nylander; Jan M van Ree; Lars Terenius
To investigate the effect of naloxone on a putative memory consolidation process underlying reacquisition of heroin and cocaine conditioned place preference, four studies were conducted in male Sprague-Dawley rats using a common procedure involving: place conditioning (0.3 or 1mg/kg heroin or 20mg/kg cocaine; x4 sessions), extinction (vehiclex4 sessions), and reconditioning (0 or 1mg/kg heroin or 20mg/kg cocaine; x1 session). Systemic naloxone injections (0, 1 and 3mg/kg) or bilateral intra-ventral tegmental area (VTA) naloxone methiodide infusions (2 nmol in 0.5 microl x side) were administered at different times following reconditioning. Post-reconditioning administration of naloxone dose-dependently blocked, attenuated and had no effect on reacquisition of heroin CPP when administered immediately, 1h and 6h after reconditioning, respectively. The highest dose of naloxone also blocked reacquisition of cocaine CPP, and did not produce a conditioned place aversion in heroin-naïve and heroin pre-treated animals. Post-reconditioning infusions in the VTA, but not in adjacent structures, blocked reacquisition of heroin CPP when administered immediately, but not 6h, after reconditioning. These data suggest that reacquisition of drug-cues associations involves a memory consolidation process sensitive to manipulations of the endogenous opioid system, and indicate that opioid receptors in the VTA may be critically involved in the re-emergence of drug seeking behavior. PMID:19857583
Sticht, Martin; Mitsubata, Jackie; Tucci, Mark; Leri, Francesco
... immediately: difficulty breathing; extreme drowsiness; slow, shallow breathing; fast, slow, pounding, or irregular heartbeat; faintness; severe dizziness; or confusion.The risk that you will experience serious or life-threatening side effects of methadone is greatest when you first start ...
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.
de Castro, Ana; Concheiro, Marta; Shakleya, Diaa M.; 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 ?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.
Shakleya, Diaa M.; Dams, Riet; Choo, Robin E.; Jones, Hendree; Huestis, Marilyn A.
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.
Lankenau, Stephen E.; Wagner, Karla D.; Jackson Bloom, Jennifer; Sanders, Bill; Hathazi, Dodi; Shin, Charles
Background Despite growing concern about illicit methadone use in the US and other countries, there is little data about the prevalence and correlates of methadone use in large urban areas. We assessed the prevalence and examined correlates of lifetime and recent illicit methadone use in New York City (NYC). Methods 1,415 heroin, crack, and cocaine users aged 15–40 years were recruited in NYC between 2000 and 2004 to complete interviewer-administered questionnaires. Results In multivariable logistic regression, non-injection drug users who used illicit methadone were more likely to be heroin dependent, less than daily methamphetamine users and to have a heroin using sex partner in the last two months. Injection drug users who used illicit methadone were more likely to use heroin daily, share injection paraphernalia and less likely to have been in a detoxification program and to have not used marijuana in the last six months. Conclusion The results overall suggest that illicit (or street) methadone use is likely not a primary drug of choice, but is instead more common in concert with other illicit drug use.
Ompad, Danielle C; Fuller, Crystal M; Chan, Christina A; Frye, Victoria; Vlahov, David; Galea, Sandro
A new method was developed for the simultaneous detection and quantitation of 6-acetyl-morphine (MAM), amphetamine, benzoylecgonine (BZE), cocaine, codeine, dihydrocodeine, EDDP (methadone metabolite), methadone and morphine in hair. The hair samples were washed, cut into 2-cm segments, pulverized, incubated with phosphate buffer and beta-glucuronidase/aryl-sulfatase. After solid phase extraction and derivatization with pentafluoropropionic anhydride/pentafluoropropanol, the drugs were identified and measured by gas chromatography/mass spectrometry using their deuterated analogues as internal standards. The method is reproducible with detection limits under 0.1 ng/mg hair for almost all substances tested. Fifteen hair samples from five subjects of a methadone treatment program were collected in a 6-month period. The hair samples were segmented and examined for methadone, its main metabolite EDDP, and drugs of abuse. Of the 96 segments analysed, 95% were positive for methadone (mean value, 10.9 ng/mg), 76% for the metabolite EDDP (mean value, 1.2 ng/mg), 69% for opiates (mean values, MAM, 7.3 ng/mg; morphine, 2.9 ng/mg; codeine, 1.0 ng/mg) and 43% for cocaine (mean values, cocaine, 2.6 ng/mg; BZE, 1.1 ng/mg). A correlation of 0.63 was found between administered methadone dosages and concentrations measured by hair analysis. Further investigation is needed to clarify interindividual differences. PMID:8138220
Recent UK guidelines support the prescription of injectable heroin and methadone for opiate dependence, but many doctors disagree. Heroin has been prescribed in England for almost a hundred years, and the "British system" was once the subject of international curiosity. Since 1965, a prescriber licensing system has led to a great reduction in the proportion of opiate addicts treated with heroin. Recent trials in Switzerland and the Netherlands have prompted a review of British practice. It will probably remain somewhat different from continental practice, particularly with respect to long-term supervised injecting, but without adequate funding it may disappear altogether. PMID:16188711
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.
Schwartz, Robert P.; Kelly, Sharon M.; O'Grady, Kevin E.; Gandhi, Devang; Jaffe, Jerome H.
BACKGROUND. Interim methadone maintenance has been proposed as a method of providing clinically effective services to heroin addicts waiting for treatment in standard comprehensive methadone maintenance programs. METHODS. A clinic that provided initial medical evaluation, methadone medication, and AIDS education, but did not include formal drug abuse counseling or other social support services was established in New York City. A sample of 301 volunteer subjects recruited from the waiting list for treatment in the Beth Israel methadone program were randomly assigned to immediate entry into the interim clinic or a control group. RESULTS. There were no differences in initial levels of illicit drug use across the experimental and control groups. One-month urinalysis follow-up data showed a significant reduction in heroin use in the experimental group (from 63% positive at intake to 29% positive) with no change in the control group (62% to 60% positive). No significant change was observed in cocaine urinalyses (approximately 70% positive for both groups at intake and follow-up). A higher percentage of the experimental group were in treatment at 16-month follow-up (72% vs 56%). CONCLUSIONS. Limited services interim methadone maintenance can reduce heroin use among persons awaiting entry into comprehensive treatment and increase the percentage entering treatment.
Yancovitz, S R; Des Jarlais, D C; Peyser, N P; Drew, E; Friedmann, P; Trigg, H L; Robinson, J W
Methadone is a mu-opioid receptor agonist used for treating opiate dependence. The range of effective methadone doses is broad. Part of the large inter-individual variability in efficacy may be accounted for by genetic factors. Methadone is a substrate of the transporter P-glycoprotein (P-gp) 170 that is encoded by the ABCB1 (MDR1) gene. Thus, P-gp variants may play a role in methadone absorption and distribution. We assessed the association between ABCB1 polymorphisms and methadone dose requirements in 98 methadone-maintained patients. The stabilizing methadone doses were normally distributed with a mean and median dose of 160 mg/day (range 30–280 mg/day). Statistical analysis showed significant difference in genotype frequencies between the ‘higher’ (>150 mg/day) and ‘lower’ (?150 mg/day) methadone dose groups for single nucleotide polymorphism (SNP) 1236C>T (rs1128503) (experiment-wise P = 0.0325). Furthermore, individuals bearing the 3-locus genotype pattern TT-TT-TT (rs1045642, rs2032582 and rs1128503) have an approximately 5-fold chance of requiring the ‘higher’ methadone dose, while individuals heterozygous for these three SNPs have an approximately 3-fold chance of stabilizing at the ‘lower’ methadone dose (point-wise P-value = 0.026). These data suggest that specific ABCB1 variants may have clinical relevance by influencing the methadone dose required to prevent withdrawal symptoms and relapse in this population.
Methadone is a mu-opioid receptor agonist used for treating opiate dependence. The range of effective methadone doses is broad. Part of the large inter-individual variability in efficacy may be accounted for by genetic factors. Methadone is a substrate of the transporter P-glycoprotein (P-gp) 170 that is encoded by the ABCB1 (MDR1) gene. Thus, P-gp variants may play a role in
Orna Levran; Kimberly O'Hara; Einat Peles; Dawei Li; Sandra Barral; Brenda Ray; Lisa Borg; Jurg Ott; Miriam Adelson; Mary Jeanne Kreek
One therapeutic paradigm for cocaine abuse is a 24-h ‘agonist’ treatment which reduces reinforcing effects in a manner similar to the methadone maintenance model for heroin. However, 24-h dosing of dopamine (DA) agonists may induce side effects of insomnia and psychosis, as well as anergia and anhedonia which may actually potentiate abuse. Thus, it is important to determine the daily
Everett H Ellinwood; Colin Davidson; Guo-Zhong Yu; George R King; Tong H Lee
High rates of co-occurrence between posttraumatic stress (PTS) and substance use disorders (SUDs) have led to the suggestion that substance use among individuals experiencing PTS symptoms might serve a self-medication function. However, research is still needed to provide a more comprehensive evaluation of the unique associations between PTS symptom clusters and substances (licit and illicit) with both anxiolytic/depressant and stimulant properties. Consequently, this study examined the relationship between severity of different PTS symptom clusters and heroin, crack/cocaine, and alcohol dependence among 48 treatment-seeking SUD patients with a history of traumatic exposure. No evidence was found for a relationship between PTS symptom clusters and crack/cocaine or alcohol dependence; however, results suggested a relationship between hyperarousal and avoidance (inversely-related) symptoms and heroin dependence. Results are discussed in terms of their implications for understanding motivations underlying the substance of choice among individuals with PTS symptoms, as well as the development of treatments for co-occurring PTS and SUDs.
Tull, Matthew T.; Gratz, Kim L.; Aklin, Will M.; Lejuez, C.W.
A probability-based analytical sampling approach for seized containers of cocaine, Cannabis, or heroin, to answer questions of both content weight and identity, is described. It utilizes the Student's t distribution, and, because of the lack of normality in studied populations, the power of the Central Limit Theorem with samples of size 20 to calculate the mean net weights of multiple
We have found that peptide antagonists of corticotropin-releasing factor (CRF) receptors attenuate reinstatement of heroin\\u000a and cocaine seeking induced by footshock. Here we examined the effect of a non-peptide, selective CRF1 receptor antagonist, CP-154,526, on reinstatement of heroin and cocaine seeking induced by footshock. Rats were trained to\\u000a self-administer heroin or cocaine (0.1 and 1.0?mg\\/kg per infusion, IV, respectively) for
Y. Shaham; Suzanne Erb; Shirley Leung; Yvona Buczek; Jane Stewart
Objective: This study was undertaken to determine (1) the methadone serum trough level adequate to prevent withdrawal symptoms in heroin-addicted pregnant women and (2) whether the methadone serum trough level in symptomatic women with withdrawal symptoms differs from that of asymptomatic women. Study Design: Pregnant women addicted to heroin were followed up prospectively between March 1, 1999, and March 1,
John Drozdick; Vincenzo Berghella; MaryKay Hill; Karol Kaltenbach
In a population-based case-control study, we assessed the relation between cocaine use and the risk of low birth weight in Alameda County, California, excluding women who used heroin and/or methadone during pregnancy. After adjustment for confounders, the relative risk of low birth weight in users of cocaine throughout pregnancy was 4.0 (95% CI = 1.8, 8.9). Cocaine use was estimated to account for 10 percent of cases of low birth weight in Black women in Alameda County.
Aims This study examined the effectiveness of methadone maintenance initiated prior to or just after release from prison at 6 months post-release. Design A three-group randomized controlled trial was conducted between September 2003 and June 2005. Setting A Baltimore pre-release prison. Participants Two hundred and eleven adult pre-release inmates who were heroin-dependent during the year prior to incarceration. Intervention Participants were assigned randomly to the following: counseling only: counseling in prison, with passive referral to treatment upon release (n = 70); counseling + transfer: counseling in prison with transfer to methadone maintenance treatment upon release (n = 70); and counseling + methadone: methadone maintenance and counseling in prison, continued in a community-based methadone maintenance program upon release (n = 71). Measurements Addiction Severity Index at study entry and follow-up. Additional assessments at 6 months post-release were treatment record review; urine drug testing for opioids, cocaine and other illicit drugs. Findings Counseling + methadone participants were significantly more likely than both counseling only and counseling + transfer participants to be retained in drug abuse treatment (P = 0.0001) and significantly less likely to have an opioid-positive urine specimen compared to counseling only participants (P = 0.002). Furthermore, counseling + methadone participants reported significantly fewer days of involvement in self-reported heroin use and criminal activity than counseling only participants. Conclusions Methadone maintenance, initiated prior to or immediately after release from prison, increases treatment entry and reduces heroin use at 6 months post-release compared to counseling only. This intervention may be able to fill an urgent treatment need for prisoners with heroin addiction histories.
Gordon, Michael S.; Kinlock, Timothy W.; Schwartz, Robert P.; O'Grady, Kevin E.
Whilst unsupervised injectable methadone and diamorphine treatment has been part of the British treatment system for decades, the numbers receiving injectable opioid treatment (IOT) has been steadily diminishing in recent years. In contrast, there has been a recent expansion of supervised injectable diamorphine programs under trial conditions in a number of European and North American cities, although the evidence regarding
Nicholas Lintzeris; John Strang; Nicola Metrebian; Sarah Byford; Christopher Hallam; Sally Lee; Deborah Zador
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.
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.
A total of 95 Caucasian opioid-dependent patients were followed over a one-year pe- riod in an outpatient methadone treatment program. The frequency of the Taq IA 1 allele of the D2 dopamine receptor (DRD2) gene was 19.0% in these patients compared with 4.6% in controls free of past and current al- cohol and other drug abuse and free of fam-
Bruce R. Lawford; Ross Mc D. Young; Ernest P. Noble; Joanne Sargent; John Rowell; Susan Shadforth; Xuxian Zhang; Terry Ritchie
Little is known about bone mineral density (BMD) in patients with heroin addiction and subsequent methadone substitution. The goal of this study was to compare bone mass density of young HIV-negative women on long-term methadone treatment to a local group of young healthy women. Eleven women (aged 20-29) with previous heroin dependence and current methadone substitution (20-140 mg, median 60, daily) for 1.5-9 (median 3) years were compared to 30 healthy women (aged 20-28). Participants were examined with dual-energy X-ray absorptiometry of the lumbar spine (L2-L4), of the total proximal hip area, and of the femoral neck. Patients and controls had neither current nor lifetime underweight condition, had comparable ages at menarche, and did not differ significantly in current body mass index (21.9 ± 4.0, respectively, 20.5 ± 1.5 kg/m(2)) in spite of a largely unhealthy lifestyle (cigarette, alcohol, and cocaine consumption in patients). Patients' total-hip parameters were marginally lower than those of controls (BMD P = 0.054, T score P = 0.049), whereas the femoral neck and lumbar spine parameters did not differ significantly between the two groups. Long-term methadone substitution in HIV-negative women seems to slightly affect bone mass density. PMID:21698454
Milos, Gabriella; Gallo, Luigi M; Sosic, Branca; Uebelhart, Daniel; Goerres, Gerhard; Haeuselmann, Hans-Jörg; Eich, Dominique
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Relatively few studies have addressed the psychometric properties of self-report measures of amphetamine use. This study examines the reliability and validity of the Risk Behavior Assessment's (RBA) lifetime and recent amphetamine-use questions. To evaluate validity, 4027 out-of-treatment primarily cocaine and heroin users provided urine samples that were compared to self-report data; to evaluate reliability, 218 completed the RBA at two time points, 48 hours apart. In the overall sample, self-reports demonstrated moderately high validity, with a 95% accuracy rate (kappa =.54). When analysis was restricted to recent amphetamine users validity was slightly lower (71.5% accuracy; kappa = .41). Test-retest data indicated good reliability for self-reports of ever having used amphetamine (kappa =.79), and amphetamine use in the past 30 days (.75 < r < .91). Out-of-treatment drug users provided accurate self-reports of amphetamine use. Reliable and valid measures are essential for describing and predicting trends in amphetamine use, evaluating the effectiveness of interventions, and developing policies and programs.
Napper, Lucy E.; Fisher, Dennis G.; Johnson, Mark E.; Wood, Michele M.
Methadone (MET) metabolism has been largely demonstrated with a high inter-individual variability and, therefore, quantification of MET is very important for therapeutic drug monitoring. A cation-selective exhaustive injection and sweeping MEKC (CSEI-Sweeping) was first developed to analyze MET and its two metabolites, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) and 2-ethyl-5-methyl-3,3-diphenyl-1-pyrroline (EMDP), in human serum. After pretreatment, the samples were electrokinetically injected into capillary (10 kV, 500s) and swept by the separation phosphate buffer (100 mM, pH 4.0) containing 20% tetrahydrofuran and 100 mM SDS at -15 kV. The LODs were 200 pg/mL for MET and EMDP, and 400 pg/mL for EDDP. Ten volunteers were administered MET (5.0-120.0 mg/day) orally for 84 days and serum samples were taken after the daily dose of MET (days 1, 2, 7, 14, 28, 56 and 84) individually. This method was used for monitoring MET and its metabolites in heroin addicts and for pharmacokinetic investigations. PMID:21862022
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
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
The relationship between the reinforcing quality of the first drug experiences and eventual habits for a variety of drugs was studied in 42 male drug abusers who were predominantly opiate addicts. These subjects volunteered for drug studies carried out by the Addiction Research Center. The degree of reinforcement they derived from their first drug experience was related to their subsequent habit. This was true for alcohol, barbiturates, minor tranquilizers, cocaine, stimulants, marijuana, glue or solvents, hallucinogens, opiates other than heroin and heroin. Positive but non-significant correlations were found for coffee and major tranquilizers. The correlation for cigarettes was contrary to expectations. Of the components to the index of reinforcement, degree of liking of a drug on the first occasion was most related to the subsequent habit. The greatest initial reinforcement scores were found for heroin, cocaine and opiates other than heroin. drugs which were not well liked on the first occasion included major tranquilizers, cigarettes, coffee, and glue. PMID:6134605
|This compilation of journal articles on cocaine includes a report describing cocaine as the recreational drug of the middle class, statistics from the United States Department of Health on health consequences of cocaine use, an article on "speedballing" (use of cocaine and heroin in combination), and a discussion of the various ways cocaine is…
This review summarizes the major metabolic pathways of the drugs of abuse, tetrahydrocannabinol, cocaine, heroin, morphine, and codeine, in humans including the involvement of isoenzymes. This knowledge may be important for predicting their possible interactions with other xenobiotics, understanding pharmaco-/toxicokinetic and pharmacogenetic variations, toxicological risk assessment, developing suitable toxicological analysis procedures, and finally for understanding certain pitfalls in drug testing. The detection times of these drugs and/or their metabolites in biological samples are summarized and the implications of the presented data on the possible interactions of drugs of abuse with other xenobiotics, ie, inhibition or induction of individual polymorphic and nonpolymorphic isoenzymes, discussed. PMID:16778732
Maurer, Hans H; Sauer, Christoph; Theobald, Denis S
Abnormal serotonergic pathways are implicated in numerous neuropsychiatric disorders including alcohol and drug dependence (abuse). The human 5-hydroxytryptamine (serotonin) receptor 1B, encoded by the HTR1B (5-HT1B) gene, is a presynaptic serotonin autoreceptor that plays an important role in regulating serotonin synthesis and release. Although there was evidence of associations of the HTR1B gene variants in the etiologies of substance use disorders, negative findings were also reported. To clarify the roles of commonly reported single nucleotide polymorphisms (SNPs) of the HTR1B gene underlying alcohol and drug dependence (abuse), we performed a meta-analysis based on the available genotype data from individual candidate gene-based association studies. Evidence of association was found between the functional SNP -161A>T (rs130058) and alcohol, cocaine, and heroin dependence (e.g., P = 0.03 and odds ratio (OR) = 1.2 (1.02, 1.42) in the combined European, Asian, African, and Hispanic populations). SNP -261T>G (rs11568817) also showed evidence of association but with different directions in Europeans and non-Europeans (e.g., P = 0.0018 with OR = 1.42 (1.14, 1.76) and P = 0.01 with ORs = 0.5 (0.3, 0.85), respectively). This meta-analysis supports the associations of HTR1B -261T>G and -161A>T with alcohol and drug abuse and further investigations are warranted in larger samples. PMID:23335468
1. Methadone is a synthetic narcotic that relieves the craving for heroin. Methadone enables the former heroin addict to feel well and unimpaired by side effects, and be free of heroin hunger. 2. Methadone Anonymous (MA) is a 12-step program (similar to Alcoholics Anonymous and Narcotics Anonymous) for individuals with addictions who are in methadone treatment programs. 3. The MA program at our facility in New York has been extremely successful. Patients carry the message to new sites and leave information for potential groups. Requests for information are received weekly, both from neighboring states and even abroad. PMID:7844771
Barry McCaffrey, the White House drug policy director, called for improved methadone maintenance treatment programs for heroin addicts. McCaffrey referred to the incarceration of heroin addicts as a failed social policy. Speaking at a heroin addiction conference sponsored by the National Institute of Drug Abuse, McCaffrey told participants that heroin addicts who are not enrolled in methadone treatment programs are exposed to HIV infection through shared drug needles and unprotected sexual relations. PMID:11364789
This study examined the impact of prison-initiated methadone maintenance at 12-months post-release. Males with pre-incarceration heroin dependence (n=204) were randomly assigned to: 1) Counseling Only: counseling in prison, with passive referral to treatment upon release; 2) Counseling+Transfer: counseling in prison with transfer to methadone maintenance treatment upon release; and 3) Counseling+Methadone: counseling and methadone maintenance in prison, continued in the community upon release. The mean number of days in community-based drug abuse treatment were, respectively, Counseling Only 23.1, Counseling+Transfer 91.3, and Counseling+Methadone 166.0, p <.01; all pairwise comparisons were statistically significant (all ps < .01). Counseling+Methadone participants were also significantly less likely than participants in each of the other two groups to be opioid-positive or cocaine-positive according to urine drug testing. These results support the effectiveness of prison-initiated methadone for males in the United States. Further study is required to confirm the findings for women.
Kinlock, Timothy W.; Gordon, Michael S.; Schwartz, Robert P.; Fitzgerald, Terrence T.; O'Grady, Kevin E.
A retrospective analysis was made of the criminal records of 57 patients successfully retained in methadone maintenance at two general practices in Sheffield. Their criminal conviction rates and time spent in prison per year were compared for the periods before and after the start of their methadone programme. Overall, patients retained on methadone programmes in the general practices studied had significantly fewer convictions and cautions, and spent significantly less time in prison than they had before the start of treatment.
Keen, J; Rowse, G; Mathers, N; Campbell, M; Seivewright, N
Background Heroin is a synthetic opioid with an extensive illicit market leading to large numbers of people becoming addicted. Heroin users often present to community treatment services requesting detoxification and in the UK various agents are used to control symptoms of withdrawal. Dissatisfaction with methadone detoxification  has lead to the use of clonidine, lofexidine, buprenorphine and dihydrocodeine; however, there remains limited evaluative research. In Leeds, a city of 700,000 people in the North of England, dihydrocodeine is the detoxification agent of choice. Sublingual buprenorphine, however, is being introduced. The comparative value of these two drugs for helping people successfully and comfortably withdraw from heroin has never been compared in a randomised trial. Additionally, there is a paucity of research evaluating interventions among drug users in the primary care setting. This study seeks to address this by randomising drug users presenting in primary care to receive either dihydrocodeine or buprenorphine. Methods/design The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS) project is a pragmatic randomised trial which will compare the open use of buprenorphine with dihydrocodeine for illicit opiate detoxification, in the UK primary care setting. The LEEDS project will involve consenting adults and will be run in specialist general practice surgeries throughout Leeds. The primary outcome will be the results of a urine opiate screening at the end of the detoxification regimen. Adverse effects and limited data to three and six months will be acquired.
Oldham, Nicola S; Wright, Nat MJ; Adams, Clive E; Sheard, Laura; Tompkins, Charlotte NE
Methadone maintenance has been evaluated since its development in 1964 as a medical response to the post-World War II heroin epidemic in New York City. The findings of major early studies have been consistent. Methadone mainte- nance reduces and\\/or eliminates the use of heroin, reduces the death rates and criminality associated with heroin use, and allows patients to improve their
A probability-based analytical sampling approach for seized containers of cocaine, Cannabis, or heroin, to answer questions of both content weight and identity, is described. It utilizes the Student's t distribution, and, because of the lack of normality in studied populations, the power of the Central Limit Theorem with samples of size 20 to calculate the mean net weights of multiple item drug seizures. Populations studied ranged between 50 and 1200 units. Identity determination is based on chemical testing and sampling using the hypergeometric distribution fit to a program macro - created by the European Network of Forensic Science Institutes (ENFSI) Drugs Working Group. Formal random item selection is effected through use of an Excel-generated list of random numbers. Included, because of their impact on actual practice, are discussions of admissibility, sufficiency of proof, method validation, and harmony with the guidelines of international standardizing bodies. PMID:20137872
|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)|
Researchers have identified the association between the use of cocaine and sexual behavior as an important risk factor for HIV infection and have attempted to elucidate the nature of this association. Several lines of research have suggested that facilitation of sexual behavior during intoxication with cocaine may be because of the direct pharmacological effects of the drug (e.g., increase in
Catalina E. Kopetz; Elizabeth K. Reynolds; Carl L. Hart; Arie W. Kruglanski; C. W. Lejuez
Longer lengths of stay in methadone treatment have been associated with greater treatment benefits such as reductions in heroin use and criminal activity. In this paper, the first of two concentrating on costs of methadone treatment, the positive monetary returns from investments in longer-term methadone treatment for opioid users who participated in NIDA's Drug Abuse Treatment Outcome Studies (DATOS) are
Patrick M. Flynn; James V. Porto; Jennifer L. Rounds-Bryant; Patricia L. Kristiansen
|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)|
Although improvement in psychosocial functioning is a common goal in substance-abuse treatment, the primary outcome measure in most cocaine trials is urinalysis-verified cocaine use. However, the relationship between cocaine use and psychosocial outcomes is not well documented. To investigate this relationship and identify the optimal urine-screen method, we retrospectively analyzed data from two 25-week randomized controlled trials of abstinence reinforcement (AR) in 368 cocaine/heroin users maintained on methadone. Cocaine use was measured thrice weekly by qualitative urinalysis, benzoylecgonine concentration (BE), and an estimate of New Uses of cocaine by application of an algorithm to BE. Social adjustment (SAS-SR), current diagnosis of cocaine dependence (DSM-IV criteria), and depression symptoms (Beck Depression Inventory) were determined at study exit. Cocaine use was significantly lower in AR groups than in controls. Across groups, in-treatment cocaine use was significantly associated with worse social adjustment, current cocaine dependence, and depression at exit. Significant differences were detected more frequently with New Uses than qualitative urinalysis or BE. Nevertheless, the amount of variance accounted for by the urine screens was typically <15%. Cocaine use during treatment, especially when measured with New Uses criteria, can predict psychosocial functioning, but cannot substitute for direct measures of psychosocial functioning.
