To test whether a combination of contingency management and methadone dose increase would promote abstinence from heroin and cocaine, we conducted a randomized controlled trial using a 2 x 3 (dosexcontingency) factorial design in which dose assignment was double-blind. Participants were 252 heroin- and cocaine-abusing outpatients on methadone maintenance. They were randomly assigned to methadone dose (70 or 100mg/day, double-blind) and voucher condition (noncontingent, contingent on cocaine-negative urines, or "split"). The "split" contingency was a novel contingency that reinforced abstinence from either drug while doubly reinforcing simultaneous abstinence from both: the total value of incentives was "split" between drugs to contain costs. The main outcome measures were percentages of urine specimens negative for heroin, cocaine, and both simultaneously; these were monitored during a 5-week baseline of standard treatment (to determine study eligibility), a 12-week intervention, and a 10-week maintenance phase (to examine intervention effects in return-to-baseline conditions). DSM-IV criteria for ongoing drug dependence were assessed at study exit. Urine-screen results showed that the methadone dose increase reduced heroin use but not cocaine use. The split 100mg group was the only group to achieve a longer duration of simultaneous negatives than its same-dose noncontingent control group. The frequency of DSM-IV opiate and cocaine dependence diagnoses decreased in the active intervention groups. For a split contingency to promote simultaneous abstinence from cocaine and heroin, a relatively high dose of methadone appears necessary but not sufficient; an increase in overall incentive amount may also be required. PMID:19101098
Epstein, David H; Schmittner, John; Umbricht, Annie; Schroeder, Jennifer R; Moolchan, Eric T; Preston, Kenzie L
The drug habits for 78 confirmed opiate addicts were studied on eight scales from the Process Association Test of Addiction (PATA) for many drug names. Through cluster analysis eight stages of addiction were defined: "to be clean", "to learn about drugs", "to hustle", "to chip" (also "to be high"), to be psychologically dependent or "to need a shot", "to be hooked" "to kick a habit" and "to be in treatment". Associations stimulated by the words heroin and morphine were very similar over the eight stages of addiction in opiate addicts. The subjects were especially inclined to associate morphine and heroin with the most severe level of addiction, "to be hooked". Associations to both methadone and cocaine were elevated at the "hooked" stage, but in other respects associations to these drugs were opposite. Thus, associations to cocaine were focused on the stage of psychological dependence and the lower intermediate stage of addiction, "to chip" and "to be high", whereas associations to methadone suggested a turning away from addiction as indicated by avoidance associations ("to come down" and "to kick a habit") as well as associations to "treatment" and "to be clean". Marijuana, Benzedrine, "goofball" (barbiturates) and alcohol habits were prominent at an intermediate stage of addiction ("to chip" and "to be high"). Avoidance associations were common for Benzedrine and "goofballs" (also pentobarbital) but not for marijuana or alcohol. "Hustling" associations were frequent for marijuana but not for alcohol. PMID:7379700
Haertzen, C A; Ross, F E
The success of methadone in treating opiate addiction has suggested that long-acting agonist therapies may be similarly useful for treating cocaine addiction. Here, we examined this hypothesis, using the slow-onset long-acting monoamine reuptake inhibitor 31,345, a trans-aminotetralin analog, in a variety of addiction-related animal models, and compared it with methadone's effects on heroin's actions in the same animal models. Systemic administration of 31,345 produced long-lasting enhancement of electrical brain-stimulation reward (BSR) and extracellular nucleus accumbens (NAc) dopamine (DA). Pretreatment with 31,345 augmented cocaine-enhanced BSR, prolonged cocaine-enhanced NAc DA, and produced a long-term (24-48?h) reduction in cocaine self-administration rate without obvious extinction pattern, suggesting an additive effect of 31,345 with cocaine. In contrast, methadone pretreatment not only dose-dependently inhibited heroin self-administration with an extinction pattern but also dose-dependently inhibited heroin-enhanced BSR and NAc DA, suggesting functional antagonism by methadone of heroin's actions. In addition, 31,345 appears to possess significant abuse liability, as it produces dose-dependent enhancement of BSR and NAc DA, maintains a low rate of self-administration behavior, and dose-dependently reinstates drug-seeking behavior. In contrast, methadone only partially maintains self-administration with an extinction pattern, and fails to induce reinstatement of drug-seeking behavior. These findings suggest that 31,345 is a cocaine-like slow-onset long-acting monoamine transporter inhibitor that may act as an agonist therapy for cocaine addiction. However, its pattern of action appears to be significantly different from that of methadone. Ideal agonist substitutes for cocaine should fully emulate methadone's actions, that is, functionally antagonizing cocaine's action while blocking monoamine transporters to augment synaptic DA.
Peng, Xiao-Qing; Xi, Zheng-Xiong; Li, Xia; Spiller, Krista; Li, Jie; Chun, Lauren; Wu, Kuo-Ming; Froimowitz, Mark; Gardner, Eliot L
A sensitive and specific method is presented to simultaneously quantify methadone, heroin, cocaine and metabolites in sweat.\\u000a Drugs were eluted from sweat patches with sodium acetate buffer, followed by SPE and quantification by GC\\/MS with electron\\u000a impact ionization and selected ion monitoring. Daily calibration for anhydroecgonine methyl ester, ecgonine methyl ester,\\u000a cocaine, benzoylecgonine (BE), codeine, morphine, 6-acetylcodeine, 6-acetylmorphine (6AM), heroin
Bertrand R. Brunet; Allan J. Barnes; Karl B. Scheidweiler; Patrick Mura; Marilyn A. Huestis
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
Musshoff, Frank; Lachenmeier, Katrin; Lichtermann, Dirk; Madea, Burkhard
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
Methadone Anonymous (MA) is a new 12-step fellowship developed for methadone maintained heroin addicts. A total of 53 MA members completed a survey assessing factors related to methadone maintenance treatment program (MMTP) entry, drug use, MA participation, beliefs concerning effectiveness of MMTP and MA, and level of social cohesiveness. Length of time in MA was associated with a decreased use of alcohol, cocaine, and marijuana. Clients rated components of MA to be significantly more helpful to recovery than MMTP treatment components. Affiliation to five MA members known best by the respondents was significantly greater than affiliation to non-MA members. Length of time in MA was positively associated with MA affiliation. Social affiliation and endorsement of 12-step principles were positively correlated. These findings suggest that MA participation has benefits not available in professionally driven MMTP, and should be further studied. PMID:12466684
Gilman, Stephen M.; Galanter, Marc; Dermatis, Helen
Methadone Anonymous (MA) is a new 12?step fellowship developed for methadone maintained heroin addicts. A total of 53 MA members completed a survey assessing factors related to methadone maintenance treatment program (MMTP) entry, drug use, MA participation, beliefs concerning effectiveness of MMTP and MA, and level of social cohesiveness. Length of time in MA was associated with a decreased use
Stephen M. Gilman; Marc Galanter; Helen Dermatis
Methadone Anonymous (MA) is a new 12-step fellowship developed for methadone maintained heroin addicts. A total of 53 MA members completed a survey assessing factors related to methadone maintenance treatment program (MMTP) entry, drug use, MA participation, beliefs concerning effectiveness of MMTP and MA, and level of social cohesiveness. Length of time in MA was associated with a decreased use
Stephen M. Gilman; Marc Galanter; Helen Dermatis
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.
Examined effectiveness of implosive therapy with heroin addicts during detoxification from methadone. Treatment groups received 12 sessions of implosive therapy or eclectic counseling and were followed for a six-week period. The implosive therapy group were the only ones to significantly reduce their methadone level during treatment and follow-up.…
Hirt, Michael; Greenfield, Heywood
A retrospective study examined the association between methadone dose and in-treatment heroin use as measured by fixed-interval urine testing in a cohort of 62 patients admitted to an Australian maintenance program. Urinalysis and methadone dose data were collected on subjects for a maximum two years and were analysed using Zeger & Liang's (1986) method for modelling longitudinal data. While allowing for patient descriptors and the time period in which urine samples were collected, the relative odds of using heroin were reduced by 2% for every 1 mg increase in the maintenance dose of methadone. It is estimated that the odds of patients maintained on 40 mg of methadone using heroin were 2.2 times those of patients maintained on 80 mg. PMID:8448501
Caplehorn, J R; Bell, J; Kleinbaum, D G; Gebski, V J
STUDY OBJECTIVE: Although the total number of self poisonings in England and Wales has dropped by 32%, the number involving methadone and\\/or heroin rose by 900% in 1974-92. Because of concern about the role of methadone in this increase, the part played by methadone and heroin in poisoning deaths in England and Wales in 1974-92 was investigated. DESIGN: A proportional
J Neeleman; M Farrell
The aim of this study was to assess the efficacy of methadone compared with buprenorphine maintenance therapy in heroin-dependent patients over a treatment period of 18 weeks. Subjects were randomized to receive either methadone or buprenorphine in a comparative double-blind study and consisted of 164 heroin-dependent male patients who met the DSM-IV criteria for heroin dependence and were seeking treatment.
It was our assumption that male heroin users have the personality traits of high impulsivity and low social interaction. Compliance regarding methadone maintenance therapy (MMT) is hypothesized to be related to personality features. We recruited 43 patients that had been receiving MMT and 43 healthy volunteers. All participants completed a Tridimensional Personality Questionnaire (TPQ). Information related to the Opiate Treatment Index (OTI) was gathered from the heroin group. The personality dimensions in the heroin user group and the control group were compared. We further investigated the association between TPQ and OTI. The heroin group presented with lower reward dependence than the control group. Regarding sub-dimensions, heroin users showed higher impulsivity and fatigability, and lower exploratory excitability and social dependence. The explosive (borderline) pattern was more common among the heroin users. The odds ratio of explosive pattern developing to heroin dependence was 4.19. Q scores of heroin use and the maximal methadone dose were associated with persistence. PMID:24666715
Huang, Wei-Lieh; Chang, Li-Ren; Chen, Ying-Zai; Chang, Hung-Chieh Wu; Hsieh, Ming H; Lin, Chein-Heng; Lin, Yu-Hsuan
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
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.
Methadone and acetylmethadol, although possessing almost all of morphine's pharmacological properties, differ from other morphine-like drugs in their longer action, more gradual and less intense withdrawal syndrome, and blockade of euphoric effect of other opiates in addicts. A high percentage of patients maintained on methadone are better able to hold employment or to be otherwise socially productive than when dependent on heroin or morphine. A review of published results and procedures used in methadone maintenance treatment programs for heroin dependence is presented. Former heroin addicts are usually maintained on 80 to 120 mg. (high dose) or 20 to 60 mg. (low dose) oral methadone daily. Some programs are reported to have produced 80% success (patients employed or otherwise socially productive). Selection of patients, availability of allied therapeutic and rehabilitative facilities, strict control of supply, record keeping and periodic evaluation are considered essential. Different criteria (“drug-free” vs. “socially productive”) for judging “success” of treatment of heroin-dependent persons by methadone maintenance and administrative problems in large-scale treatment programs constitute the principal aspects of controversy.
Sim, S. K.
Marriage has been cited as a protective factor against drug use, but the relationship between marriage and drug use has not been explored longitudinally during addiction treatment. The current study assessed individual trajectories of substance use during treatment as a function of marital status and perceived closeness of the marital relationship. A parallel-process growth model was used to (1) estimate the rate of change in percentage of cocaine-positive and heroin-positive urine samples, and (2) examine the relationship between marital status and drug use trajectories over 35 weeks, during and after treatment. Percent days of use for both drugs were lowest for married participants across all time points. Among married participants, reporting a close relationship with one's partner predicted less cocaine and heroin use. These findings suggest that being married and having a close relationship with one's spouse are associated with better outcomes over time. The causal nature of the association is suggested by previous research that has demonstrated the effectiveness of couples therapy as an adjunct to methadone maintenance. PMID:19008050
Heinz, Adrienne J; Wu, Johnny; Witkiewitz, Katie; Epstein, David H; Preston, Kenzie L
BACKGROUND: Buprenorphine, a partial mu-agonist and kappa-antagonist, has been proposed as an alternative to methadone for maintenance treatment of opioid dependence, especially for patients with concurrent cocaine dependence or abuse. This study evaluated whether higher maintenance doses of buprenorphine and methadone are superior to lower doses for reducing illicit opioid use and whether buprenorphine is superior to methadone for reducing
Richard S. Schottenfeld; Juliana Pakes; Alison Oliveto; Douglas M. Ziedonis; Thomas R. Kosten
Treating cocaine addiction using dopamine replacement strategies, treats withdrawal but not relapse. Experiments with diverse pharmacological agents shows involvement of multiple pharmacologies and new approaches are emerging to treat the drug seeking behaviour and craving associated with relapse. Neuropathological studies are showing structural and connectivity changes in the brain of addicts which appear permanent, making control of learned behaviours associated with these changes extremely challenging. Heroin addiction is treated successfully with opiate replacement strategies but relapse and switch to other drugs of abuse remains. Combination therapies are partially successful in treating co-abused substances but do little to the heroin relapse rate. As with cocaine, attention is shifting to understanding the neuropathological changes, particularly in the pre-frontal cortex and hippocampus. PMID:24565015
Detection of benzyolecgonine, the major metabolite of cocaine, in the urinalysis conducted on the first day of an inpatient heroin detoxification treatment program was studied as a predictor of discharge against medical advice (AMA). With this aim, we conducted a chart-review procedure of 275 heroin dependents (DSM-III-R) who received methadone or dextropropoxyphene chlorhydrate to treat Opioid Withdrawal Syndrome. Data were analyzed following a case-control design. The 49 (17.8%) patients who did not complete the treatment due to discharged AMA were characterized by having achieved total heroin abstinence during fewer months from the time they began consumption of this substance to the time of hospitalization (p = .001). Moreover, those patients who requested discharge AMA were characterized by more frequent detection of benzoylecgonine in their urine on the day of admission (p = .004). The value of the odds ratio of this association was 3.81 (95% CI; 1.30 to 11.04). Lastly, noncompleters due to discharge AMA were more likely to be single than ever married (p = .037). The logistic regression model confirmed that there is a significant relationship between an AMA event and the presence of benzoylecgonine in urine upon beginning detoxification and to a shorter duration of the period of total heroin abstinence. In the discussion, the influence that recent interruption of cocaine consumption has on the decision to drop out of a detoxification program AMA is considered. PMID:9143638
Pérez de los Cobos, J; Trujols, J; Ribalta, E; Casas, M
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.
Chen, Ying-Zai; Huang, Wei-Lieh; Shan, Jia-Chi; Lin, Yu-Hsuan; Chang, Hung-Chieh Wu; Chang, Li-Ren
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
To elucidate the effects of steady-state methadone exposure on responding to cocaine conditioned stimuli and on cocaine-induced alterations in central opioid, hypocretin/orexin, and D2 receptor systems, male Sprague-Dawley rats received intravenous infusions of 1 mg/kg/inf cocaine paired with an audiovisual stimulus over three days of conditioning. Then, mini pumps releasing vehicle or 30 mg/kg/day methadone were implanted (SC), and lever pressing for the stimulus was assessed in the absence of cocaine and after a cocaine prime (20 mg/kg, IP). It was found that rats treated with vehicle, but not methadone, responded for the cocaine conditioned stimulus and displayed elevated mu-opioid receptor mRNA expression in the nucleus accumbens core and basolateral amygdala, reduced hypocretin/orexin mRNA in the lateral hypothalamus, and reduced D2 receptor mRNA in the caudate-putamen. This is the first demonstration that steady-state methadone administered after cocaine exposure blocks cocaine-induced behavioral and neural adaptations. PMID:18990547
Leri, Francesco; Zhou, Yan; Goddard, Benjamin; Levy, AnneMarie; Jacklin, Derek; Kreek, Mary Jeanne
The mu-opioid receptor is the site of action of opiates and opioids. We examined whether there are differences in cytosine:guanine (CpG) dinucleotide methylation in the OPRM1 promoter between former heroin addicts and controls. We analyzed methylation at 16 CpG dinucleotides in DNA obtained from lymphocytes of 194 Caucasian former severe heroin addicts stabilized in methadone maintenance treatment and 135 Caucasian control subjects. Direct sequencing of bisulfite-treated DNA showed that the percent methylation at two CpG sites was significantly associated with heroin addiction. The level of methylation at the -18 CpG site was 25.4% in the stabilized methadone-maintained former heroin addicts and 21.4% in controls (p=0.0035, generalized estimating equations (GEE); p=0.0077, t-test; false discovery rate (FDR)=0.048), and the level of methylation at the +84 CpG dinucleotide site was 7.4% in cases and 5.6% in controls (p=0.0095, GEE; p=0.0067, t-test; FDR=0.080). Both the -18 and the +84 CpG sites are located in potential Sp1 transcription factor-binding sites. Methylation of these CpG sites may lead to reduced OPRM1 expression in the lymphocytes of these former heroin addicts. PMID:18650805
Nielsen, David A; Yuferov, Vadim; Hamon, Sara; Jackson, Colin; Ho, Ann; Ott, Jurg; Kreek, Mary Jeanne
All heroin addicts who registered for methadone treatment in Albuquerque in 1969–1971, 1019 in all, were the subjects of this follow-up study, conducted in 1991–1993. The cohort was almost entirely of Hispanic (Chicano) ethnicity, 86% male, with median age 27 at entry. We located 776, dead or alive, and we were able to interview 243 concerning many aspects of their
Avram Goldstein; James Herrera
In this study, the authors evaluated a low-cost contingency management (CM) procedure for reducing cocaine use and enhancing group therapy attendance in 77 cocaine-dependent methadone patients. Patients were randomly assigned to 12 weeks of standard treatment or standard treatment with CM, in which patients earned the opportunity to win prizes…
Petry, Nancy M.; Martin, Bonnie; Simcic, Francis
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
Lin, Wei-Che; Chou, Kun-Hsien; Chen, Chien-Chih; Huang, Chu-Chung; Chen, Hsiu-Ling; Lu, Cheng-Hsien; Li, Shau-Hsuan; Wang, Ya-Ling; Cheng, Yu-Fan; Lin, Ching-Po
The effect of the vasopressin neuropeptide des-glycinamide (Arg8)-vasopressin (DGAVP) on reducing the acquisition of intravenous heroin self-administration in rats was analyzed. When rats reduced in body weight were allowed to self-administer heroin for 1 h per day in the presence of a fixed time, non contingent food delivery schedule, it appeared that heroin intake was related in an orderly way to the unit dose of heroin delivered. DGAVP decreased heroin intake during days 4 and 5 of acquisition, especially when a high dose of heroin was delivered. DGAVP decreased heroin intake more effectively when rats were tested without the food delivery schedule and for 6 h instead of 1 h sessions per day. Structure activity relationship studies revealed that the peptide (pGlu4, Cyt6)AVP-(4-8) was the shortest active sequence mimicking the effect of DGAVP and that this peptide was somewhat more potent than DGAVP in this respect. The peptide (pGlu4,Cyt6)AVP-(4-9) increased the heroin intake of the rats. DGAVP and (pGlu4,Cyt6)-AVP-(4-8) also decreased cocaine intake of body weight reduced rats given the opportunity to self-administer cocaine intravenously in daily 6 h sessions. It is concluded that vasopressin neuropeptides may decrease the reinforcing efficacy of heroin and cocaine during acquisition of drug self-administration rather than interact with nutritional and environmental factors influencing drug taking behavior. PMID:3347140
van Ree, J M; Burbach-Bloemarts, E M; Wallace, M
Background The idea that the impact of opioid agonist treatment is influenced by the psychopathological profile of heroin addicts has not yet been investigated, and is based on the concept of a specific therapeutic action displayed by opioid agents on psychopathological symptoms. In the present report we compared the effects of buprenorphine and methadone on the psychopathological symptoms of 213 patients (106 on buprenorphine and 107 on methadone) in a follow-up study lasting 12 months. Methods Drug addiction history was collected by means of the Drug Addiction History Rating Scale (DAH-RS) and psychopathological features were collected by means of the Symptom Checklist-90 (SCL-90), using a special five-factor solution. Toxicological urinalyses were carried out for each patient during the treatment period. Results No statistically significant differences were detected in psychopathological symptoms, including 'worthlessness-being trapped', 'somatization', and 'panic-anxiety'. Methadone proved to be more effective on patients characterized by 'sensitivity-psychoticism', whereas buprenorphine was more effective on patients displaying a 'violence-suicide' symptomatology. Conclusions Heroin-dependent patients with psychiatric comorbidities may benefit from opioid agonist treatment not only because it targets their addictive problem, but also, precisely due to this, because it is effective against their mental disorder too.
Although buprenorphine is used worldwide as a safe and effective maintenance medication for opioid dependence, some countries have reported a growing incidence of abuse of this medication. Buprenorphine is considered to have lower abuse potential because of its partial agonist profile, but no studies have directly compared the reinforcing effects of buprenorphine with those of full mu opioid agonists in humans. The present double-blind, placebo-controlled, inpatient study compared the reinforcing and subjective effects of intravenously administered buprenorphine (0.5, 2 and 8 mg) and methadone (5, 10, and 20 mg). Participants (N=6) were detoxified from heroin during the first 1-2 weeks after admission. During subsequent weeks, participants received a sample drug dose and $20 on Monday, and they could self-administer either the sampled dose or $20 during one choice session per day on Thursday and Friday. Participants responded under a modified progressive ratio schedule during each choice session. All active doses maintained higher progressive ratio break points (largest completed ratio) than placebo. There were no significant differences in break point values between buprenorphine and methadone or among the different doses of drug. However, several subjective ratings, including “Good Drug Effect,” “High,” and “Liking” dose-dependently increased after administration of buprenorphine and methadone. The peak ratings for these effects did not significantly differ for the two drugs. These results demonstrate that under these experimental conditions, buprenorphine and methadone were equally effective in producing reinforcing and subjective effects.
Comer, Sandra D.; Sullivan, Maria A.; Walker, Ellen A.
Scant scientific evidence supports the efficacy of acupuncture in the treatment of opiate dependence. The purpose of this study was to examine the effectiveness of acupuncture for heroin addicts on methadone maintenance by measuring the daily consumption of methadone, variations in the 36-item Short Form Health Survey-36 (SF-36) and Pittsburgh Sleep Quality Index (PSQI) scores, and heroin craving. Sixty heroin addicts were randomly assigned to true acupuncture (electroacupuncture at the Hegu [LI4] and Zusanli [ST36] acupoints, as well as acupuncture at the Ear Shenmen) or sham acupuncture (minimal acupuncture at the Hegu and Zusanli acupoints without electrical stimulation and superficial acupuncture at the Ear Shenmen), twice weekly for 4 weeks. From week 2 onwards, the daily dose of methadone was reduced by a significantly greater amount with true acupuncture compared with sham acupuncture. True acupuncture was also associated with a greater improvement in sleep latency at follow-up. All adverse events were mild in severity. Acupuncture appears to be a useful adjunct to methadone maintenance therapy (MMT) in heroin addiction. PMID:24871652
Chan, Yuan-Yu; Lo, Wan-Yu; Li, Tsai-Chung; Shen, Lih-Jong; Yang, Szu-Nian; Chen, Yi-Hung; Lin, Jaung-Geng
Background: Cocaine abuse occurs in 40% to 60% of patients entering opioid maintenance treatment, and ef- fective pharmacotherapies are needed for this com- bined dependence. Methods: This 13-week, randomized, double-blind, pla- cebo-controlled trial evaluated the efficacy of desipra- mine hydrochloride (0 or 150 mg\\/d) plus buprenorphine hydrochloride (12 mg\\/d) or methadone hydrochloride (65 mg\\/d) in 180 opioid-dependent cocaine abusers (124
Alison H. Oliveto; Alan Feingold; Richard Schottenfeld; Peter Jatlow; Thomas R. Kosten
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.
Previous work has suggested that maintenance on the noncompetitive N-methyl-d-aspartate (NMDA) antagonist, memantine, increased the subjective effects of smoked cocaine in experienced cocaine users. To determine whether this phenomenon occurs in opioid-dependent individuals, eight (seven male, one female) methadone-maintained cocaine smokers participated in a 47-day inpatient and outpatient study to assess the effects of memantine on smoked cocaine self-administration, subjective effects, and cardiovascular responses. The participants were maintained on memantine (0 mg and 20 mg daily) for 7-10 days prior to laboratory testing, using a double-blind crossover design. Under each medication condition during inpatient phases, participants smoked a sample dose of cocaine base (0, 12, 25, and 50 mg) once, and were subsequently given five choice opportunities, 14 min apart, to self-administer that dose of cocaine or receive a merchandise voucher (US 5.00 dollars). Each cocaine dose was tested twice under each medication condition, and the order of medication condition and cocaine dose were varied systematically. Memantine maintenance did not alter the subjective or reinforcing effects of cocaine. Several cardiovascular responses, however, including peak and initial diastolic pressures following cocaine, were significantly greater during memantine maintenance, although these elevations were not clinically significant. Taken together, these findings corroborate earlier data suggesting that this dose of memantine will not be helpful in the pharmacotherapy of cocaine abuse. PMID:16445970
Collins, Eric D; Vosburg, Suzanne K; Ward, Amie S; Haney, Margaret; Foltin, Richard W
The concurrent use of cocaine and opiate combinations (speedball) has increased since the 1970s and now represents a growing subset of intravenous drug abusers. An isobolographic analysis was applied to the ascending limb of the dose–effect curves for rat self-administration of cocaine, heroin, and their combination to determine the nature of the interaction. The addition of heroin to cocaine shifted the dose–effect curve for self-administration to the left, and the modulation in reinforcing efficacy of the combination of cocaine and heroin was found to be additive. A second experiment used microdialysis to determine the effects of this drug combination on nucleus accumbens (NAc) extracellular levels of dopamine ([DA]e) in rats self-administering low doses of cocaine, heroin, or cocaine/ heroin combinations. These doses of cocaine and cocaine/heroin combinations significantly increased NAc [DA]e, while heroin alone did not. The ratio of the % baseline of [DA]e (or the dialysate concentrations of DA) to cocaine in the dialysate was higher during self-administration of cocaine/heroin combinations than with cocaine alone. These data indicate that although the interaction between cocaine and heroin in maintaining self-administration is additive, a potentiation of NAc dopaminergic neurotransmission is present, suggesting that NAc [DA]e may not be a direct measure of reinforcing efficacy and/or it is not central to the mediation of the self-administration of this drug combination.
Smith, James E; Co, Conchita; Coller, Michael D; Hemby, Scott E; Martin, Thomas J
PURPOSE: Buprenorphine is an alternative to methadone for the maintenance treatment of heroine dependence and may be effective on a thrice weekly basis. Our objective was to evaluate the effect of thrice weekly buprenorphine maintenance for the treatment of heroin dependence in a primary care clinic on retention in treatment and illicit opioid use.SUBJECTS AND METHODS: Opioid-dependent patients were randomly
PatrickG O’Connor; AlisonH Oliveto; JuliaM Shi; ElisaG Triffleman; KathleenM Carroll; ThomasR Kosten; BruceJ Rounsaville; JulianaA Pakes; RichardS Schottenfeld
The objective of the present study was to verify if severe physical health problems frequently encountered in heroin addicts and the concomitant use of alcohol and legal or illegal drugs other than heroin influenced the pharmacokinetics of the major metabolites of heroin. We conducted a 90 minutes follow-up of the plasma concentrations of the pharmaceutical heroin, named diacetylmorphine (DAM), in patients recruited in a DAM assisted treatment centre. TADAM (Traitement Assisté par DiAcétylMorphine) aimed to compare the efficacy of heroin-assisted treatment (HAT) compared with methadone maintenance treatment (MMT) for heroin users considered as treatment resistant patients and who have severe physical and mental health problems. Eleven patients were recruited. Blood samples were collected at baseline and 15, 45 and 90 minutes after DAM administration. All patients received DAM by the "chasing the dragon" route. Plasma samples were analyzed by a previously described ultra-high pressure liquid chromatography coupled to tandem mass spectrometry (UHPLC/MS-MS) method. A principal component analysis (PCA) was performed and 8 metabolite concentrations ratios were calculated to evaluate the influence of various factors (DAM dose, patient pathologies, concomitant use of medications, methadone, street heroin, alcohol and cocaine) on heroin metabolite pharmacokinetics. It seemed to be not affected by the DAM dose, patient pathologies and the concomitant use of medications, methadone, street heroin and alcohol. Cocaine use was the only parameter which showed differences in heroin pharmacokinetics. PMID:24579243
Dubois, N; Demaret, I; Ansseau, M; Rozet, E; Hubert, Ph; Charlier, C
Levo-alpha-acetylmethadol maintenance (LAAM) was compared to methadone maintenance (MM) on the behavioral performance of 315 heroin addicts before, during, and after 12 months of fully subsidized treatment. Assessments of drug use, criminal behavior, HIV risk behaviors, and employment and residential status were obtained at treatment intake and at 6, 12, and 18 months after admission. Treatment retention and in-treatment suppression of heroin use were significantly better for the LAAM group than for the MM group. Improvements were also noted during treatment in criminal behavior, criminal justice involvement, and employment status, and there were reductions in injection HIV risk and number of sexual partners. Most significant effects were primarily related to active participation in maintenance treatment. Under subsidized treatment, retention rates were two to four times that of similar clients in local community programs during the same period. LAAM was a useful and a potentially important addition to treatment options for opiate addiction, conferring greater retention and opiate suppression benefits. Its removal from application provides a historical lesson concerning the introduction of new medications into addiction health services. PMID:19023658
Anglin, M Douglas; Conner, Bradley T; Annon, Jeffrey J; Longshore, Douglas
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.
This study assessed whether attendance rates in a workplace predicted subsequent outcome of employment-based reinforcement of cocaine abstinence. Unemployed adults in Baltimore methadone programs who used cocaine (N = 111) could work in a workplace for 4 hr every weekday and earn $10.00 per hour in vouchers for 26 weeks. During an induction…
Donlin, Wendy D.; Knealing, Todd W.; Needham, Mick; Wong, Conrad J.; Silverman, Kenneth
The hypothesis that separate neural systems mediate the reinforcing properties of opioid and psychomotor stimulant drugs was tested by examining the role of mesolimbic dopamine (DA) neurons in maintaining intravenous heroin and cocaine self-administration. After local destruction of the DA terminals in the nucleus accumbens (NAcc) with 6-hydroxydopamine (6-OHDA), rats trained to self-administer cocaine and heroin on alternate days were
Hugh O. Pettit; Aaron Ettenberg; Floyd E. Bloom; George F. Koob
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
Schneider, Serge; Meys, François
Field ion spectrometry, also known as transverse field compensation ion mobility spectrometry, is a new technique for trace gas analysis that can be applied to the detection of cocaine and heroin. Its principle is based on filtering ion species according to the functional dependence of their mobilities with electric field strength. Field ion spectrometry eliminates the gating electrodes needed in conventional IMS to pulse ions into the spectrometer; instead, ions are injected in to the spectrometer and reach the detector continuously, resulting in improved sensitivity. The technique enables analyses that are difficult with conventional constant field strength ion mobility spectrometers. We have shown that a filed ion spectrometer can selectively detect the vapors from cocaine and heroin emitted from both their base and hydrochloride forms. The estimated volumetric limits of detection are in the low pptv range, based on testing with standardized drug vapor generation systems. The spectrometer can detect cocaine base in the vapor phase, at concentrations well below its estimated 100 pptv vapor pressure equivalent at 20 degrees C. This paper describes the underlying principles of field ion spectrometry in relation to narcotic drug detection, and recent results obtained for cocaine and heroin. The work has been sponsored in part by the United States Advanced Research Projects Agency under contract DAAB10-95C-0004, for the DOD Counterdrug Technology Development Program.
Carnahan, Byron L.; Day, Stephen; Kouznetsov, Viktor; Tarassov, Alexandre
Rationale: Despite numerous reports that male and female animals differ in behavioral responses to drugs, few studies have investigated\\u000a sex differences in drug-reinforced behavior. Objectives: Acquisition of IV cocaine and heroin self-administration was compared in 20 female and 22 male Wistar rats. Methods: An autoshaping procedure was used to train rats to press a lever that resulted in either a
Wendy J. Lynch; Marilyn E. Carroll
Aims Little is known about the differential effects of independent and substance-induced major depression on the longitudinal course of alcohol, cocaine and heroin disorders when studied prospectively. Design Consecutively admitted in-patients, evaluated at baseline, 6-, 12- and 18-month follow-ups. Setting Baseline evaluations in a short-stay in-patient urban community psychiatric hospital unit. Participants Adults (n = 250) with current DSM-IV cocaine, heroin and/or alcohol dependence at baseline. Measurements The Psychiatric Research Interview for Substance and Mental Disorders (PRISM), used to evaluate independent and substance-induced major depression, alcohol, cocaine and heroin dependence, and other psychiatric disorders. Outcomes for each substance: (i) time (weeks) from hospital discharge to first use; (ii) time from discharge to onset of sustained (?26 weeks) remission from dependence; (iii) time from onset of sustained remission to relapse. Findings Substance-induced major depression significantly predicted post-discharge use of alcohol, cocaine and heroin (hazard ratios 4.7, 5.3 and 6.5, respectively). Among patients achieving stable remissions from dependence, independent major depression predicted relapse to alcohol and cocaine dependence (hazard ratios 2.3 and 2.7, respectively). Conclusions Substance-induced and independent major depressions were both related to post-discharge use of alcohol, cocaine and heroin. The findings suggest the importance of clinical attention to both types of depression in substance abusing patients.
Samet, Sharon; Fenton, Miriam C.; Nunes, Edward; Greenstein, Eliana; Aharonovich, Efrat; Hasin, Deborah
Background Both compulsory detoxification treatment and community-based methadone maintenance treatment (MMT) exist for heroin addicts in China. We aim to examine the effectiveness of three intervention models for referring heroin addicts released from compulsory detoxification centers to community methadone maintenance treatment (MMT) clinics in Dehong prefecture, Yunnan province, China. Methods Using a quasi-experimental study design, three different referral models were assigned to four detoxification centers. Heroin addicts were enrolled based on their fulfillment to eligibility criteria and provision of informed consent. Two months prior to their release, information on demographic characteristics, history of heroin use, and prior participation in intervention programs was collected via a survey, and blood samples were obtained for HIV testing. All subjects were followed for six months after release from detoxification centers. Multi-level logistic regression analysis was used to examine factors predicting successful referrals to MMT clinics. Results Of the 226 participants who were released and followed, 9.7% were successfully referred to MMT(16.2% of HIV-positive participants and 7.0% of HIV-negative participants). A higher proportion of successful referrals was observed among participants who received both referral cards and MMT treatment while still in detoxification centers (25.8%) as compared to those who received both referral cards and police-assisted MMT enrollment (5.4%) and those who received referral cards only (0%). Furthermore, those who received referral cards and MMT treatment while still in detoxification had increased odds of successful referral to an MMT clinic (adjusted OR?=?1.2, CI?=?1.1-1.3). Having participated in an MMT program prior to detention (OR?=?1.5, CI?=?1.3-1.6) was the only baseline covariate associated with increased odds of successful referral. Conclusion Findings suggest that providing MMT within detoxification centers promotes successful referral of heroin addicts to community-based MMT upon their release.
This study assesses the frequency that users of illicit drugs display unprofessional behaviors in an employment setting. This research was conducted in the Therapeutic Workplace, a model employment-based treatment program for chronically unemployed adults with long-histories of illicit drug use. Unemployed adults in methadone treatment, who were opiate and cocaine dependent, showed signs of injection drug use, and recently used cocaine were hired to work for 4 hours every weekday for 7 months. Results show that while the overall incidence of many undesirable behaviors is low, a small percentage of participants had serious workplace behavior problems that might limit their success in community workplaces. This study suggests that unprofessional behavior in the workplace could contribute to chronic unemployment in this population.
Carpenedo, Carolyn M.; Needham, Mick; Knealing, Todd W.; Kolodner, Kenneth; Fingerhood, Michael; Wong, Conrad J.; Silverman, Kenneth
Heroin (or diacetylmorphine), a depressant nervous central system, is a semi-synthetic opiate. Its main adverse effect, respiratory depression, can lead to death, especially after an intravenous injection. By loss of tolerance, an overdose can be lethal following heroin use after a period of abstinence (voluntary or not). Mortality rate among heroin users is between 1 and 3%. Addiction, following a regular and continuous use, occurs in less than a quarter of persons who ever tried heroine. Heroin addicts often present with different problems (for instance, a criminal behaviour), without any obvious link with addiction. For a fraction of the addicts, addiction becomes a chronic relapsing disease, requiring a long term maintenance substitution therapy. However, relapses and sometimes continuous heroin use are frequent, For treatment resistant and severe heroin addicts, heroin-assisted treatment can be a solution. Despite the numerous available therapies, heroin is considered to be the drug with the most negative effects on the user. PMID:23888578
Demaret, I; Lemaître, A; Ansseau, M
Technological challenges in the development and testing of illicit narcotics include assuring safety of researchers and operations personnel from drug exposure, assessing the efficiency of sampling and sample handling, checking for artifacts introduced by field procedures, and maintaining quality control/quality assurance. The dye methylene blue was chosen as a simulant for cocaine HCl and heroin HCl. The similarities include the presence of fused ring systems, molecular weights over 300 g/mol, and melting points between 200 and 300 degrees C. A significant difference is that methylene blue has a much lower solubility in water than cocaine HCl and heroin HCl. Experiments have been conducted to successfully increase the solubility of the simulant to match those of cocaine HCl and heroin HCl by adding solidum methyl sulfate.
Patrick, Julie C.; Orzechowska, Grazyna E.; Poziomek, Edward J.
