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
Participants 549 heroin addicts.
Interventions Inhalable heroin (n = 375) or injectable heroin (n =
174) prescribed over 12 months. Heroin (maximum 1000 mg per day) plus
methadone (maximum 150 mg per day) compared with methadone alone (maximum 150
mg per day). Psychosocial treatment was offered throughout.
Main outcome measures Dichotomous, multidomain response index,
including validated indicators of physical health, mental status, and social
Results Adherence was excellent with 12 month outcome data available
for 94% of the randomised participants. With intention to treat analysis, 12
month treatment with heroin plus methadone was significantly more effective
than treatment with methadone alone in the trial of inhalable heroin (response
rate 49.7% v 26.9%; difference 22.8%, 95% confidence interval 11.0%
to 34.6%) and in the trial of injectable heroin (55.5% v 31.2%;
difference 24.3%, 9.6% to 39.0%). Discontinuation of the coprescribed heroin
resulted in a rapid deterioration in 82% (94/115) of those who
responded to the coprescribed heroin. The incidence of serious adverse events
was similar across treatment conditions.
Conclusions Supervised coprescription of heroin is feasible, more
effective, and probably as safe as methadone alone in reducing the many
physical, mental, and social problems of treatment resistant heroin
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
In the United Kingdom (UK), there is an extensive market for the class 'A' drug heroin and many heroin users spend time in prison. People addicted to heroin often require prescribed medication when attempting to cease their drug use. The most commonly used detoxification agents in UK prisons are currently buprenorphine and methadone, both are recommended by national clinical guidelines. However, these agents have never been compared for opiate detoxification in the prison estate and there is a general paucity of research evaluating the most effective treatment for opiate detoxification in prisons. This study seeks to address this paucity by evaluating the most routinely used interventions amongst drug users within UK prisons.
This study uses randomised controlled trial methodology to compare the open use of buprenorphine and methadone for opiate detoxification, given in the context of routine care, within three UK prisons. Prisoners who are eligible and give informed consent will be entered into the trial. The primary outcome will be abstinence status eight days after detoxification, as determined by a urine test. Secondary outcomes will be recorded during the detoxification and then at one, three and six months post-detoxification.
Current Controlled Trials ISRCTN58823759
In the United Kingdom (UK), there is an extensive market for the class 'A' drug heroin. Many heroin users spend time in prison. People addicted to heroin often require prescribed medication when attempting to cease their drug use. The most commonly used detoxification agents in UK prisons are buprenorphine, dihydrocodeine and methadone. However, national guidelines do not state a detoxification drug of choice. Indeed, there is a paucity of research evaluating the most effective treatment for opiate detoxification in prisons. This study seeks to address the paucity by evaluating routinely used interventions amongst drug using prisoners within UK prisons.
The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS) Prisons Pilot Study will use randomised controlled trial methodology to compare the open use of buprenorphine and dihydrocodeine for opiate detoxification, given in the context of routine care, within HMP Leeds. Prisoners who are eligible and give informed consent will be entered into the trial. The primary outcome measure will be abstinence status at five days post detoxification, as determined by a urine test. Secondary outcomes during the detoxification and then at one, three and six months post detoxification will be recorded.
Due to potential proarrhythmic side-effects levo-α-Acetylmethadol (LAAM) is currently not available in EU countries as maintenance drug in the treatment of opiate addiction. However, recent studies and meta-analyses underline the clinical advantages of LAAM with respect to the reduction of heroin use. Thus a reappraisal of LAAM has been demanded. The aim of the present study was to evaluate the relative impact of LAAM on QTc-interval, as a measure of pro-arrhythmic risk, in comparison to methadone, the current standard in substitution therapy.
ECG recordings were analysed within a randomized, controlled clinical trial evaluating the efficacy and tolerability of maintenance treatment with LAAM compared with racemic methadone. Recordings were done at two points: 1) during a run-in period with all patients on methadone and 2) 24 weeks after randomisation into methadone or LAAM treatment group. These ECG recordings were analysed with respect to QTc-values and QTc-dispersion. Mean values as well as individual changes compared to baseline parameters were evaluated. QTc-intervals were classified according to CPMP-guidelines.