Ghitza, Udi E.; Epstein, David H.; Preston, Kenzie L.
Methadone maintenance treatment has been shown in many studies to reduce mortality and morbidity among heroin users. However, there has been concern that widespread methadone prescribing will lead conversely to an increase in methadone-related deaths. This study in Sheffield shows no increase in methadone-related mortality over a two-year period, during which 400 untreated patients were recruited into primary care methadone treatment in the city.
Urine specimens from methadone treatment clinics were screened for various abused drugs between 1974-1979 by thin-layer chromatography (TLC) and immunoassay techniques (IAT). A comparison of the relative incidence of drugs abused reveals that IAT are more sensitive and detect far greater number of subjects abusing drugs than TLC. The results also show a significant abuse of heroin and cocaine during the period studied and a variation of the incidence of other drugs used during the same period. While these patients did not receive benzodiazepenes and tricyclic antidepressants by prescription, their abuse alone and in combination with each other was also found to be widespread. Low levels of PCP and/or its analogs were found in 1978 and 1979. The frequent finding of low levels of PCP in combination with other drugs indicates the availability of this hallucinogen and point to its use in combination with other illicit drugs such as cocaine, amphetamine, and heroin. The suggestion is made that more sensitive analytical methods for drugs screening be utilized in methadone monitoring programs, and that other classes of drugs be added than are currently required. PMID:7304510
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
Although spirituality is an integral component of some of the most popular approaches to substance abuse treatment, there is little empirical evidence for a causal relationship between spirituality and treatment success. In the present study, 169 (121 male) opiate- or cocaine-abusing treatment seekers completed the Index of Spiritual Experience (INSPIRIT), a questionnaire that assesses both spirituality and religiosity. Responses were
Adrienne Heinz; David H. Epstein; Kenzie L. Preston
Available data (this review includes old major articles and recent articles) show that, although results are heterogenous, methadone maintenance treatments (MMTs) have a real efficiency not only to reduce illicit opiate abuse (50–80% of patients under MMT did not use heroin in the preceding month) but also to reduce criminality, HIV risks and mortality, and to improve social rehabilitation, without
Heroin dependence (HD) is a chronic relapsing brain disorder characterized by a compulsion to seek and use heroin. Stress is seen as a key factor for heroin use. Methadone maintenance and the prescription of pharmaceutical heroin [diacetylmorphine (DAM)] are established treatments for HD in several countries. The present study examined whether DAM-maintained patients and methadone-maintained patients differ from healthy controls in startle reflex and cortisol levels. Fifty-seven participants, 19 of each group matched for age, sex and smoking status, completed a startle session which included the presentation of 24 bursts of white noise while eye-blink responses to startling noises were recorded. Salivary cortisol was collected three times after awakening, before, during and after the startle session. DAM was administered before the experiment, while methadone was administered afterwards. Both heroin-dependent patient groups exhibited significantly smaller startle responses than healthy controls (P < 0.05). Whereas the cortisol levels after awakening did not differ across the three groups, the experimental cortisol levels were significantly lower in DAM-maintained patients, who received their opioid before the experiment, than in methadone-maintained patients and healthy controls (P < 0.0001). Opioid maintenance treatment for HD is associated with reduced startle responses. Acute DAM administration may suppress cortisol levels, and DAM maintenance treatment may represent an effective alternative to methadone in stress-sensitive, heroin-dependent patients. PMID:20331562
Walter, Marc; Wiesbeck, Gerhard A; Degen, Bigna; Albrich, Jürgen; Oppel, Monika; Schulz, André; Schächinger, Hartmut; Dürsteler-MacFarland, Kenneth M
In 1998, two clinical trials were started in the Netherlands to evaluate the effect of coprescription of heroin and methadone on the mental and physical health and social functioning of chronic, treatment-resistant, heroin-dependent patients. Since 75 - 85% of the heroin addicts in the Netherlands use their heroin by ''chasing the dragon,'' one of the two study arms concerned the
M. G. Klous; B. Nuijen; W. van den Brink; Ree van J. M; J. H. Beijnen
We were able to show for 21 patients who were all HIV-negative at the beginning of the methadone maintenance program of the Drop-in in Zurich that they remained HIV-negative over an average period of 34 months. At the beginning of the program 48% of the patients had a good social integration with few contacts to the drug scene for buying or selling drugs. During the program this figure increased to 90%. Before starting the program 43% of these HIV-negative patients were at high risk (needle sharing). During the maintenance program 57% of the patients became clean of heroin and 76% clean of cocaine. The remaining obviously abstained from needle sharing due to a continuous information concerning HIV-prevention. We conclude that a well structured methadone maintenance program with a close, consistent and enduring relationship between staff and patients can be of great importance in HIV-prevention among IV drug abusers. PMID:2218224
This study compares interim maintenance (IM) to a waiting list condition at an opioid treatment program (OTP). As defined by US federal regulations, IM provides observed methadone dosing and emergency counseling only for a maximum of 120 days. Three hundred and nineteen individuals enrolled on an OTP waiting list were randomly assigned on a 3:2 basis to either IM or waiting list control. Outcomes were measured at OTP entry (or at 4 months from baseline for those who did not enter treatment), and 6 months thereafter. At the second follow-up, 129 (64.8%) of the IM participants reported being enrolled in an OTP, versus 33 (27.5%) of the controls, p<.001. Significant treatment conditionxtime interaction effects occurred for heroin and cocaine use (both p's<.001) and the ASI Legal composite score (p<.001). Moreover, a significant difference occurred between conditions at the second follow-up for heroin-positive drug tests (interim 48.1% versus control 72.3%, p=.001) but not for cocaine-positive drug tests. At 10 months after study enrollment, there are sustained benefits of IM as compared to waiting list in terms of increased treatment entry and reduced heroin use and criminal behavior. PMID:16793221
Schwartz, Robert P; Jaffe, Jerome H; Highfield, David A; Callaman, Jason M; O'Grady, Kevin E
The Therapeutic Workplace is an employment-based treatment for drug addiction that uses wages for work to reinforce drug abstinence. The Therapeutic Workplace has promoted abstinence from heroin and cocaine in treatment-resistant mothers in methadone treatment. This study attempted to replicate that effect in crack cocaine users recruited from community-based methadone programs. Participants were randomly assigned to a Therapeutic Workplace (n=22) or usual care control (n=25) group. Therapeutic Workplace participants were invited to work in the workplace and earn vouchers every weekday for 9 months contingent on documented opiate and cocaine abstinence. The two groups did not differ significantly on measures of cocaine or opiate use collected during study participation. Daily attendance and urinalysis results of the Therapeutic Workplace group were analyzed, and only 7 of the 22 participants initiated consistent periods of abstinence and workplace attendance. Two individuals gained access to the workplace on a few days, and 9 participants attempted to gain access to the workplace but never provided a drug-negative urine sample. Possible reasons for differences between the current study and the previous Therapeutic Workplace study are considered. Procedures that increase participant contact with the Therapeutic Workplace and its reinforcement contingencies might increase the likelihood of these individuals being successful in the treatment program. PMID:16893278
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.
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%,
|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…
Pharmaceutical heroin for inhalation was developed for a clinical trial on co-prescription of heroin and methadone to chronic treatment-resistant heroin addicts. Diacetylmorphine base was selected as the active pharmaceutical ingredient for this product with caffeine anhydrate added as an excipient. Differential scanning calorimetry and thermogravimetric analysis showed that addition of caffeine resulted in a lower melting temperature and a higher
Marjolein G. Klous; Gaby M. Bronner; Bastiaan Nuijen; Jan M. van Ree; Jos H. Beijnen
Twelve-month treatment of heroin addicts with methadone or buprenorphine normalized plasma cortisol levels, and controlled withdrawal symptoms as well as craving. During treatment, the time course of plasma cortisol levels and craving was not strictly correlated: heroin craving was more elevated at 12 than at 3 months.The results suggest a correlation between hypercortisolism, withdrawal symptoms and heroin use and suppose
The current study represents an initial investigation of the association between heroin use and anxiety sensitivity (AS). Within a sample of 172 inner-city treatment seeking drug users, AS was compared across past year (1) heroin users with no crack\\/cocaine use (n=12); (2) crack\\/cocaine users with no heroin use (n=66); (3) users of both heroin and crack\\/cocaine (n=45); and (4) individuals
C. W. Lejuez; A. Paulson; S. B. Daughters; M. A. Bornovalova; M. J. Zvolensky
The success of methadone maintenance treatment as a tool to reduce offending depends not only on the effectiveness of the treatment in reducing clients' offending, but also on the ability of the treatment to attract dependent heroin users who engage in crime. This study examines the criminal histories of 503 persons drawn from the New South Wales methadone program register.
Karen Freeman; Craig Jones; Richard Mattick; Don Weatherburn
Background Previous studies have shown elevated rates of health-related harms among Aboriginal people who use injection drugs such as heroin. Methadone maintenance therapy is one of the most effective interventions to address the harms of heroin injection. We assessed the rate of methadone use in a cohort of opioid injection drug users in Vancouver and investigated whether methadone use was associated with Aboriginal ethnic background. Methods Using data collected as part of the Vancouver Injection Drug Users Study (May 1996–November 2005), we evaluated whether Aboriginal ethnic background was associated with methadone use using generalized estimating equations and Cox regression analysis. We compared methadone use among Aboriginal and non-Aboriginal injection drug users at the time of enrolment and during the follow-up period, and we evaluated the time to first methadone use among people not using methadone at enrolment. Results During the study period, 1603 injection drug users (435 Aboriginal, 1168 non-Aboriginal) were recruited. At enrolment, 54 (12.4%) Aboriginal participants used methadone compared with 247 (21.2%) non-Aboriginal participants (odds ratio [OR] 0.53, 95% confidence interval [CI] 0.38–0.73, p < 0.001). Among the 1351 (84.3%) participants who used heroin, Aboriginal people were less likely to use methadone throughout the follow-up period (adjusted OR 0.60, 95% CI 0.45–0.81, p < 0.001). Among people using heroin but who were not taking methadone at enrolment, Aboriginal ethnic background was associated with increased time to first methadone use (adjusted relative hazard 0.60, 95% CI 0.49–0.74, p < 0.001). Interpretation Methadone use was lower among Aboriginal than among non-Aboriginal injection drug users. Culturally appropriate interventions with full participation of the affected community are required to address this disparity.
Wood, Evan; Montaner, Julio S.; Li, Kathy; Barney, Lucy; Tyndall, Mark W.; Kerr, Thomas
The prevalence of methadone-related overdose deaths is increasing worldwide and has been a topic of recent debate. Methadone-related deaths, to this point, have not been systematically reviewed in the state of Vermont. All of the methadone-related fatalities from 2001 to 2006 (total, 76 cases), which were examined by the Vermont Office of the Chief Medical Examiner were retrospectively reviewed. The mean age of the decedents was 36 years (range, 16-74 years), and 72% were male. The manners of death were classified as follows: 84% accident, 12% undetermined, and 4% suicide. The mean level of methadone was 457 ng/mL (range, 50-3793 ng/mL). The substances causing death were determined to be methadone alone in 26 (34%), methadone with only other prescribed medications in 29 (38%), methadone with only illicit drugs (excluding tetrahydrocannabinol) in 13 (17%), methadone with both illicit and prescribed medications in 5 (7%), and methadone with ethanol in 3 (4%). The methadone was obtained by illegal diversion (sale, gift, or theft) in 67% of cases. In the remaining cases (33%), the methadone was obtained by physician's prescription for chronic pain (60%), acute pain or injury (8%), methadone maintenance therapy for heroin dependence (8%), and unknown reasons (24%). The number of overdose deaths has increased 4-fold from 2001 (17 deaths) to 2006 (79 deaths). The proportion of methadone-related deaths has increased by 300% from 2001 (0.6% of reported deaths, 12% of overdose deaths) to 2006 (3% of reported deaths, 37% of overdose deaths). Methadone maintenance therapy for heroin dependence in our population comprises an insignificant number of the methadone-related deaths (3% of the decedents). In Vermont, the populations most at risk are those taking methadone for chronic pain and those obtaining diverted methadone for abuse. Education of clinicians regarding the increasing number of methadone-related deaths, the potential for abuse and diversion, and the pharmacokinetics of methadone may help halt this epidemic and reduce the number of fatalities from this drug. PMID:21030851
Objective Measurement of plasma methadone concentration to investigate the rate of clearance of methadone prescribed for heroin dependence\\u000a in the first, second and third trimesters of pregnancy. A secondary objective was to evaluate the outcome of pregnancy.\\u000a \\u000a \\u000a \\u000a Methods Longitudinal within subject study of nine pregnant opioid dependent subjects prescribed methadone at the Leeds Addiction Unit,\\u000a an outpatient community based treatment centre. Plasma
Kim Wolff; Annabel Boys; Amin Rostami-Hodjegan; Alastair Hay; Duncan Raistrick
Heroin is an illicit, highly addictive drug. It is either the most abused or the most rapidly acting member of opioids. Abusers describe a feeling of a surge of pleasurable sensation, named as "rush" or "high". Repeated administration of high doses of heroin results in the induction of physical dependence. Physical dependence refers to an altered physiological state produced by chronic administration of heroin which necessitates the continued administration of the drug to prevent the appearance of a characteristic syndrome, the opioid withdrawal or abstinence syndrome. Withdrawal symptoms may occur within a few hours after the last administration of heroin. Symptoms of the withdrawal include restlessness, insomnia, drug craving, diarrhea, muscle and bone pain, cold flashes with goose bumps, and leg movements. Major withdrawal symptoms peak between 48 and 72 hours after the last dose of heroin and subside after about a week. At this time, weakness and depression are pronounced and nausea and vomiting are common. Nevertheless, some chronic addicts have shown persistent withdrawal signs for many months or even years. Heroin addiction is considered as a behavioural state of compulsive drug use and a high tendency to relapse after periods of abstinence. It is generally accepted that compulsive use and relapse are typically associated with the status of heroin craving or heroin hunger that are difficult to define but appear to be powerful motivational significance in the addiction process. The route of administering heroin varies largely and may indicate the degree of seriousness of the individual's addiction. Intravenous administration seems to be the predominant method of heroin use, but recently a shift in heroin use pattern has been found, i.e. from injection to sniffing and smoking. Frequent injections coupled with widespread sharing of syringes increase the risk of contracting HIV, hepatitis B, C and other blood-borne infectious diseases. Long-term use of heroin has also severe medical consequences such as scarred veins, bacterial infections of blood vessels, liver and kidney diseases, and lung complications. PMID:22329304
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.
Roddy, Juliette; Steinmiller, Caren L.; Greenwald, Mark K.
OBJECTIVE: The purpose of this study is to evaluate women receiving methadone maintenance during pregnancy.STUDY DESIGN: Thirty-two pregnancies in women receiving methadone maintenance were matched by gestational age to women with a positive urine screen for cocaine at delivery and to drug-free controls. Pregnancy outcome variables were compared, including birth weight and neonatal morbidity. Analysis was by ?2 and t
Haywood L. Brown; Kathy A. Britton; Danielle Mahaffey; Edward Brizendine; A. Kinney Hiett; Mureena A. Turnquest
Co-dependence on opiates and cocaine occurs in about 60% of patients entering methadone treatment and has a poor prognosis. However, we recently found that desipramine (DMI) could be combined with buprenorphine to significantly reduce combined opiate and cocaine use among these dually dependent patients. Furthermore, contingency management (CM) has been quite potent in reducing cocaine abuse during methadone maintenance. To
Thomas Kosten; Alison Oliveto; Alan Feingold; James Poling; Kevin Sevarino; Elinore McCance-Katz; Susan Stine; Gerardo Gonzalez; Kishor Gonsai
This study assessed the effectiveness of a brief abstinence reinforcement procedure for initiating cocaine abstinence in methadone maintenance patients. On Monday of the test week, 72 cocaine-abusing methadone patients were offered a $100 voucher if urine samples collected on Wednesday indicated that they had abstained from cocaine across that 2-day period. A patient was considered abstinent and the voucher delivered
Elias Robles; Kenneth Silverman; Kenzie L Preston; Edward J Cone; Elizabeth Katz; George E Bigelow; Maxine L Stitzer
Background Heroin addiction is a chronic relapsing disease, best treated with opioid-agonist substitution therapy such as methadone maintenance. However, a subset of the most severely affected individuals do not benefit sufficiently from this treatment. The North American Opiate Medication Initiative (NAOMI) is a randomized clinical trial (RCT) to evaluate the hypothesis that pharmaceutical-grade heroin, diacetylmorphine (DAM) is more effective in
Eugenia Oviedo-Joekes; Bohdan Nosyk; David C Marsh; Daphne Guh; Suzanne Brissette; Candice Gartry; Michael Krausz; Aslam Anis; Martin T Schechter
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. We now include cocaine with methamphetamines, heroin, and ephedrine as illicit drugs that can cause cerebral vasculitis. PMID:3656626
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.
Gray, Teresa R.; Choo, Robin E.; Concheiro, Marta; Williams, Erica; Elko, Andrea; Jansson, Lauren M.; Jones, Hendree 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
This study attempts to analyse potential gender differences among a group of heroin addicts seeking treatment at a university-based medical centre. The central modality of treatment at this centre is the use of methadone maintenance. Among those patients entering this program there seems to be an emerging pattern of males who tend to use heroin as their opiate of choice,
Icro Maremmani; Canoniero Stefania; Matteo Pacini; Angelo G. I. Maremmani; Marina Carlini; Francesca Golia; Joseph Deltito; Liliana DellOsso
An 18-year addiction career, 1985-2003, for 157 heroin dependent subjects (73% men; 49% human immunodeficiency virus seropositive) admitted for the first time to Stockholm's Methadone Maintenance Treatment program during 1989 to 1991 was analyzed with data from seven official registers and patient records. Regression analyses and incidence rates for various outcomes were calculated for subjects in first methadone maintenance treatment
Ingrid Davstad; Marlene Stenbacka; Anders Leifman; Anders Romelsjö
To characterize prescription opioid dependent patients in a methadone maintenance treatment (MMT) program, a detailed retrospective chart review of new admissions (1997–1999, n=178, mean age=34.5±0.7 years, 65% male) was conducted. At admission most patients (83%) had been using prescription opioids (±heroin). Four groups were identified: 24% had used prescription opioids only; 24% used prescription opioids initially and heroin later; 35%
Bruna Brands; Joan Blake; Beth Sproule; Douglas Gourlay; Usoa Busto
Heroin-assisted treatment (HAT) is a solution for improving the condition of treatment-resistant heroin addicts. Since 1994, six randomized controlled trials have concluded that HAT is more efficacious than oral methadone for severe heroin addicts. We visited seven HAT treatment centres in four countries in order to observe diacetylmorphine (DAM) administration and to study the main concerns of the staff. Nurses were concerned by the risk taken if a previously intoxicated patient received his dose of DAM. Another concern was the smuggling of DAM doses. The HAT centres face a dilemma: treating patients while at the same time allowing their risky street habits in the centre. PMID:22074590
Relatively few methadone programs emphasize vocational skills training in their service delivery protocols. As a result, this study was conducted to determine the contribution of background demographic, vocational and clinical characteristics in differentiating chronically unemployed methadone clients from those regularly or intermittently employed over a 3-year period of time. Three-hundred eighty heroin addicts, from five urban methadone treatment programs, participated in the study. Using the multiple logistic regression approach, nine variables were found to be significantly related to unemployment risk. PMID:2242713
Hermalin, J A; Steer, R A; Platt, J J; Metzger, D S
Drug smuggling by internal bodily concealment is a well-recognized international problem, particularly in view of the difficulty of its detection and the potential for large financial gains. This mode of transport can have serious medical complications, including drug intoxication--sometimes fatal--as well as intestinal obstruction by foreign bodies (FBs). We discuss a case of heroin 'bodypacking' (the ingestion of heroin filled condoms) with its resultant complications. The initial medical management and indications for surgery are discussed, and the relevant literature reviewed. Images Fig. 1 Fig. 2 Fig. 3
We report on the 6-month outcome of a retrospective analysis of additional treatment services for patients entering a methadone maintenance program who transferred from community methadone treatment programs (n = 83) or entered off the street (n = 83) not currently on methadone. Patients were participating in a clinical treatment trial examining the effectiveness of Community Reinforcement Approach and Relapse Prevention. Patients in the methadone transfer group were using less heroin at intake than patients newly initiated onto methadone and both groups improved from additional treatment services in the following problem areas specifically: drug, alcohol, legal, employment, social, and in some measures of psychiatric distress. Therefore, both groups of patients in this study benefited from additional treatment services. PMID:10435261
|This script, with music, lyrics and dialog, was written especially for youngsters to inform them of the potential dangers of various drugs. The author, who teaches in an elementary school in Harlem, New York, offers Miss Heroin as her answer to the expressed opinion that most drug and alcohol information available is either too simplified and…
Background Health Related Quality of Life (HRQL) of opiate users has been studied in treatment settings, where assistance for drug use was sought. In this study we ascertain factors related to HRQL of young opiate users recruited outside treatment facilities, considering both genders separately. Methods Current opiate users (18-30 y) were recruited in outdoor settings in three Spanish cities (Barcelona, Madrid, Sevilla). Standardised laptop interviews included socio-demographic data, drug use patterns, health related issues, the Severity of Dependence Scale (SDS) and the Nottingham Health Profile (NHP). Results A total of 991 subjects (73% males), mean age = 25.7 years were interviewed. The mean global NHP score differed by gender (women: 41.2 (sd:23.8); men:34.1(sd:23.6);p < 0.05). Multivariate analysis was implemented separately by gender, variables independently related with global NHP score, both for males and females, were heroin and cocaine SDS scores. For women, only other drug related variables (alcohol intake and length of cocaine use) were independently associated with their HRQL. HIV+ males who suffered an opiate overdose or had psychiatric care in the last 12 months perceived their health as poorer, while those who had ever been in methadone treatment in the last 12 months perceived it as better. The model with both genders showed all factors for males plus quantity of alcohol and an interaction between gender and HIV status. Conclusions Heroin users were found to be at a considerable risk of impaired HRQL, even in these young ages. A score approaching severity of dependence was the factor with the strongest relation with it.
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 genomewide and multigene association studies, we found association of several new genes and new variants of known genes with heroin addiction. Finally, we describe 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
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.
Yuferov, Vadim; Levran, Orna; Proudnikov, Dmitri; Nielsen, David A.; Kreek, Mary Jeanne
Replacement therapy with the synthetic mu-opioid agonist methadone is an efficacious treatment for opioid abuse. While much is known about methadone's pharmacology, its discriminative stimulus properties remain largely unexplored. The present study sought to establish methadone discrimination in rats. Moreover, some research suggests that route of administration alters the discriminative stimulus of methadone. Thus, the present study also compared intraperitoneal (i.p.) and subcutaneous (s.c.) routes of administration. Male Sprague-Dawley rats were trained to discriminate 3.0mg/kg methadone (i.p.) from vehicle in a two-lever discrimination procedure. Generalization tests were conducted with a variety of compounds administered i.p. and s.c. Methadone fully substituted for itself, yielding ED(50)s of 1.5mg/kg (i.p.) and 0.2mg/kg (s.c.). Naltrexone (i.p.), an opioid antagonist produced a dose-dependent reduction in methadone-appropriate responding. The methadone stereoisomers fully substituted for methadone when given s.c.; however, when administered i.p., (+) and (-) methadone produced partial and no substitution, respectively. Heroin fully generalized to methadone regardless of administration route, while morphine fully substituted when given s.c., but not i.p. The kappa-agonist U50-488 failed to generalize to methadone with either route of administration. These results demonstrated that methadone's discriminative stimulus is mediated through mu-opioid receptor activity and is similar to that of commonly abused opioids (heroin, morphine). Additionally, route of administration produced differential results for many of the drugs tested, suggesting decreased drug bioavailability following i.p. administration due to hepatic first pass metabolism. Taken together, these results suggest that methadone's shared subjective effects with abused opioids, as well as its unique metabolic properties contribute to its efficacy in opioid maintenance therapy. PMID:19443130
Vann, Robert E; Wise, Laura E; Varvel, Stephen A; Philibin, Scott D; Walentiny, D Matthew; Porter, Joseph H
Background Despite its effectiveness, methadone maintenance is rarely provided in American correctional facilities. This study is the first randomized clinical trial in the US to examine the effectiveness of methadone maintenance treatment provided to prisoners with pre-incarceration heroin addiction. Methods A three-group randomized controlled trial was conducted between September 2003 and June 2005. Two hundred-eleven Baltimore pre-release inmates who were heroin dependent during the year prior to incarceration were enrolled in this study. Participants were randomly assigned to the following: Counseling Only: counseling in prison, with passive referral to treatment upon release (n = 70); Counseling + Transfer: counseling in prison with transfer to methadone maintenance treatment upon release (n = 70); and Counseling + Methadone: methadone maintenance and counseling in prison, continued in a community-based methadone maintenance program upon release (n = 71). Results Two hundred participants were located for follow-up interviews and included in the current analysis. The percentages of participants in each condition that entered community-based treatment were, respectively, Counseling Only 7.8%, Counseling + Transfer 50.0%, and Counseling + Methadone 68.6%, p < .05. All pairwise comparisons were statistically significant, (all ps < .05). The percentage of participants in each condition that tested positive for opioids at one month post-release were, respectively, Counseling Only 62.9%, Counseling + Transfer 41.0%, and Counseling + Methadone 27.6%, p < .05, with the Counseling Only group significantly more likely to test positive than the Counseling + Methadone group. Conclusions Methadone maintenance initiated prior to or immediately after release from prison appears to have beneficial short-term impact on community treatment entry and heroin use. This intervention may be able to fill an urgent treatment need for prisoners with heroin addiction histories.