Rationale Exposure to intermittent episodes of social defeat stress can increase drug seeking and leads to intense drug taking in rats.\\u000a \\u000a \\u000a \\u000a Objectives This study investigated the consequences of repeated, intermittent social defeat stress on patterns of drug self-administration\\u000a in rats with access to heroin, cocaine, or a heroin–cocaine combination (“speedball”).\\u000a \\u000a \\u000a \\u000a \\u000a Methods Male Long-Evans rats were either handled (controls) or subjected to 25-min social
Fabio C. Cruz; Isabel M. Quadros; Koen Hogenelst; Cleopatra S. Planeta; Klaus A. Miczek
A total of 95 Caucasian opioid-dependent patients were followed over a one-year period in an outpatient methadone treatment program. The frequency of the TaqI A(1) allele of the D(2) dopamine receptor (DRD2) gene was 19.0% in these patients compared with 4.6% in controls free of past and current alcohol and other drug abuse and free of family history of alcohol and other drug abuse (p = 0.009). Twenty-two of these patients dropped out of the methadone program (Group A), 54 had a successful treatment (Group B), and 19 had a poor treatment (Group C) outcome. The frequency of the A(1) allele was highest in Group C (42.1%), followed by Group A (22.7%) and was lowest in Group B (9.3%). The more than fourfold higher frequency of the A(1) allele in the poor treatment outcome group compared with the successful treatment outcome group was significant (p = 0.00002). Moreover, the average use of heroin (grams/day) during the year prior to study entry was more than twice as great in patients with the A(1)(+) allele (A(1)/A(1) or A(1)/A(2) genotype) than those with the A(1)(-) allele (A(2)/A(2) genotype) (A(1)(+) allele = 0.55 +/- 0. 10, A(1)(-) allele = 0.25 +/- 0.05; p = 0.003). The results indicate that DRD2 variants are predictors of heroin use and subsequent methadone treatment outcome and suggest a pharmacogenetic approach to the treatment of opioid dependence. PMID:11054765
Lawford, B R; Young, R M; Noble, E P; Sargent, J; Rowell, J; Shadforth, S; Zhang, X; Ritchie, T
Genetic factors are believed to account for 30-50% of the risk for cocaine and heroin addiction. Dynorphin peptides, derived from the prodynorphin (PDYN) precursor, bind to opioid receptors, preferentially the kappa-opioid receptor, and may mediate the aversive effects of drugs of abuse. Dynorphin peptides produce place aversion in animals and produce dysphoria in humans. Cocaine and heroin have both been shown to increase expression of PDYN in brain regions relevant for drug reward and use. Polymorphisms in PDYN are therefore hypothesized to increase risk for addiction to drugs of abuse. In this study, 3 polymorphisms in PDYN (rs1022563, rs910080 and rs1997794) were genotyped in opioid-addicted [248 African Americans (AAs) and 1040 European Americans (EAs)], cocaine-addicted (1248 AAs and 336 EAs) and control individuals (674 AAs and 656 EAs). Sex-specific analyses were also performed as a previous study identified PDYN polymorphisms to be more significantly associated with female opioid addicts. We found rs1022563 to be significantly associated with opioid addiction in EAs [P = 0.03, odds ratio (OR) = 1.31; false discovery rate (FDR) corrected q-value]; however, when we performed female-specific association analyses, the OR increased from 1.31 to 1.51. Increased ORs were observed for rs910080 and rs199774 in female opioid addicts also in EAs. No statistically significant associations were observed with cocaine or opioid addiction in AAs. These data show that polymorphisms in PDYN are associated with opioid addiction in EAs and provide further evidence that these risk variants may be more relevant in females. PMID:22443215
Clarke, T-K; Ambrose-Lanci, L; Ferraro, T N; Berrettini, W H; Kampman, K M; Dackis, C A; Pettinati, H M; O'Brien, C P; Oslin, D W; Lohoff, F W
Background Cocaine use remains a major problem within methadone maintenance programs. Disulfiram’s efficacy in reducing cocaine use has been demonstrated in several trials, but its relative efficacy among individuals who use versus abstain from alcohol remains unclear Treatment approaches which seek to enhance substance users’ involvement in self-help activities (Twelve Step Facilitation, TSF) have been associated with better outcomes among alcohol and cocaine users, but have rarely been evaluated among methadone-maintained cocaine-opioid users. Methods We conducted a randomized, placebo controlled, double blind (for medication condition), factorial (2×2) trial with 4 treatment conditions: Disulfiram plus TSF, disulfiram plus standard counseling only, placebo plus TSF, and placebo plus standard counseling in the context of a community-based methadone maintenance program. Participants (N=112) received either disulfiram (250 mg/d) or placebo in conjunction with daily methadone maintenance. Results Assignment to TSF was associated with less cocaine use throughout treatment and a higher number of cocaine-negative urines. While there were no significant main effects of disulfiram versus placebo, individuals without an alcohol use disorder demonstrated greater reductions in cocaine use over time when assigned to disulfiram. Conclusions TSF appears feasible in this methadone maintenance program and was associated with modest reductions in cocaine use, an often intractable problem in this setting. Support for the efficacy of disulfiram was weaker, as it appeared effective only for those without a current alcohol use disorder for this sample.
Carroll, Kathleen M.; Nich, Charla; Shi, Julia M.; Eagan, Dorothy; Ball, Samuel A.
The purpose of this experiment was to investigate the regulation of drug intake in rats (n = 20) self-administering heroin or cocaine during daily 5-hr sessions. Operant chambers were equipped with 2 levers and associated stimulus lights. A response on the lever with stimuli signaling an increase in dose size increased the infusion duration by 3 s, and a response
Wendy J. Lynch; Lynda P. LaBounty; Marilyn E. Carroll
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.
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 durations of abstinence (LDA) than ST participants, and CM conditions did not differ significantly in outcomes or amount of reinforcement earned. Although long-term abstinence did not differ by group, LDA during treatment was the best predictor of abstinence at 9 months. Thus, reinforcement with prizes was similar to voucher CM in promoting LDA, which is associated with posttreatment benefits. PMID:18085914
Petry, Nancy M; Alessi, Sheila M; Hanson, Tressa; Sierra, Sean
Pregnancy in substance-abusing women with HIV/AIDS presents a complex clinical challenge. Opioid-dependent women need treatment with opioid therapy during pregnancy to protect the health of mother and developing fetus. However, opioid therapies, methadone and buprenorphine, may have drug interactions with some HIV medications that can have adverse effects leading to suboptimal clinical outcomes. Further, many opioid-dependent individuals have problems with other forms of substance abuse, for example, cocaine abuse, that could also contribute to poor clinical outcomes in a pregnant woman. Physiological changes, including increased plasma volume and increased hepatic and renal blood flow, occur in the pregnant woman as the pregnancy progresses and may alter medication needs with the potential to exacerbate drug interactions, although there is sparse literature on this issue. Knowledge of possible drug interactions between opioids, other abused substances such as cocaine, HIV therapeutics, and other frequently required medications such as antibiotics and anticonvulsants is important to assuring the best possible outcomes in the pregnant woman with opioid dependence and HIV/AIDS.
McCance-Katz, Elinore F.
Pregnancy in substance-abusing women with HIV/AIDS presents a complex clinical challenge. Opioid-dependent women need treatment with opioid therapy during pregnancy to protect the health of mother and developing fetus. However, opioid therapies, methadone and buprenorphine, may have drug interactions with some HIV medications that can have adverse effects leading to suboptimal clinical outcomes. Further, many opioid-dependent individuals have problems with other forms of substance abuse, for example, cocaine abuse, that could also contribute to poor clinical outcomes in a pregnant woman. Physiological changes, including increased plasma volume and increased hepatic and renal blood flow, occur in the pregnant woman as the pregnancy progresses and may alter medication needs with the potential to exacerbate drug interactions, although there is sparse literature on this issue. Knowledge of possible drug interactions between opioids, other abused substances such as cocaine, HIV therapeutics, and other frequently required medications such as antibiotics and anticonvulsants is important to assuring the best possible outcomes in the pregnant woman with opioid dependence and HIV/AIDS. PMID:20965297
McCance-Katz, Elinore F
Objective To determine whether supervised medical prescription of heroin can successfully treat addicts who do not sufficiently benefit from methadone maintenance treatment. Design Two open label randomised controlled trials. Setting Methadone maintenance programmes in six cities in the Netherlands. Participants 549 heroin addicts. Interventions Inhalable heroin (n = 375) or injectable heroin (n = 174) prescribed over 12 months. Heroin
Wim van den Brink; Vincent M Hendriks; Peter Blanken; Maarten W J Koeter; Zwieten van B. J; Ree van J. M
This essay reviews four texts which critically analyse methadone maintenance therapy using Foucault as a key theoretical framework: [Friedman, J., & Alicea, M. (2001). Surviving heroin: Interviews with women in methadone clinics. Florida: University Press of Florida], [Bourgois, P. (2000). Disciplining addictions: The bio-politics of methadone and heroin in the United States. Culture Medicine and Psychiatry, 24, 165–195], [Bull, M.
Rats were trained to lever press for intravenous cocaine (1.0 mg\\/kg\\/injection) and then switched to bromocriptine (0.3, 1.0, or 3.0 mg\\/kg\\/injection) on a FR-1 reinforcement schedule. Bromocriptine sustained responding at all three doses; hourly drug intake increased linearly with log-dose. In a second experiment, animals were trained to respond for cocaine (1.0 mg\\/kg\\/injection) or heroin (0.1 mg\\/kg\\/injection) reinforcement; drug was
R. A. Wise; A. Murray; M. A. Bozarth
Abstract Background This study examined racial differences in the prevalence of sexual risk behaviors and their associations with sexually transmitted diseases (STDs) among recent heroin-using and cocaine-using women. Methods Participants were 214 women (59% black, 41% white) who were recruited during 2002–2010 using targeted sampling to participate in a study in Baltimore, Maryland, and reported using heroin, cocaine, or crack during the previous 6 months. Participants completed self-report questionnaires about their drug use, sexual risk behaviors, and lifetime history of one of six STDs, including gonorrhea, syphilis, chlamydia, genital herpes, genital warts, or trichomoniasis. Results More black women (50%) than white women (28%) reported a lifetime STD. Although there were no racial differences in the lifetime prevalence of sexual risk behaviors assessed, there were racial differences in the sexual behaviors associated with ever having a lifetime STD. Simple logistic regressions revealed that ever having a casual sex partner or anal sex were correlates of having a lifetime STD among black women but not among white women. Multiple logistic regression analyses revealed that ever having a casual sex partner was significantly associated with having a lifetime STD among black women, and ever trading sex for money was significantly associated with having a lifetime STD among white women. Conclusions Findings are consistent with national studies and elucidate racial disparities in STDs and associated sexual behaviors among recent heroin-using and cocaine-using women. Findings underscore the need to tailor STD prevention interventions differently for black and white recent heroin-using and cocaine-using women.
Floyd, Leah J.; Penniman, Typhanye V.; Hulbert, Alicia; Gaydos, Charlotte; Latimer, William W.
An examination of America's attempts to cope with the problem of heroin (and other drug) addiction must proceed through an analysis of the basic responses to the problem--penal, behavioral and medical--from two quite different, and frequently conflicting, vantage points: that of the individual addict and that of the society as a whole. (Author/NQ)
Objective: Determine the prevalence and compare some genetic markers involved in addictive behavior in a group of addicts to derivative of coca (cocaine/crack) or heroin and a control group of non-addicted people matched for gender, age and ethnicity. Methods: A 120 addicts and 120 non-addicts Colombian male were surveyed and genotyped for 18 polymorphism of the OPRM1, DRD2, DRD4, SLC6A3, SLC6A4, ABCB1, D?H and CYP2B6 genes. For the identification of alleles markers were used mini-sequencing and fragment multiplex PCR techniques; ethnicity of cases and controls was analyzed with 61 AIMs. Results: The age of onset use of heroin or coca derivatives (cocaine/crack) was 16.5±6 years and 99.2% of them consume several illicit drugs. It showed that controls and addicts belong to the same ethnic group. Significant differences between addicts and controls in relation to schooling, marital status, social security family history of substance abuse (p <0.001), Int8-VNTR SLC6A3 gene (p= 0.015) and SNP 3435C>T ABCB1 gene (p= 0.001) were found. Conclusion: The present results indicate that the VNTR- 6R polymorphism of the gene SLC6A3 and the genotype 3435CC in the ABCB1 gene, are both associated with addictive behavior to heroin or cocaine.
Henao, Julieta; Beltran, Leonardo; Porras, Liliana; Gonzalez, Martha; Cruz, Raquel; Carracedo, Angel
The ?-opioid receptor (MOR) binds exogenous and endogenous opioids and is known to mediate the rewarding effects of drugs of abuse. Numerous genetic studies have sought to identify common genetic variation in the gene encoding MOR (OPRM1) that affects risk for drug addiction. The purpose of this study was to examine the contribution of rare coding variants in OPRM1 to the risk for addiction. Rare and low frequency variants were selected using the National Heart Lung and Blood Institute - Exome Sequencing Project (NHLBI-ESP) database, which has screened the exomes of over 6500 individuals. Two SNPs (rs62638690 and rs17174794) were selected for genotyping in 1377 European American individuals addicted to heroin and/or cocaine. Two different SNPs (rs1799971 and rs17174801) were genotyped in 1238 African American individuals addicted to heroin and/or cocaine. Using the minor allele frequencies from the NHLBI-ESP dataset as a comparison group, case-control association analyses were performed. Results revealed an association between rs62638690 and cocaine and heroin addiction in European Americans (p=0.02; 95% C.I. 0.47 [0.24-0.92]). This study suggests a potential role for rare OPRM1 variants in addiction disorders and highlights an area worthy of future study. PMID:23454283
Clarke, Toni-Kim; Crist, Richard C; Kampman, Kyle M; Dackis, Charles A; Pettinati, Helen M; O'Brien, Charles P; Oslin, David W; Ferraro, Thomas N; Lohoff, Falk W; Berrettini, Wade H
The ?-opioid receptor (MOR) binds exogenous and endogenous opioids and is known to mediate the rewarding effects of drugs of abuse. Numerous genetic studies have sought to identify common genetic variation in the gene encoding MOR (OPRM1) that affects risk for drug addiction. The purpose of this study was to examine the contribution of rare coding variants in OPRM1 to the risk for addiction. Rare and low frequency variants were selected using the National Heart Lung and Blood Institute –Exome Sequencing Project (NHLBI-ESP) database, which has screened the exomes of over 6500 individuals. Two SNPs (rs62638690 and rs17174794) were selected for genotyping in 1377 European American individuals addicted to heroin and/or cocaine. Two different SNPs (rs1799971 and rs17174801) were genotyped in 1238 African American individuals addicted to heroin and/or cocaine. Using the minor allele frequencies from the NHLBI-ESP dataset as a comparison group, case-control association analyses were performed. Results revealed an association between rs62638690 and cocaine and heroin addiction in European Americans (p=0.02; 95% C.I. 0.47 [0.24–0.92]). This study suggests a potential role for rare OPRM1 variants in addiction disorders and highlights an area worthy of future study.
Clarke, Toni-Kim; Crist, Richard C.; Kampman, Kyle M.; Dackis, Charles A.; Pettinati, Helen M.; O'Brien, Charles P.; Oslin, David W.; Ferraro, Thomas N.; Lohoff, Falk W.; Berrettini, Wade H.
The study represents an attempt at employing segmental hair analysis in complex poisonings with xenobiotic mixtures of heroine - cocaine - amphetamines in the context of the cause of death as a consequence of complex interaction mechanisms which occurred prior to death. Two cases of complex poisonings: heroine - cocaine and heroine - cocaine - amphetamines were analyzed and documented with macro- and microscopic examinations and complex toxicological examinations, including the analysis of classic biological material, i.e. samples of selective blood, and alternative material, i.e. hair samples. Determinations of opioids, cocaine and its metabolite and amphetamines in the hair biological matrix were performed using high performance liquid chromatography--atmospheric pressure chemical ionization--tandem mass spectrometry (HPLC-APCI-MS-MS). Segmental hair analysis of the investigated cases indicated a prolonged intake of similar psychoactive substances and a developed adaptation of the addicted to interaction mechanisms, which, however, led gradually to multiorgan anatomopathological changes, and in consequence to death. PMID:21180103
Rojek, Sebastian; K?ys, Ma?gorzata; Rzepecka-Wo?niak, Ewa; Konopka, Tomasz
... a lack of accepted safety for use under medical supervision. What are the common places of origin? Heroin is processed from morphine, a naturally occurring substance extracted from the seed pod of certain varieties of poppy plants grown in: Southeast Asia (Thailand, Laos, and Myanmar ( ...
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
Hair of young subjects (N = 36) suspected for drug abuse was analysed for morphine, codeine, heroin, 6-acetylmorphine, cocaine, methadone, amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), and 3,4-methylenedioxyethylamphetamine (MDEA). The analysis of morphine, codeine, heroin, 6-acetylmorphine, cocaine, and methadone in hair included incubation in methanol, solid-phase extraction, derivatisation by the mixture of propionic acid anhydride and pyridine, and gas chromatography/mass spectrometry (GC/MS). For amphetamine, methamphetamine, MDA, MDMA, and MDEA analysis, hair samples were incubated in 1M sodium hydroxide, extracted with ethyl acetate, derivatised with heptafluorobutyric acid anhydride (HFBA), and assayed by GC/MS. The methods were reproducible (R.S.D. = 5.0-16.1%), accurate (85.1-100.6%), and sensitive (LoD = 0.05-0.30ng/mg). The applied methods confirmed consumption of heroin in 18 subjects based on positive 6-acetylmorphine. Among these 18 heroin consumers, methadone was found in four, MDMA in two, and cocaine in two subjects. Cocaine only was present in two, methadone only in two, methamphetamine only in two, and MDMA only in seven of the 36 subjects. In two out of nine coloured and bleached hair samples, no drug was found. Despite the small number of subjects, this study has been able to indicate the trend in drug abuse among young people in Croatia. PMID:11909652
Skender, L; Karaci?, V; Brci?, I; Bagari?, A
The present study examined Social Control processes in drug cessation among adults. Social Control theory posits that the association between drug use and the drug use of a person’s social network results from an individual seeking out similar peers. The data included 629 individuals who reported past-year heroin or cocaine use at baseline and had follow-up data in a community study in Baltimore, MD. Negative binomial regression modeling indicated that the reduction in social network drug use was significantly greater for quitters than those who did not quit. Compared to non-quitters at baseline, the IRR of the number of drug-using network members was 0.86 for quitters at baseline, 0.71 for non-quitters at follow-up, and 0.28 for quitters at follow-up (all p < 0.05). These findings support Social Control theory in adult drug use cessation. Future research should extend the length of follow-up and assess bidirectional influences.
Buchanan, Amy S.; Latkin, Carl A.
Abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis are well documented in men using illicit drugs and/or infected with HIV; however, less is known about HPA function, or the health consequence of HPA dysfunction, in their female counterparts. People with depression exhibit hypercortisolemia, and depression is common in people with HIV or substance use problems. The current study investigated cortisol secretion in 209 demographically matched men and women, stratified by their HIV and drug use status. Self-reported depressive symptoms were evaluated using a standardized, validated questionnaire (CES-D). Women reported more depressive symptoms than men (p=.01). Male and female drug users exhibited higher cortisol concentrations (p=.03), and were more likely to report depressive symptoms (p=.04), than non-users. Depression was related to elevated cortisol concentrations for the study population (p=.03), and women with elevated cortisol concentrations were significantly more depressed than all other participants (p=.05). While it is unknown whether high cortisol concentrations precede depressive symptoms or vice versa, these data indicate that higher cortisol concentrations are associated with depressive symptoms in heroin and cocaine users, and that this association is more pronounced in women than men. HIV status did not act in an additive or synergistic way with drug use for either cortisol or CES-D measures in the current study. Unique therapies to treat the endocrine and mental health consequences of illicit drug use in men and women deserve consideration as depressive symptoms, and high cortisol concentrations associated with depressive symptoms, differ by gender. PMID:16157457
Wisniewski, Amy B; Brown, Todd T; John, Majnu; Cofranceso, Joseph; Golub, Elizabeth T; Ricketts, Erin P; Wand, Gary; Dobs, Adrian S
Methadone is used to divert heroin addicts from using stronger drugs. Rate of crimes committed by drug addicts has fallen considerably after putting them on methadone. Despite criticisms, methadone use seems to be encouraging for the future. (PS)
Bazell, Robert J.
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
John R. Mario
Hair specimens were collected from 322 subjects and analyzed as part of an experimental study administering household surveys during 1997 to a high-risk community sample of adults from Chicago, Illinois. Toxicologic results were compared with survey responses about recent and lifetime drug use. About 35% of the sample tested positive for cocaine, and 4% tested positive for heroin. Sample prevalence
Michael Fendrich; Timothy P. Johnson; Seymour Sudman; Joseph S. Wislar; Vina Spiehler
Methadone treatment for heroin addiction does not touch the roots of the drug problem" and to think that the use of another drug can solve the profound and complex task facing us is indeed an illusion." (Author/AL)
Lennard, Henry L.; And Others
We recently provided evidence for a functional link between cannabinoid and opioid endogenous systems in relapse to heroin-seeking behaviour in rats. In the present study, we aimed at investigating whether the previously observed cross-talk between cannabinoids and opioids could be extended to mechanisms underlying relapse to cannabinoid-seeking behaviour after a prolonged period of abstinence. In rats previously trained to intravenously self-administer the synthetic cannabinoid receptor (CB1) agonist WIN 55,212-2 (12.5 ?g kg?1 inf?1) under a fixed ratio (FR1) schedule of reinforcement, noncontingent nonreinforced intraperitoneal (i.p.) priming injections of the previously self-administered CB1 agonist (0.25 and 0.5 mg kg?1) as well as heroin (0.5 mg kg?1), but not cocaine (10 mg kg?1), effectively reinstate cannabinoid-seeking behaviour following 3 weeks of extinction. The selective CB1 receptor antagonist SR 141716A (0.3 mg kg?1 i.p.) does not reinstate responding when given alone, but completely prevents the cannabinoid-seeking behaviour triggered by WIN 55,212-2 or heroin primings. The nonselective opioid antagonist naloxone (1 mg kg?1 i.p.) has no effect on operant behaviour per sè, but significantly blocks cannabinoid- and heroin-induced reinstatement of cannabinoid-seeking behaviour. These results provide the first evidence of drug-induced reinstatement of cannabinoid-seeking behaviour, and further strengthen previous findings on a cross-talk between the endogenous cannabinoid and opioid systems in relapse mechanisms to drug-seeking.
Spano, M Sabrina; Fattore, Liana; Cossu, Gregorio; Deiana, Serena; Fadda, Paola; Fratta, Walter
The purpose of this study was to determine if methadone-maintained patients (MMP) with cocaine dependence (CD) and/or adult Attention Deficit Hyperactivity Disorder (ADHD) exhibited compounded cognitive dysfunction associated with their poly-substance use and/or co-morbid psychiatric diagnoses. The sample consisted of 79 MMP (59% male, 51% Caucasian), maintained on methadone doses ranging from 40-130 mg/day, who were placed into one of four diagnostic categories: (1) a control group (no ADHD, no CD) (n = 24), (2) CD alone (n = 18), (3)ADHDalone (n = 18), and (4)ADHD+ CD(n = 19). The California Computerized Assessment Package (CalCAP) was administered to assess cognitive functioning requiring focused and sustained attention in a standardized fashion. There were no group differences on Simple Reaction tasks. Compared to the control group, the ADHD+ CD group was slower and less accurate on 33% of the Choice Reaction (CR) tasks. Specifically, individuals in the ADHD + CD group and the ADHD alone group performed significantly worse on tasks measuring attention and psychomotor responding. These tasks are associated with broader cognitive skills in working memory, language discrimination and flexibility of cognitive sets that may have implications for treatment outcome. Diagnostic services capable of identifying cognitive deficits among MMP with ADHD and/or CD are needed to maximize the likelihood of treatment success and to serve as an indicator for the efficacy of therapeutic approaches. PMID:17088222
Brooks, Daniel J; Vosburg, Suzanne K; Evans, Suzette M; Levin, Frances R
This study examined the dose-related efficacy of disulfiram for treating cocaine dependence in methadone-stabilized cocaine dependent participants. Design One hundred sixty-one cocaine-and opioid-dependent volunteers were entered into a 14-week, double blind, randomized, placebo-controlled clinical trial at two sites. Methods Participants were stabilized on methadone during weeks 1–2 and received disulfiram at 0, 62.5, 125 or 250 mg/day during weeks 3–14. All participants also received weekly cognitive behavioral therapy. Thrice-weekly urine samples and weekly self-reported drug use assessments were obtained. Results Baseline subject characteristics, retention and drug use did not differ across groups. Outcome analyses were performed on those who participated beyond week 2. Opioid positive urine samples and self-reported opioid use did not differ by treatment group. The prevalence of alcohol use was low prior to and during the trial and did not differ by treatment group. Cocaine-positive urines increased over time in the 62.5 and 125 mg disulfiram groups and decreased over time in the 250 mg disulfiram and placebo groups (p<0.0001). Self-reported cocaine use increased in the 125 mg disulfiram group relative to the other three treatment groups (p=0.04). Conclusions Disulfiram may be contraindicated for cocaine dependence at doses less than 250 mg/day. Whether disulfiram at higher doses is efficacious in reducing cocaine use in dually cocaine and opioid dependent individuals needs to be determined.
Oliveto, Alison; Poling, James; Mancino, Michael J.; Feldman, Zachary; Cubells, Joseph F.; Pruzinsky, Rhonda; Gonsai, Kishorchandra; Cargile, Christopher; Sofuoglu, Mehmet; Chopra, Mohit P.; Gonzalez-Haddad, Gerardo; Carroll, Kathleen M.; Kosten, Thomas R.
Pregnancy in substance-abusing women with HIV\\/AIDS presents a complex clinical challenge. Opioid-dependent women need treatment with opioid therapy during pregnancy to protect the health of mother and developing fetus. However, opioid therapies, methadone and buprenorphine, may have drug interactions with some HIV medications that can have adverse effects leading to suboptimal clinical outcomes. Further, many opioid-dependent individuals have problems with
Elinore F. McCance-Katz
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
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…
Do It Now Foundation, Phoenix, AZ.
Introduction Functional imaging studies of addiction following protracted abstinence have not been systematically conducted to look at the associations between severity of use of different drugs and brain dysfunction. Findings from such studies may be relevant to implement specific interventions for treatment. The aim of this study was to examine the association between resting-state regional brain metabolism (measured with 18F-fluorodeoxyglucose Positron Emission Tomography (FDG-PET) and the severity of use of cocaine, heroin, alcohol, MDMA and cannabis in a sample of polysubstance users with prolonged abstinence from all drugs used. Methods Our sample consisted of 49 polysubstance users enrolled in residential treatment. We conducted correlation analyses between estimates of use of cocaine, heroin, alcohol, MDMA and cannabis and brain metabolism (BM) (using Statistical Parametric Mapping voxel-based (VB) whole-brain analyses). In all correlation analyses conducted for each of the drugs we controlled for the co-abuse of the other drugs used. Results The analysis showed significant negative correlations between severity of heroin, alcohol, MDMA and cannabis use and BM in the dorsolateral prefrontal cortex (DLPFC) and temporal cortex. Alcohol use was further associated with lower metabolism in frontal premotor cortex and putamen, and stimulants use with parietal cortex. Conclusions Duration of use of different drugs negatively correlated with overlapping regions in the DLPFC, whereas severity of cocaine, heroin and alcohol use selectively impact parietal, temporal, and frontal-premotor/basal ganglia regions respectively. The knowledge of these associations could be useful in the clinical practice since different brain alterations have been associated with different patterns of execution that may affect the rehabilitation of these patients.
Moreno-Lopez, Laura; Stamatakis, Emmanuel A.; Fernandez-Serrano, Maria Jose; Gomez-Rio, Manuel; Rodriguez-Fernandez, Antonio; Perez-Garcia, Miguel; Verdejo-Garcia, Antonio
High doses of pharmaceutical graded heroin in combination with methadone are prescribed nowadays in a Dutch trial with methadone treatment refractory heroin addicts. Heroin is prescribed either through intravenous injection or inhalation. One of the major risks of using opioids is ventilatory depression. In this study, the effect of heroin on oxygen saturation rate (SpO2) in a group of opioid
Elisabeth J. Rook; Jos H. Beijnen; Wim van den Brink; Jan M van Ree
Cardiovascular complications of cocaine abuse include myocardial ischemia and infarction, dysrhythmias, cardiomyopathies and aortic dissection. The case in point pertains to a 26-year-old, Caucasian male, substance abuser who suffered a thoracic aortic dissection following the use of crack cocaine. The autopsy and histological findings showed a connective tissue abnormality including a focal microcystic medial necrosis and a fragmentation of the elastic fibers in the arterial walls. Blood concentrations of cocaine and benzoylecgonine, taken individually, were considered to be within a potentially toxic range. Blood concentrations of methadone also indicated use of this drug at the same time. The small amounts of morphine found in the blood and urine were compatible with heroine or morphine use more than 24 h before death. PMID:15062953
Palmiere, Cristian; Burkhardt, Sandra; Staub, Christian; Hallenbarter, Myriam; Paolo Pizzolato, Gian; Dettmeyer, Reinhard; La Harpe, Romano
This article investigates behaviours that may be associated HIV infection among users and sellers of crack, powder cocaine and heroin in central Harlem. Chain referral sampling and other strategies were combined to acquire a sample of 637 (Users = 546; Sellers = 91) who provided urine specimens that were tested for the presence of drugs and HIV. Nearly a quarter (23.9%) of all respondents were HIV positive. Drug injectors were more than 2.5 times more likely to have HIV infections than other respondents (OR = 2.66; 95% CI 1.66–4.26). Those involved in frauds/cons were almost as likely to be HIV positive (OR = 2.58; 95% CI 1.64–4.06). Those with a marital status of being separated, divorced or widowed were twice as likely to be HIV infected (OR 2.16; 95% CI 1.43–3.25). Respondents currently having multiple partner sex (OR = 1.66; 95% CI 1.1–2.51) or who were female (OR = 1.66; 95% CI 1.12–2.45) were more than 1.5 times more likely to be HIV positive. Thus, controlling for lifetime drug injection and current multiple partner sex, other factors, such as participating in frauds/cons, as well as relationship status and being female, were also associated with HIV infection.
DAVIS, W. REES; JOHNSON, B. D.; RANDOLPH, D.; LIBERTY, H. J.
Changes in sleep architecture and continuity are frequent side effects of drugs of abuse, and complaints of poor sleep are often reported by recovering drug abusers. As part of a Phase 1 assessment of the safety and efficacy of 4 and 8 mg\\/day of buprenorphine treatment, the sleep patterns of 20 male opiate-and cocaine-dependent patients were quantified by using standard
Scott E. Lukas; Cynthia M. Dorsey; Nancy K. Mello; Jack H. Mendelson; Leslie H. Lundahl; Michelle Sholar; Steven L. Cunningham
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 = 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 odds ratio = 1.42 (1.14, 1.76) and P = 0.01 with odds ratio = 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.
Cao, Jian; LaRocque, Emily; Li, Dawei
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
Cao, Jian; LaRocque, Emily; Li, Dawei
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.
Imaging time-of-flight secondary ion mass spectroscopy ( ToFSIMS) is a practical tool for studying the movement of molecules on material surfaces as a function of time. The high detection sensitivity, rapid data acquisition and reasonable spatial resolution present ideal conditions for such studies. An application of ToFSIMS is presented characterizing the diffusion of large molecules on gold-coated Si wafers. Polydimethylsiloxane (PDMS) was selected for study because it contaminates material surfaces and can be detected easily. Also, the temperature dependent diffusion properties of hydrochlorinated heroin and cocaine are presented as part of a forensic application. While the PDMS diffusion could be explained by a two-dimensional ( 2-D) Brownian motion with a Gaussian probability distribution function (pdf) with a diffusion coefficient of 1.6 ? m^2/sec, the cocaine and to a lesser extent heroin were observed to move nearly freely on the surfaces as though they were part of a 2-D gas evaporating in 2-D from a condensed phase. The results could be described reasonably well using an extreme Lévi pdf with an index of stability ?<= 0.01.
Avci, Recep; Maccagnano, Sara; Bohannan, Gary; Gresham, Gary; Groenewold, Gary
The aim of this study was to determine whether oral sustained release d-amphetamine (SR-AMP) reduces cocaine and opioid/cocaine combination (‘speedball'-like) seeking in volunteers with current opioid dependence and cocaine dependence. Following outpatient buprenorphine (BUP) 8?mg/day stabilization without SR-AMP, eight participants completed a 3-week in-patient study with continued BUP 8?mg/day maintenance and double-blind ascending SR-AMP weekly doses of 0, 30, and 60?mg/day, respectively. After 3 days (Saturday–Monday) stabilization at each SR-AMP weekly dose (0, 15, or 30?mg administered at 0700 and 1225 each day), on Tuesday–Friday mornings (0900–1200 hours), participants sampled four drug combinations in randomized, counterbalanced order under double-blind, double-dummy (intranasal cocaine and intramuscular hydromorphone) conditions: cocaine (COC 100?mg+saline); hydromorphone (COC 4?mg+HYD 24?mg); ‘speedball' (COC 100?mg+HYD 24?mg); and placebo (COC 4?mg+saline). Subjective and physiological effects of these drug combinations were measured. From 1230 to 1530 hours, participants could respond on a choice, 12-trial progressive ratio schedule to earn drug units (1/12th of total morning dose) or money units (US$2). SR-AMP significantly reduced COC, but not HYD or speedball, choices and breakpoints. SR-AMP also significantly reduced COC subjective (eg, abuse-related) effects and did not potentiate COC-induced cardiovascular responses. This study shows the ability of SR-AMP to attenuate COC self-administration, as well as its selectivity, in cocaine/heroin polydrug abusers. Further research is warranted to ascertain whether SR-AMP combined with BUP could be a useful dual-agonist pharmacotherapy.
Greenwald, Mark K; Lundahl, Leslie H; Steinmiller, Caren L
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)
A woman with schizophrenia in methadone treatment was admitted for treatment of psychotic symptoms and cocaine addiction. Her prescribed medication was a 400 mg daily dose of methadone. It became evident during her hospitalisation that she was only taking a small part of the medication herself and she sold the rest of the methadone to finance her addiction of cocaine. To address this kind of misuse of prescribed medication, this paper examines the importance of following guidelines put forward by the NBH (National Board of Health). PMID:19091198
Nielsen, Mette Odegaard; Hetmar, Ole
Methadone has been defined as an agent to draw addicts out of the street life into "straight" society. However, the complementary perspective of the streets sees methadone as a new, widely available drug to be integrated into a subculture previously dominated by heroin. This article discusses the adaptation to methadone and its implications. (NQ)
This study examined the uses of diverted methadone and buprenorphine among opiate-addicted individuals recruited from new admissions to methadone programs and from out-of-treatment individuals recruited from the streets. Self-report data regarding diversion were obtained from surveys and semi-structured qualitative interviews. Approximately 16% (n=84) of the total sample (N=515) reported using diverted (street) methadone 2–3 times per week for six months or more, and for an average of 7.8 days (SD=10.3) within the past month. The group reporting lifetime use of diverted methadone as compared to the group that did not report such use was less likely to use heroin and cocaine in the 30 days prior to admission (ps < .01) and had lower ASI Drug Composite scores (p < .05). Participants in our qualitative sub-sample (n=22) indicated that street methadone was more widely used than street buprenorphine and that both drugs were largely used as self-medication for detoxification and withdrawal symptoms. Participants reported using low dosages and no injection of either medication was reported.
Mitchell, Shannon Gwin; Kelly, Sharon M.; Brown, Barry S.; Reisinger, Heather Schacht; Peterson, James A.; Ruhf, Adrienne; Agar, Michael H.; O'Grady, Kevin E.; Schwartz, Robert P.
This is a cross-sectional study in which we compared the perceived quality of life (QoL) of patients receiving outpatient treatment for cocaine (n = 727) and heroin dependence (n = 469), by analyzing differences by gender and time in treatment. Participants were recruited from addictive behavior centers in Spain in 2004. The World Health Organization Quality of Life Assessment Instrument (WHOQOL-Bref) was used as a measure. Analysis of covariance and multivariate linear regression were used. This study shows the relevance of considering the role of gender in QoL studies, and the need to evaluate the effectiveness of treatment in the improvement of QoL. Limitations of the study were noted. PMID:24712297
Morales-Manrique, Claudia Cristina; Tomás-Dols, Sófía; Zarza-González, María; Vidal-Infer, Antonio; Alvarez, F Javier; Valderrama-Zurián, Juan C
Objective To compare HCV and HIV infection among heroin addicts in MMT and not in MMT in two large cities in central China. Methods A total of 541 heroin addicts were recruited from MMT clinics and voluntary detoxification centers in Changsha and Wuhan, China. Structured questionnaires collected data on their socio-demographics, clinical status, risk behaviors, and their knowledge of HIV. Their HIV serostatus and Hepatitis C virus (HCV) serostatus were determined by testing antibodies in blood serum. Results We observed a higher prevalence of HCV infection among MMT heroin addicts (82.3%) than that in the non-MMT group (50.6%). However, our findings indicated that the heroin addicts in MMT had less drug or sexual HIV/HCV risk behaviors and more knowledge about HIV than non-MMT addicts. The heroin addicts in MMT had a significantly higher percentage of individuals who always used condoms (44.9%) compared with patients in the non-MMT group (14.6%, p?=?0.039), and they had more knowledge about HIV than non-MMT individuals (p<.001). The percentage of HIV-positive addicts in the MMT group (0.7%) and non-MMT group (0.8%) were almost same. Conclusion Our study indicated that the rate of HCV infection among heroin addicts among MMT or non-MMT settings in central China is very high. The non-MMT heroin addicts have higher risk of becoming infected with HCV in the future, while at present they have lower rates of HCV infection than MMT heroin addicts. Although rates of HIV infection among MMT and non-MMT heroin addicts are low now, they are all at great risk of becoming infected with HIV in the future, especially for non-MMT heroin addicts. We should use the MMT sites as a platform to improve the control of HCV and HIV infection in heroin addicts.