Complete ECG data sets could be obtained in 53 patients (31 LAAM-group, 22 methadone-group). No clinical cardiac complications were observed in either group. After 24 weeks, patients receiving LAAM showed a significant increase in QTc-interval (0.409 s ± 0.022 s versus 0.418 s ± 0.028 s, p = 0.046), whereas no significant changes could be observed in patients remaining on methadone. There was no statistically significant change in QTc-dispersion in either group. More patients with borderline prolonged and prolonged QTc-intervals were observed in the LAAM than in the methadone treatment group (n = 7 vs. n = 1; p = 0.1).
In this controlled trial LAAM induced QTc-prolongation in a higher degree than methadone. Given reports of severe arrhythmic events, careful ECG-monitoring is recommended under LAAM medication.
LAAM; methadone; opiate addiction; cardiac arrhythmia; QTc-interval
Heroin dependence is a major health and social problem associated with increased morbidity and mortality that adversely affects social circumstances, productivity, and healthcare and law enforcement costs. In the UK and many other Western countries, both methadone and buprenorphine are recommended by the relevant agencies for detoxification from heroin and for opioid maintenance therapy. However, despite obvious benefits due to its unique pharmacotherapy (eg, greatly reduced risk of overdose), buprenorphine has largely failed to overtake methadone in managing opioid addiction. The experience from the developing world (based on data from India) is similar. In this article we compare the advantages and disadvantages of the use methadone and buprenorphine for the treatment of opioid addiction from both a developed and developing world perspective; and explore some of the reasons why buprenorphine has not fulfilled the expectations predicted by many in the addictions field.
Addiction; buprenorphine; detoxification; maintenance; methadone; opiate
Despite its effectiveness, methadone maintenance is rarely provided in American correctional facilities. This study is the first randomized clinical trial in the US to examine the effectiveness of methadone maintenance treatment provided to prisoners with pre-incarceration heroin addiction.
A three-group randomized controlled trial was conducted between September 2003 and June 2005. Two hundred-eleven Baltimore pre-release inmates who were heroin dependent during the year prior to incarceration were enrolled in this study. Participants were randomly assigned to the following: Counseling Only: counseling in prison, with passive referral to treatment upon release (n = 70); Counseling + Transfer: counseling in prison with transfer to methadone maintenance treatment upon release (n = 70); and Counseling + Methadone: methadone maintenance and counseling in prison, continued in a community-based methadone maintenance program upon release (n = 71).
Two hundred participants were located for follow-up interviews and included in the current analysis. The percentages of participants in each condition that entered community-based treatment were, respectively, Counseling Only 7.8%, Counseling + Transfer 50.0%, and Counseling + Methadone 68.6%, p < .05. All pairwise comparisons were statistically significant, (all ps < .05). The percentage of participants in each condition that tested positive for opioids at one month post-release were, respectively, Counseling Only 62.9%, Counseling + Transfer 41.0%, and Counseling + Methadone 27.6%, p < .05, with the Counseling Only group significantly more likely to test positive than the Counseling + Methadone group.
Methadone maintenance initiated prior to or immediately after release from prison appears to have beneficial short-term impact on community treatment entry and heroin use. This intervention may be able to fill an urgent treatment need for prisoners with heroin addiction histories.
methadone maintenance; drug abuse treatment; prisoners; heroin addiction
This study aimed to determine the relative effectiveness of 12-months of Interim Methadone (IM; supervised methadone with emergency counseling only for the first 4 months of treatment), Standard Methadone treatment (SM; with routine counseling) and Restored Methadone treatment (RM: routine counseling with smaller caseloads).
A randomized controlled trial was conducted comparing: IM, SM, and RM treatment. IM lasted for 4 months after which participants were transferred to SM.