Gordon, Michael S.; Schwartz, Robert P.; O'Grady, Kevin; Fitzgerald, Terrence T.; Wilson, Monique
Objectives To clarify the mechanisms and risk factors of methadone toxicity and to describe the findings of deaths related to methadone use Design Retrospective review of case notes in the records of the San Francisco Medical Examiner comparing the findings in cases where methadone was deemed the cause of death with findings in decedents where methadone was an incidental finding, and with 50 age-matched, disease and drug free, trauma victims. Results 38 cases out of the 3317 processed by our office during 1997-1998 were identified in which methadone had been detected. Cases were mostly male 28/38 (74%) and white, 28/38 (74%). In 17 of 38 cases death was deemed to have been caused by methadone toxicity. For the group the mean blood methadone concentration for all 38 patients, was 957 ng/ml SD =.681, SE =.14). The mean blood concentration of the main methadone metabolite (EDDP) was 253 ng/ml, SD = 529 ng/ml, SE =.089. The mean ratio of methadone in the blood to EDDP in the blood was 13.6:1 Values were not significantly different between cases in which methadone toxicity was the cause of death and in those in which it was an incidental finding. Cocaine, or the cocaine metabolite benzoylecgonine, was detected in the blood or urine of 16/38 cases (42%); morphine in one-third (13/38) and methamphetamine in only one. Pulmonary edema was evident in all cases, coronary artery disease in 9/38 (24%) and cirrhosis in 7/38 (18%) of the methadone users. Necrotizing fasciitis was the cause of death in 4 of the 38 methadone users (11%). Nationally, a sizeable percent of methadone deaths are from drugs diverted from treatment programs. Conclusions The presence of methadone is often an incidental finding during postmortem examination which is unrelated to the cause of death. Postmortem measurements of methadone or its metabolite, or both, cannot be used in isolation to identify which deaths are associated with methadone toxicity.
Heroin dependence may cause an economic burden and has an impact on quality of life (QOL). However, assessments of economic cost are scarce and the relationship between economic cost and QOL is unclear in the Asian population. In the present study, an established questionnaire was modified to assess the economic cost and its association with QOL. A total of 121 volunteer subjects in a methadone maintenance therapy programme and 157 normal controls were enrolled. The total economic cost of heroin dependency is US$ 18,310 per person-year. The direct cost is US$ 11,791 per person-year (64% of the total cost), mostly consisting of the cost of heroin and other illegal drugs. The indirect cost is US$ 6519 (36% of the total cost) per person-year, most of which arises from productivity loss caused by unemployment and incarceration. The QOL of heroin-dependent patients is poorer than that of healthy controls in all domains. The overall QOL is negatively related to direct cost and total cost. The economic cost of heroin dependency is huge, equal to 1.07 times the average gross domestic product per capita. Reduction of the economic cost to society and the economic burden for heroin users is important. PMID:23477899
Lin, Shih-Hsien; Chen, Kao Chin; Lee, Sheng-Yu; Hsiao, Chih-Yin; Lee, I Hui; Yeh, Tzung Lieh; Chen, Po See; Lu, Ru-Band; Yang, Yen Kuang
To characterize sleep disorders in methadone maintenance treatment (MMT) patients, we evaluated sleep quality of 101 non-selective patients from our MMT clinic in Israel between July, 2003 and July, 2004 by using the self-report questionnaire Pittsburgh Sleep Quality Index (PSQI). Patients’ urine tests were analyzed for methadone metabolite, opiates, benzodiazepine, cocaine, cannabis and amphetamines. Their urine results for drug abuse
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…
Clients' perceptions and attitudes toward methadone treatment programs are frequently overlooked in substance abuse research. Given the importance of methadone maintenance as a harm-reduction strategy and clients' concerns about treatment, it is essential to understand perceptions and attitudes toward existing programs. Using data from the 2009 National HIV Behavioral Surveillance system with injection drug users in Denver, CO, we evaluated participants' experiences with methadone clinics and examined predictive factors associated with ever being a client of a methadone clinic. Costs of services, perceptions of staff not caring about the client, and attitudes toward the counseling services seemed to be the major barriers to program retention. Besides heroin use, previous attempt at self-detoxification and being infected with hepatitis C were the strongest predictors of ever being on methadone treatment. Addressing the barriers to program retention and encouraging treatment engagement are essential to embracing methadone maintenance as a harm-reduction strategy for injection drug users. PMID:21371849
More than 2.4 million people are currently incarcerated in the United States, many as a result of drug-related offenses. In addition, more than 200,000 active heroin addicts pass through the correctional system annually. New evidence suggests that both providing prisoners with referrals for community-based methadone programs and providing methadone prior to release reduces recidivism and adverse health and social consequences associated with drug use. This article reports the programmatic challenges associated with initiating methadone treatment in the Rhode Island correctional system. Significant obstacles to implementing methadone treatment include: stigma associated with pharmacological treatment, misconceptions regarding the nature of opioid addiction, logistics of control and storage of methadone, increased work load for nursing staff, and general safety and control concerns. The authors discuss strategies to address these barriers and conclude that providing methadone prior to inmate release is a feasible intervention with the potential to mitigate drug-related health and social harms.
McKenzie, Michelle; Nunn, Amy; Zaller, Nickolas D.; Bazazi, Alexander R.; Rich, Josiah D.
More than 2.4 million people are currently incarcerated in the United States, many as a result of drug-related offenses. In addition, more than 200,000 active heroin addicts pass through the correctional system annually. New evidence suggests that both providing prisoners with referrals for community-based methadone programs and providing methadone prior to release reduces recidivism and adverse health and social consequences associated with drug use. This article reports the programmatic challenges associated with initiating methadone treatment in the Rhode Island correctional system. Significant obstacles to implementing methadone treatment include: stigma associated with pharmacological treatment, misconceptions regarding the nature of opioid addiction, logistics of control and storage of methadone, increased work load for nursing staff and general safety and control concerns. The authors discuss strategies to address these barriers and conclude that providing methadone prior to inmate release is a feasible intervention with the potential to mitigate drug-related health and social harms. PMID:19736902
McKenzie, Michelle; Nunn, Amy; Zaller, Nickolas D; Bazazi, Alexander R; Rich, Josiah D
A pilot study was initiated in seven methadone injecting patients to examine whether intravenous methadone use in patients in oral methadone maintenance treatment could be decreased by increased oral methadone dose. During the study, patients had a standardized methadone dose increase for three weeks, followed by a 12-week follow-up period. Mean methadone doses prior to, and at the end of
C. B. Eap; C. Felder; K. Powell Golay; C. Uehlinger
Interviews were previously conducted with 72 heroin-addicted female street prostitutes who spread HIV by sharing injection paraphernalia and engagin in unprotected sex with multiple male customers. Most were willing to enroll in free methadone maintenance if made available. Forty-one female addict-prostitutes subsequently entered free methadone maintenance. Twenty-five remained in treatment after one year. Their peronal income from prostitution and other
Opioid addiction is a chronic disease with high genetic contribution and a large inter-individual variability in therapeutic response. The goal of this study was to identify pharmacodynamic factors that modulate methadone dose requirement. The neurotrophin family is involved in neural plasticity, learning, memory and behavior and deregulated neural plasticity may underlie the pathophysiology of drug addiction. Brain-derived neurotrophic factor (BDNF) was shown to affect the response to methadone maintenance treatment. This study explores the effects of polymorphisms in the nerve growth factor (? polypeptide) gene, NGFB, on the methadone doses required for successful maintenance treatment for heroin addiction. Genotypes of 14 NGFB polymorphisms were analyzed for association with the stabilizing methadone dose in 72 former severe heroin addicts with no major co-medications. There was significant difference in methadone doses required by subjects with different genotypes of the NGFB intronic single-nucleotide polymorphism rs2239622 (P=0.0002). These results may have clinical importance. PMID:21358750
Levran, O; Peles, E; Hamon, S; Randesi, M; Zhao, C; Zhang, B; Adelson, M; Kreek, M J
Opioid addiction is a chronic disease with high genetic contribution and a large inter-individual variability in therapeutic response. The goal of this study was to identify pharmacodynamic factors that modulate methadone dose requirement. The neurotrophin family is involved in neural plasticity, learning memory and behavior and deregulated neural plasticity may underlie the pathophysiology of drug addiction. BDNF was shown to affect the response to methadone maintenance treatment. This study explores the effects of polymorphisms in the nerve growth factor (beta polypeptide) gene, NGFB, on the methadone doses required for successful maintenance treatment for heroin addiction. Genotypes of 14 NGFB polymorphisms were analyzed for association with the stabilizing methadone dose in 72 former severe heroin addicts with no major co-medications. There was significant difference in methadone doses required by subjects with different genotypes of the NGFB intronic SNP rs2239622 (P = 0.0002). These results may have clinical importance.
Heroin misuse in pregnancy is a significant health and social problem, and it can have an adverse effect on the mother and the baby. Although heroin and methadone have no specific teratogenic potential, 48-94% of children exposed in utero will have neonatal abstinence syndrome (NAS). The primary aim of this case report is to raise awareness of NAS among clinicians and to remind them that although very common, it is not inevitable. The risk of NAS can be further minimised by offering comprehensive and co-ordinated antenatal care that addresses the various biopsychosocial needs of the pregnant woman. Further, a brief description of NAS and a review of evidence in the field of management of opioid misuse in pregnancy, as relevant to this case, are provided. We have also included the patient's own reflections on her pregnancy and treatment. PMID:22328902
There is a paucity of studies in the literature documenting failure rates of outpatient detoxification from heroin. This study reports on the results of the 21-day ambulatory treatment program at the Miami Veterans Administration Hospital. Heroin users with less than a 2-year history of opiate use must complete the detoxification process within 21 days according to federal regulations. The results of this study indicate 100% "unsuccessful drug rehabilitation" utilizing the 21-day outpatient detoxification treatment modality, a finding similar to studies conducted to evaluate results of inpatient methadone treatment programs. PMID:591146
This study examined associations between substance use behaviors and self-reported health among hospitalized heroin users. Of the 112 participants, 53 (47%) reported good or better health. In multivariable logistic regression models, each day of heroin use in the last month was associated with an 8% lower odds of reporting health as good or better (OR=.92; 95% CI 0.87, 0.97, p<.05). Cocaine, cannabis, cigarettes, alcohol use, unintentional overdose, nor injection drug use was associated with health status. PMID:24045030
Meshesha, Lidia Z; Tsui, Judith I; Liebschutz, Jane M; Crooks, Denise; Anderson, Bradley J; Herman, Debra S; Stein, Michael D
We report the clinical, MR imaging, and proton MR spectroscopy findings in a middle-aged woman with proved methadone-induced toxic leukoencephalopathy. The imaging characteristics of this unusual condition have been reported only rarely in the medical literature. We show that the imaging findings in methadone-induced toxic leukoencephalopathy are similar, though not identical, to previously reported cases of neurologic deterioration due to heroin inhalation. PMID:19892815
Salgado, R A; Jorens, P G; Baar, I; Cras, P; Hans, G; Parizel, P M
Abstract Objective To describe the characteristics of a national cohort of pregnant women on methadone maintenance treatment (MMT) and to provide treatment outcome data for integrated care programs. Design Retrospective chart review. Setting Three different integrated care programs in geographically distinct cities: the Toronto Centre for Substance Use in Pregnancy in Toronto, Ont; the Herzl Family Practice Centre in Montreal, Que; and the Sheway clinic in Vancouver, BC. Participants Pregnant women meeting criteria for opioid dependence and attending an integrated care program between 1997 and 2009. Women were excluded if they were on MMT only for chronic pain. Main outcome measures Patient demographic characteristics, concurrent medical and psychiatric disorders, and substance use outcome data. Results A total of 102 opioid-dependent pregnancies were included. The mean age was 29.7 years and 64% of women were white. Women in Montreal were more likely to have partners and had fewer children. Differences in living and housing situations among the sites tended to resolve by the time of delivery. Almost half of this cohort tested positive for hepatitis C. Women had a high prevalence of depression and anxiety across all sites. Half of this cohort was on MMT before conception and for the other half, MMT was initiated at a mean gestational age of 20.7 weeks, resulting in a mean dose of 82.4 mg at delivery. At the first visit, polysubstance use was common. Prescription opioid use was more frequent in Toronto and heroin use was more prevalent in Vancouver and Montreal. For the entire population, significant reductions were found by the time of delivery for illicit (P < .001) and prescription opioids (P = .001), cocaine (P < .001), marijuana (P = .009), and alcohol use (P < .001). Conclusion Despite geographic differences, all 3 integrated care programs have been associated with significant decreases in substance use in pregnant opioid-dependent women.
ABSTRACT QUESTION One of my patients is currently using methadone for maintenance of opioid dependence. She wants to breastfeed. Is breastfeeding safe for her infant? ANSWER The exposure of infants to methadone through their mothers’ breast milk is minimal. Women using methadone for treatment of opioid dependence should not be discouraged from breastfeeding. The benefits of breastfeeding largely outweigh any theoretical minimal risks.
Glatstein, Miguel Marcelo; Garcia-Bournissen, Facundo; Finkelstein, Yaron; Koren, Gideon
|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…
Methadone medical maintenance (MMM) is a model for the treatment of opioid dependence in which a monthly supply of methadone is distributed in an office setting, in contrast to more highly regulated settings where daily observed dosing is the norm. We assessed patient characteristics and treatment outcomes of an MMM program initiated in the Bronx, New York, in 1999 by conducting a retrospective chart review. Participant characteristics were compared with those of patients enrolled in affiliated conventional methadone maintenance treatment programs. Patients had diverse ethnicities, occupations, educational backgrounds, and income levels. Urine toxicology testing detected illicit opiate and cocaine use in 0.8% and 0.4% of aggregate samples, respectively. The retention rate was 98%, which compares favorably with the four other MMM programs that have been reported in the medical literature. This study demonstrates that selected patients from a socioeconomically disadvantaged population remained clinically stable and engaged in treatment in a far less intensive setting than traditional methadone maintenance.
Harris, Kenneth A.; Arnsten, Julia H.; Joseph, Herman; Hecht, Joe; Marion, Ira; Juliana, Patti; Gourevitch, Marc N.
Objectives: Mortality among 507 patients in a methadone program over a 1-year period was assessed. Methods: Mortality was determined for patients in treatment (n=397), and 12 months later for those discharged (n=110). Results: Of discharged patients, 8.2% (9\\/110) had died, of which six were caused by heroin overdose. None of the discharged clients were in treatment at the time of
An 18-year addiction career, 1985-2003, for 157 heroin dependent subjects (73% men; 49% human immunodeficiency virus seropositive) admitted for the first time to Stockholm's Methadone Maintenance Treatment program during 1989 to 1991 was analyzed with data from seven official registers and patient records. Regression analyses and incidence rates for various outcomes were calculated for subjects in first methadone maintenance treatment at the end of the observation period, discharged from first methadone maintenance treatment, in second methadone maintenance treatment, and discharged from second methadone maintenance treatment. Being human immunodeficiency virus positive (HR = 3.8), lodging (HR = 1.9) and prison sentence (HR = 1.7) predicted mortality for the 45% deceased. Approximately 70% of living subjects participated in methadone maintenance treatment at some period each year. Subjects in first or second methadone maintenance treatment had less criminality and had spent more time in methadone maintenance treatment (70% to 100%) than those discharged from first or from second methadone maintenance treatment (50%). Efforts and interventions should be intensified to increase time in treatment also for those with high problem severity. PMID:19197594
Davstad, Ingrid; Stenbacka, Marlene; Leifman, Anders; Romelsjö, Anders
Background: In Switzerland, 1,035 patients were accepted for admission to the medically controlled prescription of narcotics programme (PROVE) from 1 January 1994 until 31 December 1996. Heroin, methadone, and morphine were prescribed. This paper presents the prevalence and incidence of HIV and hepatitis B\\/C infections in the sociomedical context of the participants. Methods: Admission criteria were a minimum age of
THOMAS STEFFEN; RICHARD BLATTLER; FELIX GUTZWILLER; MARCEL ZWAHLEN
The efficacy of methadone treatment in reducing the rate of positive urinalyses for opiates has been repeatedly assessed in outpatient intravenous heroin users (IHUs), but not in IHUs hospitalized for coexisting diseases. The aim of the present study, performed on 83 IHUs, was to assess the rate of drug-free urinalyses for addictive drugs over a 13-day period of hospitalization. The
M. CATERINA GRASSI; M. LUISA BENCETTI; ALESSIO MARIA CARICATI; PAOLO NENCINI
Studied counselor personal characteristics associated with effective counseling of heroin addicts in a methadone treatment program. The counselors, 25 Black former addicts, were given the MMPI, the Intraversion-Extroversion Scale from the Maudsley Personality Inventory, the Social Desirability Scale, and Banta's People in General Scale. Effectiveness was assessed by comparing each counselor's clients with clients assigned to others, and was operationalized
BACKGROUND: In order to improve the delivery of health services for chronic medical conditions in our methadone clinic, we added an onsite health screening and brief health counseling to the treatment plans for patients receiving methadone maintenance treatment at the Atlanta Veterans Affairs Medical Center (VAMC). We then conducted a follow up retrospective chart review to assess whether this intervention improved health outcome for those patients. METHODS: We reviewed the charts of one hundred and two patients who received treatment at Atlanta VAMC methadone clinic between 2002 and 2008. We sought to determine whether our increased health education and screening intervention was associated with improved: 1) Improved drug addiction outcome (as measured by comparing percentage of opiate and cocaine positive drug screens from admission to most recent). 2) Basic health screening, (as measured by the patient's compliance with primary care physicians (PCP) appointments and current smoking status). 3) Management of co-occurring medical conditions (as measured by levels of LDL cholesterol, hemoglobin A1c, and systolic blood pressure (SBP). 4) Presence of QTc prolongation (difference in QTc between baseline and most recent EKG). RESULTS: Illicit drug use (opiate and cocaine) markedly decreased in patients overall. The effect was more robust for those successfully "retained" (n=55, p<0.0001) in treatment, compared to those who "dropped out" (n=40, p=0.05) of treatment. Compliance with PCP appointments was high (82% and 88% before and after the onsite intervention, respectively) for "retained" patients. LDL cholesterol level was within normal range for all patients. A1c improved by 40% after the onsite intervention as reflected by the decreased percentage of patients with A1c > 7 % from before to after the intervention (90% vs. 50%, p=0.05). However, the prevalence of uncontrolled hypertension did not significantly improve after the onsite intervention (38% vs. 28%, p=0.34). As might be expected with MMT, the prevalence of QTc prolongation actually increased from 399 m sec. (+/- 92) to 439 msec. (+/- 22) after the onsite intervention (p=0.003). CONCLUSIONS: Our retrospective study supports the previous literature that methadone maintenance therapy is effective in reducing illicit drug use. Although patients with history of heroin dependence and in methadone maintenance treatment are at increased risk for chronic medical conditions like hepatitis C and diabetes, there are minimal federal guidelines for medical care, except than a physical exam upon admission, and basic screening for some infectious diseases e.g. HIV and Hepatitis C for those patients. Our study demonstrated the need for and potential benefit of enhancing the delivery of health promotion services for chronic medical conditions in methadone maintained patients. Improving management of hepatitis C, diabetes, hypertension, and other related conditions, in this high risk, difficult-to-treat, and underserved population may reduce their morbidity and premature mortality. PMID:20823944
Background In order to improve the delivery of health services for chronic medical conditions in our methadone clinic, we added an onsite health screening and brief health counseling to the treatment plans for patients receiving methadone maintenance treatment at the Atlanta Veterans Affairs Medical Center (VAMC). We then conducted a follow up retrospective chart review to assess whether this intervention improved health outcome for those patients. Methods We reviewed the charts of one hundred and two patients who received treatment at Atlanta VAMC methadone clinic between 2002 and 2008. We sought to determine whether our increased health education and screening intervention was associated with improved: 1) Improved drug addiction outcome (as measured by comparing percentage of opiate and cocaine positive drug screens from admission to most recent). 2) Basic health screening, (as measured by the patient's compliance with primary care physicians (PCP) appointments and current smoking status). 3) Management of co-occurring medical conditions (as measured by levels of LDL cholesterol, hemoglobin A1c, and systolic blood pressure (SBP). 4) Presence of QTc prolongation (difference in QTc between baseline and most recent EKG). Results Illicit drug use (opiate and cocaine) markedly decreased in patients overall. The effect was more robust for those successfully “retained” (n=55, p<0.0001) in treatment, compared to those who “dropped out” (n=40, p=0.05) of treatment. Compliance with PCP appointments was high (82% and 88% before and after the onsite intervention, respectively) for “retained” patients. LDL cholesterol level was within normal range for all patients. A1c improved by 40% after the onsite intervention as reflected by the decreased percentage of patients with A1c > 7 % from before to after the intervention (90% vs. 50%, p=0.05). However, the prevalence of uncontrolled hypertension did not significantly improve after the onsite intervention (38% vs. 28%, p=0.34). As might be expected with MMT, the prevalence of QTc prolongation actually increased from 399 m sec. (+/- 92) to 439 msec. (+/- 22) after the onsite intervention (p=0.003). Conclusions Our retrospective study supports the previous literature that methadone maintenance therapy is effective in reducing illicit drug use. Although patients with history of heroin dependence and in methadone maintenance treatment are at increased risk for chronic medical conditions like hepatitis C and diabetes, there are minimal federal guidelines for medical care, except than a physical exam upon admission, and basic screening for some infectious diseases e.g. HIV and Hepatitis C for those patients. Our study demonstrated the need for and potential benefit of enhancing the delivery of health promotion services for chronic medical conditions in methadone maintained patients. Improving management of hepatitis C, diabetes, hypertension, and other related conditions, in this high risk, difficult-to-treat, and underserved population may reduce their morbidity and premature mortality.
Functioning across several life domains, in the first cohort of illicit heroin users to be prescribed injectable diamorphine (pharmaceutical heroin) as an adjunct to treatment within a community drugs service, was assessed in a cross-sectional study with a 6-month follow-up. Case-control matching procedures were employed to compare outcomes in this group with an oral methadone-prescribed sample, attending different clinics within
|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…
Preston, Kenzie L.; Ghitza, Udi E.; Schmittner, John P.; Schroeder, Jennifer R.; Epstein, David H.
Recent studies show that proinflammatory cytokines might be related to the development of opioid dependence (physiological, psychological, or both). In a double-blind, randomly stratified clinical trial investigating whether add-on dextromethorphan (60-120 mg/day) attenuated inflammation and the combined use of opioids in heroin-dependent patients undergoing methadone maintenance treatment, we evaluated whether inflammation is related to the progression of opioid dependence. All participants (107 heroin-dependent patients and 84 nondependent healthy controls) were recruited from National Cheng Kung University Hospital. Their plasma cytokine levels were measured to evaluate the effect of add-on dextromethorphan. Plasma TNF-? and IL-8 levels were significantly higher in long-term heroin-dependent patients than in healthy controls (p?0.001). Chronic heroin-use-induced TNF-? and IL-8 levels were significantly (p?0.05) attenuated in patients treated for 12 weeks with add-on dextromethorphan. Moreover, both tolerance to methadone and the combined use of opioids were significantly (p?0.05) attenuated in patients taking dextromethorphan. We conclude that dextromethorphan might be a feasible adjuvant therapeutic for attenuating inflammation and inhibiting methadone tolerance and combined opioid use in heroin-dependent patients. PMID:22990619
Chen, Shiou-Lan; Lee, Sheng-Yu; Tao, Pao-Luh; Chang, Yun-Hsuan; Chen, Shih-Heng; Chu, Chun-Hsien; Chen, Po See; Lee, I Hui; Yeh, Tzung Lieh; Yang, Yen Kuang; Hong, Jau-Shyong; Lu, Ru-Band
Although endocrine abnormalities are recognized in opiate users, very little is known about the range of hormones affected, their pathophysiology and their clinical relevance. various endocrine abnormalities have been reported in these patients including, increased prolactin levels and abnormalities in sexual hormone. Path physiological mechanism postulated does explain these findings including direct action of heroin or methadone at the hypothalamic pituitary level. The aim of this study was to explore the effects of heroin and methadone maintenance treatment on the plasma prolactin levels and sexual function. Material and methods: We evaluated 20 male narcotic addicts maintained of methadone more than 3 years on oral high dose methadone 60-120 mgr/day. Patients taking neuroleptic therapy were excluded from the study because neuroleptic-included hyperprolactinemia. We also evaluated group of twenty male heroin addicts on the street heroin .The prolactin plasma levels were assayed using the chemiluminescent immunometric essay (CLIA)--high sensitive methods. The normal range of prolactin levels was 1,5-17 ng/ml (53-360 nmol/l) for men and 1,90-25,0 ng/ml for women. The sexual function was assessed using a Questionnaire: International Index of Erectile Function (IIEF) with 15 items in four levels of sexual function. The differences between two examination groups were determined by a students t test. The results show that street heroin addicts (55% of them have high level of prolactin) have significantly higher plasma prolactin levels (p = 0.006) then the group of methadone maintenance patients (only 15% of them have high prolactin level). In our study, when we compared sexual dysfunction in examination groups in some domains, we did not find statistical significant results (sexual desire p = 0.52 and overall satisfaction p = 0.087). But in domains of erectile function p = 0.011 and orgasm function p = 0.033 we got statistical significant results. PMID:23678840
We examined the effects of urine testing frequency on treatment outcome in a contingent methadone take-home program. Study patients who submitted<80% opiate and\\/or cocaine positive urines during a 5-week baseline received 60 mg methadone throughout the study, submitted urine samples on Monday, Wednesday, and Friday, and were randomized into one of three take-home incentive conditions. Study patients could receive three
Mary Ann Chutuape; Kenneth Silverman; Maxine L Stitzer
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.
...drugs. The relevant substances include: opium or cocaine and their derivatives (morphine, heroin, codeine); marijuana; synthetic narcotics (demerol, methadones); and dangerous nonnarcotic drugs (barbiturates, benzedrine)....
...drugs. The relevant substances include: opium or cocaine and their derivatives (morphine, heroin, codeine); marijuana; synthetic narcotics (demerol, methadones); and dangerous nonnarcotic drugs (barbiturates, benzedrine)....
...drugs. The relevant substances include: opium or cocaine and their derivatives (morphine, heroin, codeine); marijuana; synthetic narcotics (demerol, methadones); and dangerous nonnarcotic drugs (barbiturates, benzedrine)....
...drugs. The relevant substances include: opium or cocaine and their derivatives (morphine, heroin, codeine); marijuana; synthetic narcotics (demerol, methadones); and dangerous nonnarcotic drugs (barbiturates, benzedrine)....