Wang, Xuyi; Tan, Linxiang; Li, Yi; Zhang, Yao; Zhou, Dongyi; Liu, Tieqiao; Hao, Wei
We studied profile of patients (n=1782) treated in specialized centers and general practice (GP) enrolled in methadone maintenance treatment (MMT) programs during 2001 in the Swiss Canton of Vaud. We found that GPs treated the majority of patients (76%). Specialized centers treated a higher proportion of patients with uncontrolled intravenous use of cocaine and heroin, and prescribed neuroleptics as concomitant medication three times more frequently than GPs. Patients treated in specialized centers were more likely to undergo screening for HIV, HBV, HCV, and receive complete HBV immunization. In conclusion, specialized centers are more likely to treat severely addicted patients and patients with a poor global assessment (physical, psychiatric, and social). PMID:17891659
Pelet, Anne; Doll, Sebastien; Huissoud, Thérèse; Resplendino, Janine; Besson, Jacques; Favrat, Bernard
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.
Saifan, Chadi; Barakat, Iskandar; El-Sayegh, Suzanne
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
Niamh Ryder; Walter Cullen; Joseph Barry; Gerard Bury; Eamon Keenan; Bobby P Smyth
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
Drug abuse and addiction have assumed the proportions of a national plague, with heroin addiction occupying the center of concern. The military services have been affected by the turmoil produced. A review of methadone maintenance as a medical treatment f...
M. E. Perkins
Summary The abuse of psychoactive drugs by women of childbearing age has placed an untoward burden on the fetus, new-born and child. This included: marijuana- 2.9%; cocaine-1.1%; with lesser percentages of other illicit drugs. Effective methadone maintenance prevents the onset of opioid abstinence syndrome for 24- 36 hours, reduces or eliminates drug craving, and blocks the euphoric effects of illicit
Loretta P. Finnegan
The mental and physical capabilities of drivers in traffic are often seriously challenged these days. Not only do they need to concentrate on driving, predict connections between various phenomena, take appropriate judgements in current situations and foresee the sequence of measures to be taken, but they are also expected to be emotionally stable, etc. The problem with drugs in traffic is often encountered when assessing the actual safe driving capability of a person in a given moment, for example after a car accident or a police check, or medical check-ups that are required for a driving license. The Road Traffic Safety Law considers methadone a drug. Drug addicts do not meet the health standards required of drivers. This research program deals with the attitude of drivers who are in methadone maintenance treatment programs with respect to the driving ability as well as the effects of methadone use in combination with other drugs on driving. It has been established that drivers undergoing the methadone maintenance program, regularly drive not only under the influence of methadone but also under the influence of marijuana (20%) and heroin (18%) and sometimes under the influence of marijuana (58.6%), heroin (55.7%), and alcohol (48.6%). Certain initiatives have been taken by some therapists to give, under certain circumstances, a clean bill of health to responsible methadone maintenance patients who have an adequate level of responsibility for themselves and their deeds, in order to help them obtain a driving license. Since it has been established that methadone maintenance patients use methadone quite commonly in combination with illegal drugs and/or alcohol, the classification of this type of addicts among possible driving candidates remains disputable. Long term interdisciplinary research is still required to determine the basic principles required to asses and possibly admit this type of drivers to participate in traffic, as well as to determine which professional therapists can participate and evaluate the driving capabilities of these patients. PMID:12137290
Bilban, M; Bilban Jakopin, C
Methadone maintenance is a relatively new method for treating heroin addiction. Controversy and questions remain about the drug itself and its use of methadone. The author was engaged by The Drug Abuse Council to prepare these descriptions of four methadone programs and the accompanying summary. The evolution of these programs is examined, and the…
This essay reviews four texts which critically analyse methadone maintenance therapy using Foucault as a key theoretical framework: [Friedman, J., & Alicea, M. (2001). Surviving heroin: Interviews with women in methadone clinics. Florida: University Press of Florida], [Bourgois, P. (2000). Disciplining addictions: The bio-politics of methadone and heroin in the United States. Culture Medicine and Psychiatry, 24, 165-195], [Bull, M. (2008). Governing the heroin trade: From treaties to treatment. Ashgate: Aldershot], and [Fraser, S., & valentine, k. (2008). Substance & substitution: Methadone subjects in liberal societies. New York: Palgrave Macmillan]. Taken together these works demonstrate one trajectory in the development of critical drug studies over the past decade. While all four view MMT as a regulatory technology which aims to create productive and obedient subjects, their understandings of the power relations of the clinic are quite distinct. The first two texts emphasise the social control of drug users, the third, issues of governmentality and liberal political practice, while the fourth engages with ontological questions about substances themselves. Thus while Foucauldian analysis has become familiar in social studies of drugs and alcohol, new uses for its conceptual tools continue to emerge. PMID:19101132
Racemic methadone (MET) is administered to heroin users undergoing methadone maintenance therapy (MMT) in Australia. The enantiomers of methadone possess different pharmacological effects, and the enantioselective metabolism of methadone to its two major metabolites, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) and 2-ethyl-5-methyl-3,3-diphenyl-1-pyrroline (EMDP) has been demonstrated. Therefore, a stereoselective method capable of quantifying methadone, EDDP and EMDP in biological samples could be of benefit
Tamsin Kelly; Philip Doble; Michael Dawson
Health and psychosocial service needs that may be co-morbid with opioid addiction may impede the success of drug treatment among patients attending methadone maintenance treatment programs (MMTPs). This longitudinal panel study investigates whether receipt of services from one or more helping professionals outside of the MMTP confers a benefit for drug treatment outcomes among a random sample of male MMTP patients (N = 356). Each participant was interviewed 3 times, with 6 months between each interview. Since this observational study did not employ random assignment, propensity score matching was employed to strengthen causal validity of effect estimates. Results support hypotheses that receiving additional off-site services has significant beneficial effects in increasing the likelihood of abstaining from cocaine, heroin, and any illicit drug use over both the ensuing 6 month and 12 month time periods. These findings indicate that receipt of additional medical and/or psychosocial services enhances the efficacy of methadone treatment in increasing abstinence from illicit drug use.
Wu, Elwin; El-Bassel, Nabila; Gilbert, Louisa; Chang, Mingway; Sanders, Glorice
Buprenorphine has been studied extensively since 1978 when it was initially proposed as an alternative to methadone for treatment of opioid dependence. Early work by Jasinski, Mello, Mendelson and their colleagues demonstrated buprenorphine's low physical abuse potential and its ability to substitute for heroin and reduce heroin self-administration in opiate-dependent humans. The subsequent early clinical studies suggested that, in clinical
Walter Ling; Donald R Wesson
This action kit was created in response to a rise in heroin use. Facts are provided about the scope of heroin use since it is the one illegal drug that is growing in popularity in some areas among young people. A brief explanation of some treatment options is provided including detoxification, methadone treatment, other medications, and behavioral…
Join Together, Boston, MA.
... early 1970s, public concern over veterans returning from Vietnam with heroin addiction prompted the government to establish ... another promising intervention for prisoners with heroin addiction histories. Ongoing research collaborations that involve scientists working together ...
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
A repeated measures design was used to evaluate methadone maintenance (MM) treatment effects for 720 heroin addicts who entered MM in Southern California in 1971-1978. Compared to pretreatment measures, results show significant improvement for methadone users. Level of improvement was affected by sex, ethnicity, and treatment duration. (TJH)
Hser, Yih-Ing; And Others
Physicians have reported alcoholism and opioid addiction as co-morbid conditions since the 19th century. From the inception of methadone maintenance treatment, heroin addicts with serious alcohol conditions have enrolled in methadone maintenance programs . Programs that treat alcoholism, including the traditional addiction inpatient rehabilitation programs of the Addiction Treat- ment Centers (ATCs) operated by New York State, have based their
STEVEN S. KIPNIS; ANNE HERRON; JOHN PEREZ; HERMAN JOSEPH
Psychiatric comorbidity, particularly depressive disorders, is associated with continued substance use and poor social functioning among methadone maintained patients. Evidence suggests similar neurochemical and environmental pathways may link the two disorders and it is reasonable to hypothesize that pharmacological and environmental factors play important roles in the treating comorbid depression and substance use. The present study tested the efficacy of sertraline for treating syndromally defined depressive disorders among non-abstinent methadone maintained opiate dependent patients. The moderating effects of environmental context on treatment outcome were also examined. Ninety-five patients were randomized in a 12-week, double-blind, placebo-controlled trial of sertraline, a serotonin-selective re-uptake inhibitor. There was no main effect of sertraline on either depression or substance use outcomes. However, sertraline demonstrated significant ameliorative effects on depression among patients with a more positive environment or less negative environment. The odds of being abstinent from heroin and cocaine were greater for patients on sertraline in environments with relatively less adversity. The findings support the hypothesis that contextual factors moderate the efficacy of pharmacological treatment for depression among methadone patients. They also suggest future research should examine a pharmacological treatment that is combined with a behavioral intervention targeting the accessibility of reinforcement or reducing the impact of aversive environmental interactions. PMID:15099656
Carpenter, Kenneth M; Brooks, Adam C; Vosburg, Suzanne K; Nunes, Edward V
The occurrence of illicit substances in the air was investigated in various world locations and ambient conditions. The analytical procedure optimized for cocaine, methadone and cocaethylene, based upon soxhlet extraction with organic solvent, clean-up through column chromatography, gas chromatographic separation and mass spectrometric detection, allowed the detection of the three compounds at levels as low as approximately 1 pg m(-3) in air samples of approximately 500 m3. Apart from Algiers, Algeria, and Pancevo, Serbia, cocaine was found in all cities investigated and its concentration ranged from picograms to nanograms/cubic meter (e.g., Rome, Italy, 22/97 pg m(-3); Santiago, Chile, 2.2/3.3 ng m(-3)). By contrast, the concentrations of methadone and cocaethylene in the air were always lower than the limit-of-detection allowed by the method. The procedure adopted was unsuitable for measuring cannabinoids and allowed only the identification of cannabinol. It was also poor in limit-of-detection with regards to heroin (35 pg m(-3)), however this compound could be identified in airborne particulates in Oporto, Portugal. Atmospheric concentrations of cocaine appeared to correlate to drug prevalence in the Italian regions investigated. PMID:19081126
Cecinato, Angelo; Balducci, Catia; Nervegna, Graziano
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
The partial µ-opiate agonist, buprenorphine, is the subject of recent evaluation as a potential pharmacotherapy for cocaine dependence. This paper reviews the extant preclinical and clinical evidence of buprenorphine effectiveness in treating cocaine abuse, including data from our large methadone comparison trial and a smaller buprenorphine dose ranging study. Although buprenorphine appears to reduce cocaine self-administration in studies of non-opiate
Peggy A. Compton; Walter Ling; V. Charles Charuvastra; Donald R. Wesson
Results of this study indicate that at present employers are not ready to accept methadone maintained patients into their firms. The stigma placed on heroin addicts by employers is a very important issue when the treated patient tries to make it in the employment field. More employer education is needed. (Author)
This study aims to asses the influence of inhalable heroin on pulmonary function in chronic heroin-dependent patients treated with inhalable heroin. Among 32 patients (all cigarette smokers), a spirometric test was conducted at baseline and after an average period of 10 months of treatment with medically prescribed heroin. Patients showed a high frequency of pulmonary dysfunction at baseline [34%, with percentage of forced expiratory volume in 1 s (%FEV1)<80%]. However, after excluding those who started pulmonary treatment (n=2) or who used heroin intravenously only (n=2), no statistically significant differences in %FEV1 between baseline and follow-up were observed (n=28; mean %FEV1 86% at baseline vs. 91% at follow-up; p=0.09). This small and relatively brief study suggests that 10 months of co-prescribed inhalable heroine base does not seem to (further) deteriorate pulmonary function in chronic, cigarette smoking treatment refractory heroin addicts. Screening for and treatment of pulmonary dysfunction is recommended for methadone patients with and without co-prescribed heroin. PMID:21422758
Buster, M C A; van den Brink, W; van Brussel, G H A; van Ree, J 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.
Ordean, Alice; Kahan, Meldon; Graves, Lisa; Abrahams, Ronald; Boyajian, Talar
Methadone maintenance has been evaluated since its development in 1964 as a medical response to the post-World War II heroin epidemic in New York City. The findings of major early studies have been consistent. Methadone maintenance reduces and/or eliminates the use of heroin, reduces the death rates and criminality associated with heroin use, and allows patients to improve their health and social productivity. In addition, enrollment in methadone maintenance has the potential toreduce the transmission of infectious diseases associated with heroin injection, such as hepatitis and HIV. The principal effects of methadone maintenance are to relieve narcotic craving, suppress the abstinence syndrome, and block the euphoric effects associated with heroin. A majority of patients require 80-120 mg/d of methadone, or more, to achieve these effects and require treatment for an indefinite period of time, since methadone maintenance is a corrective but not a curative treatment for heroin addiction. Lower doses may not be as effective or provide the blockade effect. Methadone maintenance has been found to be medically safe and nonsedating. It is also indicated for pregnant women addicted to heroin. Reviews issued by the Institute of Medicine and the National Institutes of Health have defined narcotic addiction as a chronic medical disorder and have claimed that methadone maintenance coupled with social services is the most effective treatment for this condition. These agencies recommend reducing governmental regulation to facilitate patients access to treatment. In addition, they recommend that the number of programs be expanded, and that new models of treatment be implemented,if the nationwide problem of addiction is to be brought under control. The National Institutes of Health also recommend that methadone maintenance be available to persons under legal supervision, such as probationers, parolees and the incarcerated. However, stigma and bias directed at the programs and the patients have hindered expansion and the effective delivery of services. Professional community leadership is necessary to educate the general public if these impediments are to be overcome. PMID:11064485
Joseph, H; Stancliff, S; Langrod, J
Preclinical and clinical studies suggest that GABAB receptor agonists selectively decrease cocaine use. The behavioral mechanism for the interaction between baclofen and cocaine in humans is not known, nor have its effects been characterized in individuals dependent on both cocaine and methadone. The objective of this study is to determine how maintenance on baclofen influences smoked cocaine's reinforcing and subjective effects, mood and cocaine craving prior to and after the initiation of cocaine use in cocaine-dependent volunteers with and without concurrent opioid dependence. Nontreatment-seeking volunteers (10 nonopioid dependent; seven methadone maintained), residing on an in-patient research unit for 21 days, were maintained on each baclofen dose (0, 30, 60 mg po) for 7 days. A smoked cocaine dose-response curve (0, 12, 25, 50 mg) was determined twice: on days 3-4 and days 6-7 of each baclofen maintenance condition. Cocaine sessions began with a sample trial, when participants smoked the cocaine dose available that session, and five choice trials, when participants chose between smoking the available cocaine dose or receiving one 5 dollars merchandise voucher. The results show that in the nonmethadone group, baclofen (60 mg) decreased self-administration of a low cocaine dose (12 mg). In the methadone group, baclofen decreased craving for cocaine. In both groups, baclofen decreased cocaine's effects on heart rate. Baclofen did not alter cocaine's robust subjective effects (eg 'High,' 'Stimulated') for either group. The results from this laboratory study appear consistent with clinical evidence showing that baclofen decreases cocaine use in nonopioid-dependent patients seeking treatment for cocaine dependence. The distinct pattern of effects in methadone-maintained participants suggests baclofen may not be effective in opioid-dependent cocaine users. PMID:16407903
Haney, Margaret; Hart, Carl L; Foltin, Richard W
The document presents a collection of articles about heroin. Article 1 provides general information on heroin identification, drug dependence, effects of abuse, cost, source of supply, and penalties for illegal heroin use. Article 2 gives statistical information on heroin-related deaths in the District of Columbia between 1971 and 1982. Article 3…
Do It Now Foundation, Phoenix, AZ.
In this article, the results are discussed of a literature study on nursing care for heroin addicts in out-patient methadone maintenance clinics in the Netherlands and the United States. In the Netherlands, the most important aim of methadone maintenance is to limit the harm caused by heroin use. Community based methadone maintenance is the subject in several Dutch evaluation studies. Care is described in these studies, however the medical role is not distinguished from the nursing role and functions. Research variables are basic care assumptions and client satisfaction. In the USA, heroin misuse is considered a disease more than in the Netherlands. Nurses in the American methadone maintenance clinics have a more independent function compared with the nurses in the Netherlands. The main variables in the American studies on nursing care in the out-patient methadone maintenance clinics are the nursing process as well as the development and testing of nursing interventions. Further nursing research concerning the methadone maintenance clinics in the Netherlands is needed because the nursing contribution in maintaining and improving the basic health status of the heroin misuser is of vital importance. The American nursing research and the associated outcomes could be used as a guideline. PMID:9385233
Loth, C A; van de Wijngaart, G F
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
Previous research indicates that female rats acquire cocaine and heroin self-administration at a faster rate than male rats, and female rats with endogenous estrogen, or ovariectomized (OVX) rats with estrogen replacement acquire cocaine self-administration more rapidly than female rats with estrogen either surgically or chemically blocked. The purpose of this investigation was to extend the above findings to the acquisition
Megan E. Roth; Anne G. Casimir; Marilyn E. Carroll
The major pharmacological effects of heroin can be traced back to some structural properties of the morphine molecule. The analgesic effects of heroin derive from the two active metabolites, 6-O-acetylmorphine and morphine, which bind specifically to the mu-opioid receptors of the central nervous system. mu-receptors also mediate other pharmacological actions of heroin i.e. respiratory depression, euphoria and physical dependence. Heroin is more potent and faster acting than morphine as an analgesic drug. Presently, there is a considerable dispute whether heroin should be legalized for the treatment of pain in terminal cancer. Chronic administration of heroin results in the development of tolerance. It is characterized by a shortened duration and decreased intensity of the analgesic, euphoric, sedative and other CNS-depressant effects. Tolerance to opioids is due to increased adaptation of the cells which changes their receptor sites after chronic exposure to the drug. Toxicity of heroin depends markedly on the route of administration in animal studies. Variable composition of street heroin or sudden loss of tolerance can cause fatal heroin overdose of addicts. Respiratory arrest is the most common reason for death among heroin addicts. PMID:15112443
In rats, reexposure to heroin-paired contexts after extinction of lever responding in a different context reinstates heroin seeking. Previous reports indicate that ventral hippocampus/Ca1 region plays a critical role in cocaine-, cue- and context-induced reinstatement of cocaine seeking. Here, we examined whether ventral subiculum, the output region of ventral hippocampus, is involved in context-induced reinstatement of heroin seeking. We found that reversible inactivation of ventral subiculum, but not posterior Ca1, with the gamma-aminobutyric acid agonists muscimol?+?baclofen decreased context-induced reinstatement of heroin seeking. Our findings, together with previous studies on cocaine seeking, indicate a critical role of ventral subiculum in context-induced relapse across drug classes. PMID:23231571
Bossert, Jennifer M; Stern, Anna L
We compared two strategies of prize-based contingency management (CM) in methadone-maintained outpatients. Urine was tested thrice weekly for 5 weeks pre-CM, 12 weeks CM, and 8 weeks post-CM. Participants were randomly assigned to a cocaine contingency (four prize draws for each cocaine-negative urine, N = 29) or an opiate-cocaine contingency (one…
Preston, Kenzie L.; Ghitza, Udi E.; Schmittner, John P.; Schroeder, Jennifer R.; Epstein, David H.
Purpose: The purpose of this paper is to review the research evidence on recent British trends in the use of heroin and/or crack-cocaine by young people in order to appraise the scale and nature of the contemporary health problem they pose. Design/methodology/approach: The approach consists of a narrative review of the main current data sources on…
The aim of this study was to assess cognitive functions in two clinical conditions, namely during heroin detoxification and during substitution treatment by methadone. Two groups of chronic heroin user inpatients, meeting DSM-III-R criteria for concurrent opiate dependence, were tested using an auditory oddball paradigm of P300. The first group (four women and six men) were drug-free and the second (five women, ten men) received methadone treatment. Patients were also compared to a control group of non-dependent healthy subjects (five women, nine men). The patients were recorded 6-10 days after the beginning of either detoxification or methadone treatment. There were significant P300 alterations in the two patient groups, with amplitude decrease and latency increase, at a time when self-reported signs of withdrawal were absent or minimal. Paradoxically, the reaction time was accelerated in the two groups of patients, who also showed increased discrimination errors. These abnormalities were found with a lesser degree in the methadone-treated group than in detoxification patients. PMID:11488228
Attou, A; Figiel, C; Timsit-Berthier, M
Previous studies have shown that the use of behavior modification techniques, specifically the use of token reinforcement systems, can produce positive changes in the behavior of heroin addicts within a hospital setting. A token economy program was assessed to determine the effectiveness of such a program with patients in an outpatient methadone…
Kelly, John S.; Gambatese, Richard J.
The present study evaluated the relationship between diagnoses of cocaine and sedative dependence and drug use early in treatment among opioid-dependent patients in methadone substitution therapy. New admissions (n = 138) were assessed via the Structured Clinical Interview for the DSM III-R (SCID) for presence of Axis I and Axis II disorders and followed for five weeks on standard methadone
Michael Kidorf; Robert K. Brooner; Van L. King; Mary Ann Chutuape; Maxine L. Stitzer
In nine experienced users of cocaine, we examined the urge to use cocaine or other drugs following a 40 mg dose of intravenous (IV) cocaine with and without oral pretreatment with 2.5 mg bromocriptine. The urge to use cocaine was assessed with a questionnaire constructed to assess both “wanting” and “craving” for cocaine or other drugs. Fifteen minutes after the
Jerome H. Jaffe; Nicola G. Cascella; Karen M. Kumor; Michael A. Sherer
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.
Maremmani, Angelo Giovanni Icro; Pacini, Matteo; Rovai, Luca; Rugani, Fabio; Dell'Osso, Liliana; Maremmani, Icro
Buprenorphine has rarely been administered as an opioid agonist maintenance therapy in a correctional setting. This study introduced buprenorphine maintenance in a large urban jail, Rikers Island in New York City. Heroin-dependent men not enrolled in community methadone treatment and sentenced to 10-90 days in jail (N=116) were voluntarily randomly assigned either to buprenorphine or methadone maintenance, the latter being the standard of care for eligible inmates at Rikers. Buprenorphine and methadone maintenance completion rates in jail were equally high, but the buprenorphine group reported for their designated post-release treatment in the community significantly more often than did the methadone group (48% vs. 14%, p<.001). Consistent with this result, prior to release from Rikers, buprenorphine patients stated an intention to continue treatment after release more often than did methadone patients (93% vs. 44%, p<.001). Buprenorphine patients were also less likely than methadone patients to withdraw voluntarily from medication while in jail (3% vs. 16%, p<.05). There were no post-release differences between the buprenorphine and methadone groups in self-reported relapse to illicit opioid use, self-reported re-arrests, self-reported severity of crime or re-incarceration in jail. After initiating opioid agonist treatment in jail, continuing buprenorphine maintenance in the community appears to be more acceptable to offenders than continuing methadone maintenance. PMID:18930603
Magura, Stephen; Lee, Joshua D; Hershberger, Jason; Joseph, Herman; Marsch, Lisa; Shropshire, Carol; Rosenblum, Andrew
Ingestion of balloons containing illicit substances along with the potential toxic sequelae associated with these ingestions have been described in the literature. This report describes the successful bronchoscopic retrieval of a cocaine balloon after aspiration. A 39-year-old man was witnessed swallowing several balloons that were thought to contain heroin. Shortly after ingestion, the patient became unconscious and required nasotracheal intubation.
Daniel J Cobaugh; Sandra M Schneider; John G Benitez; Michael P Donahoe
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
Jungen, Hilke; Andresen-Streichert, Hilke; Müller, Alexander; Iwersen-Bergmann, Stefanie
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.
The present report is an intent-to-treat analysis involving secondary data drawn from the first randomized clinical trial of prison-initiated methadone in the United States. This study examined predictors of treatment entry and completion in prison. A sample of 211 adult male prerelease inmates with preincarceration heroin dependence were randomly…
Gordon, Michael S.; Kinlock, Timothy W.; Couvillion, Kathryn A.; Schwartz, Robert P.; O'Grady, Kevin
A sensitive and selective ultra performance liquid chromatographic-tandem mass spectrometric method was developed and fully validated for the simultaneous determination of (in order of chromatographic elution) methylecgonine, pholcodine, morphine, hydromorphone, oxymorphone, norcodeine, codeine, dihydrocodeine, oxycodone, 6-Monoacetylmorphine (6-MAM), hydrocodone, ethylmorphine, norfentanyl, benzoylecgonine, tramadol, normeperidine, meperidine, cocaine, pentazocine, cocaethylene, fentanyl, norbuprenorphine, 2-ethylidine-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), buprenorphine, propoxyphene, and methadone in blood. The matrixes analyzed during the validation experiments were as follows: citrated blank plasma for calibrators, fluoride blank plasma for internal quality control (QC), lyophilized serum for external QC, fluoride plasma and whole blood for authentic samples, and lyophilized serum and whole blood for proficiency testing schemes. Samples were extracted with cation exchange solid-phase extraction cartridges. The target drugs were separated and quantified in a chromatographic run of 8.1 minutes using 0.1% formic acid in water and methanol (with 0.1% formic acid) as mobile phase. The limit of quantification ranged from 0.5 to 2.5 ng/mL depending on the compound and the therapeutic concentration. The intra- and interassay precision was less than 15% for all the compounds (except for pentazocine and EDDP, which was <20%) determined with 2 internal and 2 external QC samples, and the bias was within ±15% (except for methylecgonine, which was <20%). Extraction efficiency was greater than 70% for all the compounds except for EDDP. Matrix effects were evaluated with authentic blood samples (n = 10), and they ranged from 47 to 95%, but they were compensated for most analytes using deuterated analogs as internal standards. Prepared samples were stable for 62 hours in the autosampler. This method was successfully applied to authentic samples (n = 120), involving the use of heroin, cocaine, tramadol, and methadone, and to proficiency testing schemes. PMID:23783166
Fernández, María del Mar Ramírez; Wille, Sarah M R; Kummer, Nathalie; Di Fazio, Vincent; Ruyssinckx, Evi; Samyn, Nele
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
Nonfatal heroin overdoses and suicide attempts are both common among heroin addicts, but there is limited knowledge about the association between them. The sample in the present study consisted of 149 regular heroin users in Malmo, Sweden. Out of these 98 had taken an unintentional heroin overdose at some time and 51 had made at least one attempt…
Bradvik, Louise; Frank, Arne; Hulenvik, Per; Medvedeo, Alvaro; Berglund, Mats
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…
Longshore, Douglas; And Others
Substitute methadone prescribing is one of the main modes of treatment for opiate dependence. This study examined the relationship between methadone dose (measured by daily dose and methadone's active (R)-enantiomer blood levels) and opiate receptor function. Nine subjects on substitute methadone (30 - 90 mg daily) received three subcutaneous injections 1.5 hours apart (saline, 5 mg and 10 mg hydromorphone, a short-acting opiate agonist) followed by measures of functional response in particular saccadic eye movements (SEMs), as well as self-report measures. Ten mg of hydromorphone significantly slowed SEM parameters (peak velocity by 15%, p < 0.005; peak acceleration by 20%, p < 0.025; peak deceleration by 26%, p < 0.025) and the SEM velocity changes correlated significantly with (R)-methadone levels (r = 0.844, p < 0.005) and with the oral dose of methadone being taken (r = 0.829, p < 0.005). Although a similar trend was observed for 5 mg, this was not significant. These finding suggest that, at higher methadone doses (resulting in higher plasma concentrations), there is significant tolerance to the action of agonists. Such studies may help in refining our understanding of the actions of methadone and the SEM measure could help in defining the degree of tolerance in individuals using street heroin. PMID:12745417
Melichar, J K; Myles, J S; Eap, C B; Nutt, D J
Objective: To evaluate an experimental heroin maintenance programme. Design: Randomised trial. Setting: Outpatient clinic in Geneva, Switzerland. Subjects: Heroin addicts recruited from the community who were socially marginalised and in poor health and had failed in at least two previous drug treatments. Intervention: Patients in the experimental programme (n=27) received intravenous heroin and other health and psychosocial services. Control patients (n=24) received any other conventional drug treatment (usually methadone maintenance). Main outcome measures: Self reported drug use, health status (SF-36), and social functioning. Results: 25 experimental patients completed 6 months in the programme, receiving a median of 480?mg of heroin daily. One experimental subject and 10 control subjects still used street heroin daily at follow up (difference 44%; 95% confidence interval 16% to 71%). Health status scores that improved significantly more in experimental subjects were mental health (0.58 SD; 0.07 to 1.10), role limitations due to emotional problems (0.95 SD; 0.11 to 1.79), and social functioning (0.65 SD; 0.03 to 1.26). Experimental subjects also significantly reduced their illegal income and drug expenses and committed fewer drug and property related offences. There were no benefits in terms of work, housing situation, somatic health status, and use of other drugs. Unexpectedly, only nine (38%) control subjects entered the heroin maintenance programme at follow up. Conclusions: A heroin maintenance programme is a feasible and clinically effective treatment for heroin users who fail in conventional drug treatment programmes. Even in this population, however, another attempt at methadone maintenance may be successful and help the patient to stop using injectable opioids. Key messages A heroin maintenance programme may be a useful treatment option for patients who do not succeed in conventional drug treatment programmes Patients randomly allocated to the Geneva heroin maintenance programme fared better that patients in conventional drug treatments in terms of street drug use, mental health, social functioning, and illegal activities Results of the trial apply only to a subgroup of severely addicted people who failed repeatedly in conventional drug treatments This evaluation does not distinguish between the effects of heroin itself and the effects of other medical and psychosocial services that were provided as part of the programme There was less demand for the heroin maintenance programme than anticipated and most control subjects declined entry into the programme at the end of the study
Perneger, Thomas V; Giner, Francisco; del Rio, Miguel; Mino, Annie
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.
Faskowitz, Andrew J.; Kramskiy, Vladimir N.; Pasternak, Gavril W.
The Hmong are a distinct ethnic group from Laos. Little is known about how opiate addicted Hmong respond to methadone maintenance treatment. Therefore, opium addicted Hmong (exclusive route of administration: smoking) attending an urban methadone maintenance program in Minneapolis, Minnesota were matched by gender and date of admission with predominately heroin addicted non-Hmong (predominant route of administration: injection) attending the same program and both groups were evaluated for 1-year treatment retention, stabilization dose of methadone, and urine drug screen results. Hmong had greater 1-year treatment retention (79.8%) than non-Hmong (63.5%; p<0.01). In both groups, methadone dose was significantly associated with retention (p=0.005). However, Hmong required lower doses of methadone for stabilization (mean 49.0 mg versus 77.1 mg; p<0.0001). For both groups, positive urine drug screens were associated with stopping treatment. Further research to determine levels of tolerance, psychosocial, and pharmacogenetic factors contributing to differences methadone treatment outcome and dosing in Hmong may provide further insight into opiate addiction and its treatment.
Bart, Gavin; Wang, Qi; Hodges, James S.; Nolan, Chris; Carlson, Gregory
Stercoral perforation of the colon is a rare but serious complication of chronic constipation. We present a case of stercoral perforation requiring subtotal colectomy in a 41-year-old female who had been on methadone maintenance for a history of long-term intravenous heroin use. Our case highlights the importance of prompt and thorough surgical intervention in the successful treatment of this rare condition.
Sakharpe, A.; Lee, Y. K.; Park, G.; Dy, V.
The present study compared in a clinical non-experimental setting the efficacy of buprenorphine (BUP) and methadone (METH) in the treatment of opioid dependence: all the subjects included in the study showed severe long-lasting heroin addiction. Participants (154) were applicants to a 12 weeks treatment program, who were assigned to either METH (78) (mean doses 81.5±36.4mg) or BUP (76) (mean doses
G Gerra; F Borella; A Zaimovic; G Moi; M Bussandri; C Bubici; S Bertacca
Argues that most of the underlying assumptions of presently recommended solutions to the problem of heroin addiction are unreasonable, unwarranted, or at least open to more than one interpretation. (DM)
Wilson, James Q.; And Others
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
The aim of this work was to automate a sample preparation procedure extracting morphine, hydromorphone, oxymorphone, norcodeine, codeine, dihydrocodeine, oxycodone, 6-monoacetyl-morphine, hydrocodone, ethylmorphine, benzoylecgonine, cocaine, cocaethylene, tramadol, meperidine, pentazocine, fentanyl, norfentanyl, buprenorphine, norbuprenorphine, propoxyphene, methadone and 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine from urine samples. Samples were extracted by solid-phase extraction (SPE) with cation exchange cartridges using a TECAN Freedom Evo 100 base robotic system, including a hydrolysis step previous extraction when required. Block modules were carefully selected in order to use the same consumable material as in manual procedures to reduce cost and/or manual sample transfers. Moreover, the present configuration included pressure monitoring pipetting increasing pipetting accuracy and detecting sampling errors. The compounds were then separated in a chromatographic run of 9 min using a BEH Phenyl analytical column on a ultra-performance liquid chromatography-tandem mass spectrometry system. Optimization of the SPE was performed with different wash conditions and elution solvents. Intra- and inter-day relative standard deviations (RSDs) were within ±15% and bias was within ±15% for most of the compounds. Recovery was >69% (RSD < 11%) and matrix effects ranged from 1 to 26% when compensated with the internal standard. The limits of quantification ranged from 3 to 25 ng/mL depending on the compound. No cross-contamination in the automated SPE system was observed. The extracted samples were stable for 72 h in the autosampler (4°C). This method was applied to authentic samples (from forensic and toxicology cases) and to proficiency testing schemes containing cocaine, heroin, buprenorphine and methadone, offering fast and reliable results. Automation resulted in improved precision and accuracy, and a minimum operator intervention, leading to safer sample handling and less time-consuming procedures. PMID:24790061
Ramírez Fernández, María del Mar; Van Durme, Filip; Wille, Sarah M R; di Fazio, Vincent; Kummer, Natalie; Samyn, Nele
Methadone maintenance treatment (MMT) is the standard of care during pregnancy for opioid-dependency, showing efficacy in improving prenatal care and reducing risk of relapse. By design, however, MMT is only intended to prevent withdrawal thus facilitating cognitive behavioural interventions. In order to maximize the benefits of MMT, it is essential that methadone is both properly prescribed and that additional addiction treatment is concurrently administered. This study aims to determine the effectiveness of MMT engagement in high-risk pregnant women in reducing polydrug use by objective laboratory examination of neonatal meconium. Patients and Methods Over a 29-month period, the Motherisk Laboratory at the Hospital for Sick Children in Toronto analyzed meconium samples as per request by social services and hospitals for drugs of abuse. Results Of the 904 meconium samples received, 273 were tested for methadone with 164 positive and 109 negative for methadone. Almost half of the methadone positive samples (46.34%) were also positive for at least one other opioid compound, which did not differ statistically from the methadone-negative control samples (46.79%; Chi square test, p=0.94). No differences were found between the methadone positive and negative groups in rates of concurrent amphetamines, cocaine, cannabis, and alcohol use indicating a similar risk of polydrug use between pregnant women taking or not taking methadone in this population. Discussion The high rates of additional opioid and other drug use in the MMT group, suggest that MMT is failing this population of patients. It is possible that methadone doses during pregnancy are not appropriately adjusted for changes in pharmacokinetic parameters (e.g. blood volume, renal function) during the second and third trimesters. This may result in sub-therapeutic dosing creating withdrawal symptoms leading to additional substance use. Alternatively, these results may be demonstrating a substantial lack in delivery of addiction support services in this vulnerable population.
Delano, Kaitlyn; Gareri, Joey; Koren, Gideon
Over the years, nominative estimates of heroin prevalence have been consistently higher than self-reports of heroin use. During this time, nominative data have generally followed mainstream patterns of drug use: nominative estimates for young adults and for males are higher than nominative estimates for older persons, youth, and females; moreover, the recent downward trends in drug use have been replicated by the nominative heroin data. Thus, the overall picture presented by the nominative data--similar patterns but higher levels of prevalence--seems to support the validity of the new approach. Nevertheless, considerable caution should be exercised in interpreting nominative data. This is chiefly because a substantial minority of nominators cannot report the number of other close friends of the heroin user who also "know." While missing data has been handled by a conservative imputation rule, the fact that so many persons are unable to provide an answer to this key question casts doubt on the accuracy of the answers that were given. In fact, the nominative approach might tend to produce over-estimates, because of the potential for undercounts of the numbers of others who "know." Additional tests of validity should be performed, such as application of the nominative approach to nonsensitive behaviors or minimally sensitive behaviors, such as marijuana use or perhaps cocaine use. Certainly, the overall validity of the nominative heroin data would be supported if in future surveys new nominative heroin estimates for relatively unstigmatized forms of drug use proved to be similar to self-reported levels of use, thus pointing to the unique difference in estimates that might be observed for heroin. Finally, in interpreting the heroin estimates presented here, it should be remembered that both the nominative and self-report estimates refer to heroin use in the household population of the United States. Thus, many heroin addicts and other users who reside in various unconventional living arrangements would not be included in the counts presented here. Among the excluded groups are transients residing in rooming houses or "crashing" in the home of one "friend" after another or who are incarcerated in jails or confined to residential drug treatment centers. This is a caution for interpreting the estimates presented in this paper, not a criticism of the nominative technique itself.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:3929108
Miller, J D
The aims were to identify predictors of treatment retention in an Israeli methadone maintenance treatment (MMT) clinic, and to compare the findings to other international settings. We prospectively studied 492 patients admitted since 1993 through 10 years to an Israeli MMT clinic associated with a university-affiliated tertiary care medical center. Analyses (Kaplan Meier and Cox regression) included methadone dose and urinalysis results (for methadone, cocaine, opiates, benzodiazepines, THC, amphetamines) of each patient in the first month and after 1 year in treatment (or during the last month if the stay was >3 months and <1 year) and patients' characteristics (modified ASI). The 1-year retention rate was 74.4%; 65.8% stopped opiate abuse after 1 year in treatment. On admission, 13.6% of patients had used cocaine: there was a net decrease of 61.6% after 1 year. Factors predicting prolonged retention in MMT treatment (Cox regression) were daily methadone dose of 100mg or greater, negative urine for opiates after 1 year, and being a parent on admission. We conclude that our good outcome results (high rate of retention after 1 year (74.4%), high proportion of opiate abuse cessation (65.8%), and net reduction in cocaine abuse, similar to normal standards in other MMT clinics elsewhere in the world, justify the expansion of the MMT clinic network in Israel in order to make treatment available to all those who need it. A protocol favoring higher methadone dosage as appropriate is recommended. PMID:16219428
Peles, Einat; Schreiber, Shaul; Adelson, Miriam
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 throughout the months prior to filling in the questionnaire and their maintenance methadone doses were recorded. Drug abuse was defined by at least one positive urine test. Methadone serum levels were available in 55 patients, assessed by Gas Chromatography Mass Spectroscopy. The patients' self-reported chronic pain questionnaires and their diagnosed psychiatric disorders were analyzed. Out of the 101 study patients, 78.2% were male, 52.5% had psychiatric disorders, 46.5% reported having chronic pain and 46.5% had positive urine for benzodiazepine. The mean daily methadone dose was 157+/-52.9 mg. The mean PSQI score was 9+/-4.8 (75.2% had scores >5 indicating "poor sleepers"). PSQI scores were higher in patients with positive urine for benzodiazepine, chronic pain and psychiatric disorders and they correlated with years of opiate abuse before admission to MMT, and with the methadone dose (r=0.48, p<0.0005). The latter two also correlated with each other. The PSQI was not correlated with duration in MMT, gender, age, abuse of opiates, cannabis or cocaine. We concluded that sleep disorders should be evaluated and treated among MMT patients, particularly in those with psychiatric disorders, benzodiazepine abuse, chronic pain and high methadone dose. PMID:16154297
Peles, Einat; Schreiber, Shaul; Adelson, Miriam
The current paper examines critically the literature on deaths attributed to heroin overdose, and examines the characteristics and circumstances of such deaths. In particular, the dominance of the widely held belief that heroin-related fatalities are a consequence of overdose is challenged. Deaths attributed to overdose represented in the literature are typically older, heroin-dependent males not in drug treatment at the
SHANE DARKE; DEBORAH ZADOR
The 1999 Federal regulations extend the treatment options of methadone-maintained opi- oid-dependent patients from specialized clinics to office-based opioid therapy (OBOT). OBOT allows primary care physicians to coordinate methadone therapy in this group with ongo- ing medical care. This patient group tends to be poorly understood and underserved. Methadone maintenance therapy is the most widely known and well-researched treatment for
LAURIE LIMPITLAW KRAMBEER; WILLIAM VON MCKNELLY; WILLIAM F. GABRIELLI; ELIZABETH C. PENICK
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
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
Harris, Magdalena; Rhodes, Tim
Exposure to addictive drugs has been associated with disrupted brain white matter integrity. A few studies have examined the white matter deficits in heroin users; however, the results were influenced by the use of substitution drugs such as methadone and buprenorphine. The present study assessed the alteration in white matter integrity and heroin-related neuropathology in heroin dependents who had not received any replacement therapy using quantitative diffusion tensor imaging (DTI). The study comprised 17 heroin-dependent (HD) subjects and 15 matched healthy controls (HC). Fractional anisotropy (FA) and eigenvalues (??, ?||) of white matter in the whole brain were measured and compared using a voxel-based analysis. The correlation between DTI measurements in identified regions and history of heroin exposure was tested by partial correlation analysis. Compared with HCs, HD subjects displayed decreased FA in the bilateral frontal lobe sub-gyrus, cingulate gyrus, medial frontal gyrus, extra-nuclear, left temporal lobe sub-gyrus and right superior frontal gyrus. Among these regions, the HD group had significantly increased ?? in the bilateral frontal lobe sub-gyrus, cingulate gyrus and extra-nuclear relative to the HC group. There were no group differences in ?||. In addition, there were no significant correlations between duration of heroin use or accumulated dosage and FA or ?? values. In conclusion, chronic heroin-dependent subjects had widespread disruption of white matter structural connectivity located mainly in anterior and superior regions of the brain. Damage to myelin other than axons was the primary pathological feature in the brain of the heroin user. PMID:23895765
Li, Wei; Li, Qiang; Zhu, Jia; Qin, Yue; Zheng, Ying; Chang, Haifeng; Zhang, Dongsheng; Wang, Hanyue; Wang, Lina; Wang, Yarong; Wang, Wei
This qualitative study documents the pathways to injecting heroin by users in Philadelphia and San Francisco before and during a pharmaceutical opioid pill epidemic. Data was collected through in-depth, semi-structured interviews (conducted between 2010 and 2012) that were, conducted against a background of longer-term participant-observation, ethnographic studies of street-based drug users and dealers in Philadelphia (2007-12) and San Francisco (1994-2007, 2012). Philadelphia and San Francisco were selected for their contrasting political economies, immigration patterns and source type of heroin. In Philadelphia the ethnographers found heroin injectors, usually white users, who had started their opiate using careers with prescription opioids rather than transitioning from other drugs. In both Philadelphia and San Francisco, most of the young heroin injectors interviewed began, their drug-use trajectories with opioid pills--usually Percocet (oxycodone and acetaminophen), generic short acting oxycodone or, OxyContin (long-acting oxycodone)--before transitioning to heroin, usually by nasal inhalation (sniffing) or smoking at first, followed by injecting. While most of the Philadelphia users were born in the city or its suburbs and had started using both opioid pills and heroin there, many of the San Francisco users had initiated their pill and sometimes heroin use elsewhere and had migrated to the city from around the country. Nevertheless, patterns of transition of younger injectors were similar in both cities suggesting an evolving national pattern. In contrast, older users in both Philadelphia and San Francisco were more likely to have graduated to heroin injection from non-opiate drugs such as cannabis, methamphetamine and cocaine. Pharmaceutical opioid initiates typically reported switching to heroin for reasons of cost and ease-of-access to supply after becoming physically and emotionally dependent on opioid pills. Many expressed surprise and dismay at their progression to sniffing and subsequently to injecting heroin. Historically and structurally these users found themselves caught at the intersection of two major developments in the opiate supply: (1) an over 500% increase in opiate pill prescription from 1997 to 2005 resulting in easy access to diverted supplies of less stigmatized opiates than heroin and (2) a heroin supply glut, following the US entry of Colombian-sourced, heroin in the early 1990s, that decreased cost and increased purity at the retail level. A nationwide up-cycle of heroin use may be occurring among young inner city, suburban and rural youth fueled by widespread prescription opioid pill use. PMID:24238956
Mars, Sarah G; Bourgois, Philippe; Karandinos, George; Montero, Fernando; Ciccarone, Daniel
The effects of maintenance on venlafaxine, which blocks both norepinephrine and serotonin reuptake, on the response to smoked cocaine (0, 12, 25, or 50 mg) in 7 opioid-free and 7 methadone-maintained cocaine abusers was examined during a 42-day study. Participants received venlafaxine (225 mg daily) and placebo as part of a double-blind crossover design. Cocaine significantly increased heart rate, blood
Richard W. Foltin; Amie S. Ward; Eric D. Collins; Margaret Haney; Carl L. Hart; Marian W. Fischman
Background Illicit use of methadone and buprenorphine has been described as a growing problem in Sweden in recent years, and has been associated with an increased drug-related mortality. Critics claim that the substances have become popular among adolescents and that they function as a gateway to heroin use. The aim of this study is to investigate, firstly, the extent to which illicit use of methadone and buprenorphine occurs among adolescents and young adults in Sweden, and secondly, at what stage in a user’s drug career these substances tend to appear. Methods The study is based on surveys and structured interviews on drug use among various populations of young people, in addition to qualitative interviews with 86 informants who, in their professional capacity, encounter adolescents or young adults who are using illicit drugs. Results Illicit use of methadone and buprenorphine is rare among young people in Sweden. According to high school surveys, less than 0.1% have tried these substances. Among young drug users in general, few have tried the substances, and there is nothing to indicate that they act as gateway drugs. Among adolescents and young adults with severe drug problems, however, the illicit use of methadone and buprenorphine is more common (54% in a compulsory care sample). These substances normally enter the drug career late, and few use them as their main drug of choice. Other prescription drugs, like benzodiazepines and tramadol, are used by adolescents to a far greater extent. Diversion and illicit use of methadone and buprenorphine is not seen as a serious problem by the professionals interviewed. A general view is that the substances are mainly used by people with a heroin or polydrug addiction, often for “self-medication” purposes. However, several informants express concern that methadone and buprenorphine may cause fatalities among young drug users without an opioid tolerance. Conclusions Illicit use of methadone and buprenorphine among young drug users is not a widespread problem in Sweden. Harm-reduction measures should target drug users with more severe problems, among whom illicit use of methadone and buprenorphine is more common and pose a medical risk. Illicit use of other prescription drugs, which are less controlled and more widely used by young people, is an important issue for further research.
Deuterium-labeled methadone has been used to study the urinary excretion of racemic methadone, R-(-)- and S-(+)-methadone in adult maintenance patients. In three cases studied, the pharmacologically active enantiomer, R-(-)-methadone, had a significantly ...
D. L. Hachey M. J. Kreek P. D. Klein
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
An open randomized study lasting 12 months was performed to evaluate the efficacy of methadone or buprenorphine to suppress alcohol use in two hundred and eighteen heroin addicts with alcohol dependence. Daily maintenance doses of methadone were 80, 120, 160, and 200 mg/day, while doses of buprenorphine were 8, 16, 24, and 32 mg/day. As expected, both treatments were able to reduce both heroin use and addiction severity (measured with ASI interview). However, although both medications were able to suppress alcohol use, the highest dose of buprenorphine was better than the highest dose of methadone, in reducing alcohol craving, ethanol intake (measured as daily number of drinks), and the ASI subscale of alcohol use. The mechanism underlying the effects of the opioid maintenance therapy on the reduction of alcohol intake is still unclear. The results of the present study may represent the first clinical evidence of the potential effective use of the highest doses of buprenorphine for the suppression of ethanol intake in heroin addicts with alcohol dependence. PMID:18801404
Nava, Felice; Manzato, Ezio; Leonardi, Claudio; Lucchini, Alfio
Methadone is the recommended pharmacotherapy for opioid-dependent pregnant women. The primary aims of this study were to determine whether a dose-concentration relationship exists between cumulative maternal methadone dose, methadone and metabolite concentrations in maternal hair during pregnancy and whether maternal hair methadone and metabolite concentrations predict neonatal outcomes. Materials and Methods Hair specimens were collected monthly from opioid-dependent mothers enrolled in methadone treatment and 4 of their infants. Hair specimens were segmented (3cm), washed (maternal hair only) and analyzed for methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) and 2-ethyl-5-methyl-3,3-diphenylpyrroline (EMDP) by liquid chromatography tandem mass spectrometry. Results There was large inter-subject variability and no dose-concentration relationship for cumulative methadone dose and methadone, EDDP, EMDP or total concentrations in hair. For individual women, a positive trend was noted for cumulative methadone dose and methadone and EDDP concentrations in hair. There was a positive linear trend for cumulative methadone dose and EDDP/methadone ratio in maternal hair, perhaps reflecting methadone’s induction of its own metabolism. Maternal methadone concentrations were higher than those in infant hair, and infant EDDP hair concentrations were higher than those in maternal hair. Maternal methadone dose, and methadone and EDDP hair concentrations were not correlated with peak infant neonatal abstinence syndrome (NAS) scores, days to peak NAS, duration of NAS, time to NAS onset, birth length, head circumference or amount of neonatal morphine pharmacotherapy. Maternal cumulative 3rd trimester methadone dose was positively correlated with infant birth weight. Conclusion Methadone and EDDP in pregnant women’s hair are markers of methadone exposure and do not predict total methadone dose, nor neonatal outcomes from in utero methadone exposure.
Himes, Sarah K; Goodwin, Robert S; Rock, Colleen M; Jones, Hendree E; Johnson, Rolley E; Wilkins, Diana G; Huestis, Marilyn A
The effects of maintenance on venlafaxine, which blocks both norepinephrine and serotonin reuptake, on the response to smoked cocaine (0, 12, 25, or 50 mg) in 7 opioid-free and 7 methadone-maintained cocaine abusers was examined during a 42-day study. Participants received venlafaxine (225 mg daily) and placebo as part of a double-blind crossover design. Cocaine significantly increased heart rate, blood pressure, cocaine choice, cocaine ratings, and ratings of positive subjective effects (e.g., "I feel high") in both groups. Venlafaxine significantly decreased the subjective effects of cocaine by 10-20% without affecting cocaine choice or cardiovascular response in both groups. Although the reduction in cocaine's effects was small, further studies using a longer venlafaxine maintenance period or a larger venlafaxine dose are warranted. PMID:12755456
Foltin, Richard W; Ward, Amie S; Collins, Eric D; Haney, Margaret; Hart, Carl L; Fischman, Marian W
This prospective study (n=190) examined correlates of alcohol use from baseline data of a longitudinal trial conducted among moderate and heavy alcohol users receiving methadone maintenance therapy (MMT). The sample included MMT clients who were 18-55 years of age, and were receiving MMT from five large methadone maintenance clinics in the Los Angeles area. Half of the sample was heavy drinkers and nearly half (46%) reported heroin use. Using a structured questionnaire, correlates of heavy alcohol use included White and Hispanic ethnicity, and fair or poor physical health combined with older age (> or =50 years). We also found that MMT clients who were younger than 50 years, regardless of health status, were more likely to be heavy drinkers. Compared with moderate alcohol consumers, a greater number of heavy alcohol users also experienced recent victimization. To optimize MMT, alcohol screening should be part of routine assessment and alcohol treatment should be made available within MMT programs. Moreover, special consideration should be provided to the most vulnerable clients, such as the younger user, those with a long-term and current history of heavy drug use, and those victimized and reporting fair or poor health. In addition, promoting attention to general physical and mental health problems within MMT programs may be beneficial in enhancing health outcomes of this population. PMID:19081204
Nyamathi, Adeline; Cohen, Allan; Marfisee, Mary; Shoptaw, Steven; Greengold, Barbara; de Castro, Viviane; George, Daniel; Leake, Barbara
This cross-sectional study examines predictors of heavy smoking among 256 male and female methadone maintenance therapy (MMT) clients from five MMT clinics in the Los Angeles area. The authors find that women report lower rates of heavy smoking than men (47% vs. 54%, respectively), in concordance with current literature pointing to gender differences in smoking behaviors. In particular, men who report heavy drinking, fair or poor health, and recent heroin use are more likely to report heavy smoking compared with men not reporting these factors. Women who report recent heroin use, a lifetime history of sex trade, and who have been ill enough to require a blood transfusion also have greater odds of reporting heavy cigarette smoking. Findings from this study may aid not only in designing gender-based smoking cessation programs for MMT clients but also in addressing the gender-based issues related to smoking in such a population. PMID:19597186
Nyamathi, Adeline M; Sinha, Karabi; Marfisee, Mary; Cohen, Allan; Greengold, Barbara; Leake, Barbara
Background: Although methadone maintenance is effective in reducing injection drug use, needle sharing, and the overall mortal- ity associated with opiate abuse, many health plans offer little or no access to methadone, and many methadone providers do not comply with treatment guidelines regarding dose, duration of treatment, or provision of ancillary services. Moral and politica l judgments have helped shape
PAUL G. BARNETT; SALLY S. HUI
Objective While access and utilization form core components in assessing the effectiveness of a health service, the concept of coverage is often neglected. In this study we propose to develop a GIS-based methodological framework for the measurement of district-based geographic coverage to examine the service effectiveness of methadone treatment programme (MTP) in Hong Kong on a regular basis. Methods To overcome the incompatibility of spatial units, population data and data of heroin addiction of the year 2001 are interpolated by population-weighted and area-weighted algorithms. Standard overlay and proximity analytical functions are used to delineate altogether 20 accessible zones around each methadone clinic at a fixed 1.5 km Euclidean distance. Geographic coverage here is defined as the percentage of heroin addicts covered by a methadone clinic within the accessible zone by district. Results A total of 6413 out of 11000 reported heroin addicts are found geographically covered. The average geographic coverage in Hong Kong is 44.6%, with the figure varying from 0% to 96% by district. One district having no clinic results in 0% coverage whereas another without a clinic yields 15.3% coverage from the clinic in adjacent district. Maps illustrating district-based geographic coverage are generated. Conclusion As continuous data collection is required for a monitoring system, the simplified approach facilitates the handling of large volume data and relevant data analysis. It is concluded that the number of methadone clinics is as important as their locations. Geographic coverage could become an important consideration for monitoring harm reduction.
Pang, Tak Ting P; Lee, Shui Shan
This study examines the relationship between heroin-assisted treatment versus methadone maintenance and the criminal activity of 1,015 individuals participating in a German model project. The main objective is to investigate how these treatments contribute to a decline of criminal behavior. The analyses are based upon self-reported criminal offence and police data on alleged criminals. Logistic regression is employed to explain the variance in the 12-month prevalence 1 year after program admission. The results clearly show a decline of criminal offences among participants receiving maintenance treatment; this decline was significantly greater in the heroin group with respect to property crimes and drug offences. The multivariate analysis reveals that the effects are due to a decrease of illegal drug use and absence from the drug scene. PMID:18594954
Löbmann, Rebecca; Verthein, Uwe
Few heroin addicts get high'' in their dreams. An exploration of the reasons for this failure provides some clues to the conflicts and other problems that retard an addict's progress in therapy. (Author)
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
Segmental hair analysis was performed to obtain information about the history of drug abuse of subjects in a rehabilitation programme. The analytical data from hair samples were correlated, when possible, with urine analysis and to toxicological anamnesis. Toxicological analysis of hair seems to be a valid tool in this specific field.
S. Strano-Rossi; A. Bermejo-Barrera; M. Chiarotti
In order to determine the role played by heroin purity in fatal heroin overdoses, time series analyses were conducted on the purity of street heroin seizures in south western Sydney and overdose fatalities in that region. A total of 322 heroin samples were analysed in fortnightly periods between February 1993 to January 1995. A total of 61 overdose deaths occurred
Shane Darke; Wayne Hall; Don Weatherburn; Bronwyn Lind
Vietnam is among the countries with the highest rate of HIV transmission through injecting drug users. HIV prevalence among injecting drug users is 20% and up to 50% in many provinces. An estimated number of drug users in the country by the end of 2011 were 171,000 in which the most common is heroin (85%). Detoxification at home, community, and in rehabilitation centers have been the main modalities for managing heroin addiction until Methadone Maintenance Treatment (MMT) was piloted in 2008. Recent reports have demonstrated positive treatment outcomes. Incidence of HIV was found remarkably low among patients on MMT. Treatment has significantly improved the quality of life as well as stability for society. The government has granted the Ministry of Health (MoH) to expand Methadone treatment to at least 30 provinces to provide treatment for more than 80,000 drug users by 2015. The Vietnam Administration for HIV/AIDS Control (VAAC) and MOH have outlined the role and responsibility of key departments at the central and local levels in implementing and maintaining MMT treatment. This paper will describe the achievements of the MMT pilot program and the scaling-up plan as well as strategies to ensure quality and sustainability and to overcome the challenges in the coming years. PMID:23227351
Nguyen, Tam T M; Nguyen, Long T; Pham, Manh D; Vu, Hoang H; Mulvey, Kevin P
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.
Discusses recent trends in heroin addiction in Washington, D.C. In 1969 a comprehensive, multimodal treatment program for addicts was introduced and a major law enforcement commitment was made to reduce the heroin supply. These factors, together with changing community attitudes, may be responsible for a remarkable decline in heroin addiction. (JR)
DuPont, Robert L.; Greene, Mark H.
In 2003, opiates other than heroin (non-heroin opiates) were the primary substance of abuse for 51,000 substance abuse treatment admissions (3 percent of all admissions). Some 47 percent of non-heroin opiate admissions were female compared with 32 percent...
The scientific study of illicit heroin use has been confined largely to those heroin users who have severe addiction problems. These members of the heroin using population are the most visible, the most in need of professional treatment, and the most easi...
M. A. Forslund M. C. Futa
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.
Egred, M; Davis, G
Background Methadone is frequently used in adult anesthesia and pain treatment. Methadone pharmacokinetics in adults are well characterized, including the perioperative period. Methadone is also used in children. There is, however, no information on methadone pharmacokinetics in children of any age. The purpose of this investigation was to determine the pharmacokinetics of intravenous methadone in children undergoing surgery. Perioperative opioid-sparing effects were also assessed. Methods Eligible subjects were children 5–18 yr undergoing general anesthesia and surgery, with an anticipated postoperative inpatient stay exceeding 3d. Three groups of 10–11 patients each received intravenous methadone HCl after anesthetic induction in ascending dose groups of 0.1, 0.2, and 0.3 mg/kg (up to 20 mg). Anesthetic care was not otherwise changed. Venous blood was obtained for 4d, for stereoselective determination of methadone and metabolites. Pain assessments were made each morning. Daily and total opioid consumption was determined. Perioperative opioid consumption and pain was determined in a second cohort, which was matched to age, sex, race, ethnicity, surgical procedure, and length of stay, but not receiving methadone. Results The final methadone study cohort was 31 adolescents (14 ± 2 yr, range 10–18) undergoing major spine surgery for a diagnosis of scoliosis. Methadone pharmacokinetics were linear over the dose range 0.1–0.3 mg/kg. Disposition was stereoselective. Methadone administration did not dose-dependently affect postoperative pain scores, and did not dose-dependently decrease daily or total postoperative opioid consumption in spinal fusion patients. Conclusions Methadone enantiomers disposition in adolescents undergoing surgery was similar to that in healthy adults.
Sharma, Anshuman; Tallchief, Danielle; Blood, Jane; Kim, Thomas; London, Amy; Kharasch, Evan D.
Hemagglutination-inhibition (HI) procedures for the detection and measurement of several abused drugs have been further developed and evaluated. Tests for morphine and for methadone have been applied to more than 30,000 urine specimens. The results of fur...
C. T. Liu F. L. Adler
Exposure of the developing foetus to drugs of abuse during pregnancy may lead to persistent abnormalities of brain systems involved in drug addiction. Mice prenatally exposed to cocaine (25 mg/kg), physiological saline or non-treated during the last 7 days of pregnancy were evaluated in adulthood for the rewarding properties of cocaine (3, 25 and 50 mg/kg), using the conditioned place preference procedure. Dams treated with physiological saline gained significantly less weight over the course of gestation than controls; no other differences were observed in the maternal and offspring data. All the animals developed preference to 3 and 25 mg/kg of cocaine, but those treated prenatally with cocaine did not develop preference after receiving the highest cocaine dose. In these mice, the motor activity in response to 50 mg/kg showed a small decrease. Although a reduced response to the highest cocaine dose can be argued, we suggest that the lack of preference obtained is more likely attributable to an increased sensitivity to the environmental cues associated during training to an aversive effect of this cocaine dose. The aversive properties of cocaine seem to be more apparent and to prevail over the rewarding action of the highest dose in exposed animals. These findings indicate that recurrent gestational cocaine exposure results in permanent (mal)adaptations of the structure and function of brain reward systems. PMID:16940772
Estelles, Josefina; Rodríguez-Arias, Marta; Maldonado, Concepción; Aguilar, María A; Miñarro, José
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)
Cantwell, John D.; Rose, Fred D.
Background Substance misuse is associated with cognitive dysfunction. We used a stop signal task to examine deficits in cognitive control in individuals with opioid dependence (OD). We examined how response inhibition and post-error slowing are compromised and whether methadone maintenance treatment (MMT), abstinence duration, and psychiatric comorbidity are related to these measures in individuals with OD. Methods Two-hundred-and-sixty-four men with OD who were incarcerated at a detention center and abstinent for up to 2 months (n?=?108) or at a correctional facility and abstinent for approximately 6 months (n?=?156), 65 OD men under MMT at a psychiatric clinic, and 64 age and education matched healthy control (HC) participants were assessed. We computed the stop signal reaction time (SSRT) to index the capacity of response inhibition and post-error slowing (PES) to represent error-related behavioral adjustment, as in our previous work. We examined group effects with analyses of variance and covariance analyses, followed by planned comparisons. Specifically, we compared OD and HC participants to examine the effects of opioid dependence and MMT and compared OD sub-groups to examine the effects of abstinence duration and psychiatric comorbidity. Results The SSRT was significantly prolonged in OD but not MMT individuals, as compared to HC. The extent of post-error slowing diminished in OD and MMT, as compared to HC (trend; p?=?0.061), and there was no difference between the OD and MMT groups. Individuals in longer abstinence were no less impaired in these measures. Furthermore, these results remained when psychiatric comorbidities including misuse of other substances were accounted for. Conclusions Methadone treatment appears to be associated with relatively intact cognitive control in opioid dependent individuals. MMT may facilitate public health by augmenting cognitive control and thereby mitigating risky behaviors in heroin addicts.
Liao, Ding-Lieh; Huang, Cheng-Yi; Hu, Sien; Fang, Su-Chen; Wu, Chi-Shin; Chen, Wei-Ti; Lee, Tony Szu-Hsien; Chen, Pau-Chung; Li, Chiang-shan R.
Psychiatric comorbidity was examined for a sample of 212 methadone patients dually addicted to opiates and cocaine, focusing on gender differences. Diagnoses were determined by the SCID for DSM-III-R. Men displayed more lifetime (but not current) substance use disorders, while women displayed more lifetime and current non-substance use disorders. There were several significant interactions among psychiatric disorders and gender. Women
Stephen Magura; Sung-Yeon Kang; Andrew Rosenblum; Leonard Handelsman; Jeffrey Foote
Background Opioid dependence treatment traditionally involves methadone clinics, for which dispensing schedules can be cumbersome. Buprenorphine, a partial agonist of the mu receptor and antagonist of the kappa receptor, is a potential outpatient alternative to methadone. Funded by a grant from the State of Maryland's Community Health Resources Commission (CHRC), the Buprenorphine Outpatient Outcomes Project (BOOP) evaluates the outcome of Suboxone (buprenorphine/naloxone) treatment on abstinence from heroin use, rates of emergency room visits and hospitalizations, legal issues, and quality of life. Methods Active heroin users were recruited between June 2007 and June 2010 and induction therapy with Suboxone was instituted during hospitalization. Once discharged, patients were followed as outpatients for maintenance treatment and counseling. Data were collected from electronic medical records, Maryland state legal records, and SF-36® Health Surveys regarding several parameters and patients were categorized according to duration of treatment with Suboxone into one of three groups: <1 month, 1–3 months, and >3 months. Results A total of 220 participants were included in the study. The age range of participants was 18–67 years with most being African American males. Eighty-three (38%) remained in the study for at least 1 month, with 37 of the 83 (45%) remaining in treatment for >3 months. Ten of the 37 (27%) never relapsed after their longest period of abstinence from heroin. During the first year after initiating treatment with Suboxone, hospitalization and emergency room visit rates for all 220 participants decreased by 45 and 23%, respectively, as compared to the year prior to starting treatment. The number of legal charges for drug possession decreased from 70 to 62. Anecdotally, the quality of life seemed to improve in those who were treated with Suboxone for longer periods of time and received regular counseling. Conclusion Overall, Suboxone is an effective treatment method for heroin addiction and is a viable outpatient therapy option. Individualized treatment plans and counseling must be implemented for maximum benefits to be seen. Retention of patients for a long duration of therapy was difficult, but for those who did remain, benefits were seen in overall health, abstinence from heroin use, cognition, and quality of life.
Sittambalam, Charmian D.; Vij, Radhika; Ferguson, Robert P.
The relationship between heroin use and street crime has been studied for the better part of this century, but the findings have been inconclusive. Research in this area has been limited to analyses of criminality in terms of arrest data, and samples have been drawn only from officially known populations of drug users. The present study focuses on a sample
James A. Inciardi
Summary Recent data on the pharmacokinetics and pharmacogenetics of methadone, taking into account its enantiomers, have been collected. In particular, it has been demonstrated that isozymes belonging to the cytochrome P450 superfamily play a major role in the metabolism of methadone. During the past ten years, a large amount of information has been collected on this enzymatic system. In particular
Chin B. Eap; Jean-Jacques Déglon; Pierre Baumann
Chlormethiazole positively modulates the gamma-aminobutyric acid (GABA)(A) receptor complex and is primarily used to treat certain life-threatening neurological events (e.g., refractory seizures and ethanol withdrawal syndrome). On account of several experimental and clinical studies reporting effectiveness against the toxic effects of heroin and methamphetamine, chlormethiazole was systematically tested in the present study for its effectiveness against cocaine-induced seizures and lethality in mice. The protective effects of chlormethiazole were evaluated against single, submaximal convulsive (75 mg/kg) or lethal (110 mg/kg) doses of cocaine. Chlormethiazole also was tested against the expression (anticonvulsant effect) and development (antiepileptogenic effect) of cocaine-kindled seizures, and against fully developed kindled seizures. Cocaine-kindled seizures were produced by a total of five daily treatments with 60 mg/kg cocaine. The inverted-screen test was used to assess behavioral side effects of chlormethiazole. Chlormethiazole protected against acute cocaine-induced convulsions (ED(50) = 7.0 mg/kg) and lethality (ED(50)= 21.8 mg/kg) with a robust separation [protective index (PI) = TD(50)/ED(50) = 22.3 and 7.2, respectively] from doses producing behavioral side effects (TD(50) = 156 mg/kg). Chlormethiazole suppressed the behavioral expression of cocaine-kindled seizures and prevented the development of sensitization to the convulsant effects of cocaine. It was also effective in suppressing fully developed kindled seizures. Relative to cocaine seizures in naive mice, chlormethiazole was equieffective, less potent (ED(50) = 22.3 mg/kg), and had a reduced protective index (PI = 3.7) against cocaine-induced seizures in kindled mice. The protective profile and protective index of chlormethiazole were superior to those of the benzodiazepines clonazepam and diazepam, which were of limited efficacy and had low protective indices (PI = approximately 1). The results of this study predict the potential utility of chlormethiazole for the treatment of life-threatening complications of cocaine abuse for which no specific treatment has yet been identified. PMID:10991973
Gasior, M; Ungard, J T; Witkin, J M
Exposure to 10 min of footshock stress (1 mA; 0.5 s on, with a mean off period of 40 s) reinstated heroin-seeking behavior in heroin-experienced, drug-free rats after many sessions of extinction and up to 6 weeks after last exposure to heroin. In reinstating the behavior, the footshock mimicked the effect of a non-contingent priming infusion of heroin (50 µg\\/kg).
Yavin Shaham; J. Stewart
Three consecutive, professionally led (as opposed to self-help) groups following the 12-step program (TSP) were integrated into a methadone maintenance treatment (MMT) program that included 32 heroin-addicted individuals in recovery. This report describes our experience in meeting the challenges that arose and our conclusions regarding the therapeutic potential of this integration. A professional therapeutic staff guided the groups. In-depth interviews of 10 participants and the reflections of the group leaders provided data for learning about the groups' experience. Initially the participants rejected the concepts of Step 1, powerlessness and unmanageability of life. The assimilation of Step 4 (defining character defect) also aroused some resistance. The participants eventually adopted the pragmatic aspects of TSP, including its terminology. The establishment of a common language of recovery helped to create group coherence and a sense of belonging, and helped to meet the needs of those who felt stigmatized by both the nonaddicted and addicted population undergoing nonmethadone recovery. TSP could be adapted to various aspects of daily life, produced a sense of self-efficacy, and stimulated motivation for change. Therapeutic implications are discussed. PMID:20921264
Ronel, Natti; Gueta, Keren; Abramsohn, Yali; Caspi, Nir; Adelson, Miriam
The drug content of hair may be affected by washing, chemical or thermal treatments, the use of cosmetics, or exposure to the environment. Knowledge concerning the effect of natural or artificial light on drug content in hair can be helpful to the forensic toxicologist, in particular when investigating drug concentrations above or below pre-determined cut-offs. The photodegradation of methadone and its metabolite, 2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) was studied in authentic positive hair samples by comparing drug concentrations determined by liquid chromatrography-high resolution mass spectrometry before and after exposure to UVB light (in vivo study). The same approach was applied in order to investigate the light sensitivity of opiates (6-monoacetylmorphine and morphine) and cocainics (cocaine and benzoylecgonine) in true positive hair. The yields of photodegradation were calculated for each drug class in eight different positive hair samples irradiated by UVB at 300?J/cm(2) obtaining averages, ranges and standard deviations. In parallel, the photostability of all the compounds as 10(-5) -10(-4) ?M standard solutions in methanol were examined by means of UVB light irradiation in the range 0-100?J/cm(2) followed by UV/Vis spectroscopic analysis and direct infusion electrospray ionization-high resolution mass spectrometry (in vitro study). In hair, methadone was shown to be significantly affected by light (photodegradation of 55% on average), while its metabolite EDDP proved to be more photostable (17%). 6-monoacetylmorphine, morphine, benzoylecgonine, and cocaine were more photostable than methadone in vivo (on average, 21%, 17%, 20%, and 11% of degradation, respectively). When irradiated in standard solutions, the target molecules exhibited a larger photodegradation than in vivo with the exception of cocaine (photodegradation for methadone up to 70%, 6-monoacetylmorphine and morphine up to 90%, benzoylecgonine up to 67%, cocaine up to 15%). Some factors possibly affecting the yields of photodegradation in hair and partially explaining the differences observed between the in vivo and the in vitro studies were also investigated, such as the colour of hair (the role of melanin) and the integrity of the keratin matrix. Copyright © 2014 John Wiley & Sons, Ltd. PMID:24817052
Favretto, Donata; Tucci, Marianna; Monaldi, Alice; Ferrara, Santo Davide; Miolo, Giorgia
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
Following the introduction of black tar heroin mainly from Mexico in the 1980s, cases of wound botulism dramatically increased\\u000a in the western United States. Contamination with spores of Clostridium botulinum of black tar heroin occurs along the distribution line. The heating of heroin powder to solubilize it for subcutaneous injection\\u000a (“skin popping”) does not kill the spores. The spores germinate
Larry E. Davis; Molly K. King
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.
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.
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.
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
This paper presents a simple and sensitive chromatographic procedure for the simultaneous determination and quantification of ephedrines, amphetamines, cocaine, cocaine metabolites, and opiates in human urine by gas chromatography-mass spectrometry. This method involves enzyme hydrolysis in the presence of a deuterated internal standard, liquid-liquid extraction, and derivatization with pentafluoropropionic anhydride and pentafluoropropanol. The recovery of each compound averaged at 65.8% or more. The limits of detection determined for each compound by using a 2-mL sample volume ranged from 5 to 50 ng/mL. The calibration curves were linear to 100 ng/mL for all compounds when determined using methamphetamine-d4 and MDMA-d5 as internal standards. This method was successfully applied for the analysis of urine samples suspected to contain intoxicants such as methamphetamine and heroin. PMID:16872781
Saito, Takeshi; Mase, Hiroyasu; Takeichi, Sanae; Inokuchi, Sadaki
Background Opioid addiction is a chronic, relapsing disease and remains a major public health challenge. Despite important expansions of access to conventional treatments, there are still significant proportions of affected individuals who remain outside the reach of the current treatment system and who contribute disproportionately to health care and criminal justice costs as well as to public disorder associated with drug addiction. The NAOMI study is a Phase III randomized clinical trial comparing injectable heroin maintenance to oral methadone. The study has ethics board approval at its Montréal and Vancouver sites, as well as from the University of Toronto, the New York Academy of Medicine and Johns Hopkins University. The main objective of the NAOMI Study is to determine whether the closely supervised provision of injectable, pharmaceutical-grade opioid agonist is more effective than methadone alone in recruiting, retaining, and benefiting chronic, opioid-dependent, injection drug users who are resistant to current standard treatment options. Methods The case study submitted chronicles the challenges of getting a heroin assisted treatment trial up and running in North America. It describes: a brief background on opioid addiction; current standard therapies for opioid addiction; why there is/was a need for a heroin assisted treatment trial; a description of heroin assisted treatment; the beginnings of creating the NAOMI study in North America; what is the NAOMI study; the science and politics of the NAOMI study; getting NAOMI started in Canada; various requirements and restrictions in getting the study up and running; recruitment into the study; working with the media; a status report on the study; and a brief conclusion from the authors' perspectives. Results and conclusion As this is a case study, there are no specific results or main findings listed. The case study focuses on: the background of the study; what it took to get the study started in Canada; the unique requirements and conditions of getting a site, and the study, approved; working with the media; recruitment into the study; a brief status report on the study; and a brief conclusion from the authors' perspectives. Trail Registration ClinicalTrials.gov registration number: NCT00175357
Gartry, Candice C; Oviedo-Joekes, Eugenia; Laliberte, Nancy; Schechter, Martin T
Diagnosing comorbid psychiatric disorders in metha-done maintained patients may help to identify subgroups with different outcomes and needs for treatment. In this study, 75 methadone maintenance clinic patients in treatment longer than 30 days were assessed with the Addiction Severity Index, Global Assessment Scale and Mini-Mental Status Exam, and were interviewed for DSM-III-R psychiatric diagnosis using the computerized Diagnostic Interview
B. J. Mason; J. H. Kocsis; D. Melia; E. T. Khuri; J. Sweeney; A. Wells; L. Borg; R. B. Millman; M. J. Kreek
This article discusses various ethical and philosophical aspects of heroin addiction. It arose as a result of the plan by the Amsterdam city council to supply free heroin to drug addicts. The objective of treatment of heroin addicts is ambivalent because what is in fact a socio-cultural problem is transformed into a medical problem. The characteristics of this treatment are made explicit through a philosophical analysis which sees the medical intervention as part of a strategy aimed at achieving social normalisation. The reason why such a social control function is practised by physicians is discussed, as well as the reason why heroin users in particular are the object of such a process. In this paper, heroin addiction is considered primarily as a cultural problem. The consequences of this for treatment and ethics form the conclusion.
ten Have, H; Sporken, P
This study examined posttreatment patterns of polysubstance use and heroin relapse in a sample of 43 adolescents (ages 14-20) entering short-term residential treatment for primary heroin use. At 12-month follow-up, youths that achieved heroin abstinence (N = 19) were significantly less likely than youths that relapsed to heroin (N = 24) to endorse…
Branson, Christopher E.; Clemmey, Philip; Harrell, Paul; Subramaniam, Geetha; Fishman, Marc
The purpose of this paper is to characterize persons who sniff heroin by examining their experiences prior to first heroin use, experiences at first use, current drug use patterns, and factors associated with progression to the daily use of heroin. Relatively little has been published about the lives and career trajectories of heroin sniffers who have little or no history
Joanne M. Kaufman; Dale D. Chitwood; Mary Comerford; Dixie Koo
This paper discusses various difficulties which arise when the staff of a methadone maintenance clinic must come to grips with the manifest and latent issues in service delivery. A solution is suggested which involves severing the tie between methadone and the behaviors which are reinforced by its use. (Author)
King, Charles H.