...drugs. The relevant substances include: opium or cocaine and their derivatives (morphine, heroin, codeine); marijuana; synthetic narcotics (demerol, methadones); and dangerous nonnarcotic drugs (barbiturates, benzedrine)....
...drugs. The relevant substances include: opium or cocaine and their derivatives (morphine, heroin, codeine); marijuana; synthetic narcotics (demerol, methadones); and dangerous nonnarcotic drugs (barbiturates, benzedrine)....
|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…
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.
AIMS This study examines the frequency and severity of arrest charges among heroin addicts randomly assigned to either interim methadone maintenance (IM) or to remain on a waiting list for methadone treatment. It was hypothesized that IM participants would have a: 1) lower number of arrests at 6 and 12 months and 2) lower mean crime severity scores at 6 and 12 months post-baseline. METHODS Available official arrest data were obtained for all 319 study participants for a period of 2 years before and after study enrollment. Crime severity ratings of charges were made using an established measure of crime severity. FINDINGS Participants randomly assigned to IM as compared to those on a waiting list had a significant reduction in number of arrests at 6 but not at 12 months from study enrollment. There were no significant differences in whether participants were arrested for a more severe crime but frequency of severe crime was relatively low in both groups. Additional post hoc analyses based on whether participants were in methadone treatment at 4 and 10 months after original random assignment to treatment condition revealed that those participants not in treatment at these follow-up assessment points were significantly more likely to be arrested and to have a higher mean crime severity rating at 12 and 24 months post-baseline assessment. CONCLUSIONS IM as compared to the waiting list condition, had a significant reduction in number of officially- recorded arrests from baseline to 6 months post-baseline. Those who were enrolled in methadone treatment at the 4 and 10 month follow-up assessment, regardless of initial assignment, had fewer arrests at 12 and 24 months post-baseline.
Schwartz, Robert P.; Jaffe, Jerome H.; O'Grady, Kevin E.; Kinlock, Timothy W.; Gordon, Michael S.; Kelly, Sharon M.; Wilson, Monique E.; Ahmed, Ashraf
OBJECTIVE--To assess recruitment to and work-load associated with methadone maintenance clinics in general practice; to investigate the characteristics of patients and outcomes associated with treatment. DESIGN--Study of case notes. SETTING--Methadone maintenance clinics run jointly by general practitioners and drug counsellors in two practices in Glasgow. PARTICIPANTS--46 injecting drug users receiving methadone maintenance during an 18 month period, 31 of whom were recruited to clinic based methadone maintenance treatment and 15 of whom were already receiving methadone maintenance treatment from the general practitioners. Mean (SD) age of patients entering treatment was 29.6 (5.5) years; 29 were male. They had been injecting opiates for a mean 9.9 (5.1) years, and most had a concurrent history of benzodiazepine misuse. Average reported daily intake of heroin was approximately 0.75 g. Participants in treatment had high levels of preexisting morbidity, and most stated that they committed crime daily. RESULTS--2232 patient weeks of treatment were studied. Mean duration of treatment during the study period was 50.7 (21.1) weeks and retention in treatment at 26 weeks was 83%. No evidence of illicit opiate use was obtained at an average of 78% of patients' consultations where methadone had been prescribed in the previous week; for opiate injection the corresponding figure was 86%. CONCLUSIONS--Providing methadone maintenance in general practice is feasible. Although costs are considerable, the reduction in drug use, especially of intravenous opiates, is encouraging. Attending clinics also allows this population, in which morbidity is considerable, to receive other health care.
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
Methadone and buprenorphine are commonly used as oral substitutes in opiate maintenance programs to treat persons who are dependent on heroin. During these programs, patients are not allowed to continue using illicit drugs. Abstinence can easily be monitored by urine tests with immunochemical methods. It is well known that the intravenous abuse of heroin substitutes like methadone or buprenorphine has become common as well. The methadone-prescribing physician has no opportunity to check whether the opiate maintenance treatment patient takes his substitution medicines orally as intended or continues with his intravenous misuse now substituting the methadone instead of injecting heroin. In Germany, substitutes are available as liquids and tablets that contain carbohydrates as adjuvants. Sucrose is used to increase viscosity in liquids, while lactose is needed for pressing tablets (e.g., Methaddict(®) and Subutex(®)). In case of oral ingestion, disaccharides are broken down into monosaccharides by disaccharidases in the small intestine. These monosaccharides are absorbed into the blood stream by special monosaccharide transporters. Disaccharidases do not exist in blood, thus sucrose and lactose are not split if substitute medicines are injected intravenously. Our assumption, therefore, was that they are excreted unchanged in urine. We investigated a method for the detection of disaccharides in urine as markers of intravenous abuse of substitutes. Urine samples of 26 intravenous substitute abusers showed all positive results for lactose (76.9%) and/or sucrose (73.1%). The method is assumed to be useful to detect intravenous abuse of substitutes. PMID:24099717
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
Cocaine is the second most commonly used illicit drug after cannabis in the general population. Cocaine is a powerful stimulating agent of the central nervous system and a highly addictogenic drug. Somatic and psychiatric consequences of cocaine addiction are major and clinically relevant. The increasing consumption of cocaine and the importance of its consequences justify an update of our knowledge about cocaine addiction. PMID:23888579
New entrants to methadone maintenance treatment programs (MMTP) have been reported to have different drug use patterns than re-admissions. This study assesses differences between 211 re-admissions and 128 new admissions to a NYC MMTP. Those new to MMTP were found to be less likely to have ever injected drugs, have used more types of drugs, and used heroin at higher
Sherry Deren; Marjorie F. Goldstein; Don C. Des Jarlais; Beverly L. Richman; Sung-Yeon Kang; Peter L. Flom
|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…
Gordon, Michael S.; Kinlock, Timothy W.; Couvillion, Kathryn A.; Schwartz, Robert P.; O'Grady, Kevin
Objectives This purpose of this study was to explore the following question: Are there gender differences among older individuals with a history of heroin addiction with regard to social and family relationships and health problems? Methods Eight gender-specific focus groups were conducted with 38 (19 women, 19 men) older (50+ years) individuals with long-term histories of heroin dependence. Four groups were conducted in a methadone maintenance (MM) clinic and four groups were derived from the Los Angeles community. Results Modest gender differences were observed, but mainly in the focus-group dynamics. Women typically described the impact of their addiction on their families, while men typically described their surprise at still being alive. Hepatitis C was the primary health concern in all groups; mental health issues were also discussed. Discussion Remarkable gender differences were not apparent in the qualitative experiences of these participants. Instead, we found overriding similarities related to the interactive effects of drug use and aging. Longitudinal studies of this population as they age and interact with the health-care system and other social systems will help to untangle the complicated relationship between aging, drug addiction, gender, and health.
The authors found similar attitudes toward methadone and methadone treatment programs in 75 detoxification and 115 methadone maintenance clients. Both groups expressed considerable ambivalence--although they viewed methadone as capable of helping them end their herioin addiction, they were concerned about possible methadone dependence and about side effects, both real and imagined. The authors stress the societal context of such concern and suggest that, althought they are not easily allayed, limiting the duration of methadone maintenace from the outset of treatment may be an ameliorative factor. PMID:1124804
Methadone and buprenorphine are used in maintenance therapy for heroin addicts. In this study, we compared their effects on\\u000a adenylate cyclase (AC) activity in human embryonic kidney (HEK) 293 cells stably overexpressing human ?-opioid receptor (MOR)\\u000a and nociceptin\\/opioid receptor-like 1 receptor (ORL1) simultaneously. After acute exposure, methadone inhibited AC activity;\\u000a however, buprenorphine induced compromised AC inhibition. When naloxone was introduced
The focus of drug policy in the UK has shifted markedly in the past 5 years to move beyond merely emphasising drug abstinence towards maximising individuals' opportunities for recovery. The UK government continues to recognise the prescribing of narcotic medications indicated for opiate dependence as a key element of these individuals' recovery journey. This article describes a small, naturalistic comparison of the efficacy of the two most commonly prescribed opiate substitute medications in the UK--methadone hydrochloride (methadone oral solution) and Suboxone (buprenorphine-naloxone sublingual tablets)--for reducing current heroin users' (n = 34) days of heroin use, and preventing short-term abstainers (n = 37) from relapsing to regular heroin use. All patients had been prescribed either methadone or Suboxone for maintenance for 6 months prior to intake. Results showed that when controlling for a number of patient-level covariates, both methadone and Suboxone significantly reduced current users' days of heroin use between the 90 days prior to intake and at the 8-month follow-up, with Suboxone yielding a significantly larger magnitude reduction in heroin use days than methadone. Methadone and Suboxone were highly and equally effective for preventing relapse to regular heroin use, with all but 3 of 37 (91.9%) patients who were abstinent at intake reporting past 90-day point prevalence heroin abstinence at the 8-month follow-up. Overall, prescribing methadone or Suboxone for eight continuous months was highly effective for initiating abstinence from heroin use, and for converting short-term abstinence to long-term abstinence. However, the study design, which was based on a relatively small sample size and was not able randomise patients to medication and so could not control for the effects of potential prognostic factors inherent within each patient group, means that these conclusions can only be made tentatively. These positive but preliminary indications of the comparative efficacy of methadone and Suboxone for treating opiate dependence now require replication in a well-powered, randomised controlled trial. PMID:22703715
In a retrospective case control study at the University of Frankfurt, Germany, 101 babies born to opiate-addicted mothers were identified from birth charts from 1988 to 1995. After birth, they developed a withdrawal syndrome (neonatal abstinence syndrome). Fifty control infants and their mothers were selected from neonatal wards. The group of opiate-exposed babies was subdivided into a group born to mothers without methadone treatment (n = 48) and a group born to mothers who were enrolled in a methadone program (n = 51). The methadone infants had a significantly higher mean birth weight (2822 g) than children in the group without methadone (2471 g). The abstinence syndrome was much more intense in the methadone group (convulsions 47.1%) than in heroin-exposed babies without methadone treatment (convulsions 27.1%). Women in methadone maintenance programs lived in more stable socioeconomic conditions than opiate-addicted women without methadone substitution. Moreover, they cared significantly better for their babies: 81.3% of the methadone mothers visited their children on a regular basis and 90.9% cared adequately. The data emphasize the need in future research to look more closely at the role of methadone treatment programs in the development of opiate-exposed babies. PMID:11042868
Ziegler, M; Poustka, F; von Loewenich, V; Englert, E
The charge to the Committee on Federal Regulation of Methadone Treatment was to study current Department of Health and Human Services (DHHS) standards for narcotic addiction treatment and the regulation of methadone treatment programs pursuant to those st...
Compared drug-related risk behavior of drug users whose preferred injection drug was cocaine and users with preference for heroin or no preference between the two drugs (total n=422). Found cocaine preference unrelated to likelihood of needle sharing overall, needle sharing with strangers, needle sharing at shooting galleries, and failure to use…
This study examines the relationship between heroin-assisted treatment versus methadone maintenance and the criminal activity\\u000a of 1,015 individuals participating in a German model project. The main objective is to investigate how these treatments contribute\\u000a to a decline of criminal behavior. The analyses are based upon self-reported criminal offence and police data on alleged criminals.\\u000a Logistic regression is employed to explain
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
Methadone and buprenorphine are used in maintenance therapy for heroin addicts. In this study, we compared their effects on adenylate cyclase (AC) activity in human embryonic kidney (HEK) 293 cells stably overexpressing human ?-opioid receptor (MOR) and nociceptin/opioid receptor-like 1 receptor (ORL1) simultaneously. After acute exposure, methadone inhibited AC activity; however, buprenorphine induced compromised AC inhibition. When naloxone was introduced after 30 min incubation with methadone, the AC activity was enhanced. This was not observed in the case of buprenorphine. Enhancement of the AC activity was more significant when the incubation lasted for 4 h, and prolonged exposure to buprenorphine elevated the AC activity as well. The removal of methadone and buprenorphine by washing also obtained similar AC superactivation as that revealed by naloxone challenge. The study demonstrated that methadone and buprenorphine exert initially different yet eventually convergent adaptive changes of AC activity in cells coexpressing human MOR and ORL1 receptors. PMID:21671107
Based upon findings relating to the reinstatement of responding from the animal laboratory, the present study investigated whether methadone, a synthetic opiate, would prime the desire to use heroin for its pleasant effect (i.e. for positive reinforcement) compared to clonidine, a non-opiate drug, in detoxifying opiate addicts (n = 16). In-patient opiate addicts were tested at maximum withdrawal and minimal
Smoking is highly prevalent (85%-98%) in methadone maintenance treatment (MMT) patients. Methadone has been shown to increase cigarette smoking in a dose-dependent manner, whereas smoking/nicotine has been shown to increase methadone self-administration and reinforcing properties. The objective of this study was to evaluate methadone-nicotine interactions in MMT patients during trough and peak methadone effect conditions. Subjective effects of nicotine (administered by cigarette smoking, 4 mg of nicotine gum and placebo gum) and methadone and their combination were assessed in 40 regularly smoking, stabilized MMT patients using a randomized, placebo-controlled, within-subject study design. Subjects responded to a battery of subjective assessments before and after nicotine administration both before methadone administration (cycles 1 and 2) and 3 hours after methadone administration (cycles 3 and 4). There was a main effect of methadone on the decrease of opioid withdrawal scores (P < 0.001), and cigarette smoking enhanced this effect (day x methadone interaction, P = 0.031). Both nicotine and methadone had main effects on the decrease of nicotine withdrawal scores (P < 0.001 and P = 0.001, respectively); this was associated with the cigarette day (day x nicotine interaction, P = 0.003, and day x methadone interaction, P = 0.004). Nicotine plasma levels were highest on the cigarette smoking day (P < 0.001). Methadone and nicotine shared main effects on the increase of ratings of euphoria and drug liking and on the decrease of restlessness, irritability, and depression. The overall results may help to explain high smoking rates in the MMT population and may account for reports of increased positive effects of methadone when the drugs are taken together. PMID:19440076
Elkader, Alexander K; Brands, Bruna; Selby, Peter; Sproule, Beth A
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
Heroin use in pregnancy is a worldwide problem. Methadone maintenance treatment has definite advantages for the mother and is currently recommended in the UK. There is, however, increasing evidence of adverse effects upon developing cortical and visual function in children of treated heroin-addicted mothers. The longer-term implications of this are not yet clear, and are confounded by poly-drug misuse and ongoing social deprivation. There is a paucity of evidence regarding outcome for infants who require pharmacological treatment for neonatal abstinence syndrome compared to those who have only mild symptoms. Well-controlled studies of the treatment of heroin misuse in pregnancy that take account of both neonatal and longer term outcomes for the child are urgently required. PMID:20584799
Evidence suggests that patients on opiate maintenance therapy for the treatment of addiction present with opioid-induced hyperalgesia (OIH). This study compared the experimental (cold-pressor, electrical stimulation) pain responses of 82 treatment-seeking heroin-dependent adults randomized to methadone (METH, n = 11) or buprenorphine (BUP, n = 64) therapy, with matched drug free controls (n = 21). Heroin-dependent participants were evaluated at baseline (treatment entry), medication (METH or BUP) stabilization (4-8 weeks), and chronic administration (12-18 weeks), at trough (just prior to dosing) and peak (3 hours after dosing) plasma levels. Collection of the control group’s pain responses occurred twice during a single session, three hours apart. Baseline comparisons indicate that heroin-dependent individuals demonstrate significantly shorter latencies to threshold and tolerance for cold-pressor pain than the control group. Across pain stimuli and time points, little change in pain responses were found over time, the exception being cold pressor pain tolerance, for which hyperalgesia significantly increased at trough METH/BUP levels in both groups as they stabilized in treatment. We conclude that heroin-dependent individuals are hyperalgesic, and that once stabilized in treatment, are not different in pain responses regardless of treatment agent. The effects of non-pharmacologic therapy and previous heroin use may explain increased hyperalgesia found with treatment. Perspective To better understand the clinical phenomenon of OIH, this article describes experimental pain responses of heroin-dependent participants both prior to and over the course of maintenance therapy with methadone or buprenorphine. Hyperalgesia is present with illicit and treatment opioid use, and does not appear to appreciably improve over the course of treatment.
Compton, Peggy; Canamar, Catherine P.; Hillhouse, Maureen; Ling, Walter
Heroin users on methadone maintenance treatment (MMT) have elevated rates of co-morbid depression and are associated with higher relapse rates for substance abuse. Structural abnormalities in MMT patients have been reported but their impact on clinical performance is unknown. We investigated differences in gray matter volume (GMV) between 27 MMT patients and 23 healthy controls by voxel-based morphometry and correlated
Adequate methadone dosing in methadone maintenance treatment (MMT) for opioid addiction is critical for therapeutic success. One of the challenges in dose determination is the inter-individual variability in dose-response. Methadone metabolism is attributed primarily to cytochrome P450 enzymes CYP3A4, CYP2B6 and CYP2D6. The CYP2B6*6 allele [single nucleotide polymorphisms (SNPs) 785A>G (rs2279343) and 516G>T (rs3745274)] was associated with slow methadone metabolism. To explore the effects of CYP2B6*6 allele on methadone dose requirement, it was genotyped in a well-characterized sample of 74 Israeli former heroin addicts in MMT. The sample is primarily of Middle Eastern/European ancestry, based on ancestry informative markers (AIMs). Only patients with no major co-medication that may affect methadone metabolism were included. The stabilizing daily methadone dose in this sample ranges between 13 and 260mg (mean 140±52mg). The mean methadone doses required by subjects homozygous for the variant alleles of the CYP2B6 SNPs 785A>G and 516G>T (88, 96mg, respectively) were significantly lower than those of the heterozygotes (133, 129mg, respectively) and the non-carriers (150, 151mg, respectively) (nominal P=0.012, 0.048, respectively). The results remain significant after controlling for age, sex and the ABCB1 SNP 1236C>T (rs1128503), which was previously shown to be associated with high methadone dose requirement in this population (P=0.006, 0.030, respectively). An additional 77 CYP2B6, CYP3A4 and CYP2D6 SNPs were genotyped. Of these, 24 SNPs were polymorphic and none showed significant association with methadone dose. Further studies are necessary to replicate these preliminary findings in additional subjects and other populations. PMID:21790905
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
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,
The manual was prepared primarily for the use of those planning to launch new methadone treatment programs or improve existing ones. Stress is placed on how to organize and administer a successful treatment program rather than on how merely to dispense me...
Contingency management (CM) rapidly reduces cocaine use, but its effects subside after treatment. Cognitive-behavioral therapy (CBT) produces reductions months after treatment. Combined, the 2 might be complementary. One hundred ninety-three cocaine-using methadone-maintained outpatients were randomly assigned to 12 weeks of group therapy (CBT or a control condition) and voucher availability (CM contingent on cocaine-negative urine or noncontingent). Follow-ups occurred 3,
David H. Epstein; Wesley E. Hawkins; Lino Covi; Annie Umbricht; Kenzie L. Preston
Methadone implant formulations elaborated with polylactide-co-glycolide (PLGA) and polylactic acid (PLA) for 1 week and 1 month release duration, respectively, were evaluated in vitro and in vivo. One-week implants prepared with methadone clorhydrate, methadone clorhydrate\\/methadone base blend or methadone base were tested in vitro. Results showed that the methadone release rate decreased as the methadone base increased. The best release
... Information for Healthcare Professionals Methadone Hydrochloride text version. The issues described in this communication ... More results from www.fda.gov/drugs/drugsafety/postmarketdrugsafetyinformationforpatientsandproviders
Several substances besides tobacco are inhaled for recreational purposes, including marijuana, crack cocaine, amyl and butyl nitrites, heroin, methamphetamine, and phencyclidine. Abuse of most of these inhaled substances has risen in recent years, thereby increasing concern about potential pulmonary and other medical complications. Regular marijuana use can lead to extensive airway injury and alterations in the structure and function of alveolar macrophages, potentially predisposing to pulmonary infection and respiratory cancer. Crack cocaine use can lead to a variety of acute pulmonary complications, including severe exacerbations of asthma and an acute lung injury syndrome associated with a broad spectrum of histopathologic changes ("crack lung"). Habitual cocaine smoking may also produce more subtle long-term pulmonary consequences due to chronic alveolar epithelial and microvascular lung injury. Heroin inhalation can induce severe and even fatal exacerbations of asthma. Pulmonary consequences of inhaled amyl and butyl nitrites, crystalline methamphetamine (ice), and phencyclidine have been less well documented. PMID:11224724
Methadone maintenance treatment is evidenced as a successful harm reduction initiative in regard to the prevention of blood borne viruses and other injecting related harms. This is attributable to reductions in heroin use and injecting equipment sharing incidents, yet the means by which these are achieved are rarely elaborated. Methadone diversion is predominantly presented in a negative light; associated with overdose and other harms. In our qualitative London-based study with 37 people who inject drugs, 35 on substitution therapies, we found that methadone self regulation and diversion played a prominent role in helping participants to manage their drug use, prevent withdrawal, cement social relationships, and inadvertently protect against hepatitis C transmission. The ability of participants to enact these 'indigenous harm reduction strategies' was constrained to various degrees by their treatment dosing protocols. In this article we explore the strategies participants enacted with methadone, the role of 'generous constraints' in this enactment and the associated production and reduction of risk. In order to reengage people who inject drugs with harm reduction interventions, it is necessary for initiatives to take stock of the indigenous strategies that individuals are already utilising and - in the case of methadone self regulation - support them by the implementation of more generous constraints. PMID:23199896
Drug addicts are prone to infection with viruses including hepatitis-B and HIV. Besides indirect effects as a consequence of lifestyle, heroin and methadone may also enhance the risk of infections by a direct immunotoxic effect affecting resistance. In addition to general toxicological screening, we therefore performed a screening for potential immunotoxicity of morphine and methadone. Rats treated orally with different dosages of morphine or methadone for 6 weeks showed only a minor effect of overt toxicity on liver and spleen at the high dose, whereas at lower doses an increase in the relative weight of the mesenteric lymph nodes and an increase in cell density in the medullary cords were observed histopathologically, indicating a specific effect on humoral immunity. This specific immunotoxic effect was corroborated by an increased IgG concentration in serum (significant for the methadone-treated group). Further immunotoxicological research is needed aimed at revealing the potential risk of opiate use with respect to immune function. In conclusion, the present paper showed the toxicological profile of morphine and methadone in an extended 28 day subchronic study. Specific immunotoxicological effects were observed at doses where no effects were seen in routine toxicological evaluation, suggesting that the immune system is sensitive to opiates. PMID:7499032
van der Laan, J W; Krajnc, E I; Krajnc-Franken, M A; van Loveren, H
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.
Ryder, Niamh; Cullen, Walter; Barry, Joseph; Bury, Gerard; Keenan, Eamon; Smyth, Bobby P
Buprenorphine, a partial mu opioid agonist, is an experimental medication under development for the treatment of opioid dependence as an alternative to methadone maintenance. The present study examined the relationship between level of opioid physical dependence and response to buprenorphine administration as part of a program to develop procedures for transferring patients from methadone to buprenorphine treatment. This laboratory study
S. L. Walsh; H. L. June; K. J. Schuh; K. L. Preston; G. E. Bigelow; M. L. Stitzer
Heroin addiction is a chronic complex disease with a substantial genetic contribution. This study was designed to identify genetic variants that are associated with susceptibility to develop heroin addiction, by analyzing 1350 variants in 130 candidate genes. All subjects had Caucasian ancestry. The sample consisted of 412 former severe heroin addicts in methadone treatment, and 184 healthy controls with no history of drug abuse. Nine variants, in six genes, showed the lowest nominal P values in the association tests (P < 0.01). These variants were in non-coding regions of the genes encoding the mu (OPRM1; rs510769, rs3778151), kappa (OPRK1; rs6473797), and delta opioid receptors, (OPRD1; rs2236861, rs2236857 and rs3766951), the neuropeptide galanin (GAL; rs694066), the serotonin receptor subtype 3B (HTR3B; rs3758987) and the casein kinase 1 isoform epsilon (CSNK1E; rs1534891). Several haplotypes and multi-locus genotype patterns showed nominally significant associations (e.g. OPRM1; P = 0.0006 and CSNK1E; P = 0.0007). Analysis of a combined effect of OPRM1 and OPRD1 showed that rs510769 and rs2236861 increase the risk of heroin addiction (P = 0.0005). None of these associations remained significant after adjustment for multiple testing. This study suggests the involvement of several genes and variants in heroin addiction that is worthy of future study.
Levran, O.; Londono, D.; O'Hara, K.; Nielsen, D. A.; Peles, E.; Rotrosen, J.; Casadonte, P.; Linzy, S.; Randesi, M.; Ott, J.; Adelson, M.; Kreek, M. J.
Glial cell line-derived neurotrophic factor (GDNF) activity in ventral tegmental area (VTA) mediates the time-dependent increases in cue-induced cocaine-seeking after withdrawal (incubation of cocaine craving). Here, we studied the generality of these findings to incubation of heroin craving. Rats were trained to self-administer heroin for 10 days (6-h/day; 0.075 mg/kg/infusion; infusions were paired with a tone-light cue) and tested for cue-induced heroin-seeking in extinction tests after 1, 11 or 30 withdrawal days. Cue-induced heroin seeking was higher after 11 or 30 days than after 1 day (incubation of heroin craving), and the time-dependent increases in extinction responding were associated with time-dependent changes in GDNF mRNA expression in VTA and nucleus accumbens. Additionally, acute accumbens (but not VTA) GDNF injections (12.5-?g/side) administered 1–3 h after the last heroin self-administration training session enhanced the time-dependent increases in extinction responding after withdrawal. However, the time-dependent increases in extinction responding after withdrawal were not associated with changes in GDNF protein expression in VTA and accumbens. Additionally, interfering with endogenous GDNF function by chronic delivery of anti-GDNF monoclonal neutralizing antibodies (600-ng/side/day) into VTA or accumbens had no effect on the time-dependent increases in extinction responding. In summary, heroin self-administration and withdrawal regulate VTA and accumbens GDNF mRNA expression in a time-dependent manner, and exogenous GDNF administration into accumbens but not VTA potentiates cue-induced heroin seeking. However, based on the GDNF protein expression and the anti-GDNF monoclonal neutralizing antibodies manipulation data, we conclude that neither accumbens nor VTA endogenous GDNF mediates the incubation of heroin craving.
Airavaara, Mikko; Pickens, Charles L.; Stern, Anna L.; Wihbey, Kristina A.; Harvey, Brandon K.; Bossert, Jennifer M.; Liu, Qing-Rong; Hoffer, Barry J.; Shaham, Yavin
Glial cell line-derived neurotrophic factor (GDNF) activity in ventral tegmental area (VTA) mediates the time-dependent increases in cue-induced cocaine-seeking after withdrawal (incubation of cocaine craving). Here, we studied the generality of these findings to incubation of heroin craving. Rats were trained to self-administer heroin for 10 days (6 hours/day; 0.075 mg/kg/infusion; infusions were paired with a tone-light cue) and tested for cue-induced heroin-seeking in extinction tests after 1, 11 or 30 withdrawal days. Cue-induced heroin seeking was higher after 11 or 30 days than after 1 day (incubation of heroin craving), and the time-dependent increases in extinction responding were associated with time-dependent changes in GDNF mRNA expression in VTA and nucleus accumbens. Additionally, acute accumbens (but not VTA) GDNF injections (12.5 µg/side) administered 1-3 hours after the last heroin self-administration training session enhanced the time-dependent increases in extinction responding after withdrawal. However, the time-dependent increases in extinction responding after withdrawal were not associated with changes in GDNF protein expression in VTA and accumbens. Additionally, interfering with endogenous GDNF function by chronic delivery of anti-GDNF monoclonal neutralizing antibodies (600 ng/side/day) into VTA or accumbens had no effect on the time-dependent increases in extinction responding. In summary, heroin self-administration and withdrawal regulate VTA and accumbens GDNF mRNA expression in a time-dependent manner, and exogenous GDNF administration into accumbens but not VTA potentiates cue-induced heroin seeking. However, based on the GDNF protein expression and the anti-GDNF monoclonal neutralizing antibodies manipulation data, we conclude that neither accumbens nor VTA endogenous GDNF mediates the incubation of heroin craving. PMID:21182575
Airavaara, Mikko; Pickens, Charles L; Stern, Anna L; Wihbey, Kristina A; Harvey, Brandon K; Bossert, Jennifer M; Liu, Qing-Rong; Hoffer, Barry J; Shaham, Yavin
The ?-opioid receptor is the site of action of many endogenous opioids as well as opiates. We hypothesize that differences in DNA methylation of specific CpG dinucleotides between former severe heroin addicts in methadone maintenance treatment and control subjects will depend, in part, upon ethnicity. DNA methylation analysis of the ?-opioid receptor gene (OPRM1) promoter region was performed on African-Americans (118 cases, 80 controls) and Hispanics (142 cases, 61 controls) and these were compared with a similar Caucasian cohort from our earlier study. In controls, a higher methylation level was found in the African-Americans compared with the Hispanics or Caucasians. Significant experiment-wise differences in methylation levels were found at the ?25 and +12 CpG sites in the controls among the three ethnicities. The overall methylation level of the CpG sites were significantly higher in the former heroin addicts when compared with the controls (point-wise P = 0.0457). However, in the African-Americans, the degree of methylation was significantly decreased experiment-wise in the former heroin addicts at the +12 CpG site (P = 0.0032, Bonferroni corrected general estimating equations). In Hispanics, the degree of methylation was increased in the former heroin addicts at the ?25 (P < 0.001, experiment-wise), ?14 (P = 0.001, experiment-wise), and +27 (P < 0.001, experiment-wise) CpG sites. These changes in methylation of the OPRM1 promoter region may lead to altered expression of the ?-opioid receptor gene in the lymphocytes of former heroin addicts who are stabilized in methadone maintenance treatment.
Nielsen, David A.; Hamon, Sara; Yuferov, Vadim; Jackson, Colin; Ho, Ann; Ott, Jurg; Kreek, Mary Jeanne
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
Previous research has shown that a majority of drug-dependent subjects respond to drug cues in the laboratory with increased craving; however, approximately one-third are not cue responsive. The current study examined differences between responders and nonresponders to cocaine cues in a sample of 69 cocaine-dependent methadone patients. Subjects completed questionnaires assessing selected dimensions of addiction and participated in a cue-reactivity
S. Kelly Avants; Arthur Margolin; Thomas R. Kosten; Ned L. Cooney
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
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 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
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
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.
BACKGROUND: Romantic partnerships between drug-using couples, when they are recognized at all, tend to be viewed as dysfunctional, unstable, utilitarian, and often violent. This study presents a more nuanced portrayal by describing the interpersonal dynamics of 10 heroin and cocaine-using couples from Hartford, Connecticut. RESULTS: These couples cared for each other similarly to the ways that non-drug-using couples care for
Although cocaine is a widely abused illicit substance that is known to cause death, deaths due to its use appear to occur in a minority of those who use it. This report was designed to review drug-related deaths due to cocaine, and the concomitant use of other drugs/medications. A retrospective review of drug deaths at the Bexar County Medical Examiner's Office in San Antonio, Texas, was undertaken for cases where cocaine was one of the drugs implicated in causing death. Analysis was performed comparing the concentrations of cocaine and benzoylecgonine present and the absence or presence of other drugs. The data obtained showed that cocaine was toxic over a large range with deaths occurring at concentrations ranging from 0.01 to 78 mg/L. Analyses also indicated an increased lethality when cocaine is used in combination with ethanol, heroin, opiates, and antidepressant/antipsychotic medications, which is consistent with previous reports and research. Antihistamine data showed that there may be relationship between increased toxicity and co-ingestion, although more research is necessary. PMID:21394957
Aim: To determine whether changes in orthoptic status take place during withdrawal from heroin and/or methadone. Method: A prospective study of patients, using a repeated measures design, attending a 5 day naltrexone compressed opiate detoxification programme. Results: 83 patients were seen before detoxification (mean age 27.1 (SD 4.6) years) and 69 after detoxification. The horizontal angle of deviation became less exo/more eso at distance (p<0.001) but no significant change was found at near (p?=?0.069). Stereoacuity, visual acuity, and convergence were found to be reduced in the immediate post-detoxification period. Prism fusion range, refractive error, subjective accommodation, and objective accommodation at 33 cm did not reduce but a small decrease was found in objective accommodation at 20 cm. Conclusions: The eso trend found in these patients may be responsible for the development of acute concomitant esotropia in some patients undergoing heroin detoxification. However, the mechanism for this trend does not appear to be caused by divergence insufficiency or sixth nerve palsy.
To improve the electrocardiogram screening process and early detection of patients at high risk for cardiac arrhythmias, the authors created a model in their clinic where they provided an onsite electrocardiogram screening that might be feasible and practical. The authors then performed a retrospective chart review to access the efficacy and feasibility of their new onsite procedure in identifying methadone maintained patients at high risk for cardiac arrhythmias. Records from all patients who are currently or had previously been maintained on methadone in the methadone maintenance program at the Atlanta VA Medical Center between 2002 and 2009 were evaluated. Of the 140 patients treated at the clinic between 2002 and 2009, 85 were excluded from the study because they had been treated as guests (had been in treatment in other clinics but received methadone dosing temporarily from our clinic), were treated in the clinic for less than 6 months, or dropped out of treatment. Thus, 55 patient charts were selected for review. Most patients (95%) received baseline and annual electrocardiogram screening. The average baseline QTc was (417 +/- 30) and most recent QTc (442 +/- 25). This QTc prolongation from baseline showed statistical significance (P < .0001). Sixty-seven percent of patients had statistically significant QTc prolongation from baseline but was less than 450 ms (mean: 428 +/- 16, P = .008). Twenty-seven percent of patients had statistically significant QTc prolongation from baseline of more 450 ms but was less than 500 ms (mean: 460 +/- 8, P < .0001). Six percent of patients had statistically significant QTc prolongation from baseline of more 500 ms (mean: 503 +/- 1.15, P = .027). Recent cocaine use was the only individual variable that showed statistically significant correlation with QTc prolongation (F = 6.98, P = .01). The authors demonstrated in this study that providing an onsite electrocardiogram screening with a focus on patient education and limiting the referral to specialty care for patients at high risk for cardiac arrhythmias could be practical and feasible. PMID:20390695
Pharmacotherapy response was compared in 94 cocaine-abusing methadone patients with (n = 75) and without (n = 19) antisocial personality disorder (ASP), in a 12-week, randomized, double-blind trial using desipramine 150 mg daily (n = 30), amantadine 300 mg daily (n = 33), and placebo (n = 31). Retention was lower for the ASP group (ASP 9.6 weeks vs. non-ASP
Josiane Leal; Douglas M. Ziedonis; Thomas R. Kosten
Selective D1 dopamine agonists represent a potential pharmacotherapy for the treatment of cocaine addiction. Here we report that systemic injections of the novel D1 agonist ABT-431 lack the ability to induce cocaine-seeking behavior, and completely attenuate the ability of cocaine to induce this behavior in rats tested in a reinstatement paradigm. Similar doses suppress the initiation of cocaine self-administration, and produce an extinction-like response pattern in animals that subsequently initiate self-administration, without altering responding maintained by food pellets. There was no tolerance to this effect over 4 days of testing. The results suggest that ABT-431 attenuates the motivation to seek cocaine, and masks the reinforcing effects of cocaine during self-administration. The profile of ABT-431 is similar to the behavioral effects of other structurally distinct D1 agonists, and is consistent with the desired profile of a "methadone-like" compounds for cocaine addiction. PMID:10911927
Background More than 50% of incarcerated individuals have a history of substance use, and over 200,000 individuals with heroin addiction pass through American correctional facilities annually. Opiate replacement therapy (ORT) with methadone or buprenorphine is an effective treatment for opiate dependence and can reduce drug-related disease and recidivism for inmates. Provision of ORT is nevertheless a frequently neglected intervention in the correctional setting. Objective and Methods We surveyed the 50 state; Washington, District of Columbia (DC); and Federal Department of Corrections' medical directors or their equivalents about their facilities' ORT prescribing policies and referral programs for inmates leaving prison. Results We received responses from 51 of 52 prison systems nationwide. Twenty-eight prison systems (55%) offer methadone to inmates in some situations. Methadone use varies widely across states: over 50% of correctional facilities that offer methadone do so exclusively for pregnant women or for chronic pain management. Seven states' prison systems (14%) offer buprenorphine to some inmates. The most common reason cited for not offering ORT was that facilities “prefer drug-free detoxification over providing methadone or buprenorphine.” Twenty-three states' prison systems (45%) provide referrals for some inmates to methadone maintenance programs after release, which increased from 8% in 2003; 15 states' prison systems (29%) provide some referrals to community buprenorphine providers. Conclusion Despite demonstrated social, medical, and economic benefits of providing ORT to inmates during incarceration and linkage to ORT upon release, many prison systems nationwide still do not offer pharmacological treatment for opiate addiction or referrals for ORT upon release.
Interim methadone (IM; with emergency counseling only) 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 with 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
Robert P. Schwartz; Sharon M. Kelly; Kevin E. O'Grady; Devang Gandhi; Jerome H. Jaffe
Several policy changes are being debated in New York State that may affect the financing and delivery of methadone maintenance treatment. The goals of this article are to provide greater understanding of the potential impact of managed care on methadone treatment in New York State, and greater understanding of the consequences of arbitrary limits on methadone treatment. Toward these goals,
Several sociodemographic, drug use pattern, and clinical variables were investigated in two groups of heroin addicts. Inclusion in one group or the other depended on the addict's attitude toward or against receiving treatment for the addiction. Those who rejected treatment differed significantly in the following: they were younger and belonged to larger families; they started cannabis and amphetamine use earlier, and used for a longer time; they used cocaine and heroin more frequently, and alcohol less frequently; and they suffered more often from a number of somatic and personality disorders. Implications for future research on the addiction are discussed. PMID:2341206
|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.…
Throughout literary history, particular roles have been assigned to heroes and heroines, representing as well the male and female roles in society. Male aggressiveness and female submissiveness have generally been rewarded. Such stereotypical views continued through the years until the late nineteenth century when Thomas Hardy began to write novels that show a new kind of heroine. This heroine goes
Interest in oral fluid as an alternative matrix for monitoring drug use is due to its ease-of-collection and non-invasiveness; however, limited data are available on the disposition of drugs into oral fluid. The objective of this research was to provide data on the presence and concentrations of heroin, cocaine and multiple metabolites in oral fluid after illicit opioid and cocaine use. Thrice weekly oral fluid specimens (N=403) from 16 pregnant opiate-dependent women were obtained with the Salivette® oral fluid collection device. Evidence of heroin (N=62) and cocaine (N=130) use was detected in oral fluid by LC-APCI-MS/MS. 6-Acetylmorphine (6-AM), heroin and morphine were the major opiates detected, with median concentrations of 5.2, 2.3, and 7.5 ?g/L, respectively. Cocaine and benzoylecgonine (BE) had median concentrations of 6.4 and 3.4 ?g/L. Application of the Substance Abuse Mental Health Services Administration (SAMHSA) recommended cutoffs for morphine and codeine (40 ?g/L), 6-AM (4 ?g/L) and cocaine and BE (8 ?g/L), yielded 28 opiate- and 50 cocaine-positive specimens. Oral fluid is a promising alternative matrix to monitor opiate and cocaine use in drug testing programs. These data guide interpretation of oral fluid test results and evaluate currently proposed SAMHSA oral fluid testing cutoffs.
Dams, Riet; Choo, Robin E.; Lambert, Willy E.; Jones, Hendree; Huestis, Marilyn A.
Fatal overdose and drug-related mortality are key harms associated with heroin use, especially injecting drug use (IDU), and are a significant contribution to premature mortality among young adults. Routine mortality statistics tend to underreport the number of overdose deaths and do not reflect the wider causes of death associated with heroin use. Cohort studies could provide evidence for interpreting trends in routine mortality statistics and monitoring the effectiveness of strategies that aim to reduce drug-related deaths. We aimed to conduct a retrospective mortality cohort study of heroin users recruited from an anonymous reporting system from specialist drug clinics. Our focus was to test whether (1). specialist agencies would agree to participate with a mortality cohort study, (2). a sample could be recruited to achieve credible estimates of the mortality rate, and (3). ethical considerations could be met. In total, 881 heroin users were recruited from 15 specialist drug agencies. The overall mortality rate of the cohort of heroin users was 1.6 (95% confidence interval [CI], 1.1 to 2.2) per 100 person-years. Mortality was higher among males, heroin users older than 30 years, and injectors, but not significantly higher after adjustment in a Cox proportional hazard model. Among the 33 deaths, 17 (52%) were certified from a heroin/methadone or opiate overdose, 4 (12%) from drug misuse, 4 (12%) unascertained, and 8 (24%) unrelated to acute toxic effects of drug use. Overall, the overdose mortality rate was estimated to be at least 1.0 per 100 person-years. The standardized mortality ratio (SMR) was 17 times higher for female and male heroin users in the cohort compared to mortality in the non-heroin-using London population aged 15-59 years. The pilot study showed that these studies are feasible and ethical, and that specialist drug agencies could have a vital role to play in the monitoring of drug-related mortality. PMID:12791803
Introduction Acute intoxication with drugs of abuse in children is often only the tip of the iceberg, actually hiding chronic exposure.\\u000a Analysis using non-conventional matrices such as hair can provide long-term information about exposure to recreational drugs.\\u000a \\u000a \\u000a \\u000a \\u000a Case presentation We report the case of a one-month-old Caucasian boy admitted to our pediatric emergency unit with respiratory distress and\\u000a neurological abnormalities. A routine
Xavier Joya; Bibiana Fríguls; Marta Simó; Ester Civit; Rafael de la Torre; Antonio Palomeque; Oriol Vall; Simona Pichini; Oscar Garcia-Algar
The sublingual combination of buprenorphine and naloxone (Suboxone(®)) and Methadone Maintenance Therapy have been found effective in treating heroin addiction. A new analytical method suitable for the simultaneous determination of buprenorphine, norbuprenorphine, methadone and naloxone in human plasma by means of liquid chromatography with coulometric detection has been developed. The chromatographic separation was achieved with a phosphate buffer-acetonitrile mixture as the mobile phase on a cyano column. The monitoring cell of the coulometric detector was set at an oxidation potential of +0.600 V. A rapid clean-up procedure of the biological samples using a microextraction by packed sorbent technique has been implemented, employing a C8 sorbent inserted into a syringe needle. The extraction yield values were satisfactory for all analytes (>85%). The calibration curves were linear over a range of 0.25-20.0 ng mL(-1) for buprenorphine and norbuprenorphine, 3.0-1000.0 ng mL(-1) for methadone and 0.13-10.0 ng mL(-1) for naloxone. The sensitivity was also high with limits of detection of 0.08 ng mL(-1) for both buprenorphine and norbuprenorphine, 0.9 ng mL(-1) for methadone and 0.04 ng mL(-1) for naloxone. The intraday and interday precision data were always satisfactory. The method was successfully applied to plasma samples obtained from former heroin addicts treated with opioid replacement therapy. PMID:21839210
Somaini, Lorenzo; Saracino, Maria Addolorata; Marcheselli, Chiara; Zanchini, Silvia; Gerra, Gilberto; Raggi, Maria Augusta
Hepatitis C virus (HCV) antibody is present in most patients enrolled in methadone maintenance programs. Therefore, interactions between the HCV protease inhibitor telaprevir and methadone were investigated. The pharmacokinetics of R- and S-methadone were measured after administration of methadone alone and after 7 days of telaprevir (750 mg every 8 h [q8h]) coadministration in HCV-negative subjects on stable, individualized methadone therapy. Unbound R-methadone was measured in predose plasma samples before and during telaprevir coadministration. Safety and symptoms of opioid withdrawal were evaluated throughout the study. In total, 18 subjects were enrolled; 2 discontinued prior to receiving telaprevir. The minimum plasma concentration in the dosing interval (Cmin), the maximum plasma concentration (Cmax), and the area under the plasma concentration-time curve from h 0 (time of administration) to 24 h postdose (AUC0–24) for R-methadone were reduced by 31%, 29%, and 29%, respectively, in the presence of telaprevir. The AUC0–24 ratio of S-methadone/R-methadone was not altered. The median unbound percentage of R-methadone increased by 26% in the presence of telaprevir. The R-methadone median (absolute) unbound Cmin values in the absence (10.63 ng/ml) and presence (10.45 ng/ml) of telaprevir were similar. There were no symptoms of opioid withdrawal and no discontinuations due to adverse events. In summary, exposure to total R-methadone was reduced by approximately 30% in the presence of telaprevir, while the exposure to unbound R-methadone was unchanged. No symptoms of opioid withdrawal were observed. These results suggest that dose adjustment of methadone is not required when initiating telaprevir treatment. (This study has been registered at ClinicalTrials.gov under registration no. NCT00933283.)
Verboven, Peter; Vandevoorde, Ann; Vinck, Petra; Snoeys, Jan; Boogaerts, Griet; De Paepe, Els; Van Solingen-Ristea, Rodica; Witek, James; Garg, Varun
... 18 percent were referred by an alcohol or drug abuse care provider. Among adolescent heroin admissions, males were more likely than females to be referred to treatment by the criminal justice system (39 vs. 25 percent). ... alcohol or drug abuse care provider (15 vs. 21 percent). Table 2. ...
Drug use self-reports were compared with urinalysis for 248 clients in four methadone treatment programs. The validity of self-reporting based on urinalysis as a criterion depended on the type of drug examined. Opiate reporting was least valid, while benzodiazepine and cocaine reporting were moderately and highly valid, respectively. EMIT urinalysis was far more useful as a criterion of validity than TLC urinalysis. Self-reports helped identify drug users who were missed by urinalysis because of the latter's limited detection period, but urinalysis in turn detected an equal number of drug users missed by the interviews. The age of clients and the type of interviewer directly affected the rate of underreporting. Some respondents systematically denied disvalued behaviors (i.e., drug use and criminality), leading to a spurious correlation between these behaviors. This has important implications for future research. PMID:3679632
Magura, S; Goldsmith, D; Casriel, C; Goldstein, P J; Lipton, D S
Interest in oral fluid as an alternative matrix for monitoring drug use is due to its ease-of-collection and non-invasiveness; however, limited data are available on the disposition of drugs into oral fluid. The objective of this research was to provide data on the presence and concentrations of heroin, cocaine and multiple metabolites in oral fluid after illicit opioid and cocaine
Riet Dams; Robin E. Choo; Willy E. Lambert; Hendree Jones; Marilyn A. Huestis
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.
Nguyen, Tam T. M.; Nguyen, Long T.; Pham, Manh D.; Vu, Hoang H.; Mulvey, Kevin P.
Waiting lists for methadone treatment have existed in many U.S. communities, but little is known nationally about what patient and service system factors are related to admission delays that stem from program capacity shortfalls. Using a combination of national data sources, this study examined patterns in capacity-related admission delays to outpatient methadone treatment in 40 U.S. metropolitan areas (n=28,920). Patient characteristics associated with admission delays included racial/ethnic minority status, lower education, criminal justice referral, prior treatment experience, secondary cocaine or alcohol use, and co-occurring psychiatric problems. Injection drug users experienced fewer delays, as did self-pay patients and referrals from healthcare and addiction treatment providers. Higher community-level utilization of methadone treatment was associated with delay, whereas delays were less common in communities with higher utilization of alternative modalities. These findings highlight potential disparities in timely admission to outpatient methadone treatment. Implications for improving treatment access and service system monitoring are discussed.
Gryczynski, Jan; Schwartz, Robert P.; Salkever, David S.; Mitchell, Shannon Gwin; Jaffe, Jerome H.
Waiting lists for methadone treatment have existed in many U.S. communities, but little is known nationally about what patient and service system factors are related to admission delays that stem from program capacity shortfalls. Using a combination of national data sources, this study examined patterns in capacity-related admission delays to outpatient methadone treatment in 40 U.S. metropolitan areas (N = 28,920). Patient characteristics associated with admission delays included racial/ethnic minority status, lower education, criminal justice referral, prior treatment experience, secondary cocaine or alcohol use, and co-occurring psychiatric problems. Injection drug users experienced fewer delays, as did self-pay patients and referrals from health care and addiction treatment providers. Higher community-level utilization of methadone treatment was associated with delay, whereas delays were less common in communities with higher utilization of alternative modalities. These findings highlight potential disparities in timely admission to outpatient methadone treatment. Implications for improving treatment access and service system monitoring are discussed. PMID:21821378
Gryczynski, Jan; Schwartz, Robert P; Salkever, David S; Mitchell, Shannon Gwin; Jaffe, Jerome H
The purpose of this investigation was to examine the predictive utility of the stages-of-change scales of the University of Rhode Island Change Assessment (URICA; E. A. McConnaughy, J. O. Prochaska, & W. F. Velicer, 1983) questionnaire in a heroin-addicted polysubstance-abusing treatment sample. Ninety-six participants completed the URICA at the beginning of a 29-week treatment period that required thrice-weekly urine drug screens. Multivariate multiple regression analysis indicated that after controlling for demographic variables, substance abuse severity, and treatment assignment, the stages-of- change scales added significant variance to the prediction of heroin- and cocaine-free urine samples. The Maintenance scale was positively related to cocaine-free urines and length in treatment. The implications of these findings for treatment and for measuring readiness among individuals using multiple substances while taking maintenance medications are discussed. PMID:15238052
Henderson, Melinda J; Saules, Karen K; Galen, Luke W
A case of methadone poisoning with recovery is reported. An increased incidence of poisoning may occur because of recent innovations in the usage of this drug. A brief discussion of the drug and the treatment of acute intoxication is included. (Author)
Greater improvement in posttreatment outcomes has been shown in programs that tailor frequency and type of services to unique client needs. Using a sample of 635 clients (199 females and 436 males) admitted to three community-based methadone treatment programs, this study examined gender differences in services needed and provided during the first 3 months of treatment. Results revealed that compared
Grace A Rowan-Szal; Lois R Chatham; George W Joe; Ed. D; D. Dwayne Simpson
This paper uses Australian heroin seizure data, along with estimates of the size of the Australian heroin market to evaluate the impact of drug law enforcement on the 2001 Australian heroin shortage from the percentage of the market seized. It also critically examines international heroin production trends and published reports on the causes of the Australian heroin shortage. Its conclusion is that previous studies may have overstated the success of drug law enforcement and that the most likely explanation for Australia's 2001 heroin shortage was a significant decline in heroin production world-wide, due to a general move away from heroin production in the countries of Southeast Asia and the prohibition on opium growing by the Taliban regime in Afghanistan. PMID:17920258
Methadone is administered as a racemic mixture, although its analgesic and respiratory effects are attributed to R-isomer activity at the mu-opioid receptor (MOP). Recently, we observed a four-fold increase in inspiratory time in three-day old guinea pigs following an injection of racemic methadone. We hypothesized that this effect was due to augmentation of R-methadone induced respiratory depression by the S-methadone isomer. In the current longitudinal study, we injected three-, seven-, and fourteen-day old neonatal guinea pigs with saline, R-methadone, S-methadone, or R- plus S-methadone in order to characterize the roles of the individual isomers, as well as the synergistic effects of co-administration. Using plethysmography, we measured respiratory parameters while breathing room air and during a 5% CO2 challenge. S-methadone alone had no respiratory effects. However, the R- plus S-methadone group showed greater respiratory depression and increased inspiratory time than the R-methadone group in the youngest animals, suggesting that the respiratory effects of R-methadone are augmented by S-methadone in early development.
Silverman, Daniel A. N.; Nettleton, Rosemary T.; Spencer, Katherine B.; Wallisch, Michael; Olsen, George D.
To assess the views of opiate-dependent individuals about supervised methadone consumption. Three groups of opinions were sought: (i). new patients referred for assessment and treatment, using rating scales; (ii). the consensus view of the Methadone Alliance (a national users' forum); and (iii). the consensus view of a local service users' forum. All three groups expressed the view that supervised consumption has an important place in methadone treatments. Users understand the need for daily supervision of methadone and are generally willing to accept it. Users' views provide support for the introduction of flexible methadone prescribing regimes incorporating supervised consumption. Privacy in pharmacies and the possibility of moving away from supervision are important elements in an acceptable programme. Supervised consumption is an important component of safe, effective and responsible methadone prescribing. PMID:12745415
A 29-year-old man presented with comatose after methadone intoxication. Cerebral tomography only showed cortico-subcortical hypodense signal in the right cerebellar hemisphere. Brain MRI showed a rare imaging of FLAIR and DWI hyperintensities in the two cerebellar hemispheres as well as basal ganglia (globi pallidi), compatible with methadone overdose. To our knowledge this is the first reported case of both cerebellar and basal ganglia involvement in methadone overdose.