Background Methadone Maintenance Treatment is a useful method for opioid dependents, which results in harm reduction and increased quality of life in opioid dependents. The prevalence of psychiatric disorders in addicts is higher than in the general population which can interfere with the course and treatment of substance dependents and decrease the efficacy of treatment. Methods This descriptive, cross-sectional study was aimed to determine the correlation between psychiatric disorders and methadone dosage. It was performed on 154 patients of Kerman Shahid Beheshti Hospital’s Methadone Clinic during a six month period from Dec 2010 to Jul 2011. The study population was chosen by convenience sampling. The searching tools were Socio-Demographic Questionnaire, psychiatric structured interview based on DSM-IV-TR, Beck Depression Inventory, Young Mania Rating Scales, and Anxiety and Depression Rating Scales. Findings Significant correlations were observed between increased methadone dosage and antisocial personality disorder. In addition, significant positive correlations were observed between increased methadone dosage and Hamilton anxiety scores, Hamilton depression scores and Young Mania scores. Conclusion High methadone dosage may be a marker of coexisting psychiatric disorders in patients on methadone maintenance treatment which indicates the necessity of devoting further attention to this group. Psychiatric services should be open and accessible to the patients, especially those who seek treatment voluntarily. Early diagnosis and treatment of patients with coexisting psychiatric disorders may increase the efficacy of methadone maintenance treatment.
Parvaresh, Nooshin; Masoudi, Arman; Majidi-Tabrizi, Shiva; Mazhari, Shahrzad
A middle age man presented with disorientation and memory impairment due to bilateral hippocampal strokes secondary to cocaine use. This is the second report of cocaine induced hippocampi ischaemic strokes. In contrast to the previous report, this middle age man did not have cardiac arrest.
Morales Vidal, Sarkis Gibran; Hornik, Alejandro; Morgan, Christopher
The aim of this review was to update and summarize the scientific knowledge on the long term outcomes of the different pharmacological treatment options for opioid dependence currently available and to provide a critical discussion on the different treatment options based on these results. We performed a literature search using the PubMed databases and the reference lists of the identified articles. Data from research show that the three pharmacological options reviewed are effective treatments for opioid dependence with positive long term outcomes. However, each one has its specific target population and setting. While methadone and buprenorphine are first line options, heroin-assisted treatment is a second line option for those patients refractory to treatment with methadone with concomitant severe physical, mental, social and/or functional problems. Buprenorphine seems to be the best option for use in primary care offices. The field of opioid dependence treatment is poised to undergo a process of reinforcement and transformation. Further efforts from researchers, clinicians and authorities should be made to turn new pharmacological options into clinical reality and to overcome the structural and functional obstacles that maintenance programmes face in combatting opioid dependence. PMID:23145768
Garcia-Portilla, Maria Paz; Bobes-Bascaran, Maria Teresa; Bascaran, Maria Teresa; Saiz, Pilar Alejandra; Bobes, Julio
The extensive use of methadone for the treatment of opiate addiction increases significantly the need for quantitative determination of methadone in urine and tissues. Existing spectrophotometric methods are limited in sensitivity by the low molar absorpt...
H. E. Hamilton J. E. Wallace J. T. Payte K. Blum
Cocaine abuse today has reached greater heights than it did during the first cocaine epidemic in the late nineteenth century. It is estimated that one out of every four Americans has used cocaine and some six million people in the US use it regularly. Although cocaine affects all systems in the body, the central nervous system (CNS) is the primary target. Cocaine blocks the reuptake of neurotransmitters in the neuronal synapses. Almost all CNS effects of cocaine can be attributed to this mechanism. Euphoria, pharmacological pleasure and intense cocaine craving share basis in this system. The effects of cocaine on other organ systems, in addition to its effects on the CNS, account for the majority of the complications associated with cocaine abuse. In this paper, the CNS effects following cocaine administration and their treatment are discussed. PMID:8314357
Prakash, A; Das, G
Aims?Methadone is widely used in maintenance programs for opioid-dependent subjects. The aims of the study were to quantify the distribution and excretion of methadone in human milk during the early postnatal period and to investigate exposure of breast fed infants to the drug. Methods?Blood and milk samples were obtained from 12 breast feeding women who were taking methadone in daily doses ranging from 20–80?mg (0.3–1.14?mg?kg?1?). Blood was also obtained from eight of their infants. Methadone concentration in these samples was quantified by h.p.l.c. The infants were observed for withdrawal symptoms. Results?The mean (95% CI) milk/plasma ratio was 0.44 (0.24–0.64). Exposure of the infants, calculated assuming an average milk intake of 0.15?l?kg?1?day?1 and a bioavailability of 100% was 17.4 (10.8–24)??g?kg?1?day?1. The mean infant dose expressed as a percentage of the maternal dose was 2.79 (2.07–3.51)%. Methadone concentrations in seven infants were below the limit of detection for the h.p.l.c. assay procedure, while one infant had a plasma methadone concentration of 6.5??g?l?1. Infant exposure to methadone via human milk was insufficient to prevent the development of a neonatal abstinence syndrome which was seen in seven (64%) infants. No adverse effects attributable to methadone in milk were seen. Conclusions?We conclude that exposure of breast fed infants to methadone taken by their mothers is minimal and that women in methadone maintenance programs should not be discouraged from breast feeding because of this exposure.
Wojnar-Horton, R. E.; Kristensen, J. H.; Yapp, P.; Ilett, K. F.; Dusci, L. J.; Hackett, L. P.
Expectations about future behavior have been shown to have a positive relationship with subsequent behavior. For patients in drug treatment, recovery should manifest changes in drug use and in cognitive perceptions of being able to refrain from use. The present study identified latent patterns of the longitudinal relationship between drug use expectation and illegal drug use during treatment. Latent variable mixture modeling identified three patterns of change over successive 3-month intervals during treatment: Improvers (48%), Decliners (33%), and Continuing Users (19%). The sample consisted of 497 patients in community-based outpatient methadone treatment. The utility of the latent patterns was shown through their relationship to treatment engagement, where Continuing Users had lower counseling rapport and time in treatment. These latent patterns also differed on drug use measures at follow-up. Additional analyses of expectations with measures of opioid use, cocaine use, or criminality yielded similar latent patterns. Expectations about future drug use were found to be a useful measure of cognitive change corresponding to drug use change. Its potential as a brief treatment management tool is noted. PMID:17218066
Joe, George W; Flynn, Patrick M; Broome, Kirk M; Simpson, D Dwayne
We examined methadone maintenance therapy (MMT) use among HIV-positive injection drug users (IDU) in Vancouver. Among 353 participants, 199 (56.3%) were on MMT at baseline, and 48 initiated MMT during follow-up. Female gender (adjusted odds ratio [AOR] = 1.73, 95% CI: 1.14 – 2.62) and antiretroviral therapy use (AOR = 2.04, 95% CI: 1.46 – 2.86) were positively associated with MMT use, while frequent heroin injection (AOR = 0.34, 95% CI: 0.23–0.50), public injection (AOR = 0.76, 95% CI: 0.59 – 0.97), syringe borrowing (AOR = 0.54, 95% CI: 0.32 – 0.90), and non-fatal overdose (AOR = 0.58, 95% CI: 0.36 – 0.92) were negatively associated with MMT use. The rate of discontinuation of MMT was 12.46 (95% CI: 8.28 – 18.00) per 100 person years. Frequent heroin use (adjusted hazards ratio = 4.49, 95%CI: 1.81 – 11.13) was positively associated with subsequent discontinuation of MMT. These findings demonstrate the benefits of MMT among HIV-positive IDU and the need to improve access to and retention in MMT.
Pettes, Tyler; Wood, Evan; Guillemi, Silvia; Lai, Calvin; Montaner, Julio; Kerr, Thomas
The work adjustment of 26 methadone-maintained corporate employees was evaluated. Results indicated: (a) relative to their nonmethadone-maintained coworkers, the methadone-maintained employees had comparable job performance and superior punctuality and attendance; and (b) the methadone-maintained skilled laborers were satisfied with their…
Yankowitz, Robert; Randell, Joan
Objective: Methadone poisoning can occur accidentally or intentionally for suicide or homicide purposes. The aim of this study was to evaluate the epidemiological and clinical manifestations of Methadone poisoning. Methods: A descriptive analytical study was performed from 2010 to 2012 in the poisoning emergency and clinical toxicology departments of Noor hospital affiliated with Isfahan University of Medical Sciences (Isfahan, Iran). All patients with Methadone poisoning within this period of time were investigated. Different variables were recorded in a checklist. Findings: A total of 385 patients were studied. About 85.7% had ingested only Methadone and 14.3% had ingested other medications with Methadone. Mean ± standard deviation of the age was 32.1 ± 15 years (range: 1-90). Most of the patients were male (76.4%). Nearly 40% of the patients were narcotic addicts, 25.5% were addicts under surveillance of Methadone maintenance therapy centers and 34.5% were non-addicts. Intentional poisoning was observed in most of the patients (57.7%). Most of the patients had a low level of consciousness on admission (58.2%). Respiratory depression and hypotension was observed in 35.6% and 12.7% of the cases as the most common symptoms. Regarding vital signs, there was a significant difference in respiratory rate on admission among different evaluated groups (P = 0.02). Length of hospital stay was 18.79 ± 0.72 h (range: 4-240 h, median: 15 h). About 57 patients (25.8%) from the intentionally poisoned patients and 19 patients (12.3%) from the unintentionally poisoned patients had a history of psychiatric disorder (P = 0.001). Most of the patients survived without complications. Conclusion: Addiction, age, gender, attempt to suicide and a history of psychiatric disorder were of the most important factors effective in Methadone poisoning, which should be considered in the public training and prevention of poisoning.
Taheri, Fatemeh; Yaraghi, Ahmad; Sabzghabaee, Ali Mohammad; Moudi, Maryam; Eizadi-Mood, Nastaran; Gheshlaghi, Farzad; Farajzadegan, Ziba
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
Keller, R W; Snyder-Keller, A
Interactions between HIV and opioid dependence therapies are known to occur. We sought to determine if such interactions occurred between methadone and elvitegravir boosted with cobicistat (EVG/COBI). We performed a within-subject open-label pharmacokinetic and pharmacodynamic study of 11 HIV-seronegative subjects stabilized on at least 2 weeks of methadone. Subjects underwent baseline and steady-state evaluation of the effect of elvitegravir 150 mg once a day (QD) boosted with 150 mg QD of cobicistat (EVG/COBI) on methadone pharmacokinetic parameters. Safety and pharmacodynamics were monitored throughout the study. Compared to baseline values, the R-methadone mean area under the concentration-time curve to the end of the dosing period (AUCtau) (5,550 versus 6,210 h · ng/ml) and mean maximum concentration of drug in serum (Cmax) (316 versus 337 ng/ml) did not significantly increase in the presence of EVG/COBI. Compared to baseline values, the S-methadone mean AUCtau (7,040 versus 7,540 h · ng/ml) and mean Cmax (446 versus 452 ng/ml) did not significantly increase in the presence of EVG/COBI. The AUCtau, Cmax, and Ctau of elvitegravir and cobicistat did not significantly differ from those of historical controls. Opioid withdrawal or overdose was not observed among subjects in this study. The addition of EVG/COBI to stabilized patients receiving methadone did not affect methadone pharmacokinetics and pharmacodynamics. These two agents can be safely coadministered.
Winkle, P.; Custodio, J. M.; Wei, X.; Rhee, M. S.; Kearney, B. P.; Ramanathan, S.; Friedland, Gerald H.
The records of 21 patients admitted to hospital from January 1985 to December 1988 for acute headache associated with cocaine intoxication were reviewed. Fifteen patients were identified who experienced headaches with migrainous features in the absence of neurological or systemic complications. None of them had a history of cocaine-unrelated headaches or a family history of migraine, and all had a favourable outcome. Three possible mechanisms of cocaine-related vascular headaches are discussed which depend on the interval between cocaine ingestion and development of the headache. We postulate that acute headaches following cocaine use may relate to the sympathomimetic or vasoconstrictive effects of cocaine, while headaches following cocaine withdrawal or exacerbated during a cocaine "binge" may relate to cocaine-induced alteration of the serotoninergic system.
Dhuna, A; Pascual-Leone, A; Belgrade, M
Aims To undertake an exploratory study to examine the characteristics of patients in narcotic treatment programs who started their use of black tar heroin either as inhalers or as injectors and to compare them with those who started as inhalers but shifted to injecting. Other studies in this area have used subjects using other forms of heroin more amenable to inhaling. Participants, Design, and Measurement A purposive sample of 199 patients in 6 methadone programs in Texas were interviewed in 2002-2003 using a structured instrument. Findings At admission to treatment, those who were heroin inhalers were more likely to be African American, to live with their families, to have income from wages, and to report fewer days of problems on most of the ASI measures. Those who shifted from inhaling to injecting were more likely to be Hispanic and to have had mental health problems that interfered with their lives and to have had less nurturing while growing up. Injectors were older at this treatment admission, had more treatment episodes and more times in jail, and were more likely to have hepatitis C, AIDS, or gonorrhea. There were high levels of physical and mental problems and histories of traumatization as children and adults for almost all the respondents. Males were as likely as females to have been sexually abused as children or as adults. Conclusions The high rates of mental and physical problems among all the clients interviewed showed the need for comprehensive services to be delivered within the substance abuse treatment programs. Histories of trauma and sexual abuse should be addressed for both male and female clients.
Maxwell, Jane Carlisle; Spence, Richard T.
Objectives: Social workers will increasingly be required to attend to the cost-effectiveness of practices, programs, and policies. In the area of substance abuse, there is little evidence to suggest that social workers' decisions are based on evidence of either effectiveness or costs. Method: This article provides an overview of existing evidence…
Schilling, Robert; Dornig, Katrina; Lungren, Lena
This report addresses the societal problems related to opiate drug use and offers a new, rational approach toward controlling the demand for, and abuse of, illicit narcotics in Arizona. This report includes statistics on Arizona's heroin addict population...
A carefully controlled comparison of the personality characteristics of heroin addict (n=27) and nonaddict (n=20) offenders was carried out so as to avoid methodological problems associated with earlier studies. (Editor)
Platt, Jerome J.
Heroin use patterns in Mississippi are investigated, and prevention and control strategies are evaluated. Data were collected through interviews with drug misusers and treatment and law enforcement officials. Data were also obtained from a review of the l...
The use of phenytoin (PHT) as a cocaine adulterant was reported decades ago; that practice is still current. Ironically PHT has also been used for the treatment of cocaine dependence. A drug smuggler developed PHT toxicity after swallowing several rocks of crack. We investigated the current trends of PHT as a cocaine adulterant and its toxicological implications. We also reviewed the clinical use of PTH in relation to cocaine. The use of PHT as cocaine cut is a current practice. This may affect the clinical manifestations and the management of the cocaine-related visits to the emergency department.
Roldan, Carlos J.
Cocaine dependence is an enduring problem and years of research and drug development has yet to produce an efficacious pharmacotherapy. Recent clinical research suggests that chronic treatment with amphetamine-like medications produces tolerance to cocaine’s reinforcing effects and may offer a viable pharmacotherapy. Three methamphetamine-dependent participants that had been in our clinical laboratory experiments and previously addicted to cocaine are reviewed. Data obtained from initial screen and informal conversation suggested that all participants considered methamphetamine to have helped them stop using cocaine and eliminate cocaine craving. Methamphetamine also significantly decreased their alcohol consumption but did not alter cannabis or nicotine use.
Haile, Colin N.; De La Garza, Richard; Newton, Thomas F.
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
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".
Degenhardt, Louisa; Day, Carolyn; Gilmour, Stuart; Hall, Wayne
Methadone is the major opioid substitution therapy for opioid dependence. Dosage is highly variable and is often controlled by the patient and prescriber according to local and national policy and guidelines. Nevertheless many genetic factors have been investigated including those affecting its metabolism (CYP2B6-consistent results), efflux transport (P-gp-inconsistent results), target ?-opioid receptor (?-opioid receptor-inconsistent results) and a host of other receptors (DRD2) and signaling elements (GIRK2 and ARRB2; not replicated). None by themselves have been able to substantially explain dosage variation (the major but not sole end point). When multiple genes have been combined such as ABCB1, CYP2B6, OPRM1 and DRD2 a greater contribution to dosage variation was found but not as yet replicated. As stabilization of dosage needs to be made rapidly, it is imperative that larger internationally based studies be instigated so that genetic contribution to dosage can be properly assessed, which may or may not tailor to different ethnic groups and each country's policy towards an outcome that benefits all. PMID:24956254
Somogyi, Andrew A; Barratt, Daniel T; Ali, Robert L; Coller, Janet K
Advantage was taken of a natural experiment to investigate the relationship of clinic objectives and procedures with retention in methadone maintenance. Assessment, maximum dose, and time in treatment data on 238 patients were summarized using Cox regression. While allowing for patient descriptors and maximum dose of methadone, those subjects assigned to a strongly abstinence-oriented program were 26% (95% C.I., 18 to 33%), 98% (66 to 137%), 213% (132 to 322%), and 393% (224 to 651%) more likely to leave treatment in the first, second, third, fourth 6 months of treatment, respectively, than those subjects assigned to a more laissez-faire program. PMID:8380283
Caplehorn, J R; McNeil, D R; Kleinbaum, D G
Background Methadone is currently the most frequently used substance in the treatment of short-term and particularly long-term opiate dependence. Patients' beliefs about the adverse effects of methadone on function of organs, especially liver, have widely affected the use of this substance. This study aimed to determine the effects of methadone on liver enzyme levels in patients on methadone maintenance treatment. Methods In a retrospective study, a total of 94 patients undergoing methadone maintenance therapy were recruited from Shahid Beheshti Hospital (Kerman, Iran). Liver enzyme levels in all patients were tested every six months from the onset of treatment until 24 months. The relations between test results and age, gender, and methadone dose were then evaluated. Data was analyzed using logistic regression with random data plan. Findings At the 24th month, alanine aminotransferase (ALT) levels in 4 patients (4.3%) and aspartate aminotransferase (AST) levels in 3 patients (3.2%) were above normal. Among 46 patients (50%) who had normal alkaline phosphatase (ALP) levels after 24 months, 26 subjects were younger than 40 and 20 subjects were over 40 years of age. The mean age of subjects with abnormal ALP levels and the mean methadone dose were 39.9 years and 19.55 cc, respectively. Conclusion The results of this study indicated the significant effect of methadone on ALP levels. These effects can account for cholestatic pattern liver injury (obstruction). Further prospective studies including greater samples of patients with heart and liver complications and encompassing other drugs are required to confirm our findings.
Eslami-Shahrbabaki, Mahin; Haghdoost, Ali Akbar; Mashaiekhi, Azadeh; Khalili, Navid; Amini-Ranjbar, Zahra; Ghayomi, Alireza
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.
The purpose of this study was to determine the significance of possible relationships between birth order and polydrug use patterns of heroin addicts prior to undergoing treatment. Overrepresentation of "only child" heroin addicts was evident among the population studied. (Author)
Lerner, Steven E.; Linder, Ronald L.
Despite 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.
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
Hays, J R; Gay, W
Methadone maintenance treatment (MMT) is the most widely available pharmacotherapy for opioid addiction and has been shown to be an effective and safe treatment over a period of 40 years. Although women comprise approximately 40% of clients currently being treated in MMT programs, comparatively little research geared specifically toward this group has been published. This article begins with an overview
Mary Jeanne Kreek; Lisa Borg; Elizabeth Ducat; Brenda Ray
A study of four methadone clinics, the addicts treated at these clinics, and their families, reveals basic dissonances in treatment ideology and professional-paraprofessional relationships which, combined with the addict's particular mode of functioning, make significant change in his behavior improbable. (Author)
Schwartzman, John; Bokos, Peter
Analysis of employment patterns of methadone maintenance clients had indicated that the majority were not employed at time of program admission. At time of evaluation, 70 percent of the sample were employed; 88 percent of these clients had previous work histories and brought marketable skills with them. (Author)
Bloch, Harriet I.; And Others
This report presents data from the 2002 Treatment Episode Data Set (TEDS) on admissions where cocaine was the primary substance of abuse reported. It compares smoked cocaine (primarily crack or rock cocaine) admissions with non-smoked cocaine (primarily p...
...Drugs 8 2009-04-01 2009-04-01 false Cocaine and cocaine metabolite test system. 862.3250 Section 862... Clinical Toxicology Test Systems Â§ 862.3250 Cocaine and cocaine metabolite test system. (a)...
...Drugs 8 2010-04-01 2010-04-01 false Cocaine and cocaine metabolite test system. 862.3250 Section 862... Clinical Toxicology Test Systems Â§ 862.3250 Cocaine and cocaine metabolite test system. (a)...
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…
McCrary, Judy H.
Jane Austen champions practicality and compatibility versus purely romantic or mercenary sentiment in her novels, and through narrative techniques she preserves her heroines from imprudent marriages. Austen's heroines do not fall madly in love at first sight, but rather they acquiesce to marriage through reason and discernment. She endows her heroines with qualities that make them worthy of her interference
The rapid metabolism of heroin to 6-acetylmorphine and its slower conversion to morphine has led many to believe that heroin and morphine act through the same receptors and that the differences between them are due to their pharmacokinetics. We now present evidence strongly implying that heroin and two potent mu drugs, fentanyl and etonitazine, act through a unique receptor mechanism
Grace C. Rossi; George P. Brown; Liza Leventhal; Ke Yang; Gavril W. Pasternak
In 2000, an unusual increase of morbidity and mortality among illegal injecting drug users in the UK and Ireland was reported and Clostridium novyi was identified as the likely source of the serious infection, although infections due to C. botulinum and Bacillus cereus were also reported. Because heroin was a possibile source of infection, this study investigated the microflora of heroin samples seized in England during 2000 and 2002. Two methods were developed for the examination of the microflora of heroin. The first consisted of suspension of the drug in maximum recovery diluent (MRD) which was inoculated directly into Clostridium Botulinum Isolation Cooked Meat Broth (CBI). The second method rendered the heroin soluble in citric acid, concentrated particulate material (and bacterial cells) by filtration and removed heroin residues by washing with citric acid and phosphate-buffered saline before placing the filter in CBI broth. Duplicate CBI broths from both methods were incubated without heating and after heating at 60 degrees C for 30 min. Subcultures were made after incubation for 7 and 14 days on to eight different solid media. The methods were evaluated with heroin samples spiked with either C. botulinum or C. novyi spore suspensions; recovery of 10 spores in the original sample was demonstrated. Fifty-eight heroin samples were tested by citric acid solubilisation and 34 by the MRD suspension technique. Fifteen different gram-positive species of four genera were recognised. No fungi were isolated. Aerobic endospore-forming bacteria (Bacillus spp. and Paenibacillus macerans) were the predominant microflora isolated and at least one species was isolated from each sample. B. cereus was the most common species and was isolated from 95% of all samples, with B. licheniformis isolated from 40%. Between one and five samples yielded cultures of B. coagulans, B. laterosporus, B. pumilus, B. subtilis and P. macerans. Staphylococcus spp. were isolated from 23 (40%) samples; S. warneri and S. epidermidis were the most common and were cultured from 13 (22%) and 6 (10%) samples respectively. One or two samples yielded cultures of S. aureus, S. capitis and S. haemolyticus. The remainder of the flora detected comprised two samples contaminated with C. perfringens and two samples with either C. sordellii or C. tertium. Multiple bacterial species were isolated from 43 (74%) samples, a single species from the remaining 15. In 13 samples B. cereus alone was isolated, in one B. subtilis alone and in one sample B. pumilus alone. C. botulinum and C. novyi were not isolated from any of the heroin samples. Recommendations for the optimal examination of the microflora of heroin are given. PMID:12448685
McLauchlin, J; Mithani, V; Bolton, F J; Nichols, G L; Bellis, M A; Syed, Q; Thomson, R P M; Ashton, J R
Blood toxicology results for deaths attributed to heroin overdose during 1995 in the South Western Sydney (SWS) region (n=39) were compared with those of a sample of 100 current SWS heroin users who had injected within the preceding 24 h. Heroin-related deaths had a higher median concentration of morphine than current heroin users (0.35 versus 0.09 mg\\/l). However, there was
Shane Darke; Sandra Sunjic; Deborah Zador; Tania Prolov
Cocaine was considered incapable of producing dependence in 1980 but was proclaimed the "drug of greatest national public health concern" by 1984. Clinical consensus in 1980 held that cocaine did not produce a withdrawal syndrome, but recent clinical investigations demonstrate that cocaine produces unique abuse and withdrawal patterns that differ from other major abused drugs. Evolving pre-clinical research over the past two decades now suggests that chronic cocaine abuse produces neurophysiological alterations in specific central nervous system systems that regulate the capacity to experience pleasure. These evolving clinical and pre-clinical constructs have led to applications of promising experimental pharmacological treatments for cocaine abuse.
Gawin, F. H.; Kleber, H. D.
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.
The aim of this study is to characterize patients with chronic pain in methadone maintenance treatment (MMT). Between September and December, 2003, 170 consecutive patients from an MMT clinic participated in a questionnaire survey on pain (duration and severity). Chronic pain was defined as current pain lasting for >or=6 months. The patients' maintenance methadone dosage and urine tests for drug abuse during the month before and of the survey were recorded. Of the 170 patients, 94 (55.3%) experienced chronic pain. They had a significantly higher proportion of chronic illness (74.5%) compared to non-pain patients (44.7%) (Fisher's Exact Test P<0.0005). Twelve (12.8%) of the chronic pain patients scored their pain as mild, 38 (40.4%) as moderate, 22 (23.4%) as severe and 22 (23.4%) as very severe. Pain duration significantly correlated with pain severity (Pearson R=0.3, P>0.0005) and was significantly associated with methadone daily dosage: patients with pain duration of >or=10 years (n=26) were receiving the highest methadone dosage (182.1+/-59.2 mg/day), those with pain duration from 1 to 10 years (n=59) 160.9+/-56.2 mg/day, and those with pain duration of <1 year (n=9) 134.2+/-73.2 mg/day. Patients in the non-pain group (n=76) were receiving 147.1+/-52.8 mg/day of methadone (ANOVA, F=3.1, P=0.03). We conclude that pain duration and severity significantly correlated. Although methadone was not prescribed for the treatment of pain but rather for opiate addiction, the patients in the MMT clinic with prolonged pain were prescribed a significantly higher methadone dosage compared to patients with short pain duration, and non-pain patients. PMID:15661442
Peles, Einat; Schreiber, Shaul; Gordon, Jacob; Adelson, Miriam
Cocaine is a white crystalline powder that is prepared from the leaf of the Erythroxylon coca bush, which is grown in Peru and Bolivia. It was first identified by a German chemist named Albert Niemann in the mid-19th century, when it was initiated as a tonic/elixir in medicines to treat real or envisioned illnesses. The mechanism of action of cocaine is to block the reuptake of dopamine, an important neurotransmitter. Cocaine was used medically as a local anesthetic to perform eye, ear, nose, or throat surgery, although it has long since been replaced. Now, it is generally sold on the streets as a powder to be snorted in order to increase alertness and temporary feelings of pleasure.
Sensitive and inexpensive sensors play a significant role in the analysis of drugs and drug metabolites. Specifically, reliable in vivo detection of cocaine and cocaine metabolites serves as a useful tool in research of the body's reaction to the drug and in the treatment of the drug addiction. We present here a promising cocaine biosensor to be used in the human body. The sensor's active element consists of piezoresistive microcantilevers coated with an oligonucleotide-based aptamer as the cocaine binder. In vitro cocaine detection was carried out by flowing a cocaine solution over the microcantilevers. Advantages of this device are its low power consumption, its high sensitivity, and its potential for miniaturization into an implantable capsule. The limit of detection for cocaine in distilled water was found to be 1 ng/ml.
Srijanto, Bernadeta; Cheney, Christine P.; Hedden, David L.; Gehl, Anthony; Ferrell, Thomas L.
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-hr heroin self-administration sessions. One hr after each heroin self-administration session, monkeys chose between heroin (0-0.1 mg/kg/inj) and food (1 gm pellets) during 2-hr choice sessions. Under these conditions, heroin maintained a dose-dependent increase in heroin choice, such that monkeys responded primarily for food when low heroin doses were available (0- 0.01 mg/kg/inj) and primarily for heroin when higher heroin doses were available (0.032-0.1 mg/kg/injection). Periods of spontaneous withdrawal were intermittently introduced by omitting one 21-hr heroin self-administration session, and test drugs were administered during these withdrawal periods. Untreated withdrawal robustly increased heroin choice during choice sessions. Withdrawal-associated increases in heroin choice were completely suppressed by the mu opioid agonist morphine (0.032-0.32 mg/kg/hr IV), but not by the alpha-2 noradrenergic agonist clonidine (0.01-0.1 mg/kg/hr IV), the dopamine/norepinephrine releaser amphetamine (0.032-0.1 mg/kg/hr IV), or the kappa opioid antagonist 5?-guanidinonaltrindole (1.0 mg/kg IM). The corticotropin releasing factor 1 antagonist antalarmin (1.0-10 mg/kg/day IM) produced a morphine-like suppression of withdrawal-associated increases in heroin choice in one of three monkeys. These results suggest that mechanisms of withdrawal-associated increases in the relative reinforcing efficacy of opioid agonists may be different from mechanisms of many other somatic, mood-related and motivational signs of opioid withdrawal.
Negus, S. Stevens; Rice, Kenner C.
This case study looks at cocaine, including its addictive properties and the chemistry involved in the synthesis of the drug in its different forms. The lesson can be used to teach nucleophilic addition reactions, nucleophilic acyl substitution, and cocaine metabolism. The material was designed for use in an undergraduate organic chemistry course but could also be used in medicinal chemistry coursework. The case study and teaching notes may be downloaded in PDF format. The site also includes a section for instructor feedback where general comments may be read and contributed.
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.
Following the introduction of black tar heroin mainly from Mexico in the 1980s, cases of wound botulism dramatically increased in the western United States. Contamination with spores of Clostridium botulinum of black tar heroin occurs along the distribution line. The heating of heroin powder to solubilize it for subcutaneous injection ("skin popping") does not kill the spores. The spores germinate in an anaerobic tissue environment and release botulinum toxin type A or B. Unless skin abscesses are found in the patient, the clinical diagnosis is often challenging. Facilitation of the compound muscle action potential by repetitive nerve stimulation at 20 to 50 Hz is an important and rapid diagnostic test. Definite diagnosis is made by detection of botulinum toxin in serum or isolation of C botulinum from the abscess. Early treatment with equine ABE botulinum antitoxin obtained from the Centers for Disease Control and Prevention often shortens the time on a ventilator. PMID:18957182
Davis, Larry E; King, Molly K
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 advances in this field and considers prospects for development of a robust therapy aimed at aiding recovering drug users avoid addiction relapse.
Brimijoin, Stephen; Gao, Yang
Mice and rats were tested for reduced sensitivity to cocaine-induced hyper-locomotion after pretreatment with anti-cocaine antibody or cocaine hydrolase (CocH) derived from human butyrylcholinesterase (BChE). In Balb/c mice, direct i.p. injection of CocH protein (1 mg/kg) had no effect on spontaneous locomotion, but it suppressed responses to i.p. cocaine up to 80 mg/kg. When CocH was injected i.p. along with a murine cocaine antiserum that also did not affect spontaneous locomotion, there was no response to any cocaine dose. This suppression of locomotor activity required active enzyme, as it was lost after pretreatment with iso-OMPA, a selective BChE inhibitor. Comparable results were obtained in rats that developed high levels of CocH by gene transfer with helper-dependent adenoviral vector, and/or high levels of anti-cocaine antibody by vaccination with norcocaine hapten conjugated to keyhole limpet hemocyanin (KLH). After these treatments, rats were subjected to a locomotor sensitization paradigm involving a “training phase" with an initial i.p. saline injection on day 1 followed by 8 days of repeated cocaine injections (10 mg/kg, i.p.). A 15-day rest period then ensued, followed by a final “challenge" cocaine injection. As in mice, the individual treatment interventions reduced cocaine-stimulated hyperactivity to a modest extent, while combined treatment produced a greater reduction during all phases of testing compared to control rats (with only saline pretreatment). Overall, the present results strongly support the view that anti-cocaine vaccine and cocaine hydrolase vector treatments together provide enhanced protection against the stimulatory actions of cocaine in rodents. A similar combination therapy in human cocaine users might provide a robust therapy to help maintain abstinence.
Carroll, Marilyn E.; Zlebnik, Natalie E.; Anker, Justin J.; Kosten, Thomas R.; Orson, Frank M.; Shen, Xiaoyun; Kinsey, Berma; Parks, Robin J.; Gao, Yang; Brimijoin, Stephen
Opioid abuse and addiction have increased in frequency in the United States over the past 20 years. In 2009, an estimated 5.3 million persons used opioid medications nonmedically within the past month, 200 000 used heroin, and approximately 9.6% of African Americans used an illicit drug. Racial and ethnic minorities experience disparities in availability and access to mental health care, including substance use disorders. Primary care practitioners are often called upon to differentiate between appropriate, medically indicated opioid use in pain management vs inappropriate abuse or addiction. Racial and ethnic minority populations tend to favor primary care treatment settings over specialty mental health settings. Recent therapeutic advances allow patients requiring specialized treatment for opioid abuse and addiction to be managed in primary care settings. The Drug Addiction Treatment Act of 2000 enables qualified physicians with readily available short-term training to treat opioid-dependent patients with buprenorphine in an office-based setting, potentially making primary care physicians active partners in the diagnosis and treatment of opioid use disorders. Methadone and buprenorphine are effective opioid replacement agents for maintenance and/or detoxification of opioid-addicted individuals. However, restrictive federal regulations and stigmatization of opioid addiction and treatment have limited the availability of methadone. The opioid partial agonist-antagonist buprenorphine/naloxone combination has proven an effective alternative. This article reviews the literature on differences between buprenorphine and methadone regarding availability, efficacy, safety, side-effects, and dosing, identifying resources for enhancing the effectiveness of medication-assisted recovery through coordination with behavioral/psychological counseling, embedded in the context of recovery-oriented systems of care.
Bonhomme, Jean; Shim, Ruth S.; Gooden, Richard; Tyus, Dawn; Rust, George
The invention is directed to a binding ligand for cocaine and other neurotransmitter receptors in the brain. Specifically, a novel family of compounds, represented by 3beta-(4-iodophenyl)-tropan-2beta-carboxylic acid methyl ester tartrate shows high bindi...
M. J. Kuhar F. I. Carroll J. W. Boja A. H. Lewin P. Abraham
Partial Contents: Cocaine Addiction as a Neurological Disorder: Implications for Treatment; Brain Atrophy and Chronic Cocaine Abuse: Background and Work in Progress; Neurologic Complications of Cocaine; Psychomotor and Electroencephalographic Sequelae of ...
M. D. Majewska
Morphine conjugate vaccines have effectively reduced behavioral effects of heroin in rodents and primates. To better understand how these effects are mediated, heroin and metabolite distribution studies were performed in rats in the presence and absence of vaccination. In non-vaccinated rats 6-monoacetylmorphine (6-MAM) was the predominant opioid in plasma and brain as early as 1 minute after i.v. administration of heroin and for up to 14 minutes. Vaccination with morphine conjugated to keyhole limpet hemocyanin (M-KLH) elicited high titers and concentrations of antibodies with high affinity for heroin, 6-MAM, and morphine. Four minutes after heroin administration vaccinated rats showed substantial retention of all three opioids in plasma compared to controls and reduced 6-MAM and morphine, but not heroin, distribution to brain. Administration of 6-MAM rather than heroin in M-KLH vaccinated rats showed a similar drug distribution pattern. Vaccination reduced heroin-induced analgesia and blocked heroin-induced locomotor activity throughout 2 weeks of repeated testing. Higher serum opioid-specific antibody concentrations were associated with higher plasma opioid concentrations, lower brain 6-MAM and morphine concentrations, and lower heroin-induced locomotor activity. Serum antibody concentrations over 0.2 mg/ml were associated with substantial effects on these measures. These data support a critical role for 6-MAM in mediating the early effects of i.v. heroin and suggest that reducing 6-MAM concentration in brain is essential to the efficacy of morphine conjugate vaccines.