Background The past two decades have seen an increase in heroin-related morbidity and mortality in the United States. We report on trends in US heroin retail price and purity, including the effect of entry of Colombian-sourced heroin on the US heroin market. Methods The average standardized price ($/mg-pure) and purity (% by weight) of heroin from 1993 to 2004 was from obtained from US Drug Enforcement Agency retail purchase data for 20 metropolitan statistical areas. Univariate statistics, robust Ordinary Least Squares regression and mixed fixed and random effect growth curve models were used to predict the price and purity data in each metropolitan statistical area over time. Results Over the 12 study years, heroin price decreased 62%. The median percentage of all heroin samples that are of South American origin increased an absolute 7% per year. Multivariate models suggest percent South American heroin is a significant predictor of lower heroin price and higher purity adjusting for time and demographics. Conclusion These analyses reveal trends to historically low-cost heroin in many US cities. These changes correspond to the entrance into and rapid domination of the US heroin market by Colombian-sourced heroin. The implications of these changes are discussed.
Ciccarone, Daniel; Unick, George J; Kraus, Allison
Background Heroin coming into the United States historically comes from three widely dispersed geographical regions: Southwest Asia, Southeast Asia and Mexico. A fourth source of US-bound heroin, from Colombia, originated in the early 1990s. The fact that the four heroin sources produce differing morphologies and qualities of heroin has not been critically examined. In addition, it is not well established how the contemporary competing dynamics of interdiction, or restriction of heroin flows across international boundaries, and neoliberal, e.g., global expansion of free trade, policies are affecting heroin markets. This paper will highlight changes in the US heroin market, including source trends, the political economy of the now dominant source and the resultant effects on the heroin risk environment by US region. Methods Using a structural and historical framework this paper examines two decades of secondary data sources, including government and drug control agency documents, on heroin flows together with published work on the political and economic dynamics in Latin America. Results Co-occurring neoliberal economic reforms may have contributed to paradoxical effects of US/Colombian interdiction efforts. Since entering the US market, heroin from Colombia has been distributed at a much higher quality and lower retail price. An increasingly exclusive market has developed with Mexican and Colombian heroin gaining market share and displacing Asian heroin. These trends have had dramatic effects on the risk environment for heroin consumers. An intriguing factor is that different global sources of heroin produce substantially different products. Plausible associations exist between heroin source/form and drug use behaviours and harms. For example, cold water-soluble powdered heroin (sources: Asia, Colombia) may be associated with higher HIV prevalence in the US, while low-solubility “black tar” heroin (BTH; source: Mexico) is historically used in areas with reduced HIV prevalence. BTH is associated with soft tissue infections caused by Clostridium bacteria. Conclusion Source and type of heroin are structural factors in the risk environment of heroin users: source dictates distribution and type predicts practice. How specific types of heroin are used and with what risk is therefore distributed geographically. Continued flux in the heroin market and its effects on the risk environment for drug users deserves further attention.
BACKGROUND: Methadone is effective treatment for opioid addiction, but regulations restrict its use. Methadone medical maintenance treats\\u000a stabilized methadone patients in a medical setting, but only experimental programs have been studied.\\u000a \\u000a \\u000a OBJECTIVE: To evaluate the implementation of the first methadone medical maintenance program established outside a reseach setting.\\u000a \\u000a \\u000a \\u000a \\u000a DESIGN: One-year program evaluation.\\u000a \\u000a \\u000a \\u000a \\u000a SETTING: A public hospital and a community opioid
Joseph O. Merrill; T. Ron Jackson; Beryl A. Schulman; Andrew J. Saxon; Asaad Awan; Sonja Kapitan; Molly Carney; Lyndia C. Brumback; Dennis Donovan
A rapid second-derivative procedure for distinguishing cocaine and other local anesthetics is described. This technique appeared to be particularly useful in the detection of cocaine in binary mixtures. It is of great value in forensic toxicology, resolving cocaine-lidocaine, cocaine-procaine, cocaine-tetracaine, and cocaine-benzocaine mixtures, for which zero-order UV spectroscopy fails. PMID:3184888
...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...
Cocaine is the second commonest illicit drug used and the most frequent cause of drug related deaths. Its use is associated with both acute and chronic complications that may involve any system, the most common being the cardiovascular system. Cocaine misuse has a major effect in young adult drug users with resulting loss of productivity and undue morbidity with cocaine related cardiac and cerebrovascular effects. Many cocaine users have little or no idea of the risks associated with its use. Patients, health care professionals, and the public should be educated about the dangers and the considerable risks of cocaine use. This review concentrates on the cardiovascular effects of cocaine and their management.
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 was conducted. Patients were categorized into two groups: patients on a methadone dose of 60 to 100 mg daily (n = 34) and patients on a methadone dose greater than 100 mg daily (n = 25). Those charts were compared for urine drug screens for opiates and cocaine (first four from admission and most recent four screens), retention or drop out from the program, and Addiction Severity Index (ASI) composite score at admission and most recent score. The results of the first and last four urine drug screens for opiates showed that the moderate dose group was positive 23% and 17%, respectively. However, the high dose group was positive 14% and 8%, respectively. These results showed statistical significance (Chi-Square = 8.04, df = 3 and p =.03). ASI scores for drugs did not show statistically significant improvement for the moderate dose group (p =.19) but showed statistically significant improvement for the high dose group (p =.0002) when the result of the first and last ASI scores among each group were compared. The ASI scores for family problems showed statistically significant improvement for the moderate dose group (p =.03). High doses of methadone greater than 100 mg daily may provide a better outcome for illicit opiate use among some patients who would not respond to moderate doses. PMID:20155609
In humans, exposure to contexts previously associated with heroin use can provoke relapse. In rats, exposure to heroin-paired contexts after extinction of drug-reinforced responding in different contexts reinstates heroin seeking. This effect is attenuated by inhibition of glutamate or dopamine transmission in nucleus accumbens shell, or inactivation of ventral medial prefrontal cortex (vmPFC). Here, we used an anatomical asymmetrical disconnection procedure to demonstrate that an interaction between glutamatergic projections from vmPFC to accumbens shell and local dopamine D1 postsynaptic receptors contributes to context-induced reinstatement of heroin seeking. We also combined the marker of neuronal activity, Fos, with the retrograde tracer Fluoro-Gold (FG) to assess activation in this pathway during context-induced reinstatement. Rats were trained to self-administer heroin for 12 days; drug infusions were paired with a discrete tone-light cue. Lever-pressing was subsequently extinguished in a non-drug-associated context in the presence of the discrete cue. Rats were then tested in the heroin- or extinction-associated contexts under extinction conditions. Injections of muscimol+baclofen into vmPFC in one hemisphere and D1-family receptor antagonist SCH 23390 into the contralateral or ipsilateral accumbens shell decreased context-induced reinstatement. Unilateral injections of muscimol+baclofen into vmPFC or SCH 23390 into the accumbens shell had no effect. Context-induced reinstatement was associated with increased Fos expression in vmPFC neurons, including those projecting to accumbens shell, with higher double-labeling in the ipsilateral projection than in the contralateral projection. Our results demonstrate that activation of glutamatergic projections from ventral mPFC to accumbens shell, previously implicated in inhibition of cocaine relapse, promotes heroin relapse.
Bossert, Jennifer M.; Stern, Anna L.; Theberge, Florence R.M.; Marchant, Nathan J.; Wang, Hui-Ling; Morales, Marisela; Shaham, Yavin
Rationale A genetic component may be involved in different stages of the progression of drug addiction. Heroin users escalate unit doses and frequency of self-administration events over time. Rats that self-administer drugs of abuse over extended sessions escalate the amount of drug infused over days. Objectives Using a recently developed model of extended-access self-administration allowing for subject-controlled dose-escalation of the unit dose, thus potentially escalating the unit dose and number of infusions, we compared for the first time two genetically different inbred rat strains, Fischer and Lewis. Methods Extended (18h/day) self-administration lasted for 14 days. Rats had access to two active levers associated with two different unit doses of heroin. If a rat showed preference for the higher unit dose, then the available doses were escalated in the following session. Four heroin unit doses were available (20, 50, 125, 250 ?g/kg/infusion). Results Fischer rats did not escalate the unit dose of heroin self-administered; daily amount of heroin administered remained low, with a mean daily intake of 1.27±0.22 mg/kg/session. In marked contrast, Lewis rats escalated the total daily amount of heroin self-administered from 3.94±0.82 mg/kg on the day 1 to 8.95±2.2 mg/kg on day 14; almost half of the subjects preferred a higher heroin dose than Fischer rats. Conclusion These data are consistent with the hypothesis that Lewis rats are prone to opiate taking and escalation, and are in agreement with our previous data obtained with cocaine.
Picetti, Roberto; Caccavo, Jilda A.; Ho, Ann; Kreek, Mary Jeanne
Contingency management (CM) rapidly reduces cocaine use, but its effects subside after treatment. Cognitive–behavioral therapy (CBT) produces reductions months after treatment. Combined, the 2 might be complementary. One hundred ninety-three cocaine-using methadone-maintained outpatients were randomly assigned to 12 weeks of group therapy (CBT or a control condition) and voucher availability (CM contingent on cocaine-negative urine or noncontingent). Follow-ups occurred 3, 6, and 12 months posttreatment. Primary outcome was cocaine-negative urine (urinalysis 3 times/week during treatment and once at each follow-up). During treatment, initial effects of CM were dampened by CBT. Posttreatment, there were signs of additive benefits, significant in 3- versus 12-month contrasts. Former CBT participants were also more likely to acknowledge cocaine use and its effects and to report employment.
Epstein, David H; Hawkins, Wesley E; Covi, Lino; Umbricht, Annie; Preston, Kenzie L
Longer retention in drug abuse treatment is associated with better patient outcomes and research indicates the first 12 months of methadone treatment are critical to patient success. Nevertheless, large-scale multi-site longitudinal studies over the past three decades indicate that the majority of patients drop out during the first year of methadone treatment. Through an examination of 42 qualitative interviews with patients prematurely discharged from six methadone treatment programs in Baltimore, this paper highlights factors patients describe as contributing to their reasons for being discharged within the first 12 months of the treatment. The two most consistent themes are program-related factors and incarceration. The former factors are richly described through patients’ words and underscore the ways in which patients’ perceptions of control exerted by the program and by the medication and misunderstandings of program structure can lead to premature discharge. Patients’ reasons for discharge were compared to counselors’ reasons as indicated in discharge summary forms. An analysis of the patterns of agreement and disagreement are presented. Patient-centered program and policy implications are discussed.
Reisinger, Heather Schacht; Schwartz, Robert P.; Mitchell, Shannon Gwin; Peterson, James A.; Kelly, Sharon M.; O'Grady, Kevin E.; Marrari, Erica A.; Brown, Barry S.; Agar, Michael H.
Background To expand its public-sector treatment capacity, Baltimore City made buprenorphine treatment accessible to low-income, largely African American residents. This study compares the characteristics of patients entering methadone treatment v. buprenorphine treatment to determine whether BT was attracting different types of patients. Methods Participants consisted of two samples of adult heroin-dependent African Americans. The first sample was newly-admitted to a health center or a mental health center providing buprenorphine (N=200), and the second sample was newly-admitted to one of two hospital-based methadone programs (N=178). The Addiction Severity Index (ASI) and the Friends Supplemental Questionnaire were administered at treatment entry and data were analyzed with logistic regression. Results BT participants were more likely to be female (p=.017) and less likely to inject (p=.001). Participants with only prior buprenorphine treatment experience were nearly five time more likely to enter buprenorphine than methadone treatment (p<.001). Those with experience with both treatments were more than twice as likely to enter BT (OR=2.7, 95% CI=1.11–6.62; p=.028). In the 30 days prior to treatment entry, BT participants reported more days of medical problems (p=.002) and depression (p=.044), and were more likely to endorse a lifetime history of depression (p<.001). Conclusion Methadone and buprenorphine treatment provided in the public sector may attract different patient subpopulations. Providing buprenorphine treatment through drug treatment programs co-located with a health and mental health center may have accounted for their higher rates of medical and psychiatric problems and appears to be useful in attracting a diverse group of patients into public-sector funded treatment.
Mitchell, Shannon Gwin; Kelly, Sharon M.; Gryczynski, Jan; Myers, C. Patrick; Jaffe, Jerome H.; O'Grady, Kevin E.; Olsen, Yngvild K.; Schwartz, Robert P.
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
The case of a 21-year-old man who suffered a myocardial infarction after using cocaine and amphetamines is reported. A brief literature review provides evidence of cocaine's potential cardiovascular effects. (Author/MT)
|The case of a 21-year-old man who suffered a myocardial infarction after using cocaine and amphetamines is reported. A brief literature review provides evidence of cocaine's potential cardiovascular effects. (Author/MT)|
... one of the most frequently reported drugs by medical examiners in drug abuse deaths. 2 Before You Risk It… Know the law. Heroin is an illegal Schedule I drug, meaning that it is in the group of the most highly addictive drugs. Get the facts. Any method of heroin use—snorting, smoking, swallowing, ...
Longer retention in drug abuse treatment is associated with better patient outcomes, and research indicates the first 12 months of methadone treatment are critical to patient success. Nevertheless, large-scale multisite longitudinal studies over the past three decades indicate that the majority of patients drop out during the first year of methadone treatment. Through an examination of 42 qualitative interviews with
Heather Schacht Reisinger; Robert P. Schwartz; Shannon Gwin Mitchell; James A. Peterson; Sharon M. Kelly; Kevin E. OGrady; Erica A. Marrari; Barry S. Brown; Michael H. Agar
|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…
Objective Daily methadone maintenance is the standard of care for opiate dependency during pregnancy. Previous research has indicated that single-dose maternal methadone administration significantly suppresses fetal neurobehaviors. The purpose of this study was to determine if split-dosing would have less impact on fetal neurobehavior than single-dose administration. Methods Forty methadone-maintained women were evaluated at peak and trough maternal methadone levels on single- and split-dosing schedules. Monitoring sessions occurred at 36 and 37 weeks gestation in a counterbalanced study design. Fetal measures included heart rate, variability, accelerations, motor activity and fetal movement-heart rate coupling (FM-FHR). Maternal measures included heart period, variability, skin conductance, respiration and vagal tone. Repeated measure analysis of variance was used to evaluate within-subject changes between split- and single-dosing regimens. Results All fetal neurobehavioral parameters were suppressed by maternal methadone administration, regardless of dosing regimen. Fetal parameters at peak were significantly lower during single vs. split methadone administration. FM-FHR coupling was less suppressed from trough to peak during split-dosing vs. single-dosing. Maternal physiologic parameters were generally unaffected by dosing condition. Conclusion Split- dosed fetuses displayed less neurobehavioral suppression from trough to peak maternal methadone levels as compared to single-dosed fetuses. Split-dosing may be beneficial for methadone-maintained pregnant women.
Jansson, Lauren M.; DiPietro, Janet A.; Velez, Martha; Elko, Andrea; Knauer, Heather; Kivlighan, Katie T.
For opiate-dependent injection drug users infected with HIV, methadone therapy may facilitate adherence to complex highly active antiretroviral therapy (HAART) regimens. Current HAART regimens include one or more nucleoside analogues. We investigated the effects of methadone on the pharmacokinetics of the tablet formulation of didanosine (ddI) and of stavudine (d4T) in 17 study subjects on stable methadone therapy and in 10 untreated controls. Methadone treatment reduced the measured areas under the time-concentration curve (AUC0-6) by 63% for ddI (p =.04) and by 25% for d4T (p =.005) and the extrapolated AUCs for the full dosing interval (AUC0-12) by 57% for ddI (p =.11) and by 23% for d4T (p =. 02). Peak drug concentrations (Cmax) were reduced by 66% (p =.007) and 44% (p =.001) for ddI and d4T, respectively. The effects on AUC and Cmax appeared to result primarily from decreases in bioavailability. Methadone also delayed drug absorption. Trough levels for methadone did not differ significantly from those in historical controls, suggesting that ddI and d4T did not substantially alter methadone disposition. The results suggest that larger doses of the tablet formulation or an alternate formulation may be needed when didanosine is given to study subjects treated with methadone. PMID:10969348
Rainey, P M; Friedland, G; McCance-Katz, E F; Andrews, L; Mitchell, S M; Charles, C; Jatlow, P
Cocaine use and abuse, an ancient custom, is once again commonplace. While severe toxicity appears to be rare, overt poisoning including death can occur. This report documents nine cases of death associated with cocaine use; in three of these cocaine appears to be causative. Toxicologic analysis of body fluids and tissues was affirmative and levels are reported. Cocaine should be considered in serious drug overdose-reactions, especially after illicit injection. PMID:618156
Lundberg, G D; Garriott, J C; Reynolds, P C; Cravey, R H; Shaw, R F
PurposeCocaine abuse is an ongoing epidemic in the United States. Priapism associated with cocaine use has been reported only twice in the urological literature. To our knowledge we report the first series of priapism associated with cocaine use and the first case associated with the use of this drug in its solid form, known as crack.
ANDREW L. ALTMAN; ALLEN D. SEFTEL; SCOTT L. BROWN; NEHEMIA HAMPEL
We conducted a 6-week, single-blind study of acupuncture for cocaine dependence in methadone-maintained patients (N = 40) for the purpose of identifying an appropriate needle puncture control for use in future large-scale clinical trials. Patients were randomly assigned to receive daily acupuncture in three auricular sites plus one body site (LI-4), or in control sites within 2–3 mm of the
S. Kelly Avants; Arthur Margolin; Patrick Chang; Thomas R. Kosten; Stephen Birch
|This study examined posttreatment patterns of polysubstance use and heroin relapse in a sample of 43 adolescents (ages 14-20) entering short-term residential treatment for primary heroin use. At 12-month follow-up, youths that achieved heroin abstinence (N = 19) were significantly less likely than youths that relapsed to heroin (N = 24) to…
Branson, Christopher E.; Clemmey, Philip; Harrell, Paul; Subramaniam, Geetha; Fishman, Marc
Specific deuterium labeling of methadone and use of gas chromatography-mass spectroscopy technique permits rapid and quanitative determination of the ratio of the labeled to unlabeled drug in body fluids. A trideuertiomethadone (methadone-d3) was shown to have exactly the same analgesic activity and toxicity in mice as methadone. The rates of absorption, distribution, and excretion of methadone-d3 and methadone were identical in rats. These observations suggest that methadone-d3 may be used as an in vivo marker for monitoring methadone intake of patients, and thus may improve the effectiveness of methadone treatment programs. PMID:941022
Hsia, J C; Tam, J C; Giles, H G; Leung, C C; Marcus, H; Marshman, J A; Leblanc, A E
Methadone Maintenance Treatment (MMT) is among the most widely studied treatments for opiate dependence with proven benefits for patients and society. When misused, however, methadone can also be lethal. The issue of methadone diversion is a major concern for all MMT programs. A potential source for such diversion is from those MMT patients who receive daily take home methadone doses. Using a reverse phase high performance liquid chromatography method, seven of the nine patients who were randomly selected to have all of their remaining methadone take home doses (within a 24 hour period) analyzed, returned lower than expected quantities of methadone. This finding suggests the possibility that such patients may have tampered with their daily take home doses. Larger prospective observational studies are clearly needed to test the supposition of this pilot study.
Toxicological analysis of hair is becoming a popular method for investigating past, chronic use of illicit drugs. Several analytical methods using immunometry, chromatography and mass spectrometry have been reported. In this work, capillary electrophoresis was first used for the determination of illicit drugs, such as cocaine and morphine, in the hair of heroin and cocaine users. After rapid washing, hair samples were incubated overnight in 0.25 M HCl at 45 degrees C and the mixtures were extracted with ready-to-use Toxi-tubes A. The organic phase was evaporated and the residue dissolved in a suitable amount of electrophoresis buffer. Free zone capillary electrophoretic determinations of morphine, the main heroin metabolite, and cocaine were accomplished in 0.05 M borate buffer (pH 9.2) at a potential of 15,000 V, with UV detection at 214 and 238 nm, respectively. The use of the less selective wavelength of 200 nm allowed the simultaneous detection of both compounds. Efficient separations (up to 350,000 theoretical plates) and accurate and precise determinations (intra-day R.S.D.s in the range 3-5%) of cocaine and morphine in hair extracts were easily achieved. The analytical sensitivity was sufficient to determinate as little as 0.15 ng/mg of cocaine and morphine in hair using 100-mg samples. Interferences from more than 90 therapeutic drugs and drugs of abuse were excluded. PMID:8331140
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 guidelines. However, these agents have never been compared for opiate detoxification in the prison estate and there is a general paucity of research evaluating the most effective treatment for opiate detoxification in prisons. This study seeks to address this paucity by evaluating the most routinely used interventions amongst drug users within UK prisons. Methods/Design This study uses randomised controlled trial methodology to compare the open use of buprenorphine and methadone for opiate detoxification, given in the context of routine care, within three UK prisons. Prisoners who are eligible and give informed consent will be entered into the trial. The primary outcome will be abstinence status eight days after detoxification, as determined by a urine test. Secondary outcomes will be recorded during the detoxification and then at one, three and six months post-detoxification. Trial registration Current Controlled Trials ISRCTN58823759
Sheard, Laura; Wright, Nat MJ; Adams, Clive E; Bound, Nicole; Rushforth, Bruno; Hart, Roger; Tompkins, Charlotte NE
Rational and objectives. \\u000a Acute 1-day food deprivation stress reinstates heroin seeking in rats, but the generality of this effect to other drugs, and\\u000a its underlying mechanisms, are largely unknown. Here we studied whether food deprivation would reinstate cocaine seeking and\\u000a whether the stress hormone, corticosterone, is involved in this effect.\\u000a \\u000a \\u000a \\u000a Methods. \\u000a Rats were trained to press a lever for cocaine
Uri Shalev; Michela Marinelli; Michael H. Baumann; Pier-Vincenzo Piazza; Yavin Shaham
Prevalence of prescription opioid abuse has increased dramatically in recent years in the United States generally, and a similar pattern of increasing prescription opioid use has also been noted among patients seeking treatment for opioid dependence. This study presents results from an internal quality assurance project conducted by an outpatient methadone maintenance (MM) treatment clinic which sought to examine the extent of ongoing oxycodone abuse among patients that might be going undetected with current urinalysis-testing methods. One hundred five MM patients provided 437 urine samples over a 6-week period. Samples were analyzed using the clinic's usual enzyme multiplied immunoassay test (EMIT) opiate assay (300 ng/ml opiate cutpoint) and a supplemental oxycodone test strip (100 ng/ml oxycodone cutpoint). The EMIT assay identified only 6% (20/437) of samples as positive for oxycodone, whereas the oxycodone test strip indicated that 19% (83/437) tested positive for recent oxycodone use. Inspection of patient characteristics revealed that oxycodone users were more likely to report a prescription opioid as their primary drug at intake, be in MM treatment for a significantly shorter duration, and provide significantly more opioid- and cocaine-positive urine samples. Overall, these data illustrate the potential importance of monitoring for ongoing oxycodone use in MM clinics. Although future efforts should examine this question using more rigorous experimental methods, findings from this initial project have implications for clinical issues such as evaluating patient stability in treatment, making medication-dosing decisions, and determining patient eligibility for methadone take-home privileges. PMID:18295434
Dunn, Kelly E; Sigmon, Stacey C; McGee, Mark R; Heil, Sarah H; Higgins, Stephen T
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.
Dunn, Kelly E.; Sigmon, Stacey C.; McGee, Mark R.; Heil, Sarah H; Higgins, Stephen T.
A 27-year-old man who was a heroin addict had light flashes in front of the right eye and a hemicentral scotoma immediately after intravenous cocaine. The initial ophthalmoscopic appearance was of a white foreign body lying over the papillomacular bundle of the retina in the right eye. This ophthalmoscopic finding was consistent with intraocular talc, cornstarch, or lactose, common diluting agents that are present in intravenous injections of heroin, cocaine, or methylphenidate hydrochloride, and are known to cause systemic embolic phenomena in chronic drug abusers. This glistening crystal on the surface of the retina changed and evolved into a noninfectious but inflammatory organization of retinal granuloma, in which the foreign body crystal could still be visualized at the apex of the lesion. The anterior and posterior segments of the eye remained free of inflammatory signs throughout the course of the organization of the retinal granuloma. PMID:373453
Michelson, J B; Whitcher, J P; Wilson, S; O'Connor, G R
Background The majority of opioid-dependent individuals in the US in need of drug treatment are not receiving it. It would be useful to understand the characteristics of individuals entering and failing to enter methadone treatment. Methods Participants were opioid-dependent adults in Baltimore Maryland recruited from new admissions to one of six methadone treatment programs (n=351) and from the streets from among non-treatment seekers (n=164). At study enrollment, participants were administered the Addiction Severity Index, AIDS Risk Assessment, Community Assessment Inventory, Attitudes toward Methadone Scale, Motivation for Treatment Scale and a urine drug test. A series of logistic regression analyses were conducted to determine the best model to predict treatment entry. Results The final logistic regression analysis showed that predictors of treatment entry included: being African-American, being on parole or probation, having lower rates of self-reported cocaine use and criminal activity, higher employment functioning, and greater perceptions of support from family and community for behavioral change. In addition, in-treatment participants were more likely to have a more extensive prior history of drug abuse treatment, greater desire to seek help in coping with their drug problem, and more positive view of methadone. Conclusions The distinctions between those entering and those not pursuing MTP entry have significance for the structure of outreach programs and reaffirm the need to supplement the current practices of voluntary and coerced treatment entry with one of encouraged treatment entry through outreach.
Schwartz, Robert P.; Kelly, Sharon M.; O'Grady, Kevin E.; Mitchell, Shannon Gwin; Brown, Barry S.
Admissions to treatment for heroin abuse have increased in recent years among the adolescent and young adult population, yet few studies have described whether, and to what extent, young heroin users differ from their non heroin-using peers. This exploratory study presents quantitative and qualitative data obtained from lifetime heroin and non heroin-using adolescents and young adults in a long-term, step-down
Methadone prescription is a controversial topic. While many believe that it is an effective treatment for opiate dependency, others argue that it is not successful in reducing either the addiction or even injecting behaviour. In this debate, Dr Robertson makes the case that methadone has been well tested, is cheap and acceptable to the patient and results in visible improvement. Dr Daniels argues that methadone treatment is philosophically ill-conceived, ethically dubious, and costly. He also highlights evidence that the treatment is potentially harmful to both patients and those in contact with them. PMID:22693699
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
This study identifies structural-level factors influencing methadone maintenance therapy (MMT) program implementation in China. Twenty-eight service providers and 560 randomly selected clients from 28 MMT clinics in the study area underwent face-to-face interviews. Number of clients, retention rate, coverage, and structural-level factors, were collected from a survey of service providers. Individual-level factors and self-reported illicit drug use information were obtained from clients. Urine specimens were collected from the client participants to test for heroin use. Clinics affiliated with the local CDC had more clients, higher retention rates, and broader coverage than those not affiliated with the CDC. Longer operating hours, incentive for compliant clients, and comprehensive services were positively associated with client recruitment and coverage. Comprehensive services and incentives for compliant clients were negatively associated with concurrent illicit drug use. Comprehensive services should be incorporated into the MMT program. Extended operating hours and incentives for compliant clients should be implemented.
Aortic dissection is a rare, potentially catastrophic vascular emergency. Early recognition of the clinical manifestations, rapid confirmation using imaging modalities, urgent administration of appropriate medication and expedient selection of definitive long-term therapy are key to preserving life and reducing morbidity. In recent years it has become increasingly clear that there is a relation between cocaine and aortic dissection. Cocaine serves as both a predisposing factor to aortic dissection due to its effect on aortic connective tissue and as a precipitating factor due to its propensity to produce abrupt and severe hypertension. While similarities exist in the clinical features and diagnostic methods between cocaine-related aortic dissection and aortic dissection unrelated to cocaine use, there are important differences in management between these two syndromes which are rooted in the pharmacology and physiology of cocaine. An understanding of these differences is key to effective early and long-term management of cocaine-related aortic dissection. PMID:20233907
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
Heroin use causes considerable harm to individual users including dependence, fatal and nonfatal overdose, mental health problems, and blood borne virus transmission. It also adversely affects the community through drug dealing, property crime and reduced public amenity. During the mid to late 1990s in Australia the prevalence of heroin use increased as reflected in steeply rising overdose deaths. In January 2001, there were reports of an unpredicted and unprecedented reduction in heroin supply with an abrupt onset in all Australian jurisdictions. The shortage was most marked in New South Wales, the State with the largest heroin market, which saw increases in price, dramatic decreases in purity at the street level, and reductions in the ease with which injecting drug users reported being able to obtain the drug. The abrupt onset of the shortage and a subsequent dramatic reduction in overdose deaths prompted national debate about the causes of the shortage and later international debate about the policy significance of what has come to be called the "Australian heroin shortage". In this paper we summarise insights from four years' research into the causes, consequences and policy implications of the "heroin shortage". PMID:16722543
Degenhardt, Louisa; Day, Carolyn; Gilmour, Stuart; Hall, Wayne
The pharmacokinetics of methadone varies greatly from person to person; so, after the administration of the same dose, considerably different concentrations are obtained in different subjects, and the pharmacological effect may be too small in some patients, too strong and prolonged in others. Methadone is mostly metabolised in the liver; the main step consists in the N-demethylation by CYP3A4 to
Anna Ferrari; Ciro Pio Rosario Coccia; Alfio Bertolini; Emilio Sternieri
This article reviews the pharmacokinetics of heroin after intravenous, oral, intranasal, intramuscular and rectal application and after inhalation in humans, with a special focus on heroin maintenance therapy in heroin dependent patients. In heroin maintenance therapy high doses pharmaceutically prepared heroin (up to 1000 mg\\/day) are prescribed to chronic heroin dependents, who do not respond to conventional interventions such as
Elisabeth J. Rook; Alwin D. R. Huitema; Wim van den Brink; Ree van J. M; Jos H. Beijnen
|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…
Methadone, a synthetic racemic opioid that primarily works as a ?-opioid receptor (OPRM1) agonist, is commonly used for the treatment of heroin addiction. Genetic association studies have reported that the OPRM1 gene is involved in the physiology of heroin and alcohol addiction. Our current study is designed to test the hypothesis that genetic polymorphisms in the OPRM1 gene region are associated with methadone dosage, plasma concentrations, treatment responses, adverse reactions and withdrawal symptoms in a methadone maintenance treatment (MMT) cohort from Taiwan. Fifteen OPRM1 single nucleotide polymorphisms (SNPs) were selected and genotyped using DNA samples from 366 MMT patients. The plasma concentrations of methadone and its metabolite were measured by high performance liquid chromatography. The results obtained using dominant model analysis indicate that the OPRM1 SNPs rs1074287, rs6912029, rs12209447, rs510769, rs3798676, rs7748401, rs495491, rs10457090, rs589046, rs3778152, rs563649, and rs2075572 are significantly associated with change-in-libido side effects (adjusted p<0.042). Using recessive model analysis, these SNPs were also found to be significantly associated with insomnia side effects in this cohort (p<0.009). The significance of the insomnia findings was mainly contributed by a subgroup of patients who had a positive urine morphine test (p<0.022), and by individuals who did not use benzodiazepine hypnotics (p<0.034). Our current data thus suggest that genetic polymorphisms in OPRM1 may influence the change-in-libido and insomnia side effects sometimes found in MMT patients. PMID:22406240
...DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Toxicology Test Systems Â§ 862.3620 Methadone test system. (a) Identification. A methadone...
Introduction Although DSM-IV criteria are widely used in making diagnoses of substance use disorders, gaps exist regarding diagnosis classification, use of dependence criteria, and effects of measurement bias on diagnosis assessment. We examined the construct and measurement equivalence of diagnostic criteria for cocaine and opioid dependences, including whether each criterion maps onto the dependence construct, how well each criterion performs, how much information each contributes to a diagnosis, and whether symptom-endorsing is equivalent between demographic groups. Methods Item response theory (IRT) and multiple indicators–multiple causes (MIMIC) modeling were performed on a sample of stimulant-using methadone maintenance patients enrolled in a multisite study of the National Drug Abuse Treatment Clinical Trials Network (CTN) (N=383). Participants were recruited from six community-based methadone maintenance treatment programs associated with the CTN and major U.S. providers. Cocaine and opioid dependences were assessed by DSM-IV Checklist. Results IRT modeling showed that symptoms of cocaine and opioid dependences, respectively, were arrayed along a continuum of severity. All symptoms had moderate to high discrimination in distinguishing drug users between severity levels. “Withdrawal” identified the most severe symptom of the cocaine dependence continuum. MIMIC modeling revealed some support for measurement equivalence. Conclusions Study results suggest that self-reported symptoms of cocaine and opioid dependences and their underlying constructs can be measured appropriately among treatment-seeking polysubstance users.
Wu, Li-Tzy; Pan, Jeng-Jong; Blazer, Dan G.; Tai, Betty; Brooner, Robert K.; Stitzer, Maxine L.; Patkar, Ashwin A.; Blaine, Jack D.
BACKGROUND: General practitioners (GPs) are being encouraged to treat more drug users but there are few studies to demonstrate the effectiveness of primary care treatment. AIM: To determine whether patients retained on methadone maintenance treatment for one year in a modern British primary care setting, with prescribing protocols based on the new national guidelines, can achieve similar harm reduction outcomes to those demonstrated in other settings, using objective outcome measures where available. DESIGN OF STUDY: Longitudinal cohort study. SETTING: The Primary Care Clinic for Drug Dependence, Sheffield. METHOD: The intervention consisted of a methadone maintenance treatment provided by GPs with prescribing protocols based on the 1999 national guidelines. The first 96 eligible consenting patients entering treatment were recruited; 65 completed the study. Outcome measures were current drug use, HIV risk-taking behaviour, social functioning, criminal activity, and mental and physical health, supplemented by urinalysis and criminal record data. RESULTS: Frequency of heroin use was reduced from a mean of 3.02 episodes per day (standard deviation [SD] = 1.73) to a mean of 0.22 episodes per day (SD = 0.54), (chi 2 = 79.48, degrees of freedom [df] = 2, P < 0.001), confirmed by urinalysis. Mean numbers of convictions and cautions were reduced by 62% (z = 3.378, P < 0.001) for all crime. HIV risk-taking behaviour, social functioning, and physical and psychological wellbeing all showed significant improvements. CONCLUSION: Patients retained on methadone maintenance treatment for one year in a primary care setting can achieve improvements on a range of harm reduction outcomes similar to those shown by studies in other, often more highly structured programmes.
Although methadone is not a new medication, its use in pain management has increased rapidly over the past decade. This article\\u000a reviews the unique pharmacologic properties of methadone, including its long-acting nature, highly variable clearance rate,\\u000a and its antagonism of the N-methyl-d-aspartate receptor. We discuss potential benefits and risks of methadone over other opioid medications. Preclinical studies\\u000a suggest methadone may
Increased drug availability can precipitate a rapid transition to compulsive drug use in both vulnerable humans and laboratory animals. Recent studies have shown that despite equivalent levels of psychomotor sensitization, only rats with prolonged, but not limited, access to cocaine self-administration respond to the priming effects of cocaine on drug seeking, as measured in a within-session reinstatement model of drug
We set out to examine the impact of treatment for heroin dependence on drug use, injecting behavior, health problems, criminality, and physical and mental health over 18 months among heroin-dependent Londoners. A total of 100 heroin users were recruited for this longitudinal prospective cohort study with repeated measures (T0 as baseline, T1 after 9 months, and T2 after 18 months). The psychiatric evaluation and assessment of drug abuse levels were determined by the CIDI and the EuropASI. Additional evaluations included the WHO-DAS II for disability assessment and the UCLA-SSI for social support. The number of days of heroin use in the 30 days previous to each single assessment significantly reduced over time (p < .001). Similar reduction levels were observed for cocaine (p < .05), benzodiazepines (p < .001), and polydrug abuse (p < .001), but not for cannabis and alcohol. The number of injecting occasions reduced in parallel, with increase in days in work and reduction of money spent for drug acquisition activities and money obtained from criminal/illegal activities. The number of subjects experiencing suicidal ideation reduced over time (p < .05). In line with previous suggestions, significant reductions in drug use, criminality, psychopathology, and injecting behavior following treatment exposure for heroin dependence were observed. It is, however, of concern that alcohol and cannabis misuse levels remained unchanged. PMID:22494230
Client attendance at individual counseling sessions in community-based methadone treatment programs was more frequent among clients with self-reported psychological problems at intake. These problems included anxiety, depression, suicidal ideation, and other symptoms suggesting psychopathology (hallucinations, difficulty controlling violence, etc.). The sample consisted of 462 clients in treatment at least 90 days, divided into two groups of no psychological problems reported at intake (no problems group, N = 341) and two or more problems reported (high problems group, N = 121). The high problems group was twice as likely to attend the treatment program's recommended minimum number of individual counseling sessions (two per month) than was the no problems group, and was more likely to discuss psychological issues in their individual counseling sessions. The high problems group showed significant decreases in drug use and illegal activity in the first 3 months after admission and did not differ significantly from the no problems group on drug-positive urines or illicit activity at month 3. Within the high problems group, clients who attended at least two individual sessions per month reported less cocaine and speedball use during treatment than those who attended fewer sessions. PMID:7595433
|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)|
Chronic pain patients who have limited access to opioids may be redirected to methadone maintenance centers for management of their pain. Unfortunately, little information exists on the incidence and characteristics of methadone maintenance patients with chronic pain. The aim of this study was to survey individuals at methadone maintenance centers in order to determine the prevalence of chronic pain and
Robert N. Jamison; Janice Kauffman; Nathaniel P. Katz
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.
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
Substitution treatment for heroin addiction, defined here as maintenance prescribing of opioid agonist drugs to opioid dependent subjects, has increased in the last decade. The recent history of substitution treatment in five countries--Canada, the U.K., Australia, Israel, and France--is reviewed. In all five countries, the critical issues around substitution treatment are similar. The first key issue concerns the balance between making treatment accessible and attractive, and minimizing diversion to the black market. The second issue concerns the role of primary health care in delivering MMT. In general, there has been increasing involvement of primary health care, with training and support for practitioners. However, there remains uncertainty and official ambivalence over whether treatment should be restricted to specialist clinics and practitioners, or available through primary care. Most importantly, underlying these issues is the problem of stigma being associated with both addiction, and with substitution treatment. The underlying problem that treatment is often at odds with community values places enormous strains on substitution treatment, and makes the treatment system vulnerable to shifting community support and abrupt, politically-driven changes in policy. PMID:12180559
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.
Prospectively collected drug abuse trend surveillance data suggest that the rate of heroin use in Washington, D.C. is rising following a two year decline in the magnitude of this problem. Supportive data include increased potency of street level heroin, increased numbers of heroin-related deaths, increased detection of heroin positive urine specimens in the D.C. Superior Court arrestee population, increased demand for addiction treatment services and rising property crime rates. Increased prevalence of heroin use has not yet been associated with an increase in incidence, suggesting that former heroin users have begun to use once again following a period of abstinence. Analysis of heroin specimens seized across the United States suggests that cities formerly dependant upon European (white) heroin have now developed a new heroin distribution system which supplies Mexican (brown) heroin. This has offset the reduction in heroin use observed during 1972-1973 concomitant with the East Coast heroin shortage and widespread introduction of addiction treatment services. PMID:1211376
|This study assessed the personal values of a group of 17 kindergarten-age children. Children participated in a classroom discussion of heroes and heroines, then drew a picture of their heroes or heroines. The researcher analyzed each child's artwork and determined the outstanding values represented by the hero or heroine. A parallel was drawn…
Seven cases of rhabdomyolysis in heroin addicts are presented. All patients showed concomitant neurological symptoms suggesting mononeuropathy, incomplete plexus lesions or myelopathy. In most cases rhabdomyolysis occurred without preceding trauma to the muscles (for example tissue compression or coma). Five patients had a history of recently resumed heroin abuse after prolonged abstinence. An allergic or toxic reaction to heroin or
The British Columbia Corrections Branch adopted a policy in 1996 of continuing methadone treatments for prisoners who were already enrolled in community methadone treatment programs prior to their incarceration. Continuing methadone treatment had been the standard of care for pregnant women for years, however, this is the first instance of maintenance therapy being made available to prisoners in Canada. Previously, patients on methadone treatment were withdrawn from the programs once they were incarcerated, as it was assumed that they were at an increased risk of using injection drugs while in prison. This program is a progressive, largely harm-reduction approach, and came after a two-year consultation with experts in the addiction and communicable disease specialties. The BC Corrections Harm Reduction Committee took the initiative of reviewing world literature on the topic and after working through their widely divergent views, came up with recommendations for the prison system. Needle exchange received unanimous support from the committee. The methadone program has followed 200 patients on continued treatment after incarceration. PMID:11365288
The mammalian target of rapamycin (mTOR) is a serine-threonine kinase that controls global protein synthesis, in part, by modulating translation initiation, a rate-limiting step for many mRNAs. Previous studies implicate mTOR in regulating stimulant-induced sensitization and antidepressive-like behavior in rodents, as well as drug craving in abstinent heroin addicts. To determine if signaling downstream of mTOR is affected by repeated cocaine administration in reward-associated brain regions, and if inhibition of mTOR alters cocaine-induced behavioral plasticity, C57BL/6J mice received 4 intraperitoneal (IP) injections of 15 mg/kg cocaine and levels of phosphorylated P70S6 kinase and ribosomal S6 protein - two translational regulators directly downstream of mTOR - were analyzed by immunoblotting across several brain regions. Cocaine place-preference and locomotor sensitization were elicited by 4 pairings of cocaine with a distinct environment and the effects of mTOR inhibition were assessed by pretreating the mice with 10 mg/kg rapamycin, 1 hr prior to (a) each saline/cocaine conditioning session, (b) a post-conditioning test or (c) a test for locomotor sensitization conducted at 3 weeks withdrawal. While systemic pretreatment with 10 mg/kg rapamycin during conditioning failed to alter the development of a cocaine place-preference or locomotor sensitization, pretreatment prior to the post-conditioning test attenuated the expression of the place-preference. Additionally, rapamycin pretreatment prior to a cocaine challenge 3 weeks post-conditioning blocked the expression of the sensitized locomotor response. These ndings suggest a role for mTOR activity, and perhaps translational control, in the expression of cocaine-induced place preference and locomotor sensitization.
Bailey, Jeffrey; Ma, Dzwokai; Szumlinski, Karen K.
In recent years, methamphetamine use has dramatically increased in Iran while there is a crucial misunderstanding about the colloquial words related to methamphetamine among health providers, policy makers, clinicians, scholars and people in the community. The word Crystal refers to methamphetamine in some parts of Iran while in some other parts of the country, Crystal refers to a high purity street-level heroin which is called Kerack and its abuse is epidemic. Methamphetamine and heroin Kerack are different drugs in Iran. Methamphetamine is a stimulant drug while heroin Kerack is an opioid. Health providers especially clinicians and emergency medicine specialists should consider colloquial words that Iranian drug users apply. Special training courses should be designed and implemented for clinicians in Iran to inform them about methamphetamine and its frequently used colloquial words in the community. This issue has important clinical and health implications. PMID:23497450
Objectives: Methadone is a synthetic opioid, an analgesic and an antiaddictive. QT prolongation as well as torsade de pointes ventricular tachycardia and death have been reported with methadone. Methadone’s proarrhythmic toxicity is related to the inhibition of cardiac IKr channel and prolongation of the action potential. We hypothesized that the 2 isomers of methadone may have different effects on the
Congrong Lin; Trudie Somberg; Janos Molnar; John Somberg
Cocaine abuse is a significant problem not only in the general population but also among pregnant women. Since cocaine readily crosses the placenta and is metabolized slowly in fetuses, they can be exposed to significant levels of cocaine for long periods. In humans the most common consequences of cocaine abuse during pregnancy include premature birth, lower birth weight, respiratory distress, bowel infarctions, cerebral infarctions, reduced head circumference, and increased risk of seizures. Behaviorally these newborns show an increased degree of "tremulousness," crying and irritability, and are over-reactive to environmental stimuli. Within a month these behaviors have recovered dramatically, but not to normal levels. Thus while there are a number of abnormalities associated with cocaine-exposed neonates, they are not imminently debilitating or life-threatening. However, the long-term consequences of this prenatal cocaine exposure remain to be elucidated. We have examined a rat model for neurochemical, neuroanatomical and behavioral changes resulting from prenatal cocaine exposure. Since cocaine is known to act by blocking the inactivation of the neurotransmitters dopamine, serotonin and norepinephrine, our studies have focused on brain dopamine (DA) and serotonin (5-HT) pathways. In this model system we have found neurochemical changes that are present at birth and that return to normal as the rat ages--similar to the recovery observed in infants. However, there are other neurochemical, anatomical and behavioral changes that persist after birth which may provide insights into the long-term consequences. It is hoped that by understanding the changes occurring in this rat model we will be better prepared to devise pharmacological interventions to circumvent the secondary consequences of prenatal cocaine exposure. These consequences might include increased susceptibility to drug addiction, seizures, depression, schizophrenia, Parkinson's disease, etc. PMID:10911932
Methadone is highly effective in treating opioid dependence, and it is also used as an analgesic for second-line management of chronic pain. However, recent increases in methadone-related deaths have instigated controversy about the use of this medication. In this paper, we evaluate risk factors for methadone mortality in opioid dependent and pain populations and present guidelines for initiating methadone treatment in these two populations to minimize the risk of death. Early research with methadone-maintained patients revealed that methadone fatalities occur primarily due to respiratory arrest during methadone induction and in the context of polysubstance use. Recent reports of methadone deaths emphasize chronic pain populations, methadone-related QTc prolongation, and the possibility of inducing Torsade de pointes (TdP), a potentially fatal ventricular arrhythmia. Retrospective analyses of these deaths show that patients who develop TdP often present with multiple risk factors, including high methadone doses, use of other medications that cause QTc prolongation, and electrolyte abnormalities. To minimize fatalities, guidelines are presented for initiating methadone in opioid treatment and pain populations that consider the drug's pharmacology along with behavioral, medical and psychiatric risk factors. PMID:20087676
The monograph includes data on cocaine as a growing public health problem; neural mechanisms of cocaine's reinforcing action; pharmacology of cocaine; animal and human effects; patterns of cocaine use; and a review of current and experimental treatments o...
Opioid-exposed infants display a wide and variable range of dysregulated neurobehavioral functioning, but the regulatory difficulties experienced by these infants outside the defined clusters of neonatal abstinence syndrome (NAS) have not been well described, and may have implications for the infant’s developmental course. This study describes the neurobehavioral functioning of neonates prenatally exposed to methadone using the NICU Network Neurobehavioral Scale (NNNS) and explores the relationships between maternal factors and infant functioning. The relationship between NNNS measures, NAS severity and need for pharmacotherapy for NAS were also evaluated. Infants who required pharmacological treatment for NAS showed more dysregulated behavior and signs of stress/abstinence as indicated by NNNS scores, but NNNS scores were not significantly correlated with maternal methadone dose. The determination of the range of the methadone exposed infant’s neurobehavioral repertoire could guide the optimal treatment of all such infants, particularly those requiring only non-pharmacological care.
Velez, Martha L.; Jansson, Lauren M.; Schroeder, Jennifer; Williams, Erica
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 patterns and called a voice mailbox daily to report their methadone dose and timing. The average proportion of daily cigarettes smoked was calculated for 2-hr blocks preceding and following methadone dose administration. For all participants, peak smoking rates occurred after methadone administration. Participants smoked a greater proportion of cigarettes in their first 2-hr block after methadone dosing (M = 0.368, SD = 0.135) than during their first 2-hr block of smoking of the day (M = 0.245, SD = 0.010; S = 85.5, p < .0001). The proportion of cigarettes smoked increased by 0.02 from more than 2 hr before methadone to the 2-hr time block before methadone, by 0.04 from the 2-hr time block before methadone to the 2-hr time block after methadone, and by 0.015 from the 2-hr time block after methadone to the next 2-hr time block. From this time block (2-4 hr after methadone), smoking decreased by 0.02 in the 4-plus hr postmethadone dose. All of these changes were statistically significant. Future research should use experimental designs to better examine whether a causal relationship exists and examine the impact of other types of opioid maintenance medications on smoking patterns. PMID:17469938
Richter, Kimber P; Hamilton, Ashley K; Hall, Sandra; Catley, Delwyn; Cox, Lisa S; Grobe, James
Supervised methadone consumption is an important part of methadone maintenance treatment (MMT) but may contribute to stigma for clients. Data from qualitative interviews with MMT clients (n = 64) conducted in 2002-2003 in Canada were analyzed using thematic analytic methods. Three themes dominated clients' accounts of supervised consumption (convenient access to services, relationships with pharmacists and dispensing staff, and attributes of the dispensing space) and were interwoven with experiences of stigmatization. While some dispensing contexts may help clients manage a stigmatized identity, others confer or make visible this identity. Reducing stigmatizing experiences within dispensing environments may improve MMT outcomes and decrease barriers to treatment. The study's limitations are noted. PMID:19444722
During the Swiss heroin prescription trials (PROVE, 1994–1996), over 1,000 heavily addicted heroin users were recruited into the program. While short- and medium-term effects of the program had been thoroughly assessed earlier, only a small body of data on the long-term effects on treated subjects was available. Data on program dropouts were particularly scarce. In order to partially fill that
Opioid withdrawal can produce a constellation of physiological and behavioral signs, including an increase in opioid self-administration. Different mechanisms mediate different withdrawal signs, and the present study used pharmacologic tools to assess mechanisms underlying withdrawal-associated increases in opioid reinforcement. Five rhesus monkeys were rendered heroin dependent via daily 21-h heroin self-administration sessions. One hour after each heroin self-administration session, monkeys
There is increasing evidence that cocaine can have serious adverse effects on the heart. Angina, myocardial infarction, coronary artery spasm, arrhythmia, and sudden death have been reported in association with its use. There have been only two reports of actual myocardial pathology. In an attempt to clarify the pathophysiology of cocaine-associated cardiotoxicity and to search for pathologic changes that might be useful forensically, we reviewed random microscopic sections of hearts from 30 cases of cocaine-associated death seen by the San Francisco Medical Examiner. The age of the patients at death ranged from 25 to 74 years (mean 33.9 years). Pathologic findings included the presence of mild atherosclerotic coronary artery disease without evidence of thrombosis in three cases, associated with mild interstitial fibrosis in one case as well as mild focal myocardial fibrosis without coronary disease in four other cases. The most notable abnormality was the presence of myocardial contraction bands in 28 (93 per cent) cases. In comparison to 20 control cases of death secondary to sedative-hypnotic overdose, the hearts from the cases of cocaine-associated contained significantly more myocardial contraction bands (P less than .001; two-sided). The diffuseness of the contraction bands correlated directly with the level of cocaine found in the urine and blood at autopsy during routine screening. The presence and number of contraction bands in these cases was independent of other drugs found in the urine and blood, the number of sections of myocardium examined, and a history of attempted resuscitation. Contraction bands may act to supply the anatomic substrate for the arrhythmias associated with cocaine use. They may also provide a morphologic marker that can be sought in suspected cases of lethal cocaine overdose. Their presence may also suggest a cause of death in cases of sudden and unexpected death in which autopsy reveals no other pathology, and a drug screen is positive for cocaine. PMID:3804323
Tazelaar, H D; Karch, S B; Stephens, B G; Billingham, M E
The hypothalamo-pituitary-adrenal (HPA) axis is involved in all aspects of cocaine self-administration. Corticosterone seems to be crucial for the acquisition of drug use since self-admin- istration does not occur unless this stress hormone is increased above a critical reward threshold. Increasing circulating levels of corticosterone also augments sensitivity to low doses of cocaine, possibly from a sensitization-associated phenomenon involving dopamine,
The gothic of the eighteenth and nineteenth centuries inherits and exemplifies the cultural division of femininity into a binary opposition between the good woman, named the “domestic victim,” and the bad woman, called the “vamp.” Radcliffe crystallized the gothic domestic victim in The Mysteries of Udolpho, in which the “happy ending” of the heroine is predicated upon her fidelity to
This article suggests that a parallel exists between the practice of tattooing and the injection of heroin as both activities are represented in a body of literature here called `Junk Narratives'. These texts include William Burroughs' Junky, Irvine Welsh's Trainspotting, Jerry Stahl's Permanent Midnight and David Foster Wallace's Infinite Jest. In these books, act and meaning, as in life, are
Subjects maintained on methadone evidence a high level of interest in quitting cigarette smoking. Readiness to quit may result, at least partially, from direct pharmacological interactions between methadone and brain nicotinic acetylcholine receptors. The aim of the present study was to assess: (1) self-reported changes in smoking habits after admission to a methadone maintenance treatment (MMT) program; (2) acute effects of methadone administration on smoking behavior in MMT patients. The study was conducted between May and December 2001, in two public outpatient MMT clinics located in Warsaw, Poland. The patients (41 men, 30 women) reported smoking fewer cigarettes after admission to the program. Most subjects (67.6%) changed their favorite brand of cigarettes after admission. Mean nicotine content (mg/cigarette) significantly decreased. On the other hand, the subjects did not report any effects of methadone administration on smoking parameters. The above findings suggest that initiation of MMT is associated with positive changes in smoking behavior. However, these changes may not be related to direct pharmacological interactions between methadone and nicotine. PMID:16040371
Background Longer tenure in methadone treatment has been associated with positive outcomes such as reductions in drug use and crime, HIV seroconversion, and overdose death. Methods Retention in treatment was examined for 351 opioid-dependent individuals who had been newly admitted to one of six methadone programs in Baltimore, Maryland. Cox proportional hazards regression was used to predict number of days retained in treatment to 90 days from baseline ASI Composite scores and Treatment Motivation scales. A second analysis predicted days in treatment to 365 days using the same baseline variables plus 3-month Motivation scales, Patient Satisfaction scales, and methadone dose in the 248 individuals who had remained in treatment at least 3 months. Analyses held constant gender, race, age, whether participants had a history of regularly smoking cocaine, whether participants were on parole/probation, and program site. Results Retention at 90 days was predicted by female gender, and greater baseline Treatment Readiness (p=.005) but lower Desire for Help (p=.010). Retention at 365 days was predicted by higher baseline ASI Medical Composite scores (p=.037) and lower Legal Composite scores (p=.039), higher 3-month Treatment Satisfaction scores (p=.008), and higher dose (p=.046). Conclusions Greater satisfaction with treatment at 3 months was a significant predictor of retention at 12 months, indicating the importance of understanding the role satisfaction plays in determining retention. Greater severity of legal problems was associated with shorter retention, suggesting that program efforts to increase services to criminal justice patients (e.g., legal counseling) may constitute a useful addition to treatment.