Pravetoni, M.; Harris, A.C.; Birnbaum, A.K.; Pentel, P.R.
Background Individuals with cocaine use disorder (CUD) chose cocaine over non-drug rewards. In two newly designed laboratory tasks with pictures, we document this modified choice outside of a cocaine administration paradigm. Methods Choice for viewing cocaine, pleasant, unpleasant, or neutral pictures - under explicit contingencies (where choice was made between two fully-visible side-by-side images) and under more implicit contingencies (where selections were made between pictures hidden under flipped-over cards) - was examined in 20 CUD and 20 matched healthy controls. Subjects also provided self-reported ratings of each picture’s pleasantness and arousal. Results Under both contingencies, CUD chose to view more cocaine pictures than control subjects, group differences that were not fully explained by the self-reported picture ratings. Further, whereas CUD’s choice for viewing cocaine pictures exceeded choice for viewing unpleasant pictures (but did not exceed choice for viewing pleasant pictures, in contrast to their self-reported ratings), healthy controls avoided viewing cocaine pictures as frequently as, or even more than, unpleasant pictures. Finally, CUD with the most cocaine viewing selections, even when directly compared to selections of the pleasant pictures, also reported the most frequent recent cocaine use. Conclusions Enhanced drug-related choice in cocaine addiction can be demonstrated even for non-pharmacological (pictorial) stimuli. This choice, which is modulated by alternative stimuli, partly transcends self-reports (possibly indicative of a disconnect in cocaine addiction between self-reports and objective behavior) to provide an objective marker of addiction severity. Neuroimaging studies are needed to establish the neural underpinnings of such enhanced cocaine-related choice.
Moeller, Scott J.; Maloney, Thomas; Parvaz, Muhammad A.; Dunning, Jonathan P.; Alia-Klein, Nelly; Woicik, Patricia A.; Hajcak, Greg; Telang, Frank; Wang, Gene-Jack; Volkow, Nora D.; Goldstein, Rita Z.
Individuals with cocaine use disorder (CUD) chose cocaine over nondrug rewards. In two newly designed laboratory tasks with pictures, we document this modified choice outside of a cocaine administration paradigm. Choice for viewing cocaine, pleasant, unpleasant, or neutral pictures-under explicit contingencies (choice made between two fully visible side-by-side images) and under more implicit contingencies (selections made between pictures hidden under flipped-over cards)-was examined in 20 CUD and 20 matched healthy control subjects. Subjects also provided self-reported ratings of each picture's pleasantness and arousal. Under both contingencies, CUD subjects chose to view more cocaine pictures than control subjects, group differences that were not fully explained by the self-reported picture ratings. Furthermore, whereas CUD subjects choice for viewing cocaine pictures exceeded choice for viewing unpleasant pictures (but did not exceed choice for viewing pleasant pictures, in contrast to their self-reported ratings), healthy control subjects avoided viewing cocaine pictures as frequently as, or even more than, unpleasant pictures. Finally, CUD subjects with the most cocaine viewing selections, even when directly compared with selections of the pleasant pictures, also reported the most frequent recent cocaine use. Enhanced drug-related choice in cocaine addiction can be demonstrated even for nonpharmacologic (pictorial) stimuli. This choice, which is modulated by alternative stimuli, partly transcends self-reports (possibly indicative of a disconnect in cocaine addiction between self-reports and objective behavior) to provide an objective marker of addiction severity. Neuroimaging studies are needed to establish the neural underpinnings of such enhanced cocaine-related choice.
Moeller, S.J.; Goldstein, R.; Moeller, S.J.; Maloney, T. Parvaz, M.A.; Dunning, J.P.; Alia-Klein, N.; Woicik, P.A.; Hajcak, G.; Telang, F.; Wang, G.-J.; Volkow, N.D.; Goldstein, R.Z.
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
In 2000, an unusual increase of morbidity and mortality among illegal injecting drug users in the UK and Ireland was reported and Clostridium novyi was identified as the likely source of the serious infection, although infections due to C. botulinum and Bacillus cereus were also reported. Because heroin was a possibile source of infection, this study investigated the microflora of
J. McLAUCHLIN; V. MITHANI; F. J. BOLTON; G. L. NICHOLS; M. A. BELLIS; Q. SYED; R. P. M. THOMSON; J. R. ASHTON
A method of separation by gas chromatography with a flame ionization detector was developed for quantifying cocaine in powders seized by the police. The method was validated by studying parameters of calibration, trueness, precision based on trueness error (or systematic bias) and random error. Total error, which is the combination of these errors, is used to confirm the method adequacy with the objectives fixed by the analyst. Accuracy profile is an efficient decision tool to do it. Results obtained with weighted regression model allow concluding that the method fits quantitation of heroin and cocaine in powders on 2 to 100% concentration (w/w) domain with 10% limits of acceptation and a risk of 5%. PMID:23622698
Dujourdy, L; Charvoz, C; Dalmasso, M; Dufour, A-B
Objective Deficits in cognitive functioning have been well-documented in persons with substance use disorders. In addition, some evidence suggests that poorer cognitive functioning predicts poorer engagement in substance abuse treatment and worse treatment outcomes. TRIAL DESIGN Non-blind, randomized clinical trial with parallel design. Methods Clients were recruited from a local methadone maintenance clinic within the first 30 days of treatment. All participants completed a comprehensive, computerized neuropsychological assessment (MicroCog) at the time they entered the clinical trial. Participants were randomized to receive 12 months of either standard methadone maintenance treatment, or methadone maintenance treatment with an integrated web-based intervention as part of treatment. The aims of the current study were to (1) characterize the cognitive functioning of clients entering methadone maintenance treatment; (2) evaluate the impact of cognitive functioning on the primary outcomes of treatment retention and opioid abstinence; and (3) determine whether cognitive functioning had a differential impact on these outcomes across treatment conditions. Randomization was non-blind and participants were stratified on past month cocaine use, prior history of methadone, LAAM or buprenorphine treatment, and counselor. Results Eighty participants were randomized to each condition (total n=160). Mean scores on MicroCog scales fell in the average and low average ranges and there were no differences in scores between treatment groups. Lower scores on General Cognitive Proficiency predicted longer study retention (?2=5.03, p < .05), though this effect was quite small. Generalized linear modeling showed that scores on all MicroCog scales except for Spatial Processing significantly predicted opioid abstinence (defined as percent of total weeks and percent of tested weeks with continuous abstinence), with lower scores predicting smaller percentages of continuous weeks of abstinence. This pattern was not evident in regression analyses in which abstinence was defined as number of total weeks of abstinence. An interaction effect was observed, whereby lower cognitive scores predicted lower levels of abstinence for participants in standard methadone maintenance treatment, but not for those who received the web-based intervention as part of methadone maintenance treatment. Conclusions Technology-based interventions may hold promise for minimizing the impact of poorer cognitive functioning on treatment outcomes.
Acosta, Michelle C.; Marsch, Lisa A.; Xie, Haiyi; Guarino, Honoria; Aponte-Melendez, Yesenia
A chronic pain patient prescribed 20 mg of methadone per day was seen at the Emergency Department within one hour following a witnessed intentional 200 mg ingestion. In addition, he was taking the serotonin re-uptake inhibitor antidepressant drugs, sertraline and venlafaxine as prescribed. Methadone is also a serotonin re-uptake inhibitor which has been involved in serotonin toxicity reactions. Initially, no
Terry T. Martinez; Daniel N. Martinez
This multimodality approach is geared primarily to the goal of abstinence. For addicts who cannot achieve this goal, methadone maintenance is suggested as the next step. The modalities described range from low-dose maintenance for clinic outpatients to intensive rehabilitation in a methadone maintenance residential center facility. (Author)
Brill, Leon; Chambers, Carl D.
Cocaine addiction remains a clinical challenge with no effective pharmacotherapy available. Trace amine associated receptor (TAAR) 1 represents a promising drug target for the modulation of dopaminergic system and stimulant abuse. This Viewpoint discusses the emerging data which strongly suggest that TAAR 1 functions as a molecular "brake" that controls the addiction-related effects of cocaine and could be a novel drug target for the development of efficacious pharmacotherapy to treat cocaine addiction. PMID:24849494
Rationale Although buprenorphine is effective in treating opioid dependence, optimal maintenance doses of buprenorphine or the buprenorphine/naloxone combination have not yet been established. Objective The present study was designed to evaluate the effects of buprenorphine/naloxone maintenance (2/0.5, 8/2, 32/8 mg sublingual) on the reinforcing and subjective effects of heroin (0, 12.5, 25, 50, and 100 mg intranasal) in heroin-dependent individuals. Methods During test weeks, participants (N=7) first sampled a dose of heroin and $20. During subsequent choice sessions, participants could choose to self administer heroin and/or money. Participants responded under a modified progressive-ratio schedule (PR 50, …, 2800) during a 10-trial self-administration task. Results Heroin break point values and subjective responses were significantly lower under 8/2 and 32/8 mg buprenorphine/naloxone compared to 2/0.5 mg. The self-administration and subjective effects data for heroin in the presence of buprenorphine/naloxone were compared to a separate control group of recently detoxified participants (N=8) in order to obtain estimates for the apparent in vivo dissociation constant (KA), the efficacy estimate (tau), and the estimated fraction of receptors remaining after buprenorphine/naloxone treatment (q). The apparent in vivo dissociation constant for heroin ranged from 50–126 mg (KA) and the efficacy estimate ranged from 13–20 (tau). In addition, 2/0.5, 8/2 and 32/8 mg buprenorphine/naloxone dose-dependently reduced the receptor population by 74%, 83%, and 91%, respectively. Conclusions These data demonstrate that both 8/2 and 32/8 mg buprenorphine/naloxone were well tolerated and effective in reducing the reinforcing and subjective effects of heroin, relative to the 2/0.5 mg dose. The data also show for the first time in humans that it is possible to quantify the efficacy and affinity of heroin for mu opioid receptors and that 80–90% of mu receptors need to be inactivated in order to obtain significant reductions in heroin-induced effects. These results have important implications for future studies in which it will be possible to obtain estimates of relative affinity and efficacy of different agonists at mu opioid receptors.
Comer, Sandra D.; Walker, Ellen A.; Collins, Eric D.
... of heroin as well as shifts in initiation patterns A new report by the Substance Abuse and ... 2008 and 2011 in heroin initiation levels and patterns. For example, although overall heroin initiation rose among ...
Objective Suicide is an important public health problem in China. Elsewhere injection drug use and HIV infection have independently been associated with suicidality, but research has often overlooked these high-risk groups in China. We determined the frequency and predictors of suicidal ideas in Chinese, HIV-infected (HIV+) and uninfected (HIV-) heroin injection drug users in treatment (IDUs) and a control sample. We hypothesized that rates of suicidal ideas would be significantly higher among IDUs compared to controls, and highest among HIV+ IDUs. Method We assessed suicidal ideas within the past two weeks in HIV+ (N = 204) and HIV- (N = 202) heroin IDUs in methadone treatment in Yunnan, a province at the intersection of the heroin and HIV epidemics, and in demographically matched, uninfected non-drug using controls (N = 201). Results Rates of suicidality were higher in IDUs than controls but there was no additive effect of HIV infection (HIV+ IDU 43.1%; HIV- IDU 37.1%; controls 8.5%). Among HIV+ IDUs suicidality was associated most strongly with a combination of prior history of major depression, low perceived social support, and experience of HIV-relevant stress, but not with AIDS diagnosis. Among HIV- IDUs suicidality was associated with prior history of major depressive or alcohol use disorder. Less than 25% of IDUs with suicidality had histories of mood or alcohol use diagnoses. Conclusion Because suicidal ideation is frequent in IDUs in China, regardless of HIV status, and is not fully accounted for by past psychiatric history, additional research may be warranted.
Jin, Hua; Atkinson, J. Hampton; Duarte, Nichole A.; Yu, Xin; Shi, Chuan; Riggs, Patricia K.; Li, Jianhua; Gupta, Saurabh; Wolfson, Tanya; Knight, Adam; Franklin, Donald; Letendre, Scott; Wu, Zunyou; Grant, Igor; Heaton, Robert K.
Aims Rectal administration of methadone may be an alternative to intravenous and oral dosing in cancer pain, but the bioavailability of the rectal route is not known. The aim of this study was to compare the absolute rectal bioavailability of methadone with its oral bioavailability in healthy humans. Methods Seven healthy subjects (six males, one female, aged 20–39 years) received 10 mg d5-methadone-HCl rectally (5 ml in 20% glycofurol) together with either d0-methadone intravenously (5 mg) or orally (10 mg) on two separate occasions. Blood samples for the LC-MS analyses of methadone and it's metabolite EDDP were drawn for up to 96 h. Noninvasive infrared pupillometry was peformed at the same time as blood sampling. Results The mean absolute rectal bioavalability of methadone was 0.76 (0.7, 0.81), compared to 0.86 (0.75, 0.97) for oral administration (mean (95% CI)). Rectal absorption of methadone was more rapid than after oral dosing with Tmax values of 1.4 (0.9, 1.8) vs. 2.8 (1.6, 4.0) h. The extent of formation of the metabolite EDDP did not differ between routes of administration. Single doses of methadone had a duration of action of at least 10 h and were well tolerated. Conclusions Rectal administration of methadone results in rapid absorption, a high bioavailability and long duration of action. No evidence of presystemic elimination was seen. Rectal methadone has characteristics that make it a potential alternative to intravenous and oral administration, particularly in cancer pain and palliative care.
Dale, Ola; Sheffels, Pamela; Kharasch, Evan D
Inhibition of phosphodiesterase-4 (PDE4), an enzyme that specifically hydrolyzes cyclic adenosine monophosphate (cAMP) increases intracellular cAMP/cAMP-response element binding protein (CREB) signaling. Activation of this signaling is considered as an important compensatory response that decreases motivational properties of drugs of abuse. However, it is not known whether PDE4 is involved in heroin seeking. Self-administration of heroin (50 ?g/kg/infusion) was performed under the fixed ratio 1 (FR1) schedule for 14 d and then drug seeking was extinguished for 10 d. The progressive ratio schedule was used to evaluate the relative motivational value of heroin reinforcement. After training, the conditioned cue or heroin priming (250 ?g/kg) was introduced for the reinstatement of heroin-seeking behavior. Pretreatment (i.p.) with rolipram (0.03-0.3 mg/kg), a prototypical, selective PDE4 inhibitor, failed to inhibit heroin self-administration under the FR1 schedule, but decreased the reward values under the progressive ratio schedule in a dose-dependent manner. In addition, rolipram decreased the reinstatement of heroin seeking induced by cues or heroin priming even at the lowest dose (0.03 mg/kg); in contrast, the highest dose (0.3 mg/kg) of rolipram was required to decrease sucrose reinforcement. Finally, the effects of rolipram on heroin-seeking behavior were correlated with the increases in expression of phosphorylated CREB in the nucleus accumbens. The study demonstrated that rolipram inhibited heroin reward and heroin-seeking behavior. The results suggest that PDE4 plays an essential role in mediating heroin seeking and that PDE4 inhibitors may be used as a potential pharmacotherapeutic approach for heroin addiction. PMID:24832929
Lai, Miaojun; Zhu, Huaqiang; Sun, Anna; Zhuang, Dingding; Fu, Dan; Chen, Weisheng; Zhang, Han-Ting; Zhou, Wenhua
Imagine that the circles, called vesicles, at the top of the images are filled with molecules of dopamine, such as the arrow labeled as "1". The vesicles fuse with the axonal membrane to release the dopamine into the area called the synaptic gap. Dopamine can then activate the next axon ("6") or be recycled into the previous axon (through "5"). Cocaine blocks the channel that takes dopamine up again ("5"), so dopamine activates the next axon continuously. This can cause extreme mood swings.
N/A N/A (None;)
Sweat patches (N=350) were collected throughout gestation from 29 opioid-dependent pregnant women participating in an outpatient methadone assisted therapy program. Volunteers provided informed consent to participate in Institutional Review Board-approved protocols. Methadone was eluted from sweat patches with sodium acetate buffer, followed by solid-phase extraction and quantification by GCMS (LOQ ?10 ng/patch). Methadone was present in all weekly patches (N=311) in concentrations ranging from 10.2 to 12,129.7 ng/patch and in 92.3% of short-term patches (N=39, worn for 12 or 24 h) in concentrations up to 3303.9 ng/patch. Correlation between patch concentrations and total amount of drug administered (r=0.224), and concentrations and duration of patch wear (r=0.129) were both weak. Although there were large intra- and inter-subject variation in sweat drug concentrations, sweat testing was an effective alternative technique to qualitatively monitor illicit drug use and simultaneously document methadone medication assisted treatment.
Barnes, Allan J.; Brunet, Bertrand R.; Choo, Robin E.; Mura, Patrick; Johnson, Rolley E.; Jones, Hendree E.; Huestis, Marilyn A.
Objective To evaluate the impact of introduction of supervision of methadone dosing on deaths related to overdose of methadone in Scotland and England between 1993 and 2008 while controlling for increased prescribing of methadone. Design Analysis of annual trends in deaths related to overdose of methadone in relation to defined daily doses of methadone prescribed. Setting Scotland and England. Population Deaths in which methadone was coded as the only drug involved or as one of the drugs implicated. Main outcome measure Annual OD4-methadone index (number of deaths with methadone implicated per million defined daily doses of methadone prescribed in that year). Results OD4-methadone declined substantially over the four epochs of four years between 1993 and 2008. It decreased significantly (P<0.05) in 10 of 12 epoch changes: in Scotland from 19.3 (95% confidence interval 15 to 24) to 4.1 (2.8 to 5.4) and finally to 3.0 (2.4 to 3.5) for methadone only deaths (and from 58 to 29 to 14 for deaths with any mention of methadone); in England from 27.1 (25 to 29) to 24.8 (23 to 27) and finally to 5.8 (5.3 to 6.3) for methadone only deaths (and from 46 to 42 to 12 for deaths with any mention of methadone). The decreases in OD4-methadone were closely related to the introduction of supervised dosing of methadone in both countries, first in Scotland (1995-2000) and later in England (1999-2005). These declines occurred over periods of substantial increases in prescribing of methadone (18-fold increase in defined daily doses per million population annually in Scotland and sevenfold increase in England). Conclusions Introduction of supervised methadone dosing was followed by substantial declines in deaths related to overdose of methadone in both Scotland and England. OD4-methadone index analyses, controlled for substantial increases in methadone prescribing in both countries, identified at least a fourfold reduction in deaths due to methadone related overdose per defined daily dose (OD4-methadone) over this period.
Background The Ministry of Health, Treatment and Medical Education of Iran has recently announced an estimated figure of 200,000 injecting drug users (IDUs). The aim of this study was to pilot a national program using demographics, types of drug abuse and prevalence of blood-borne infections among IDUs. Methods: In order to elicit data on demographics, types of drug abuse and prevalence of blood-borne infections among IDUs, a questionnaire was designed in the Bureau of Mental-Social Health and Addiction in collaboration with Iran’s Drug Control Headquarters of the Police Department. Therapeutical alliance of addiction in Shafagh Center was based on Methadone Maintenance Therapy (MMT). Results: Among 402 reported IDUs most of them were male, single and in age range of 20 to 39 years old with 72.7% history of imprisonment. Most of them had elementary and high school education and a history of addiction treatment. The majority were current users of opioid, heroin and crack. The prevalence of blood-borne infections was 65.9% and 18.8% for HCV and HIV/AIDS infections, respectively. Conclusion: Prevention programs about harm reduction, treatment and counseling should include young IDUs as a core focus of their intervention structure.
ESKANDARIEH, Sharareh; NIKFARJAM, Ali; TARJOMAN, Termeh; NASEHI, Abassali; JAFARI, Firoozeh; SABERI-ZAFARGHANDI, Mohammad-Bagher
Background: In several European countries and in Canada, clinical trials are being conducted in which heroin-addicted patients are treated with pharmaceutically prepared heroin in order to reduce the destructive behaviour that is so often associated with this drug. Objective: To develop an integrated population pharmacokinetic model for heroin (diamorphine) and its pharmacodynamically active metabolites 6-acetylmorphine, morphine, morphine-3-glucuronide and morphine-6-glucuronide. Additionally,
Elisabeth J Rook; Alwin D R Huitema; Wim van den Brink; Ree van J. M; Jos H Beijnen
Non-contingent, ‘priming’ IV drug injections led to reinstatement of heroin-reinforced responding after a period of extinction. Rats implanted with IV catheters were trained to self-administer heroin (100 µg\\/kg\\/infusion diacetylmorphine HCl) and were given test sessions consisting of a period of self-administration followed by extinction conditions. ‘Priming’ infusions of heroin and other drugs were presented during extinction and lever pressing following
Harriet de Wit; Jane Stewart
Drug overdose is a major cause of premature death and morbidity among heroin users. This article examines recent research\\u000a into heroin overdose to inform interventions that will reduce the rate of overdose death. The demographic characteristics\\u000a of overdose cases are discussed, including factors associated with overdose: polydrug use, drug purity, drug tolerance, routes\\u000a of administration, and suicide. Responses by heroin
Shane Darke; Wayne Hall
Genetic deletion of the neurokinin 1 receptor (NK1R) has been shown to decrease the reinforcing properties of opioids, but it is unknown whether pharmacological NK1R blockade has the same effect. Here, we examined the effect of L822429, a rat-specific NK1R antagonist, on the reinforcing properties of heroin in rats on short (1?h: ShA) or long (12?h: LgA) access to intravenous heroin self-administration. ShA produces heroin self-administration rates that are stable over time, whereas LgA leads to an escalation of heroin intake thought to model important dependence-related aspects of addiction. L822429 reduced heroin self-administration and the motivation to consume heroin, measured using a progressive-ratio schedule, in both ShA and LgA rats. L822429 also decreased anxiety-like behavior in both groups, measured on the elevated plus maze, but did not affect mechanical hypersensitivity observed in LgA rats. Expression of TacR1 (the gene encoding NK1R) was decreased in reward- and stress-related brain areas both in ShA and LgA rats compared with heroin-naïve rats, but did not differ between the two heroin-experienced groups. In contrast, passive exposure to heroin produced increases in TacR1 expression in the prefrontal cortex and nucleus accumbens. Taken together, these results show that pharmacological NK1R blockade attenuates heroin reinforcement. The observation that animals with ShA and LgA to heroin were similarly affected by L822429 indicates that the SP/NK1R system is not specifically involved in neuroadaptations that underlie escalation resulting from LgA self-administration. Instead, the NK1R antagonist appears to attenuate acute, positively reinforcing properties of heroin and may be useful as an adjunct to relapse prevention in detoxified opioid-dependent subjects.
Barbier, Estelle; Vendruscolo, Leandro F; Schlosburg, Joel E; Edwards, Scott; Juergens, Nathan; Park, Paula E; Misra, Kaushik K; Cheng, Kejun; Rice, Kenner C; Schank, Jesse; Schulteis, Gery; Koob, George F; Heilig, Markus
Objective. To report the one-year retention rate and the prevalence of illicit opioid use and cocaine use in the Low-Threshold/High-Tolerance (LTHT) methadone maintenance treatment (MMT) clinic located in Saint John, New Brunswick, Canada. Methods. A description of the LTHT MMT clinic is provided. The one-year retention rate was determined by collecting data on patients who enrolled in the LTHT MMT clinic between August 04, 2009 and August 04, 2010. The prevalence of illicit drug use was determined using a randomly selected retrospective cohort of 84 participants. For each participant the results of six consecutive urine tests for the most recent three months were compared to the results of the first six consecutive urine tests after program entry. Results. The one-year retention rate was 95%, 67% of the cohort achieved abstinence from illicit opioids and an additional 13% abstained from cocaine use. Conclusion. The novel feature of the LTHT MMT clinic is that patients are not denied methadone because of lack of ancillary services. Traditional comprehensive MMT programs invest the majority of financial resources in ancillary services that support the biopsychosocial model, whereas the LTHT approach utilizes a medical model and directs resources at medical management.
Christie, Timothy K. S.; Murugesan, Alli; Manzer, Dana; O'Shaughnessey, Michael V.; Webster, Duncan
Cocaine covalently modifies proteins through a reaction in which the methyl ester of cocaine acylates the -amino group of lysine residues. This reaction is highly specific in vitro, because no other amino acid reacts with cocaine, and only cocaine's methyl ester reacts with the lysine side chain. Covalently modified proteins were present in the plasma of rats and human subjects chronically exposed to cocaine. Modified endogenous proteins are immunogenic, and specific antibodies were elicited in mouse and detected in the plasma of human subjects. Covalent modification of proteins could explain cocaine's autoimmune effects and provide a new biochemical approach to cocaine's long-term actions.
Deng, Shi-Xian; Bharat, Narine; Fischman, Marian C.; Landry, Donald W.
Sudden sensorineural hearing loss is a symptom of cochlear injury. Potential aetiologies are vascular diseases, viral infections,\\u000a allergic reactions, autoimmune disorders, and traumatic rupture of the intralabyrinthe membrane. Unlike in unilateral cases\\u000a bilateral sensorineural hearing loss is often associated with specific disease entities. We report a case of sudden bilateral\\u000a deafness after intravenous heroin abuse. The putative pathophysiological mechanisms are
Andreas Schrock; Mark Jakob; Stefan Wirz; Friedrich Bootz
Drug-related memories persist long into abstinence and are potent elicitors of drug craving and relapse. We report two experiments examining whether heroin-dependent individuals are impaired in intentionally suppressing drug-related memories. Experiment 1 adopted the Item paradigm where addicts and healthy controls were presented with a list of words each followed by a remember or forget cue. Experiment 2 adopted the
Zhiling Zou; John X. Zhang; Xiting Huang; Xuchu Weng
The aim of this study was to determine the prevalence and investigate the aetiology of hypogonadism in men on methadone or buprenorphine maintenance treatment (MMT, BMT). 103 men (mean age 37.6 +/- 7.9) on MMT (n = 84) or BMT (n = 19) were evaluated using hormone assays, body mass index (BMI), serological, biochemical, demographic and substance use measures. Overall 54% of men (methadone 65%; buprenorphine 28%) had total testosterone (TT) <12.0 nm; 34% (methadone 39%; buprenorphine 11%) had TT <8.0 nm. Both methadone- and buprenorphine-treated men had lower free testosterone, luteinising hormone and estradiol than age-matched reference groups. Methadone-treated men had lower TT than buprenorphine-treated men and reference groups. Prolactin did not differ between methadone, buprenorphine groups, and reference groups. Primary testicular failure was an uncommon cause of hypogonadism. Yearly percentage fall in TT by age across the patient group was 2.3%, more than twice that expected normally. There were no associations between TT and opioid dose, cannabis, alcohol and tobacco consumption, or chronic hepatitis C viraemia. On multiple regression higher TT was associated with higher alanine aminotransferase and lower TT with higher BMI. Men on MMT have high prevalence of hypogonadotrophic hypogonadism. The extent of hormonal changes associated with buprenorphine needs to be explored further in larger studies. Men receiving long term opioid replacement treatment, especially methadone treatment, should be screened for hypogonadism. Wide interindividual differences in methadone metabolism and tolerance may in a cross-sectional study obscure a methadone dose relationship to testosterone in individuals. Future studies of hypogonadism in opioid-treated men should examine the potential benefits of dose reduction, choice of opioid medication, weight loss, and androgen replacement. PMID:17971165
Hallinan, R; Byrne, A; Agho, K; McMahon, C G; Tynan, P; Attia, J
Background Prisoners have extremely high rates of smoking with rates 3–4 times higher than the general community. Many prisoners have used heroin. The aims of this study were to investigate the impact of heroin use on smoking cessation and the social determinants of health among prisoners. Methods Secondary analysis of data from a randomised controlled trial of a multi-component smoking cessation intervention involving 425 Australian male prisoners. Inmates who, prior to imprisonment, used heroin regularly were compared to those who did not use heroin regularly. Self-reported smoking status was validated at baseline and each follow-up by measuring carbon monoxide levels. Readings exceeding 10 ppm were defined as indicating current smoking. Results Over half (56.5%) of the participants had ever used heroin while 37.7% regularly (daily or almost daily) used heroin in the year prior to entering prison. Prisoners who regularly used heroin had significantly worse social determinants of health and smoking behaviours, including lower educational attainment, more frequent incarceration and earlier initiation into smoking. Prisoners who regularly used heroin also used and injected other drugs significantly more frequently. At 12-month follow-up, the smoking cessation of prisoners who had regularly used heroin was also significantly lower than prisoners who did not regularly use heroin, a finding confirmed by logistic regression. Conclusions Regular heroin use prior to imprisonment is an important risk factor for unsuccessful attempts to quit smoking among prisoners and is also associated with worse social determinants of health, higher drug use, and worse smoking behaviours. More effective and earlier smoking cessation interventions are required for particularly disadvantaged groups. Trial registration This trial is registered with the Australian New Zealand Clinical Trials Registry 12606000229572.
This article reviews the unique pharmacological properties of methadone and outlines its appropriate clinical application, with focus upon its use in the treatment of chronic pain. Although methadone is most widely known for its use in the treatment of opioid dependence, methadone also provides effective analgesia. Patients who experience inadequate pain relief or intolerable side effects with other opioids or who suffer from neuropathic pain may benefit from a transition to methadone as their analgesic agent. Adverse effects, particularly respiratory depression and death, make a fundamental knowledge of methadone's pharmacological properties essential to the provider considering methadone as analgesic therapy for a patient with chronic pain.
Brown, R; Kraus, C; Fleming, M; Reddy, S
BACKGROUND It is suspected that there is a continuum of impairment among prenatally drug-exposed infants, such that opioid and/or poly-drug exposure confers the highest risk for adverse neonatal outcomes than other classes of substances or single substance exposures. Suitable control groups are difficult to identify. This study compared fetal neurobehavioral development and infant outcomes in offspring of three groups of pregnant women in drug treatment. Exposure groups include: Methadone + other illicit substances (MM+Poly) and two groups currently abstinent for poly drug exposures: Methadone only (MM/A) and Non-methadone (NM/A). METHODS Forty-nine women (19 MM+Poly, 18 MM/A, and 12 NM/A) underwent fetal monitoring at 36 weeks gestation at peak and trough levels of methadone (MM+Poly; MM/A) or at comparable morning and afternoon times (NM/A). Fetal heart rate (FHR), heart rate variability (FHRV) and motor activity (FM) data were collected. Infant measures included birth outcomes and Neonatal Abstinence Syndrome (NAS) assessment. RESULTS As compared to the NM/A group, cardiac measures were decreased in methadone-exposed fetuses at peak levels. FHR was significantly more suppressed in the MM+Poly group. FM was significantly lower in the MM/A versus the NM/A group at both peak and trough, indicative of more persistent exposure effects. The MM+Poly group delivered one week earlier and required NAS pharmacological treatment twice as often as the MM/A group. CONCLUSIONS Results support the notion that poly-drug exposure may potentiate the effects of methadone on the fetus and infant and highlights the need for intensified treatment for methadone-maintained women who abuse other substances.
Jansson, L.M.; Di Pietro, J.A.; Elko, A.; Williams, E.L.; Milio, L.; Velez, M.
Increasingly invertebrates are being used to investigate the molecular and cellular effects of drugs of abuse to explore basic mechanisms of addiction. However, in mammals the principle factors contributing to addiction are long-term adaptive responses to repeated drug use. Here we examined whether adaptive responses to cocaine are also seen in invertebrates using the honey bee model system. Repeated topical treatment with a low dose of cocaine rendered bees resistant to the deleterious motor effects of a higher cocaine dose, indicating the development of physiological tolerance to cocaine in bees. Cocaine inhibits biogenic amine reuptake transporters, but neither acute nor repeated cocaine treatments caused measurable changes in levels of biogenic amines measured in whole bee brains. Our data show clear short and long-term behavioural responses of bees to cocaine administration, but caution that, despite the small size of the bee brain, measures of biogenic amines conducted at the whole-brain level may not reveal neurochemical effects of the drug. PMID:23741423
Søvik, Eirik; Cornish, Jennifer L; Barron, Andrew B
Increasingly invertebrates are being used to investigate the molecular and cellular effects of drugs of abuse to explore basic mechanisms of addiction. However, in mammals the principle factors contributing to addiction are long-term adaptive responses to repeated drug use. Here we examined whether adaptive responses to cocaine are also seen in invertebrates using the honey bee model system. Repeated topical treatment with a low dose of cocaine rendered bees resistant to the deleterious motor effects of a higher cocaine dose, indicating the development of physiological tolerance to cocaine in bees. Cocaine inhibits biogenic amine reuptake transporters, but neither acute nor repeated cocaine treatments caused measurable changes in levels of biogenic amines measured in whole bee brains. Our data show clear short and long-term behavioural responses of bees to cocaine administration, but caution that, despite the small size of the bee brain, measures of biogenic amines conducted at the whole-brain level may not reveal neurochemical effects of the drug.
S?vik, Eirik; Cornish, Jennifer L.; Barron, Andrew B.
The diffusion-weighted (DW) magnetic resonance (MR) imaging findings of a patient with subacute stage of heroin-induced vacuolating myelinopathy are re- ported. The diffuse decrease of apparent diffusion coefficient (ADC) of the white matter on DW imaging is attributed to restricted water diffusion, which is known to be caused by fluid entrapment within the myelin lamellae without demyelination. Index Terms: Heroin
Cheng-Yu Chen; Kwo-Wei Lee; Chueng-Chen Lee; Shy-Chi Chin; Hsiao-Wen Chung; Robert A. Zimmerman
Cocaine-induced leukoencephalopathy is a rare neurological complication. It is most likely related to the substances used to adulterate the cocaine. Levamisole is one of the most common adulterants of cocaine and causes reversible leukoencephalopathy. Patients display severe neurological symptoms that resolve at termination of the exposure. MRI shows diffuse white matter involvement with sparing of the U fibers, without brain stem or cerebellar involvement. We describe the case of a woman with three neurologic episodes and remitting and recurrent brain white matter lesions. PMID:24199810
González-Duarte, Alejandra; Williams, Ricardo
Cocaine use has increased considerably during the last twenty years and several related complications can be identified. Clinical features of cocaine intoxication are variable, but predominantly involve cardiovascular events. Chest pain is the most main complaint; myocardial ischemia must be ruled out. Other cardiovascular manifestations are left ventricular dysfunction, arrhythmia, endocarditis and aortic dissection. Non-cardiac complications include neurological (seizures, stroke, cerebral hemorrhage), respiratory (asthma, interstitial pneumonitis, pulmonary edema), renal (acute renal failure, rhabdomyolysis) and obstetrical disorders. Detection of cocaine in the urine provides the diagnosis. Symptomatic treatment is generally given, combining conventional treatment of the complication and broad use of benzodiazepines. PMID:12218880
Guerot, Emmanuel; Sanchez, Olivier; Diehl, Jean-Luc; Fagon, Jean-Yves
AimTo examine the frequency and severity of low bone mineral density (BMD) among patients enrolled in a methadone maintenance treatment (MMT) program and to ascertain risk factors for low BMD in this population.
Theresa W. Kim; Daniel P. Alford; Alan Malabanan; Michael F. Holick; Jeffrey H. Samet
Opiate abuse has been postulated to be a cofactor in the immunopathogenesis of acquired immunodeficiency syndrome (AIDS). This study evaluated whether methadone, a drug widely prescribed for the treatment of drug abusers with opioid dependence, affects human immunodeficiency virus (HIV) infection of human immune cells. When added to human fetal microglia and blood monocyte–derived macrophage cultures, methadone significantly enhanced HIV infection of these cells. This enhancement was associated with the up-regulation of expression of CCR5, a primary coreceptor for macrophage-tropic HIV entry into macrophages. Most importantly, the addition of methadone to the cultures of latently infected peripheral blood mononuclear cells from HIV-infected patients enhanced viral activation and replication. Although the in vivo relevance of these findings remains to be determined, the data underscore the necessity of further studies to define the role of opioids, including methadone, in the immunopathogenesis of HIV infection and AIDS.
Li, Yuan; Wang, Xu; Tian, Sha; Guo, Chang-Jiang; Douglas, Steven D.; Ho, Wen-Zhe
This review examines existing cognitive experimental and brain imaging research related to cocaine addiction. In section 1, previous studies that have examined cognitive processes, such as implicit and explicit memory processes in cocaine users are reported. Next, in section 2, brain imaging studies are reported that have used chronic users of cocaine as study participants. In section 3, several conclusions are drawn. They are: (a) in cognitive experimental literature, no study has examined both implicit and explicit memory processes involving cocaine related visual information in the same cocaine user, (b) neural mechanisms underlying implicit and explicit memory processes for cocaine-related visual cues have not been directly investigated in cocaine users in the imaging literature, and (c) none of the previous imaging studies has examined connectivity between the memory system and craving system in the brain of chronic users of cocaine. Finally, future directions in the field of cocaine addiction are suggested.