Kelly, Sharon M.; O'Grady, Kevin E.; Mitchell, Shannon Gwin; Brown, Barry S.; Schwartz, Robert P.
Cocaine has high abuse liability but only a subset of individuals who experiment with it develop dependence. The DSM-IV (APA, 2000) provides criteria for diagnosing cocaine abuse and cocaine dependence as distinct disorders- the latter characterized by additional symptoms related to loss of control over drug use. In this study, two groups of cocaine users (n=8/group), matched on demographic factors and length of cocaine use history and meeting criteria for either cocaine abuse (CocAb) or cocaine dependence (CocDep), were compared on 1) measures related to impulsivity and sensation seeking, 2) response to experimenter-administered cocaine (0, 12.5, 25 and 50 mg/70 kg, iv), and 3) cocaine self-administration using a Relapse Choice and a Progressive Ratio Procedure (0, 12.5 and 25 mg/70 kg, iv). Groups did not differ on impulsivity or sensation seeking scores. After experimenter-administered cocaine, the CocAb group reported feeling more suspicious and observers rated them significantly higher on unpleasant effects (e.g., irritability, difficulty concentrating). In contrast, the CocDep group reported significantly greater desire for cocaine, which was sustained over the course of the study, and gave higher street value estimates for cocaine (p< .05). While cocaine self-administration was dose-related and generally comparable across the two procedures, the CocDep users chose to take significantly more cocaine than the CocAb users. These data suggest that, while regular long-term users of cocaine with cocaine abuse or dependence diagnoses cannot be distinguished by trait measures related to impulsivity, they do exhibit significant differences with regard to cocaine-directed behavior and response to cocaine administration.
Walsh, Sharon L.; Donny, Eric C.; Nuzzo, Paul A.; Umbricht, Annie; Bigelow, George E.
The prevalence of heroin use is rising among young people. We reviewed descriptive and treatment studies of heroin-using youth. Medline and Psychinfo were searched with the following kewords: heroin or opiate; and adolescent or young or juvenile. Nine articles describing treatment and five articles describing clinical characteristics of youth with heroin use were reviewed. Descriptive studies of heroin-using youth demonstrate
Christian J Hopfer; Elizabeth Khuri; Thomas J Crowley; Sabrina Hooks
Models of addiction and addiction memory propose that drug-associated cues elicit incentive effects in drug users, which play an important role in maintenance of drug use and relapse. Incentive effects have been demonstrated for smoking and alcohol-related cues but evidence for heroin-related cues has been inconclusive. Furthermore, it is unknown whether appetitive effects of heroin-related cues persist after prolonged abstinence, although heroin addiction is known to have high relapse rates. Therefore, we investigated implicit and explicit valence of heroin-related cues in dependent users at different stages of abstinence using affective startle modulation. In Study I, 15 current heroin users were measured before and after detoxification. Correspondingly, 15 healthy control participants were tested twice at an interval of 14 days. In Study II, 14 long-term abstinent heroin users were additionally measured in a single session. Implicit processing of drug-related stimuli was assessed using affective startle modulation by pictures of heroin and smoking scenes. Explicit reactions were measured using ratings of valence and craving. In contrast to controls, heroin-dependent participants showed a clear reduction of startle response during heroin-related pictures (p<0.05). Detoxification did not significantly change their startle responses to heroin-cues. No difference between non-detoxified current and long-term abstinent heroin users was found in implicit reactions to heroin-cues, whereas explicit measures differed between both groups (all p<0.05). After detoxification and even after prolonged abstinence, heroin cues still exert implicit appetitive effects in heroin users. This implies that drug-induced adaptations of reward circuits are long-lasting, resulting in a highly stable addiction memory. PMID:23219936
Preller, Katrin H; Wagner, Michael; Sulzbach, Christian; Hoenig, Klaus; Neubauer, Julia; Franke, Petra E; Petrovsky, Nadine; Frommann, Ingo; Rehme, Anne K; Quednow, Boris B
Although psychological characteristics of both cocaine addicts and alcoholics are well-documented, less information is available focusing on those patients who are dependent on both drugs. This study was designed to assess the differences between cocaine- and cocaine-plus-alcohol-dependent inpatients along several psychological variables. Of the 144 men that served as subjects, 113 were cocaine dependent (CD) and 31 were dependent on
Stacey C. Cunningham; Sheila A. Corrigan; Robert M. Malow; Ivan H. Smason
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
Policies and practices in methadone treatment programs (MTP) vary from one program to another with not all following currently accepted best practices. This may be in part due to lack of physician knowledge, training, and experience. In an attempt to improve clinician knowledge, an 8 hour course was developed and offered nationwide over the past 5 years covering topics important
Peter A. Demaria Jr; Robert C. Sterling; Susan Neshin; J. Thomas Payte
Clear differences in the attitudes of 1,226 adults in a Gallup survey and 130 patients in 4 methadone treatment programs were observed. Patients were more permissive on legalization of use of and education about drugs than the adult sample. PMID:1664527
Women who enter drug abuse treatment programs are likely to report histories of sexual abuse that may impact psychosocial functioning, retention, and outcomes. This study investigates differences at admission between women with and without sexual abuse histories who entered an outpatient methadone treatment program in Texas. In a sample of 137 women, 39% reported prior sexual abuse. Findings show that
Norma G. Bartholomew; Grace A. Rowan-Szal; Lois R. Chatham; Diane C. Nucatola; D. Dwayne Simpson
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
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
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
Heroin availability and purity decreased and prices increased in Australia suddenly in early 2001. The heroin market in Australia has still not returned to the status quo ante after more than six years. Benefits of the heroin shortage, including a substantial reduction in drug overdose deaths and property crime, are generally considered to have outweighed adverse effects which included increased use of other drugs, especially stimulants, with a subsequent increase in aggression, violence and mental illness. Some commentators attributed the heroin shortage to a combination of factors, while an influential study highlighted the importance of supply control asserting that increased funding and improved effectiveness of domestic drug law enforcement produced critical heroin seizures which disrupted major syndicates, thereby producing the heroin shortage. Evidence to support a critical role for drug law enforcement in the heroin shortage is weak with some recent evidence contradicting key assertions used to support the supply control hypothesis. Although the most likely interpretation is still a combination of multiple factors, the most important factors appear to have been a substantial recent reduction in source opium cultivation and heroin production in Burma, but probably also increased heroin consumption en route through China and a switch from heroin to amphetamine production in Burma. This interpretation is consistent with the international experience of several recent decades in numerous countries where national heroin shortages have occurred rarely and generally only briefly, notwithstanding vigorous and very well resourced supply control efforts. The recent reduction in heroin supply in Australia, the most severe, longest lasting and best-documented heroin shortage in the world, cannot be confidently attributed, solely or largely, to improved domestic drug law enforcement. At best, domestic law enforcement may have made a small contribution compared to several other factors. Evaluation of supply, demand and harm reduction should be held to the same standards. PMID:18554895
|Presents a preliminary phenomenological investigation to obtain a better understanding of the attitudes, motivations, feelings, and beliefs associated with the use of cocaine. Highlights an important aspect of the relationship between cocaine use and earlier experiences of empowerment. (JBJ)|
Ritonavir diminishes methadone plasma concentrations, attributed to CYP3A induction, but actual mechanisms are unknown. We determined ritonavir effects on stereoselective methadone pharmacokinetics and clinical effects (pupillary miosis) in healthy HIV-negative volunteers. Subjects received intravenous plus oral (deuterium-labeled) racemic methadone after nothing, short-term (3 day) and steady-state ritonavir. Acute and steady-state ritonavir, respectively, caused 1.5- and 2-fold induction of systemic and apparent oral R- and S-methadone clearances. Ritonavir increased renal clearance 40-50%, and stereoselectively (S>R) increased methadone hepatic N-demethylation 50-80%, extraction 2-fold, and clearance 2-fold. Bioavailability was unchanged, despite significant inhibition of intestinal P-glycoprotein. Intestinal and hepatic CYP3A was inhibited >70%. Ritonavir shifted methadone plasma concentration-miosis curves leftward and upward. Rapid ritonavir induction of methadone clearance results from increased renal clearance and induced hepatic metabolism. Induction of methadone metabolism occurred despite profound CYP3A inhibition, suggesting no role for CYP3A in clinical methadone metabolism and clearance. Ritonavir may alter methadone pharmacodynamics.
Most of the cocaine - deaths are said to be related to cardiovascular complications. This paper addresses a rather infrequent complication of chronic cocaine use, represented by the aortic dissection. The case in point pertains to a 45-year-old, caucasian male, substance abuser who suffered an aortic dissection following the use of cocaine. Blood concentrations of cocaine and benzoylecgonine were considered not to be within a potentially toxic range. PMID:21907939
Marella, Gian Luca; Furnari, Carmelo; Perfetti, Emilio; Arcudi, Giovanni
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.
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.
Attitudes and beliefs about drug abuse treatment have long been known to shape response to that treatment. Two major pharmacological alternatives are available for opioid dependence: methadone, which has been available for the past 40 years, and buprenorphine, a recently-introduced medication. This mixed methods study examined the attitudes of opioid-dependent individuals toward methadone and buprenorphine. A total of 195 participants (n = 140 who were enrolling in one of 6 Baltimore area methadone programs and n = 55 who were out-of-treatment) were administered the Attitudes toward Methadone and toward Buprenorphine Scales and a subset (n = 46) received an ethnographic interview. In-treatment group had significantly more positive attitudes toward methadone than did the out-of-treatment group (p < .001), while they did not differ in their attitudes toward buprenorphine. Both groups had significantly more positive attitudes toward buprenorphine than methadone. Addressing these attitudes may increase treatment entry and retention.
Schwartz, Robert P.; Kelly, Sharon M.; O'Grady, Kevin E.; Mitchell, Shannon Gwin; Peterson, James A.; Reisinger, Heather Schacht; Agar, Michael H.; Brown, Barry S.
Dependence on illicit drugs during pregnancy is a major public health concern as there may be associated adverse maternal, fetal, and neonatal consequences. Sweat patches (n = 389) were collected from 39 pregnant volunteers who provided written informed consent for this Institutional Review Board-approved protocol and wore patches, replaced approximately weekly, from study entry until delivery. Patches were analyzed for opiates (heroin, 6-acetylmor-phine, 6-acetylcodeine, morphine and codeine) and cocaine (cocaine, benzoylecgonine, ecgonine methyl ester, anhydroecgonine methyl ester) by solid phase extraction and gas chromatography mass spectrometry. Seventy-one percent (276) of collected sweat patches were ?5 ng per patch (limit of quantification) for one or more analytes. Cocaine was present in 254 (65.3%) patches in concentrations ranging from 5.2 to 11,835 ng per patch with 154 of these high enough to satisfy the proposed Substance Abuse and Mental Health Services Administration guidelines for a confirmatory drug test (25 ng per patch). Interestingly, 6-acetylmorphine was the most prominent opiate analyte documented in 134 patches (34.4%) with 11.3% exceeding the proposed opiate Substance Abuse and Mental Health Services Administration cut-off (25 ng per patch). Heroin was identified in fewer patches (77), but in a similar concentration range (5.3–345.4 ng per patch). Polydrug use was evident by the presence of both cocaine and opiate metabolites in 136 (35.0%) patches. Sweat testing is an effective method for monitoring abstinence or illicit drug use relapse in this high-risk population of pregnant opiate- and/or cocaine-dependent women.
Brunet, Bertrand R.; Barnes, Allan J.; Choo, Robin E.; Mura, Patrick; Jones, Hendree E.; Huestis, Marilyn A.
In the UK, few doctors prescribe diamorphine for the treatment of opiate dependence to a small number of patients. A retrospective case note review of patients receiving diamorphine in 2000 was conducted in the UK to determine how and why these patients came to receive a prescription for diamorphine. Patient eligibility criteria were examined together with doctors' stated reasons for initiating a diamorphine (heroin) prescription. Two hundred and ten sets of patients' case notes were reviewed at 27 of the 42 (64%) drug clinics in England and Wales where diamorphine was prescribed by the doctor. There appeared to be a general consensus among the few doctors who had prescribed diamorphine that it was a treatment of last resort, for those with long histories of heroin use and injecting, and those who had not responded sufficiently well to previous other treatments. However, there was also a small number of patients initiated on diamorphine without ever having previously received opiate treatments and some because they were experiencing problems injecting methadone. This reflects the UK history of the individual doctor's clinical autonomy in deciding when diamorphine is appropriate and the previous lack of nationally agreed patient eligibility criteria. PMID:17570910
Metrebian, N; Mott, J; Carnwath, Z; Carnwath, T; Stimson, G V; Sell, L
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
Slow downtitration as a methadone discontinuation method is time-consuming and associated to high dropout rates. Whereas ultra-rapid opiate detoxification methods have recently gained some popularity, they are expensive and may be associated with particular problems in methadone patients. In the present study, a 3-day detoxification procedure accelerated with a unique dose of naltrexone was used in 10 methadone-substituted patients. Whereas
Xavier Camarasa; Yasser Khazaal; Jacques Besson; Daniele Fabio Zullino
Methadone has a long and successful history in the treatment of opioid addiction. In recent years, it has become popular again—as\\u000a potent and inexpensive analgesic in patients with chronic pain. Since methadone has been used fatalities have been reported.\\u000a In our study all methadone-associated deaths in Zurich from 1998 to 2007 were analysed. Most of the 146 detected deaths of
STUDY OBJECTIVE—To use a readily available dataset to detect periods of epidemic change and to examine the progression of heroin epidemics in different geographical areas. To consider the implications of epidemic change for strategies to tackle drug misuse.?DESIGN—Comparison of trends in new treatment demand, observed incidence, and age specific population rates for treated heroin users in two geographical areas.?PARTICIPANTS—Heroin users recorded to have sought treatment.?MAIN RESULTS—The areas studied seem to show differences with respect to trends in new treatment demand, incidence of heroin use and distribution of age specific population rates; indicating that they may be at different epidemic stages.?CONCLUSIONS—These analyses show how areas may differ with respect to epidemic progression of heroin use. It is essential that government strategies, and local responses to these, should be cognisant of these dynamics.???Keywords: drug misuse; heroin; epidemic
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
Morphine and methadone are both high affinity, potent mu opioid peptide (MOP) receptor analgesics. Here we compared the antinociceptive potencies of these two drugs when administered subcutaneously (s.c.), intrathecally (i.t.) or intracerebroventricularly (i.c.v.) in both rat and mouse using the tail-flick assay. We found that both morphine and methadone were potently antinociceptive when the drugs were administered s.c., showing comparable AD50 values in both species. However, the antinociception produced by methadone, when it was administered centrally, was much weaker than that produced by centrally-administered morphine. Specifically, the AD50 value for methadone antinociception was greater than 30-fold higher at both the i.t. and i.c.v. site in mouse, and not measurable in rat. Naloxone methiodide (NLX-M), a peripherally-restricted antagonist, was used to further examine the relative contribution of central versus peripheral sites to morphine and methadone antinociception. NLX-M, when administered s.c., blocked the antinociceptive effect of either systemically- or centrally-administered methadone, but had little effect on the antinociception produced by centrally-administered morphine. Furthermore, centrally-administered NLX-M significantly blocked antinociception produced by centrally-administered morphine, but not that produced by centrally-administered methadone. Together, these results suggest that methadone antinociception is significantly dependent on an action of the drug at peripheral sites, and could provide novel insight into the neural mechanisms that distinguish morphine versus methadone antinociception.
He, Li; Kim, Joseph; Ou, Chrissi; McFadden, Whitney; van Rijn, Richard M.; Whistler, Jennifer L.
Mechanisms by which efavirenz diminishes methadone plasma concentrations are unknown. This investigation determined efavirenz influence on clinical methadone disposition and miosis, intravenous and oral alfentanil clearance (hepatic and intestinal cytochrome P450 3A4/5 (CYP3A4/5) activity), fexofenadine disposition (intestinal transporters activity), and efavirenz clearance and 8-hydroxylation (CYP2B6 activity), and human hepatocyte effects. Efavirenz induced systemic and oral alfentanil clearances two- to fivefold and induced efavirenz 8-hydroxylation. Efavirenz stereoselectively decreased methadone plasma concentrations 50-70%. Methadone systemic and oral clearances, hepatic clearance and extraction ratio, N-demethylation, and metabolite formation clearance were stereoselectively increased two- to threefold. Bioavailability decreased. Efavirenz shifted methadone concentration-miosis curves leftward and upward. Efavirenz induced hepatocyte CYP2B6 and CYP3A4 expression, activity, and methadone N-demethylation. Results show that efavirenz coinduced hepatic CYP2B6 and CYP3A4/5, coinduced hepatic and intestinal CYP3A4/5, and coinduced gastrointestinal CYP3A4/5 and efflux transporters. Methadone disposition was most consistent with efavirenz induction of hepatic CYP2B6-mediated methadone N-demethylation. Efavirenz may alter methadone pharmacodynamics. PMID:22398970
Kharasch, E D; Whittington, D; Ensign, D; Hoffer, C; Bedynek, P S; Campbell, S; Stubbert, K; Crafford, A; London, A; Kim, T
Heroin addiction is a socio-behavioral and medical condition with significant public health implications. It is known that\\u000a socioeconomic factors and population changes are important forces shaping the pattern of heroin addiction in a community.\\u000a An understanding of these factors would be useful for the planning of effective intervention strategies. We applied the GIS\\u000a technology in a study to display heroin
Phoebe Pang; Lee Phoebe; Wai-yan Leung; Shui-shan Lee; Hui Lin
Background In Italy, a large cohort study (VEdeTTE1) was conducted between 1998–2001 to evaluate the effectiveness of treatments in reducing mortality and increasing treatment retention among heroin addicts. The follow-up of this cohort (VEdeTTE2) was designed to evaluate the effectiveness of treatments on long-term outcomes, such as rehabilitation and social re-integration. The purpose of this paper is to describe the protocol of the VEdeTTE2 study, and to present the results of the pilot study carried out to assess the feasibility of the study and to improve study procedures. Methods The source population for the VEdeTTE2 study was the VEdeTTE1 cohort, from which a sample of 2,200 patients, traced two or more years after enrolment in the cohort, were asked to participate. An interview investigates drug use; overdose; family and social re-integration. Illegal activity are investigated separately in a questionnaire completed by the patient. Patients are also asked to provide a hair sample to test for heroin and cocaine use. Information on treatments and HIV, HBV and HCV morbidity are obtained from clinical records. A pilot phase was planned and carried out on 60 patients. Results The results of the pilot phase pointed out the validity of the procedures designed to limit attrition: the number of traced subjects was satisfactory (88%). Moreover, the pilot phase was very useful in identifying possible causes of delays and attrition, and flaws in the instruments. Improvements to the procedures and the instruments were subsequently implemented. Sensitivity of the biological test was quite good for heroin (78%) but lower for cocaine (42.3%), highlighting the need to obtain a hair sample from all patients. Conclusion In drug addiction research, studies investigating health status and social re-integration of subjects at long-term follow-up are lacking. The VEdeTTE2 study aims to investigate these outcomes at long-term follow-up. Results of the pilot phase underline the importance of the pilot phase when planning a follow-up study.
A 24-year-old female with 5 year history of heroin abuse experienced painless stiffness of elbow joints and weakness of shoulder and upper limb muscles. She was injecting herself 4-6 times daily alternatively in the upper extremities, sparing the lower limbs. Electromyography (EMG) showed myopathic changes in clinically affected and unaffected muscles. Magnetic resonance imaging (MRI) revealed muscle fibrosis in directly injected muscles, whereas in subcutaneous fat and within muscles of anterior and posterior compartments of both thighs, not directly injected, there were signal changes supportive of oedema and inflammation. EMG and MRI were congruent in showing abnormalities in muscles not directly injected, suggesting long distant effects of heroin or adulterants with a mechanism either toxic or immunologically mediated. PMID:23853507
Personality disorders and particularly antisocial personality disorders (APD) are quite frequent in opioid-dependent subjects. They show various personality traits: high neuroticism, high impulsivity, higher extraversion than the general population. Previous studies have reported that some but not all personality traits improved with treatment. In a previous study, we found a low rate of APD in a French population of opioid-dependent subjects. For this reason, we evaluated personality traits at intake and during maintenance treatment with methadone. Methods - The form A of the Eysenck Personality Inventory (EPI) was given to opioid addicts at intake and after 6 and 12 months of methadone treatment. Results - 134 subjects (96 males and 38 females) took the test at intake, 60 completed 12 months of treatment. After 12 months, the EPI Neuroticism (N) and the Extraversion-introversion (E) scale scores decreased significantly. The N score improved in the first 6 months, while the E score improved only during the second 6 months of treatment. Compared to a reference group of French normal controls, male and female opioid addicts showed high N and E scores. Demographic data and EPI scores of patients who stayed in treatment for 12 months did not differ significantly from those of dropouts (n=23). Patients with a history of suicide attempts (SA) started to use heroin at an earlier age and they showed a higher E score and a tendency for a higher N score at intake. Discussion - The two personality dimensions of the EPI changed during MMT, and the N score converged towards the score of normal controls. Opioid addicts differ from normal controls mostly in their N score. The EPI did not help to differentiate 12-month completers from dropouts. Higher E scores in patients with an SA history might reflect a higher impulsivity, which has been linked to suicidality in other patient groups. PMID:14615698
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
Heroin addiction is a wide-reaching problem with a spectrum of damaging social consequences. A vaccine capable of blocking heroin's effects could provide a long-lasting and sustainable adjunct to heroin addiction therapy. Heroin, however, presents a particularly challenging immunotherapeutic target as it is metabolized to multiple psychoactive molecules. To reconcile this dilemma we examined the idea of a singular vaccine with the potential to display multiple drug-like antigens; thus two haptens were synthesized, one heroin-like and another morphine-like in chemical structure. A key feature in this approach is that immunopresentation with the heroin-like hapten is thought to be immunochemically dynamic such that multiple haptens are simultaneously presented to the immune system. We demonstrate the significance of this approach though the extremely rapid generation of robust polyclonal antibody titers with remarkable specificity. Importantly, both the antinociceptive effects of heroin and acquisition of heroin self-administration were blocked in rats vaccinated using the heroin-like hapten.
Stowe, G. Neil; Vendruscolo, Leandro F.; Edwards, Scott; Schlosburg, Joel E.; Misra, Kaushik K.; Schulteis, Gery; Mayorov, Alexander V.; Zakhari, Joseph S.; Koob, George F.; Janda, Kim D.
Summary The hepatotoxic effect of heroin has been demonstrated in liver biopsies by morphometric analysis of four groups of patients: twenty-one drug abusers (DA) at the time of the biopsy, eighteen patients who had stopped drug consumption for at least six months (ex-DA), twelve patients with post-transfusional chronic active hepatitis (PTCAH), and eleven controls (CONTROL). Semiquantitative assessment showed the extent
Maria Salete Trigueiro de Araújo; Françoise Gerard; Philippe Chossegros; Luís Cristóvao Porto; Pierre Barlet; Jean-Alexis Grimaud
Opioid abuse and addiction have increased in frequency in the United States over the past 20 years. In 2009, an estimated 5.3 million persons used opioid medications nonmedically within the past month, 200000 used heroin, and approximately 9.6% of African Americans used an illicit drug. Racial and ethnic minorities experience disparities in availability and access to mental health care, including substance use disorders. Primary care practitioners are often called upon to differentiate between appropriate, medically indicated opioid use in pain management vs inappropriate abuse or addiction. Racial and ethnic minority populations tend to favor primary care treatment settings over specialty mental health settings. Recent therapeutic advances allow patients requiring specialized treatment for opioid abuse and addiction to be managed in primary care settings. The Drug Addiction Treatment Act of 2000 enables qualified physicians with readily available short-term training to treat opioid-dependent patients with buprenorphine in an office-based setting, potentially making primary care physicians active partners in the diagnosis and treatment of opioid use disorders. Methadone and buprenorphine are effective opioid replacement agents for maintenance and/or detoxification of opioid-addicted individuals. However, restrictive federal regulations and stigmatization of opioid addiction and treatment have limited the availability of methadone. The opioid partial agonist-antagonist buprenorphine/naloxone combination has proven an effective alternative. This article reviews the literature on differences between buprenorphine and methadone regarding availability, efficacy, safety, side-effects, and dosing, identifying resources for enhancing the effectiveness of medication-assisted recovery through coordination with behavioral/psychological counseling, embedded in the context of recovery-oriented systems of care. PMID:23092049
Rapid progress in the past decade with re-engineering of human plasma butyrylcholinesterase has led to enzymes that destroy cocaine so efficiently that they prevent or interrupt drug actions in the CNS even though confined to the blood stream. Over the same time window, improved gene-transfer technology has made it possible to deliver such enzymes by endogenous gene transduction at high levels for periods of a year or longer after a single treatment. This article reviews recent advanc