Background Methadone maintenance treatment is the most widely prescribed treatment for opiate dependence with proven benefits for patients. In naïve users or in case of recreational misuse, methadone can be a source of potentially lethal intoxications, resulting in fatal overdoses. A few cases of infantile intoxications have been described in the literature, some of which resulted in death. Nowadays, more than 50,000 bottles are used every day in France, most of which are thrown away in the bin. Relatives at home, especially children, can have access to these empty bottles. This study aims to determine whether the residual quantity of methadone in the bottles is associated with a risk of intoxication for someone who has a low tolerance to opiates, such as a child. Methods The methadone dosage left in a sample of 175 bottles recapped after use by the patients taking their maintenance treatment in an addiction treatment program centre was analysed during a 2-week period in March 2013. Results The mean residual quantity of methadone left in each bottle after use is 1.9?±?1.8 mg and 3.3?±?2.4 mg in the sample of 60 mg bottles. Conclusions There is a potential danger of accidental overdose with empty bottles of methadone syrup, especially for children. To take into account this hazard, several harm reduction strategies can be proposed, such as favouring the taking of the treatment within the delivery centres rather than the ‘take home’ doses, asking methadone users to bring back their used bottles, and raising patients’ awareness of the intoxication risks and the necessary everyday precautions. For stable patients with take home methadone, the use of capsules could be considered.
Objectives To estimate the cost of providing methadone maintenance treatment in Ontario, Canada, from the perspective of the public payer. Methods We analyzed a database of all patient clinic visits, laboratory tests for urine toxicology screening, and methadone scripts from a group of methadone clinics in Ontario. The database consisted of patient visits and visit information from January 1, 2003 to December 31, 2009. We estimated the cost of providing methadone maintenance treatment as the sum of physician costs, laboratory costs for urine samples (toxicology screens), methadone costs and pharmacy costs. Pharmacy costs include dispensing fees and markups. All costs are expressed in 2010 CAD. Results The database consisted of 9479 unique patients. The average age on the date of the first recorded visit was 34.3 and 62.3% were male. There were 6,425,937 patient-days of treatment and the total cost of all treatment-related services was approximately $99,491,000. The total cost was comprised of physician billing (9.8%), pharmacy costs (39.8%), methadone (3.8%), and performing urine toxicology screens (46.7%). The average cost per day in treatment was $15.48, corresponding to $5651 per year if patients were to remain in treatment continuously. Conclusions The cost of providing methadone maintenance treatment in Ontario is comparable to estimates from the United States and Australia. Scientific Significance This information is important to policy makers for planning and budgeting purposes and as part of a full cost-benefit or cost-effectiveness analysis of methadone treatment.
Zaric, Gregory S.; Brennan, Andrew W.; Varenbut, Michael; Daiter, Jeff M.
The medical outcome of heroin body stuffers has rarely been described. This study was performed to illustrate the clinical course of heroin body stuffers. A retrospective chart analysis was performed on all cases of heroin body stuffers received by a metropolitan poison control center from 2000–2004. We identified 65 heroin body stuffers. Sixty-nine percent were men with a mean age
Matthew T. Jordan; Sean M. Bryant; Steven E. Aks; Michael Wahl
Illicit heroin is rarely pure and may contain a number of other substances. The total particle size distribution in six illicit heroin preparations was analysed using a Malvern 2600 Particle Analyser and by sieving. The pattern of heroin distribution amongst these particles was determined by HPLC. The results show that a representative illicit heroin particle is approximately 45 ?m in
Assessed personality differences among Black, White, and Hispanic-American heroin addicts (N=423). Results confirmed the hypotheses that minority group heroin addicts (Blacks and Hispanics) would show better adjustment than White heroin addicts and that Hispanic-American heroin addicts would evidence personality characteristics unlike those of…
Dolan, M. P.; And Others
The availability of Southwest Asian heroin has and will continue to make moderate inroads in U.S. heroin markets; however, it is unlikely in the near term that Southwest Asian heroin will challenge or surpass South American heroin as the primary type of w...
Cocaine, including crack cocaine, was responsible for 12.8 percent of admissions to substance abuse treatment services in 2002.1 The National Survey on Drug Use and Health (NSDUH) asks persons aged 12 or older to report their use of illicit drugs, including cocaine. NSDUH defines cocaine use as use of cocaine in any form, including crack cocaine.…
Substance Abuse and Mental Health Services Administration, 2005
Individuals with current cocaine use disorders (CUD) form a heterogeneous group, making sensitive neuropsychological (NP) comparisons with healthy individuals difficult. The current study examined the effects on NP functioning of four factors that commonly vary among CUD: urine status for cocaine (positive vs negative on study day), cigarette smoking, alcohol consumption, and dysphoria. Sixty-four cocaine abusers were matched to healthy comparison subjects on gender and race; the groups also did not differ in measures of general intellectual functioning. All subjects were administered an extensive NP battery measuring attention, executive function, memory, facial and emotion recognition, and motor function. Compared with healthy control subjects, CUD exhibited performance deficits on tasks of attention, executive function, and verbal memory (within one standard deviation of controls). Although CUD with positive urine status, who had higher frequency and more recent cocaine use, reported greater symptoms of dysphoria, these cognitive deficits were most pronounced in the CUD with negative urine status. Cigarette smoking, frequency of alcohol consumption, and dysphoria did not alter these results. The current findings replicate a previously reported statistically significant, but relatively mild NP impairment in CUD as compared with matched healthy control individuals and further suggest that frequent/recent cocaine may mask underlying cognitive (but not mood) disturbances. These results call for development of pharmacological agents targeted to enhance cognition, without negatively impacting mood in individuals addicted to cocaine.
Woicik, Patricia A; Moeller, Scott J; Alia-Klein, Nelly; Maloney, Thomas; Lukasik, Tanya M; Yeliosof, Olga; Wang, Gene-Jack; Volkow, Nora D; Goldstein, Rita Z
Among agents for treatment of opioid addiction, methadone is a full mu-opioid receptor agonist, whereas buprenorphine is a partial agonist. Both are long-acting. Buprenorphine has a superior safety profile. Methadone is formulated for oral administration and buprenorphine for sublingual administration. A subdermal buprenorphine implant with a 6-month duration of action is being considered for approval by the U.S. Food and Drug Administration. Both medications reduce mortality rates and improve other outcomes. Data from a recent randomized controlled comparison of both medications (N = 1269) show better treatment retention with methadone but reduced illicit opioid use early in treatment with buprenorphine. Human immunodeficiency virus (HIV) risk behaviors were measured using the Risk Behavior Survey at baseline, 12 weeks, and 24 weeks for study completers. In the 30 days prior to treatment entry, 14.4% of the completers randomized to treatment with buprenorphine (n = 340) and 14.1% of the completers randomized to methadone treatment (n = 391) shared needles. The percent sharing needles decreased to 2.4% for buprenorphine and 4.8 for methadone in the 30 days prior to Week 24 (p < 0.0001). In the 30 days prior to treatment entry, 6.8% of the completers randomized to buprenorphine and 8.2% of the completers randomized to methadone had multiple sexual partners, with only 5.2% and 5.1%, respectively, reporting multiple partners at Week 24 (p < 0.04).
Saxon, Andrew J.; Hser, Yih-Ing; Woody, George; Ling, Walter
Abuse of prescription opioid medications has increased dramatically in the U.S. during the past decade, as indicated by a variety of epidemiological sources. However, few studies have systematically examined the relative reinforcing effects of commonly abused opioid medications. The current double-blind, placebo-controlled inpatient study was designed to compare the effects of intravenously delivered fentanyl (0, 0.0625, 0.125, 0.187, and 0.250 mg/70 kg), oxycodone (0, 6.25, 12.5, 25, and 50 mg/70 kg), morphine (0, 6.25, 12.5, 25, and 50 mg/70 kg), buprenorphine (0, 0.125, 0.5, 2, and 8 mg/70 kg), and heroin (0, 3.125, 6.25, 12.5, and 25 mg/70 kg) in morphine-maintained heroin abusers (N=8 completers maintained on 120 mg per day oral morphine in divided doses [30 mg q.i.d.]). All of the participants received all of the drugs tested; drugs and doses were administered in non-systematic order. All of the drugs produced statistically significant, dose-related increases in positive subjective ratings, such as “I feel a good drug effect” and “I like the drug.” In general, the order of potency in producing these effects, from most to least potent, was: fentanyl > buprenorphine ? heroin > morphine = oxycodone. In contrast, buprenorphine was the only drug that produced statistically significant increases in ratings of “I feel a bad drug effect” and it was the only drug that was not self-administered above placebo levels at any dose tested. These data suggest that the abuse liability of buprenorphine in heroin-dependent individuals may be low, despite the fact that it produces increases in positive subjective ratings. The abuse liabilities of fentanyl, morphine, oxycodone, and heroin, however, appear to be similar under these experimental conditions.
Comer, Sandra D; Sullivan, Maria A; Whittington, Robert A; Vosburg, Suzanne K; Kowalczyk, William J
Cocaine and its alkaloid free base “crack-cocaine” have long since been substances of abuse. Drug abuse of cocaine via oral, inhalation, intravenous, and intranasal intake has famously been associated with a number of medical complications. Intestinal ischemia and perforation remain the most common manifestations of cocaine associated gastrointestinal disease and have historically been associated with oral intake of cocaine. Here we find a rare case of two relatively uncommon gastrointestinal complications of hemorrhage and pancreatitis presenting within a single admission in a chronic crack cocaine abuser.
Carlin, Neal; Nguyen, Nhat; DePasquale, Joseph R.
Cocaine and its alkaloid free base "crack-cocaine" have long since been substances of abuse. Drug abuse of cocaine via oral, inhalation, intravenous, and intranasal intake has famously been associated with a number of medical complications. Intestinal ischemia and perforation remain the most common manifestations of cocaine associated gastrointestinal disease and have historically been associated with oral intake of cocaine. Here we find a rare case of two relatively uncommon gastrointestinal complications of hemorrhage and pancreatitis presenting within a single admission in a chronic crack cocaine abuser. PMID:24839446
Carlin, Neal; Nguyen, Nhat; DePasquale, Joseph R
Synopsis Cocaine dependence continues to be a significant public health problem and no clearly effective pharmacotherapy has yet been identified. Substitution pharmacotherapy is an effective approach for treating opioid and nicotine dependence, and accumulating evidence indicates that stimulant pharmacotherapy for cocaine dependence is a promising strategy. Broadly, stimulant medications that produce behavioral arousal, and medications across several therapeutic classes can be considered psychostimulants. To date, the available evidence is strongest for amphetamine analogs or dopaminergic agents combined with contingency management behavioral interventions as potential psychostimulant treatments for cocaine dependence. Most psychostimulants are controlled substances with inherent risks of misuse and diversion, and their use in patients with active substance use disorders is complex. As stimulant substitution treatment models for cocaine dependence are developed, particular attention to patient risk stratification is needed.
Mariani, John J.; Levin, Frances R.
In separate experiments, rats received either five intraperitoneal or five subcutaneous injections of cocaine (once daily or spaced every fourth day) prior to receiving repeated saccharin–cocaine pairings (during taste aversion conditioning). Both spaced and massed subcutaneous cocaine preexposure attenuated the subsequent acquisition of taste aversions induced by cocaine. Specifically, aversions in the preexposed subjects were acquired at a slower rate
Anthony L. Riley; Hilary F. Diamond
Background Previous research with non-drug reinforcers has shown that simultaneously presenting (compounding) an extinguished cue with another cue formerly associated with the same reinforcer can increase rates of cue-controlled behavior. The present study investigated whether an extinguished cocaine cue would energize cocaine seeking when presented simultaneously with another cocaine cue. This study also investigated whether extinction could be enhanced by subjecting an extinguished cocaine cue to further extinction after administration of reinstating injections of cocaine. Methods Rats were first trained to self-administer cocaine in the presence of three different cues. Then, one of the cues was subjected to the standard extinction treatment. Another cue was subjected to a modified extinction treatment where additional extinction sessions were preceded by non-contingent cocaine injections. The third cue was not extinguished. Results The cue subjected to standard extinction ceased to control cocaine seeking when presented alone, but significantly increased cocaine seeking when compounded with the non-extinguished cocaine cue. The cocaine cue subjected to the modified extinction treatment also significantly increased cocaine seeking occasioned by the non-extinguished cocaine cue. Conclusions Extending results of previous studies involving non-drug stimuli, the present study showed that extinguished cocaine cues can enhance cocaine seeking when compounded with other cocaine cues. These results illustrate the persistence of drug cues in controlling behavior despite extinction and highlight the need for developing treatments that eliminate this residual energizing capacity that survives extinction.
Kearns, David N.; Weiss, Stanley J.
This manuscript provides an overview of the current scientific literature on the impact of maternal drug use, specifically opioids and cocaine, during pregnancy on the acute and long-term outcomes of infants and toddlers from birth through age 3 years. Emphasis with regard to opioids is placed on heroin and opioid substitutes used to treat opioid addiction, including methadone, which has
Emmalee S. Bandstra; Connie E. Morrow; Elana Mansoor; Veronica H. Accornero
Although many studies have shown that cognitive effect expectancies are associated with drug use and drug treatment outcomes, few studies have compared effect expectancies with drug response following drug challenge. Healthy male and female volunteers (n=19, ages 21–35) who reported using cocaine 1–4 times per month completed the Cocaine Effect Expectancy Questionnaire (CEEQ: [Schafer, J. and Brown, S.A. (1991). Marijuana
Leslie H. Lundahl; Scott E. Lukas
This article discusses the predicament of historians becoming part of the history they are investigating and illustrates the issue in a particular case. The case is that of the randomized controlled trial (RCT)-more specifically, its use for testing the effects of providing heroin to severe heroin abusers. I counter the established view of the RCT as a matter of timeless logic and argue that this research design was developed in the context of administrative knowledge making under twentieth-century economic liberalism of which it epitomizes some central values. I also argue that the applicability of the RCT depends on the degree to which its advocates can define the issue to be studied according to its inherent values. Next, I demonstrate how advocates of an RCT with heroin provision in the Netherlands steered the political discussion on heroin provision and how the values of economic liberalism also shaped the results of the Dutch maintenance experiment. In addition, I relate how my analysis of this experiment became part of political debates in the Netherlands. Contrary to my intentions, adversaries of heroin maintenance used my critique on the heroin RCT as an argument against heroin maintenance. Such risks are inherent to historiography and sociology of science aiming at practical relevance while challenging treasured scientific beliefs. I conclude that it still seems better to expose arguments on unjustified certainties than to suppress them for strategic reasons. PMID:15237417
Peer-delivered HIV prevention and intervention programs play an important role in halting the spread of HIV. Rigorous scientific analysis of the forementioned programs have focused on the immediate reduction of risk-related behaviors among the target populations. In our longitudinal study of the RAP Peer Intervention for HIV, we assessed the long-term behavioral effects of a peer-led HIV intervention project with active drug users. Initial analysis of the qualitative data highlights the role of altruism as a motivator in sustaining peer educators beyond the immediate goals of the project. We contend that altruism found in volunteers is an important factor in maintaining long-term participation in HIV intervention programs and initiatives using peer educators.
Convey, Mark R.; Dickson-Gomez, Julia; Weeks, Margaret R.; Li, Jianghong
Studies in humans suggest that exposure to stress increases the probability of relapse to drug use, but until recently there has been no animal model to study the mechanisms that mediate this effect. We have developed a reinstatement procedure that allows us to study the effect of stress on relapse to drug seeking in rats. Using this procedure, we have
Yavin Shaham; Suzanne Erb; Jane Stewart
Background Ongoing drug use during methadone maintenance treatment (MMT) negatively affects outcomes of HIV/AIDS care and treatment for drug users. This study assessed changes in opioid use, and longitudinal predictors of continued opioid use during MMT among HIV-positive drug users in Vietnam, with the aim of identifying changes that might enhance program efficacy. Methods We analyze data of 370 HIV-positive drug users (mean age 29.5; 95.7% male) taking MMT at multi-sites. Opioid use was assessed at baseline, 3, 6, and 9 months using interviews and heroin confirmatory urine tests. A social ecological model was applied to explore multilevel predictors of continued opioid use, including individual, interpersonal, community and service influences. Generalized estimating equations (GEE) statistical models were constructed to adjust for intra-individual correlations. Results Over 9 month follow-up, self-reported opioid use and positive heroin urine test substantially decreased to 14.6% and 14.4%. MMT helped improve referrals and access to health care and social services. However, utilization of social integration services was small. GEE models determined that participants who were older (Adjusted Odd Ratio - AOR?=?0.97 for 1 year increase), had economic dependents (AOR?=?0.33), or were referred to TB treatment (AOR?=?0.53) were less likely to continue opioid use. Significant positive predictors of ongoing opioid use included frequency of opioid use prior to MMT, peer pressure, living with sexual partners, taking antiretroviral treatment, other health concerns and TB treatment. Conclusion These findings show that MMT in the Vietnamese context can dramatically reduce opioid use, which is known to be associated with reduced antiretroviral (ART) adherence. Disease stage and drug interactions between antiretrovirals or TB drugs and MMT could explain some of the observed predictors of ongoing drug use; these findings could inform changes in MMT program design and implementation.
Tran, Bach Xuan; Ohinmaa, Arto; Mills, Steve; Duong, Anh Thuy; Nguyen, Long Thanh; Jacobs, Philip; Houston, Stan
The study provides conclusive evidence on existence of economic barriers, namely money price and time price, to regular treatment attendance for methadone maintenance clients. The study is designed to develop improved time price measures and investigate their effect on treatment attendance. Regular attendance is essential for methadone maintenance because, form client's perspective, it may affect treatment outcomes and, from methadone
Natalia N Borisova
Prescription drug abuse is a growing public health problem. In particular, methadone-associated overdose deaths--those in which methadone may have caused or contributed to the death--have risen sharply. Before the late 1990s, methadone was used mainly to ...
Contents: The Medications Development Program: A New Initiative of the National Institute on Drug Abuse; Cocaine-Related Medical Crises: Evidence From the Drug Abuse Warning Network; Preclinical Assessment of Cocaine Toxicity: Mechanisms and Pharmacothera...
Background The treatment of opioid dependence disorder is one of the major problems in medical centers around the world. Although MMT has been the major treatment in last few years in Iran, the existence of relapse before and after detoxification is still high. Methadone treatment has had a very low percentage of complete success. Objectives To evaluate the effectiveness of matrix group interventions in improving methadone treatment in the addicted was the main goal of this research. Materials and Methods In a semi - experimental design, 24 male patients on the qualification cutoff score for the questionnaire survey (score less than 19 in depression test, and less than 21 in anxiety test) and the diagnosis of opioid dependence according to (DSM – IV) were substituted in two experimental and control groups randomly. At the beginning of the study, after the treatment period and in the follow-up phase (three months after the end of treatment), participants were evaluated by Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI) and the Anger Questionnaire (AQ), control group with no psychological treatment only took methadone. Data were analyzed using covariance analysis, chi square and Repeated Measures Analysis of Variance. Results Results showed that the effect of matrix group interventions on reducing relapse (P < 0.05), increasing the maintenance of treatment (P < 0.01), increasing the treatment compliance, reducing anger, anxiety and depression and methadone dose is more effective than methadone treatment (P < 0.05). Conclusions It seems matrix group interventions increase the effectiveness of methadone treatment by reducing the relapse prevention, the dose of methadone and remaining in treatment.
Eghbali, Hossein; Zare, Mahdi; Bakhtiari, Arva; Monirpoor, Nader; Ganjali, Alireza
Objectives - The aim of this study is to evaluate the costs and consequences of the provision of the prison methadone program in NSW, compared with no prison methadone. Methods - This study has measured the costs involved in the provision of the prison methadone program in NSW. The overall cost of the prison methadone program was estimated from a
Emma Warren; Rosalie Viney
Methodological issues related to the self-administration of cocaine and the effect of the magnitude of alternative reinforcers on cocaine self-administration were examined. Hospitalized male cocaine abusers (N = 12) were involved in an inpatient study in which the between-subjects variable was the monetary value of the alternative reinforcer, and the within-subject variable was 3 dose sizes of cocaine. Ss could
Dorothy K. Hatsukami; Timothy N. Thompson; Paul R. Pentel; Brian K. Flygare; Marilyn E. Carroll
The increasing popularity of inhaling cocaine vapor prompted the present study, to determine cocaine's fate during this process. The free base of (3H)cocaine (1 microCi/50 mg) was added to a glass pipe, which was then heated in a furnace to simulate freebasing. Negative pressure was used to draw the vapor through a series of glass wool, ethanol, acidic, and basic traps. Air flow rate and temperature were found to have profound effects on the volatilization and pyrolysis of cocaine. At a temperature of 260 degrees C and a flow rate of 400 mL/min, 37% of the radioactivity remained in the pipe, 39% was found in the glass wool trap, and less than 1% in the remainder of the volatilization apparatus after a 10-min volatilization. Reducing the air flow rate to 100 mL/min reduced the amount of radioactivity collected in the glass wool trap to less than 10% of the starting material and increased the amount that remained in the pipe to 58%. GC/MS analysis of the contents of the glass wool trap after volatilization at 260 degrees C and a flow rate of 400 mL/min revealed that 60% of the cocaine remained intact, while approximately 6 and 2% of the starting material was recovered as benzoic acid and methylecgonidine, respectively. As the temperature was increased to 650 degrees C, benzoic acid and methylecgonidine accounted for 83 and 89% of the starting material, respectively, whereas only 2% of the cocaine remained intact. Quantitation of cocaine in the vapor during the course of volatilization revealed high concentrations during the first two min and low concentrations for the remaining time.
Martin, B.R.; Lue, L.P.; Boni, J.P. (Virginia Commonwealth Univ., Richmond (USA))
The conversion of levamisole to aminorex in horses was first described in 2009 and, for the first time, confirmed in humans two years later by our laboratory. Aminorex and levamisole interfere with serotonin metabolism and both are proven cause of potentially fatal idiopathic pulmonary hypertension (IPH). Because most of the world's seizures of illicit cocaine is now contaminated with levamisole, this raises the possibility that users of levamisole adulterated cocaine users may be at risk for IPH. Here we describe the first case of IPH in a user of levamisole-contaminated cocaine. Levamisole and aminorex were both identified and quantified in hair and other biological specimens by means gas chromatography/mass spectrometry system (levamisole: urine, 75.05ng/mL; blood, 15.05ng/mL; brain, >0.15ng/g; liver, >0.15ng/g; hair, 12.15ngmg; aminorex: urine, 38.62ng/mL; blood, 8.92ng/mL, brain >0.15ng/g; liver, 0.15ng/g; hair 7.35ng/mg; cocaine, benzoylecgonine, morphine, 6-acetylmorphine, methadone, 2-ethylidine-1, 5-dimetil-3, 3 diphenylpyrrolidine were also detected). Moreover histological changes associated with IPH were observed in the lung. As IPH produces relatively non-specific symptoms in its early stages, this index case may serve as a harbinger of many more cases to come. It should also alert clinicians to the possibility that their patient may be suffering from this relatively rare disorder. PMID:24794740
Karch, Steven B; Defraia, Beatrice; Messerini, Luca; Mari, Francesco; Vaiano, Fabio; Bertol, Elisabetta
This study examined the effects of prenatal cocaine exposure on infant hypothalamic-pituitary-adrenal axis activity and reactivity at 7 months of infant age. Participants were 168 caregiver-infant dyads (87 cocaine exposed, 81 not cocaine exposed; 47% boys). Maternal behavior, caregiving instability, and infant growth and behavior were assessed,…
Eiden, Rina D.; Veira, Yvette; Granger, Douglas A.
In experimental models, prenatal cocaine exposure has been found to perturb monoaminergic development of systems implicated in modulating attention. To determine whether prenatal cocaine exposure affects infant attention, we assessed visual recognition memory and focused attention during free play. We enrolled at birth 380 infants, 113 cocaine exposed, using multiple biomarkers to assess drug exposure. Behavior was videotaped and coded
Claudia A. Chiriboga; Denise Starr; Louise Kuhn; Gail A. Wasserman
The pathophysiology of the effects of cocaine on fetal development has been described along 2 major pathways: neurochemical effects and vasoconstrictive effects. Following a summary of these effects, we suggest a ‘third pathophysiology’ in which altered fetal programming affects the acute and long-term adverse effects of in utero cocaine exposure. We describe how cocaine as a stressor alters the expression
Barry M. Lester; James F. Padbury
Novel synthetic compounds similar to heroin and its major active metabolites, 6-acetylmorphine and morphine, were examined as potential surrogate haptens for the ability to interface with the immune system for a heroin vaccine. Recent studies have suggested that heroin-like haptens must degrade hydrolytically to induce independent immune responses both to heroin and to the metabolites, resulting in antisera containing mixtures of antibodies (type 2 cross-reactivity). To test this concept, two unique hydrolytically stable haptens were created based on presumed structural facial similarities to heroin or to its active metabolites. After conjugation of a heroin-like hapten (DiAmHap) to tetanus toxoid and mixing with liposomes containing monophosphoryl lipid A, high titers of antibodies after two injections in mice had complementary binding sites that exhibited strong type 1 (“true”) specific cross-reactivity with heroin and with both of its physiologically active metabolites. Mice immunized with each surrogate hapten exhibited reduced antinociceptive effects caused by injection of heroin. This approach obviates the need to create hydrolytically unstable synthetic heroin-like compounds to induce independent immune responses to heroin and its active metabolites for vaccine development. Facial recognition of hydrolytically stable surrogate haptens by antibodies together with type 1 cross-reactivities with heroin and its metabolites can help to guide synthetic chemical strategies for efficient development of a heroin vaccine.
Matyas, Gary R.; Rice, Kenner C.; Cheng, Kejun; Li, Fuying; Antoline, Joshua F. G.; Iyer, Malliga R.; Jacobson, Arthur E.; Mayorov, Alexander V.; Beck, Zoltan; Torres, Oscar; Alving, Carl R.
Methods:\\u000a \\u000a Twenty-two patients receiving (R)-methadone maintenance treatment were switched to a double dose of (R,?S)-methadone: blood\\u000a samples were collected before and after the change, and the concentrations of the enantiomers were measured. In the second\\u000a period, during racemic methadone treatment, important interindividual variability in the stereoselective disposition of the\\u000a enantiomers of methadone was measured, with (R)\\/(S) ratios ranging from 0.63
C. B. Eap; T. Finkbeiner; M. Gastpar; N. Scherbaum; K. Powell; P. Baumann
Methadone has been the most commonly used pharmacotherapy for the treatment of opioid dependence in U.S. public sector treatment, but availability of buprenorphine as an alternative medication continues to increase. Drawing data from two community-based clinical trials that were conducted nearly contemporaneously, this study examined retention in methadone versus buprenorphine treatment over 6 months among urban African Americans receiving treatment in one of four publicly-funded programs (N=478; 178 methadone; 300 buprenorphine). Adjusting for confounds related to medication selection, survival analysis revealed that buprenorphine patients are at substantially higher risk of dropout compared to methadone patients (HR=2.43; p<.001). Buprenorphine's retention disadvantage appears to be concentrated in the earlier phases of treatment (approximately the first 50 days), after which risk of subsequent dropout becomes similar for the two medications. These findings confirm a retention disparity between methadone and buprenorphine in this population, and suggest potential avenues for future research to enhance retention in buprenorphine treatment. PMID:23566446
Gryczynski, Jan; Mitchell, Shannon Gwin; Jaffe, Jerome H; Kelly, Sharon M; Myers, C Patrick; O'Grady, Kevin E; Olsen, Yngvild K; Schwartz, Robert P
We studied stability of sense of coherence (SOC) over time and in relation to the outcomes of former heroin addicts in MMT. Between September of 2003 and April of 2006, all 90 newly admitted patients to a MMT clinic in Tel Aviv were studied and followed up for one year. A SOC (inner resources) questionnaire was done at baseline and after one year. Use of opiates, cocaine, benzodiazepines, cannabis and amphetamines in the 13 months after admission was recorded, and defined as positive if at least one urine test for any drug was positive. After one year, 77 (85.6%) stayed in treatment. SOC scores were similar at baseline and after one year, but were lower among 42 patients who still abused any drugs (118.8 + 27.4), compared with the 35 patients who did not (128.5 + 26.5, Repeated measures, Groups p = 0.003, Time effect p = 0.5, Time*Group p = 0.003). Cumulative retention revealed that 30 patients with SOC scores greater than 130 had longer retention (3.5 years, 95% CI 3.2-3.9) as compared with 60 patients with SOC scores of 130 or less (2.9 years, 95% CI 2.5-3.3). SOC is a stable parameter that can serve as a predictor for success in MMT, both as retention in treatment and drug abstinence. PMID:19999678
Abramsohn, Yali; Peles, Einat; Potik, David; Schreiber, Shaul; Adelson, Miriam
A 33-year-old man presented to our clinic with amnesia 48 hours after his first heroin inhalation. Examination showed lateral tongue biting and anterograde amnesia demonstrated by impaired performance on verbal and visual Wechsler Memory Scale-Revised tests carried out 10 days after onset, suggesting hippocampal involvement. Magnetic resonance imaging (MRI) of the brain was performed 48 hours after heroin snorting and evoked cortical laminar necrosis (CLN) of the left hippocampus without vascular abnormality. This is the first description of complete hippocampal CLN as a complication subsequent to acute intranasal heroine abuse. While the pathogenic mechanism remains uncertain, our case provides a very specific MRI lesion pattern and highlights the risk of intranasal heroin uptake-induced neurological complication. PMID:22624985
Benoilid, Aurélien; Collongues, Nicolas; de Seze, Jérôme; Blanc, Fréderic
Profound thrombocytopenia developed in a 22-year-old man after intravenous use of heroin. A high-titer, quinine-dependent, platelet-specific antibody was detected in his serum using lysis of normal platelets labeled with chromium 51 and an electroimmunoassay for measurement of platelet-associated IgG. The antibody was specific for quinine and failed to react with platelets in the presence of quinidine hydrochloride or two structural analogues of heroin. Quinine, a common adulterant found in heroin, was detected in the patient's blood and urine. On the basis of these observations, the patient was judged to have quinine-induced immunologic thrombocytopenia. To our knowledge, this report is the first to confirm that quinine used as an adulterant can induce immunologic thrombocytopenia following an injection of heroin.
Christie, D.J.; Walker, R.H.; Kolins, M.D.; Wilner, F.M.; Aster, R.H.
A case study is presented where a woman travelling from South America to the Republic of Ireland was detained at Dublin Airport and articles of clothing she had in her luggage were found to be impregnated with cocaine. The study shows that the amount of powder recovered from the garments was approximately 14% of the total weight of the garments. The cocaine was in the form of cocaine hydrochloride and the purity was approximately 80%. An examination of the garments under filtered light highlighted the areas exposed to cocaine and indicated that the method of impregnation was by pouring liquid containing cocaine onto the clothing. PMID:16382839
McDermott, Seán D; Power, John D
Cocaine is considered a leading cause of drug-related deaths. This is usually sudden, unwitnessed, and without prodromal features. It has been reported that in-hospital mortality is close to 2%. Cocaine has powerful central nervous system effects1 and acute cocaine overdose has been associated with hyperthermia, agitation, paranoid ideation, status epilepticus, ventricular fibrillation, ventricular tachycardia, and myocardial infarction (MI). The mechanisms of cocaine-related death remain poorly understood. We report a patient who survived massive cocaine ingestion with psychomotor agitation and generalized seizures followed by asystolic cardiac arrest and transient Brugada pattern on electrocardiogram (ECG).
Alraies, M. Chadi; Chamsi-Pasha, Mohammed A. R.; Baibars, Motaz; Alraiyes, Abdul Hamid
Heroin-associated nephropathy (HAN), a complication of intravenous heroin abuse, was initially recognized at Kings County Hospital in Brooklyn, NY, in the early 1970s. Our recent experience indicates that after a steady incidence of new cases of HAN throughout the mid-1980s, a sharp decrease in incidence of new cases occurred starting in 1989. We sought to explore possible explanations for what
Eli A. Friedman; T. K. S. Rao
This study documents the costs of heroin addiction in the United States, both to the addict and society at large. Using a cost-of-illness approach, costs were estimated in four broad areas: medical care, lost productivity, crime, and social welfare. We estimate that the cost of heroin addiction in the United States was US$21.9 billion in 1996. Of these costs, productivity
Tami L Mark; George E Woody; Tim Juday; Herbert D Kleber
A 48-year-old woman presented with a red, pruritic and painful skin rash on her legs bilaterally after she snorted cocaine. This was associated with fever and cough. Physical examination showed large violaceous plaques and large flaccid bullae, involving bilateral lower extremities. Blood work showed neutropoenia with absolute neutrophil count of 0.64×10(9) cells/L. Antinuclear antibody, perinuclear antineutrophil cytoplasmic antibody and anti-double-stranded DNA were positive. Biopsy showed thrombogenic vasculopathy which is consistent mainly with levamisole ingestion that was reported with levamisole ingestion. The patient was counselled to stop cocaine misuse and treated with skin emollients and antibiotics for the pneumonia that was discovered on the chest X-ray. Skin ulcers improved and she was discharged in stable condition. Ten days after discharge, she was readmitted with new lesions and worsening necrotic ulcers from the old lesions. The patient admitted to snorting cocaine again a few days after being discharged. PMID:23997085
Shawwa, Khaled; Alraiyes, Abdul Hamid; Eisa, Naseem; Alraies, M Chadi
In response to widespread concern about illegal drug use and the associated risk of the spread of HIV/AIDS, a study was undertaken to examine whether it was, in principle, feasible to conduct a trial providing heroin to dependent users in a controlled manner. Such a trial involves real ethical issues which are examined in this paper. The general issues examined are: should a trial be an experiment or an exercise in public policy?; acts and omissions; countermobilization; termination of a trial, and payment for drugs and for a trial. The specific issues examined are: selection of trial participants; privacy; issues for staff working on a trial; coupling the trial with other treatment, and issues for researchers. A number of alternative approaches to the various ethical issues are presented and discussed.
Ostini, R; Bammer, G; Dance, P R; Goodin, R E
The aim of this qualitative study was to examine the narratives of people who experience chronic pain (lasting 6 months or more) and were receiving methadone for the treatment of their opiate addiction through a major methadone clinic. This paper featured the pathway of how the participants developed chronic pain and addiction, and their beliefs of how prescription opioids would impact their addiction in the future. Thirty-four participants who experienced chronic pain and received methadone for treatment of opiate addiction were willing to tell the story of their experiences. The findings in three areas are presented: (a) whether participants experienced addiction first or pain first and how their exposures to addictive substances influenced their experiences, (b) the significance of recreational drug use and patterns of abuse behaviors leading to chronic pain, and (c) participants’ experiences and beliefs about the potential for abuse of prescription opioid used for treatment of pain.
St. Marie, Barbara
Background: The lethal effects of cocaine are unique among those of other illicit drugs because cocaine has the propensity to cause hyperthermia. The traditional view is that cocaine causes a hypermetabolic state with increased heat production. However, because cocaine-induced hyperthermia occurs primarily in hot weather, it is hypothesized that cocaine also impairs thermoregu- latory adjustments that mediate heat dissipation. Results:
Craig G. Crandall; Wanpen Vongpatanasin; Ronald G. Victor
The Housing First approach used by Pathways to Housing, Inc., was used to enhance residential independence and treatment retention of homeless, seriously mentally ill methadone patients. The Keeping Home project first secured scattered-site apartments and assertive community treatment services and then addressed patients' service needs. Three years post-implementation, methadone treatment retention for 31 Keeping Home patients versus 30 comparison participants (drawn from an administrative database) was 51.6% vs. 20% (p < .02); apartment/independent housing retention was 67.7% vs. 3% or 13% (both p's < .01). Although results firmly support Keeping Home, future research needs to address study's possible database limitations. PMID:22873188
Appel, Philip W; Tsemberis, Sam; Joseph, Herman; Stefancic, Ana; Lambert-Wacey, Dawn
To examine neuronal activation associated with incentive mo- tivation for cocaine, cocaine-seeking behavior (operant re- sponding without cocaine reinforcement) and Fos expression were examined in rats exposed to saline and cocaine priming injections and\\/or a self-administration environment. Rats were first trained to self-administer cocaine or received yoked saline administration (\\
Janet L. Neisewander; David A. Baker; Rita A. Fuchs; Ly T. L. Tran-Nguyen; Art Palmer; John F. Marshall
Objectives: This study aimed to compare the QTc interval between low and high dose methadone groups and evaluate the pattern of QTc variation. Methods: This is a prospective cohort study conducted from December 2010 till August 2011 at Malaysian University of Science's Hospital. Forty six subjects, grouped in high dose (>80mg) and low dose (<80mg) oral methadone, were followed-up at 4-weekly for QTc measurements. Relevant demographic and biochemical profiles were taken at intervals with concurrent QTc measurements. Results: No significant QTc differences between methadone dosage groups were found at Week 0 (434ms vs 444ms, p = 0.166) and week 8 (446.5ms vs 459ms, p = 0.076), but not at week 4(435ms vs 450ms, p = 0.029). However, there were significant associations between the groups with QTc prolongation at week 0 and 4 (OR 4.29(95% CI 1.01, 18.72) p=0.044 and OR 5.18 (95% CI 1.34, 20.06) p =0.013, respectively) but not at week 8 (OR 2.44 (95% CI 0.74, 8.01) p=0.139). On multivariate analysis, dose group was the sole significant factor for QTc prolongation for week 0 and 4 (p values 0.047 and 0.017, respectively), but not at week 8. Conclusion: High-dose methadone group is more likely to develop prolonged QTc than low-dose group. However, such effects were inconsistent and occurred even during chronic methadone therapy, mandating judicious QTc and serum methadone monitoring. PMID:24353706
Mohamad, Nasir; Abdul Jalal, Muhammad Irfan; Hassan, Azlie; Abdulkarim Ibrahim, Muslih; Salehuddin, Roslanuddin; Abu Bakar, Nor Hidayah
Objectives: This study aimed to compare the QTc interval between low and high dose methadone groups and evaluate the pattern of QTc variation. Methods: This is a prospective cohort study conducted from December 2010 till August 2011 at Malaysian University of Science’s Hospital. Forty six subjects, grouped in high dose (>80mg) and low dose (<80mg) oral methadone, were followed-up at 4-weekly for QTc measurements. Relevant demographic and biochemical profiles were taken at intervals with concurrent QTc measurements. Results: No significant QTc differences between methadone dosage groups were found at Week 0 (434ms vs 444ms, p = 0.166) and week 8 (446.5ms vs 459ms, p = 0.076), but not at week 4(435ms vs 450ms, p = 0.029). However, there were significant associations between the groups with QTc prolongation at week 0 and 4 (OR 4.29(95% CI 1.01, 18.72) p=0.044 and OR 5.18 (95% CI 1.34, 20.06) p =0.013, respectively) but not at week 8 (OR 2.44 (95% CI 0.74, 8.01) p=0.139). On multivariate analysis, dose group was the sole significant factor for QTc prolongation for week 0 and 4 (p values 0.047 and 0.017, respectively), but not at week 8. Conclusion: High-dose methadone group is more likely to develop prolonged QTc than low-dose group. However, such effects were inconsistent and occurred even during chronic methadone therapy, mandating judicious QTc and serum methadone monitoring.
Mohamad, Nasir; Abdul Jalal, Muhammad Irfan; Hassan, Azlie; Abdulkarim Ibrahim, Muslih; Salehuddin, Roslanuddin; Abu Bakar, Nor Hidayah
Background Little is known about whether the duration of cocaine use or an individual’s age may influence the acute effects of cocaine, patterns of use, and specific treatment needs. Objectives This post hoc analysis determined whether the duration of cocaine use or current age influenced the acute subjective response to cocaine. Data from four smoked cocaine self-administration laboratory studies were combined and analyzed to determine whether the subjective effects of a 25-mg smoked cocaine dose varied as a function of years of cocaine use or current age. Methods Thirty-six nontreatment-seeking healthy cocaine users (ages 32–49) were admitted to studies lasting from 12 to 105 days. Participants rated the subjective effects of each cocaine dose from 0 to 100 by completing a computerized self-report visual analogue scale (VAS). The main outcome measures were the change in VAS ratings between a baseline placebo dose and the first 25-mg dose of smoked cocaine. Results No significant relationship was found between the subjective effects of cocaine and years of cocaine use (mean 20.9, range 5–30) or current age (mean 41.1, range 32–49). Conclusion Among long-term cocaine users between the ages of 32 and 49, the acute subjective effects of cocaine did not vary as a function of years of cocaine use or current age. Scientific Significance These data fail to support the incentive sensitization theory for addiction by Robinson and Berridge, as cocaine “liking” and “wanting” remained the same regardless of age or years of cocaine use.
Kalapatapu, Raj K.; Bedi, Gillinder; Haney, Margaret; Evans, Suzette M.; Rubin, Eric; Foltin, Richard W.
This article examines the behavioral practices and health risks associated with preparing crack cocaine for injection. Using an ethno-epidemiological approach, injection drug users (n=38) were recruited between 1999 and 2000 from public settings in New York City and Bridgeport, Connecticut and responded to a semistructured interview focusing on crack injection initiation and their most recent crack injection. Study findings indicate that methods of preparing crack for injection were impacted by a transforming agent, heat applied to the “cooker,” heroin use, age of the injector, and geographic location of the injector. The findings suggest that crack injectors use a variety of methods to prepare crack, which may carry different risks for the transmission of bloodborne pathogens. In particular, crack injection may be an important factor in the current HIV epidemic.
Lankenau, Stephen E.; Clatts, Michael C.; Goldsamt, Lloyd A.; Welle, Dorinda L.
Discusses the wave of cocaine abuse that followed the drug's recommendation by the late nineteenth-century medical community as a cure all. Details drug addiction among ethnic and social groups at the turn of the century. Warns that drug epidemics have important social and legal consequences. Suggests legal pressure may alter the form of drug…
Courtwright, David T.
Studies in cocaine-dependent human subjects have shown differences in white matter on diffusion tensor imaging (DTI) compared to non-drug using controls. It is not known whether the FA differences seen on DTI in white matter regions of cocaine-dependent humans result from a pre-existing predilection for drug use or purely from cocaine abuse. To study the effect of cocaine on brain white matter, DTI was performed on 24 rats after continuous infusion of cocaine or saline for 4 weeks, followed by brain histology. Voxel-based morphometry analysis showed 18% decrease in fractional anisotropy (FA) in the splenium of corpus callosum (CC) in cocaine-administered animals relative to saline controls (P = 0.0001). On histology, significant increase in neurofilament expression (125%, P=0.0044) and decrease in myelin basic protein (40%, P = 0.031) was observed in the same region in cocaine-administered animals. This study supports the hypothesis that chronic cocaine use alters white matter integrity in human CC. Unlike humans, where the FA in the genu differed between cocaine users and non-users, the splenium was affected in rats. These differences between rodent and human findings could be due to a several factors that include differences in the brain structure and function between species and/or the dose, timing, and duration of cocaine administration.
Narayana, Ponnada A.; Ahobila-Vajjula, Pallavi; Ramu, Jaivijay; Herrera, Juan; Steinberg, Joel L.; Moeller, F. Gerard
Cocaine creates a strong physical addiction and is becoming recognized as one of the most dangerous illicit drugs abused today. The myth is that cocaine is harmless and nonaddictive. An estimated 30 million Americans have used cocaine, but the number may be as high as 40 million. Five to six million individuals are compulsive users. A review of the current literature revealed multiple reports of acute myocardial infarction and cerebrovascular accident with a temporal relation to cocaine use. Cocaine has also been associated with acute rupture of the aorta, cardiac arrhythmia, and sudden death. Cocaine has multisystem toxicity involving neurologic, psychiatric, obstetric, pulmonary, dermatologic, and gastrointestinal systems. The dopamine depletion hypothesis may explain why cocaine is repeatedly administered; cocaine produces a transient increase in synaptic dopamine. Alterations in dopamine neurotransmission may be responsible for the development of compulsive use patterns. When cocaine use becomes compulsive, psychosocial dysfunction, deviant behaviors, and a wide spectrum of social, financial, and family problems invariably result. Addiction, major medical complications, and death are true hazards of cocaine use.
Cregler, L. L.
The use of stimulant medications for the treatment of cocaine dependence is an evolving scientific line of research. To date, the most promising results are with the higher-potency medications, the amphetamine analogues, or a combination of a dopaminergic medication with a contingency management behavioral intervention. The development of effective pharmacotherapies for opioid and nicotine dependence using an agonist replacement approach suggests that these promising findings needs to continue to be vigorously investigated. In clinical trial reports, there are very few instances of cardiovascular adverse events, which suggests that for well-selected patients with cocaine dependence, stimulant replacement therapy can be safe. However, clinical trial eligibility criteria excludes most high-risk patients from participating, and introducing stimulant substitution to the wider treatment community would likely expose more vulnerable patients to the medical risks associated with stimulant treatment while using cocaine. As treatment development research moves forward, attention must be paid to helping clinicians select patients who are most likely to benefit from stimulant substitution treatment and how to identify those at risk. An additional concern with the use of stimulant medication treatment of cocaine dependence is prescribing controlled substances for patients with active substance use disorders. Again, within a clinical trial, medication supplies are monitored and distributed carefully in small quantities. In a community setting, misuse or diversion will be risks associated with prescribing controlled substances to patients with addictive disorders, but therapeutic strategies for monitoring and limiting that risk can be implemented. Psychostimulant pharmacotherapy is a promising line of research for the treatment of cocaine dependence, a condition for which no effective pharmacotherapy has been identified. Further research is required to confirm positive results from single-site trials, in particular the study of amphetamines as a treatment for cocaine dependence. As this literature evolves, strategies to manage the risk of prescribing controlled substances to patients with addictive disorders need to be tested and refined. Biases against using controlled substances as a treatment for cocaine dependence should be challenged, much in the way the use of agonist treatment transformed the treatment of opioid dependence despite initial resistance from the field. PMID:22640764
Mariani, John J; Levin, Frances R
Brain glutamate has been shown to play an important role in reinstatement to drug seeking, a behavior considered to be of relevance to relapse to drug taking in humans. Therefore, glutamate receptors, in particular metabotropic glutamate (mGlu) receptors, have become important targets for medication development for the treatment of drug dependence. In this review article, we focus on the mGlu7 receptor subtype, and discuss recent findings with AMN082, a selective mGlu7 receptor allosteric agonist, in animal models with relevance to drug dependence. Systemic or local administration of AMN082 into the nucleus accumbens (NAc), a critical brain region involved in reward and drug dependence processes, inhibited the reinforcing and motivational effects of cocaine, heroin and ethanol, as assessed by the intravenous drug self-administration procedure. In addition, AMN082 inhibited the reward-enhancing effects induced by cocaine, as assessed in the intracranial self-stimulation procedure, and cocaine- or cue-induced reinstatement of drug-seeking behavior. In vivo microdialysis studies indicated that systemic or intra-NAc administration of AMN082 significantly decreased extracellular ?-aminobutyric acid (GABA) and elevated extracellular glutamate, but had no effect on extracellular dopamine in the NAc, suggesting that a non-dopaminergic mechanism underlies the effects of AMN082 on the actions of cocaine. Further, data indicated that AMN082-induced changes in glutamate were the net effect of two actions: one is the direct inhibition of glutamate release by activation of mGlu7 receptors on glutamatergic neurons; another is the indirect increases of glutamate release mediated by decreases in GABA transmission. These increases in extracellular glutamate functionally antagonized cocaine-induced inhibition of NAc-ventral pallidum GABAergic neurotransmission, and therefore, the rewarding effects of cocaine. In addition, elevated extracellular glutamate activated presynaptic mGlu2/3 autoreceptors which in turn inhibited cocaine priming- or cue-induced enhancement of glutamate release and reinstatement of drug-seeking behavior. Taken together, these findings suggest that the mGlu7 receptor is an important target for medication development for the treatment of drug dependence. AMN082 or other mGlu7 receptor allosteric agonists may have potential as novel pharmacotherapies for cocaine addiction.
Li, Xia; Xi, Zheng-Xiong; Markou, Athina
ObjectiveCocaine-induced paranoia (CIP), an irrational intense suspicion of others, is a common manifestation of cocaine dependence. Both environmental and genetic factors are thought to play a role, but the specific nature of such contributions is poorly understood.
Rasmon Kalayasiri; Henry R. Kranzler; Roger Weiss; Kathleen Brady; Ralitza Gueorguieva; Carolien Panhuysen; Bao-Zhu Yang; Lindsay Farrer; Joel Gelernter; Robert T. Malison
Presently, there is a considerable interest in heroin-assisted treatment: co-prescription of heroin to certain subgroups of chronic, treatment-resistant, opioid dependent patients. In 2002, nine countries had planned (Australia, Belgium, Canada, France, Spain) or ongoing (Germany, The Netherlands, Switzerland, United Kingdom) clinical trials on this subject. These trials (and the routine heroin-assisted treatment programs that might result) will need pharmaceutical heroin
Marjolein G. Klous; Wim Van den Brink; Jan M. Van Ree; Jos H. Beijnen
Introduction: Medical associations and licensing bodies face pressure to implement quality assurance programs, but evidence-based models are lacking. To improve the quality of methadone maintenance treatment (MMT), the College of Physicians and Surgeons of Ontario, Canada, conducts an innovative quality assurance program on the basis of peer…
Strike, Carol; Wenghofer, Elizabeth; Gnam, William; Hillier, Wade; Veldhuizen, Scott; Millson, Margaret
A chronic pain patient prescribed 20 mg of methadone per day was seen at the Emergency Department within one hour following a witnessed intentional 200 mg ingestion. In addition, he was taking the serotonin re-uptake inhibitor antidepressant drugs, sertraline and venlafaxine as prescribed. Methadone is also a serotonin re-uptake inhibitor which has been involved in serotonin toxicity reactions. Initially, no symptoms of narcotic overdose (depressed central nervous system, respiration, or blood pressure) could be distinguished, and the standard narcotic urine screen was negative. No decontamination or antagonist therapy was given, and the patient was discharged to a psychiatric unit for observation. At 5 hours post-ingestion he presented in a panic with hallucinations and elevated blood pressure, pulse, and respiration. These symptoms are characteristic of serotonin syndrome which is often described as mental status changes, autonomic hyperactivity, and neuromuscular abnormalities. At 10 hours post-ingestion the patient was found unconscious. He had aspirated stomach contents into his lungs. His respiration, blood pressure, and pulse were all severely depressed. He never regained conciousness, and he died 5 days later. The medical examiner's finding was probable acute methadone intoxication. In this case serotonin syndrome appears to have opposed and delayed typical narcotic symptoms. Methadone has additional pharmacologic and toxicologic properties which may complicate the assessment and treatment in overdose situations. PMID:19544673
Martinez, Terry T; Martinez, Daniel N
A cost analysis is presented for developing a training and employment (TEP) program at four methadone treatment centers in a quasi-experimental pilot study. Average annual costs for TEP per client were derived. The methodology can be used in other projects to compare standard and TEP-enhanced substance-abuse treatment. (SLD)
French, Michael T.; And Others
This pretest/posttest study used two samples of injecting drug users (184 from street outreach and 103 from a methadone program) to assess drug use and human immunodeficiency virus risk practices. The improvement in risk behaviors at posttest suggests that intervention programs were agents of change. (SLD)
Wechsberg, Wendee M.; And Others
A review of studies on counseling with methadone clients affirmed the importance of counseling services. Support was found for analytic therapy, T-group therapy, behavioral training, reality therapy, and family therapy. There was evidence of client resistance to group therapy. (Author)
Powers, Robert J.; Powers, Henrietta B.
Methadone has been used as a pharmacotherapy for the treatment of opiate dependence since the mid-1960s. Many studies examining the benefits of methadone maintenance treatment (MMT) for opiate dependence have documented a significant reduction in both criminal behavior and the use of other opiates. Nevertheless, emerging evidence suggests that MMT may impair cognitive function. However, it is unclear as to the part methadone dose, duration of MMT or plasma level may play in any observed deficits. Given the large number of people enrolled in MMT world-wide and the potential for deficits in cognitive function, a systematic review of the research investigating the association between MMT and cognitive function seemed warranted. The following databases were searched with a combination of free-text and thesaurus terms (methadone AND cognition): MEDLINE In-Process, EMBASE, PsycINFO and EBM Reviews-Cochrane Central Register of Controlled Trials. Seventy-eight articles were retrieved of which 35 met the inclusion criteria. The majority of research suggests that MMT is associated with impaired cognitive function and that deficits extended across a range of domains. However, caution is required when interpreting these results due to the methodological limitations associated with many studies. Further research that includes a combination of psychological and physiological measures within well-controlled group comparison studies is required to more accurately assess which cognitive domains are affected. PMID:23773088
Wang, Grace Y; Wouldes, Trecia A; Russell, Bruce R
Prevalence of prescription opioid abuse has increased dramatically in recent years in the United States generally, and a similar pattern of increasing prescription opioid use has also been noted among patients seeking treatment for opioid dependence. This study presents results from an internal quality assurance project conducted by an outpatient methadone maintenance (MM) treatment clinic which sought to examine the
Kelly E. Dunn; Stacey C. Sigmon; Mark R. McGee; Sarah H. Heil; Stephen T. Higgins
Background In general, information about women who use drugs comes from studies performed in the West. Whether women in countries such as Iran are likely to enter drug treatment or how they will respond is not known. Purpose To examine the short-term impact of methadone maintenance treatment (MMT) on drug use, dependence, social functioning, crime, and human immunodeficiency virus (HIV) and hepatitis C virus (HCV) risk behavior and seroincidence in female drug users in Iran. Methods Women were eligible for inclusion in the study if they were assessed as dependent on opiates according to the International Statistical Classification of Diseases and Related Health Problems, tenth revision (ICD-10). The sample comprised 78 female heroin or opium users who attended the Persepolis women’s drug treatment clinic in Tehran between 2007 and 2008. Participants were followed up in 2009/2010. Heroin and the use of other drugs, social functioning, involvement in crime, and involvement in HIV and HCV risk behavior were measured by self-report. The prevalence and incidence of HIV and HCV were measured by serology and self-report. Findings Of the 78 women recruited, 40 were followed up, and this occurred approximately 7 months later. One in four women reported a history of drug injection. At follow-up there were significant reductions in self-reported heroin use on ICD-10 dependence scores. Subjects with more severe drug dependence at baseline were significantly more likely to be criminally active than less severely dependent subjects. Baseline prevalence for HIV and HCV was 5% and 24%, respectively. At follow-up, no one had acquired HIV infection, but one participant had acquired HCV, giving an incidence rate of 7.1 per 100 person-years. Conclusion This research provides the first evidence that Iranian female drug users can enter MMT and respond well. Within a few months of entering MMT, improvements occurred in heroin use, levels of dependence, social functioning, and HIV risk behavior. While the incidence of blood-borne viral infections was low, there was a serious risk of HIV transmission among this cohort and also to participants’ needle and sexual contacts. In a country with high levels of drug use, the high levels of HCV among female drug users require more women to enter drug treatment if an HIV epidemic is to be avoided. Many participants had a chronic drug problem and had had little or no previous exposure to MMT. The introduction or expansion of women-only drug treatment services is urgently needed in order to engage more women in treatment.
Dolan, Kate; Salimi, Shabnam; Nassirimanesh, Bijan; Mohsenifar, Setareh; Allsop, David; Mokri, Azarakhsh
We have previously shown that nicotine enhances cue-induced cocaine craving. In the present study, the effects of a nicotine antagonist, mecamylamine, on cue-induced cocaine craving were investigated. Twenty-three cocaine-dependent patients, all cigarette smokers, were randomly assigned to mecamylamine (2.5 mg tablet) or placebo in a single-dose, placebo-controlled, crossover, double-blind study. Craving and anxiety were measured before and after cocaine cues
Malcolm S Reid; Joanne D Mickalian; Kevin L Delucchi; S Paul Berger
Cocaine abuse is a problem causing world-wide concern and the number of deaths following cocaine use is increasing. Cardiovascular complications following cocaine include severe tachyarrythmias, pulmonary edema, myocardial infarction, and acute renal fail...
P. Som G. J. Wang Z. H. Oster F. F. Knapp Y. Yonekura
Presented here is a model for the diagnosis and treatment of cocaine dependence. Intrinsic in the understanding of this model is the use of the disease concept of chemical dependence. Within the construct of this model we regard cocaine dependence or "cocainism" as a disease process and part of the spectrum of the disease of chemical dependence. We note that "pure" cocainism is rare and cocaine is usually just another chemical used in the polyaddicted patient. We call cocaine the "Great Precipitator" as it often brings the polyaddicted chemically-dependent person into a crisis that requires a treatment intervention. Cocainism, with its overwhelming compulsion and destruction, often precipitates a crisis in a matter of months from first use. As psychiatrists practicing addictionology, we understand the need to deal with cocainism as a primary disease process rather than a symptom of an underlying psychiatric illness. We deal with cocainism as we deal with alcoholism. While the DSM-III requires withdrawal and tolerance changes to be an essential feature for dependence, we more easily identify the disease of cocainism by its production of intense psychological addiction. Thereby the diagnosis of the disease of cocainism, as with other drugs (including alcohol) in the spectrum of chemical dependence, is characterized by the persistent, uncontrolled, compulsive use of cocaine. This illogical, irrational compulsion with continued, repeated use of cocaine as it destroys the individual's life, is the primary symptom of this disease. In regards to specific considerations, the psychiatric complications of cocainism, which can include cocaine induced psychosis, can persist beyond the intoxication period. We also note the depression that can accompany abstinence from cocaine and often has a protracted course following initial abstinence as well. We advocate the very cautious use of any psychotropic medications after an alloted period of time since we find that many of these additional symptoms seem to dissipate during the treatment process when involved in our suggested setting. In the cases of where it is determined that additional psychiatric illness co-exist with cocaine and chemical dependence such as in "dual diagnosis" patients, we have had that success by treating both illnesses concomitantly and aggressively. The "contract" with the dual diagnosis patient has afforded excellent results in this instance. The treatment modalities most effective in this model include a treatment team with its multidisciplinary and recovering and non-recovering characteristics, and the use of the group process and peer group therapy.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:3870754
Angres, D H; Benson, W H
Children born to heroin-dependent mothers (n=83) were compared to 76 children born to heroin-dependent fathers and to 3 control groups with and without environmental deprivation and health problems. Results found that developmental delays and behavioral disorders found among heroin-exposed children resulted primarily from severe environmental…
Ornoy, Asher; And Others
Sixteen trace elements found in 309 street heroin samples, piped water and contaminated water were determined using inductively coupled plasma-mass spectrometry. All the street heroin samples were found to contain high levels of sodium, a reflection of the use of sodium bicarbonate during heroin synthesis. Additionally, this element was also found to be one of the potential contaminants acquired from the piped water. Calcium could be derived from lime while iron, aluminum and zinc could have come from the metallic container used in the processing/cutting stage. The levels of these elements remained low in the heroin and it could be due to the dilution effects from the addition of adulterants. Statistical validation was performed with six links of related heroin samples using principal component analysis to find the best pretreatment for sample classification. It was obtained that normalization followed by fourth root showed promising results with 8% errors in the sample clustering. The technique was then applied to the case samples. Finally, the result suggested that the case samples could have originated from at least two major groups respectively showing unique elemental profiles at the street level. PMID:23380066
Chan, Kar-Weng; Tan, Guan-Huat; Wong, Richard C S
Cocaine is Europe's second preferred recreational drug after cannabis but very little is known about possible cognitive impairments in the upcoming type of recreational cocaine user (monthly consumption). We asked whether recreational use of cocaine impacts early attentional selection processes. Cocaine-free polydrug controls (n?=?18) and cocaine polydrug users (n?=?18) were matched on sex, age, alcohol consumption, and IQ (using the Raven's progressive matrices), and were tested by using the Global-Local task to measure the scope of attention. Cocaine polydrug users attended significantly more to local aspects of attended events, which fits with the idea that a reduced scope of attention may be associated with the perpetuation of the use of the drug.
Colzato, Lorenza S.; van den Wildenberg, Wery P. M.; Hommel, Bernhard
Neuropsychiatric disorders are often characterized by impaired insight into behaviour. Such an insight deficit has been suggested, but never directly tested, in drug addiction. Here we tested for the first time this impaired insight hypothesis in drug addiction, and examined its potential association with drug-seeking behaviour. We also tested potential modulation of these effects by cocaine urine status, an individual difference known to impact underlying cognitive functions and prognosis. Sixteen cocaine addicted individuals testing positive for cocaine in urine, 26 cocaine addicted individuals testing negative for cocaine in urine, and 23 healthy controls completed a probabilistic choice task that assessed objective preference for viewing four types of pictures (pleasant, unpleasant, neutral and cocaine). This choice task concluded by asking subjects to report their most selected picture type; correspondence between subjects self-reports with their objective choice behaviour provided our index of behavioural insight. Results showed that the urine positive cocaine subjects exhibited impaired insight into their own choice behaviour compared with healthy controls; this same study group also selected the most cocaine pictures (and fewest pleasant pictures) for viewing. Importantly, however, it was the urine negative cocaine subjects whose behaviour was most influenced by insight, such that impaired insight in this subgroup only was associated with higher cocaine-related choice on the task and more severe actual cocaine use. These findings suggest that interventions to enhance insight may decrease drug-seeking behaviour, especially in urine negative cocaine subjects, potentially to improve their longer-term clinical outcomes.
Moeller, S.J.; Moeller, S.J.; Maloney, T.; Parvaz, M.A.; Alia-Klein, N.; Woicik, P.A.; Telang, F.; Wang, G.-J.; Volkow, N.D.; Goldstein, R.Z.
Background The ability to predict potential for relapse to substance use following treatment could be very useful in targeting aftercare strategies. Recently, a number of investigators have focused on using neural activity measured by fMRI to predict relapse propensity. The purpose of the present study was to use fMRI to investigate prospective associations between brain reactivity to cocaine and response inhibition cues and relapse to cocaine use. Methods Thirty cocaine-dependent participants with clean cocaine urine drug screens (UDS) completed a baseline fMRI scan, including a cocaine-cue reactivity task and a go/no-go response inhibition task. After participating in a brief clinical trial of D-cycloserine for the facilitation of cocaine cue extinction, they returned for a one-week follow-up UDS. Associations between baseline activation to cocaine and inhibition cues and relapse to cocaine use were explored. Results Positive cocaine UDS was significantly associated with cocaine cue activation in the right putamen and insula, as well as bilateral occipital regions. Associations between positive cocaine UDS and activation to no-go cues were concentrated in the postcentral gyri, a region involved in response execution. Conclusions Although preliminary, these results suggest that brain imaging may be a useful tool for predicting risk for relapse in cocaine-dependent individuals. Further, larger-scale naturalistic studies are needed to corroborate and extend these findings.
Prisciandaro, James J.; Myrick, Hugh; Henderson, Scott; McRae-Clark, Aimee L.; Brady, Kathleen T.
This study evaluated the ability of cocaine withdrawal symptoms, measured by the Cocaine Selective Severity Assessment (CSSA) and initial urine toxicology results, to predict treatment attrition among 128 cocaine dependent veterans participating in a 4-week day hospital treatment program. The CSSA was administered and a urine toxicology screen was obtained at intake and at the start of the day hospital
Kyle M. Kampman; Arthur I. Alterman; Joseph R. Volpicelli; Iradj Maany; Eric S. Muller; Douglas D. Luce; Ellen M. Mulholland; Abbas F. Jawad; Gargi A. Parikh; Frank D. Mulvaney; Robert M. Weinrieb; Charles P. OBrien
This study investigated the effects of prenatal cocaine exposure on infant sensorimotor development. One hundred and sixty-seven12-month-olds (74 cocaine-exposed and 93 unexposed) were assessed using the Bayley Scales of Infant Development (BSID). Ninety-seven had previously been evaluated on the Movement Assessment of Infants and the Test of Sensory Functions in Infants at age 4 months. On the BSID, the cocaine-exposed
Orphia Bass-Busdiecker; JoMarie Mascia; Jennifer Angelopoulos
We are investigating treatments for cocaine abuse based on viral gene transfer of a cocaine hydrolase (CocH) derived from human butyrylcholinesterase, which can reduce cocaine-stimulated locomotion and cocaine-primed reinstatement of drug-seeking behavior in rats for many months. Here, in mice, we explored the possibility that anti-cocaine antibodies can complement the actions of CocH to reduce cocaine uptake in brain and block centrally-evoked locomotor stimulation. Direct injections of test proteins showed that CocH (0.3 or 1mg/kg) was effective by itself in reducing drug levels in plasma and brain of mice given cocaine (10mg/kg, s.c., or 20mg/kg, i.p). Administration of cocaine antibody per se at a low dose (8 mg/kg, i.p.) exerted little effect on cocaine distribution. However, a higher dose of antibody (12 mg/kg) caused peripheral trapping (increased plasma drug levels), which led to increased cocaine metabolism by CocH, as evidenced by a 6-fold rise in plasma benzoic acid. Behavioral tests with small doses of CocH and antibody (1 and 8 mg/kg, respectively) showed that neither agent alone reduced mouse locomotor activity triggered by a very large cocaine dose (100mg/kg, i.p.). However, dual treatment completely suppressed the locomotor stimulation. Altogether, we found cooperative and possibly synergistic actions that warrant further exploration of dual therapies for treatment of cocaine abuse. PMID:22960160
Brimijoin, Stephen; Orson, Frank; Kosten, Thomas R; Kinsey, Berma; Shen, Xiao Yun; White, Sarah J; Gao, Yang
Cocaine is a potent stimulant of the central nervous system with severe addiction potential. Its abuse is a major problem worldwide. The exact mechanism of action of cocaine is still uncertain but it is known that its reinforcing and stimulant effects are related to its ability to inhibit the membrane bound dopamine transporter (DAT). This paper discusses efforts that are underway to identify ligands for possible use in the treatment of cocaine abuse. Much of this effort has been focussed on understanding cocaine interactions at DAT receptor sites.
Flippen-Anderson, Judith L.; George, Clifford; Deschamps, Jeffrey R.
Individuals who use cocaine report a variety of neuropsychiatric symptoms that are yet to be adequately targeted with treatment modalities. To address this problem requires an understanding of these symptoms and their neurobiological origins. Our paper reviewed the existing data on the neuropsychiatic implications of cocaine. We conducted a Medline search from 1984-2004 using terms, such as "cocaine", "cocaine addiction", "cocaine abuse", "cocaine neuropsychiatry" and "dual diagnosis". The search produced additional reference materials that were used in this review, although we focused on data that have likely clinical implications. The literature evidence suggested that, whereas acute cocaine overdose is potentially fatal, the ingestion of mild-to-moderate doses could result in fatal or nonfatal neuropsychiatric events. Also, chronic cocaine use may be associated with deficits in neurocognition, brain perfusion and brain activation patterns. Some of these deficits were unresolved with periods of abstinence ranging from 3-200 days. Taken together, these studies suggest the need for further investigations to fully characterize the neurobiological substrates of cocaine use disorders (CUDs) with the future possibility of more efficient treatment modalities.
Nnadi, Charles U.; Mimiko, Olubansile A.; McCurtis, Henry L.; Cadet, Jean Lud
A heritable phenotype resulting from the self-administration of cocaine in rats was delineated. We observed delayed acquisition and reduced maintenance of cocaine self-administration in male, but not female, offspring of sires that self-administered cocaine. Brain-derived neurotrophic factor (BDNF) mRNA and protein were increased in the medial prefrontal cortex (mPFC) and there was an increased association of acetylated histone H3 with BDNF promoters only in the male offspring of cocaine-experienced sires. Administration of a BDNF receptor antagonist (the TrkB receptor antagonist ANA-12) reversed the diminished cocaine self-administration in male cocaine-sired rats. In addition, the association of acetylated histone H3 with BDNF promoters was increased in the sperm of sires that self-administered cocaine. Collectively, these findings indicate that voluntary paternal ingestion of cocaine results in epigenetic reprograming of the germline resulting in profound effects on mPFC gene expression and resistance to cocaine reinforcement in male offspring.
Vassoler, Fair M.; White, Samantha L.; Schmidt, Heath D.; Sadri-Vakili, Ghazaleh; Pierce, R. Christopher
Previous studies have reported that noradrenergic antagonists alleviate some of the symptoms of opiate withdrawal and dependence. Clinical studies also have shown that modification of the noradrenergic system may help protect patients from relapse. The present study tested the hypothesis that a dysregulated noradrenergic system has motivational significance in heroin self-administration of dependent rats. Prazosin, an alpha1-adrenergic antagonist (0.5, 1.0, 1.5 and 2.0 mg/kg, i.p.), was administered to adult male Wistar rats with a history of limited (1 h/day; short access) or extended (12 h/day; long access) access to intravenous heroin self-administration. Prazosin dose-dependently reduced heroin self-administration in long-access rats but not short-access rats, with 2 mg/kg of systemic prazosin significantly decreasing 1 h and 2 h heroin intake. Prazosin also reversed some changes in meal pattern associated with extended heroin access, including the taking of smaller and briefer meals (at 3 h), while also increasing total food intake and slowing the eating rate within meals (both 3 h and 12 h). Thus, prazosin appears to stimulate food intake in extended access rats by restoring meals to the normal size and duration. The data suggest that the alpha1 adrenergic system may contribute to mechanisms that promote dependence in rats with extended access. PMID:18703080
Greenwell, Thomas N; Walker, Brendan M; Cottone, Pietro; Zorrilla, Eric P; Koob, George F
A 56-year-old-man presented with syncope and torsades de pointes secondary to methadone-induced QT prolongation. After transition from methadone to buprenorphine, a partial mu-opiate-receptor agonist and a kappa-opiate-receptor antagonist, the QT normalized and ventricular arrhythmias resolved. Buprenorphine should be used for opiate dependence and chronic pain in patients with methadone-induced QT prolongation and as first line therapy in patients with risk factors for torsades de pointes. PMID:18686025
Esses, Jason Levi; Rosman, Jonathan; Do, Lien Thanh; Schweitzer, Paul; Hanon, Sam
Background: The pharmacokinetics and dynamics of methadone are characterized by high interindividual variability. This study aimed to examine a number of factors that may contribute to this variability.Methods: Eight healthy drug-free women were administered 0.2 mg\\/kg of R,S-methadone orally. The concentrations of methadone's enantiomers in plasma and urine were monitored for 96 hours. Vital signs, blood biochemical parameters, and pupillary
David W. Boulton; Philippe Arnaud; C. Lindsay DeVane
It can be argued that an ideal anti-cocaine medication would be one that accelerates cocaine metabolism producing biologically inactive metabolites via a route similar to the primary cocaine-metabolizing pathway, i.e., hydrolysis catalyzed by butyrylcholinesterase (BChE) in plasma. However, wild-type BChE has a low catalytic efficiency against naturally occurring (-)-cocaine. Interestingly, wild-type BChE has a much higher catalytic activity against unnatural (+)-cocaine. According to available positron emission tomography (PET) imaging analysis using [(11)C](-)-cocaine and [(11)C](+)-cocaine tracers in human subjects, only [(11)C](-)-cocaine was observed in the brain, whereas no significant [(11)C](+)-cocaine signal was observed in the brain. The available PET data imply that an effective therapeutic enzyme for treatment of cocaine abuse could be an exogenous cocaine-metabolizing enzyme with a catalytic activity against (-)-cocaine comparable to that of wild-type BChE against (+)-cocaine. Our recently designed A199S/F227A/S287G/A328 W/Y332G mutant of human BChE has a considerably improved catalytic efficiency against (-)-cocaine and has been proven active in vivo. In the present study, we have characterized the catalytic activities of wild-type BChE and the A199S/F227A/S287G/A328 W/Y332G mutant against both (+)- and (-)-cocaine at the same time under the same experimental conditions. Based on the obtained kinetic data, the A199S/F227A/S287G/A328 W/Y332G mutant has a similarly high catalytic efficiency (kcat/KM) against (+)- and (-)-cocaine, and indeed has a catalytic efficiency (k(cat/)K(M) = 1.84 × 10(9) M(-1) min(-1)) against (-)-cocaine comparable to that (k(cat)/K(M) = 1.37 × 10(9) M(-1) min(-1)) of wild-type BChE against (+)-cocaine. Thus, the mutant may be used to effectively prevent (-)-cocaine from entering brain and producing physiological effects in the enzyme-based treatment of cocaine abuse. PMID:22917637
Xue, Liu; Hou, Shurong; Yang, Wenchao; Fang, Lei; Zheng, Fang; Zhan, Chang-Guo
Background Data from the US indicates that methadone-maintained populations are aging, with an increase of patients aged 50 or older.\\u000a Data from European methadone populations is sparse. This retrospective cohort study sought to evaluate the age trends and\\u000a related developments in the methadone population of Basel-City, Switzerland.\\u000a \\u000a \\u000a \\u000a \\u000a Methods The study included methadone patients between April 1, 1995 and March 31, 2003. Anonymized
Kenneth M Dürsteler-MacFarland; Marc Vogel; Gerhard A Wiesbeck; Sylvie A Petitjean
Methadone N-demethylation in vitro is catalyzed by hepatic cytochrome P4502B6 (CYP2B6) and CYP3A4, but clinical disposition is often attributed to CYP3A4. This investigation tested the hypothesis that CYP2B6 is a prominent CYP isoform responsible for clinical methadone N-demethylation and clearance, using the in vivo mechanism-based CYP2B6 inhibitor ticlopidine, given orally for 4 days. A preliminary clinical investigation with the CYP3A4/5 substrate probe alfentanil established that ticlopidine did not inhibit intestinal or hepatic CYP3A4/5. Subjects received intravenous plus oral (deuterium-labeled) racemic methadone before and after ticlopidine. Ticlopidine significantly and stereoselectively (S>R) inhibited methadone N-demethylation, decreasing plasma metabolite/methadone area under the curve ratios and metabolite formation clearances. Ticlopidine also significantly increased the dose-adjusted plasma area under the curve for R- and S-methadone by 20% and 60%, respectively, after both intravenous and oral dosing. CYP2B6 inhibition reduces methadone N-demethylation and clearance, and alters methadone concentrations, demonstrating a predominant role for CYP2B6 in clinical methadone disposition.
Kharasch, Evan D.; Stubbert, Kristi
Background Refined sugars (e.g., sucrose, fructose) were absent in the diet of most people until very recently in human history. Today overconsumption of diets rich in sugars contributes together with other factors to drive the current obesity epidemic. Overconsumption of sugar-dense foods or beverages is initially motivated by the pleasure of sweet taste and is often compared to drug addiction. Though there are many biological commonalities between sweetened diets and drugs of abuse, the addictive potential of the former relative to the latter is currently unknown. Methodology/Principal findings Here we report that when rats were allowed to choose mutually-exclusively between water sweetened with saccharin–an intense calorie-free sweetener–and intravenous cocaine–a highly addictive and harmful substance–the large majority of animals (94%) preferred the sweet taste of saccharin. The preference for saccharin was not attributable to its unnatural ability to induce sweetness without calories because the same preference was also observed with sucrose, a natural sugar. Finally, the preference for saccharin was not surmountable by increasing doses of cocaine and was observed despite either cocaine intoxication, sensitization or intake escalation–the latter being a hallmark of drug addiction. Conclusions Our findings clearly demonstrate that intense sweetness can surpass cocaine reward, even in drug-sensitized and -addicted individuals. We speculate that the addictive potential of intense sweetness results from an inborn hypersensitivity to sweet tastants. In most mammals, including rats and humans, sweet receptors evolved in ancestral environments poor in sugars and are thus not adapted to high concentrations of sweet tastants. The supranormal stimulation of these receptors by sugar-rich diets, such as those now widely available in modern societies, would generate a supranormal reward signal in the brain, with the potential to override self-control mechanisms and thus to lead to addiction.
Cantin, Lauriane; Ahmed, Serge H.