The study was conducted in two methadone treatment programs in Baltimore, MD, USA.
The study included 230 adult methadone patients newly-admitted through waiting lists.
We administered the Addiction Severity Index and a supplemental questionnaire at baseline, 4-, and 12-months post- baseline.
Measurements included retention in treatment, self-reported days of heroin and cocaine use, criminal behavior and arrests, and urine tests for heroin and cocaine metabolites.
At 12 months, on an intent-to-treat basis, there were no significant differences in retention in treatment among the IM, SM and RM groups (60.6%, 54.8% and 37.8%, respectively). Positive urine tests for the three groups declined significantly from baseline (ps<0.001 and 0.003, for heroin and cocaine metabolistes respectively) but there were no significant Group x Time interactions for these measures. Thirty-one percent of the sample reported at least one arrest during the year, but there were no significant between-group effects.
Limited availability of drug counseling services should not be a barrier to providing supervised methadone to adults dependent on heroin - at least for the first 4 months of treatment.
Interim methadone; methadone treatment; counseling; heroin addiction treatment
The objectives of this study were to determine: 1) the feasibility of expanding interim methadone treatment (IM); (2) the impact of IM on heroin and cocaine use; and (3) the effect of charging a modest fee for IM. Six clinics provided daily methadone plus emergency counseling only (IM) to heroin addicts on a waiting list for treatment. IM was provided for up to 120 days before transfer to regular methadone treatment. Drug testing was conducted at admission to IM and at transfer to MTP. Half the patients were charged $10/week for IM. Logistic regression analysis was utilized to determine the effect of fee status and other variables on transfer. Of 1,000 patients enrolled in IM, 762 patients (76.2%) were admitted to a regular MTP. For those who transferred (n = 762), opioid positive tests decreased from 89.6% to 38.4%; cocaine, from 49.9% to 44.9% from admission to transfer. Logistic regression analysis indicated that fee status at baseline was not significantly associated with transfer. When limited public resources create waiting lists, IM can allow additional patients to sharply reduce heroin use while waiting for admission to MTP.
heroin addiction; methadone treatment; interim methadone
Previously, we reported that opiate users enrolled in methadone treatment made ‘risky’ choices on a decision-making task following a loss of points compared with heroin users and healthy volunteers. One possible explanation for this behaviour is that methadone users were less sensitive to punishment on immediately preceding unsuccessful trials.
We sought to explore this finding from a neural perspective by performing a post hoc analysis of data from a previous H215O positron emission tomography study. We restricted the analysis to the opiate groups and controls, assessing differences between opiate users on methadone and those on heroin.
We found significant over-activation in the lateral orbitofrontal cortex (OFC) in methadone users compared with both heroin users and controls concomitant with the greatest overall tendency to ‘play risky’. Heroin users showed significant under-activation in this area compared with the other two groups whilst exhibiting the greatest overall tendency to ‘play safe’. Correlational analysis revealed that abnormal task-related activation of the left OFC was associated with the dose of methadone in methadone users and with the duration of intravenous heroin use in heroin users. ‘Playing safe’ following a loss of points was also negatively correlated with the activation of pregenual anterior cingulate and insula cortex in controls, but not in opiate users.
Our findings suggest that the interplay between processes involved in integrating penalty information for the purpose of response selection may be altered in opiate users. This change was reflected differentially in task-related pattern of OFC activation depending on the opiate used.
Heroin; Methadone; Orbitofrontal; Anterior cingulate; Decision making; Punishment; Feedback; Opiates; Neuroimaging
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.
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.
ClinicalTrials.gov registration number: NCT00175357
Heroin is a synthetic opioid with an extensive illicit market leading to large numbers of people becoming addicted. Heroin users often present to community treatment services requesting detoxification and in the UK various agents are used to control symptoms of withdrawal. Dissatisfaction with methadone detoxification  has lead to the use of clonidine, lofexidine, buprenorphine and dihydrocodeine; however, there remains limited evaluative research. In Leeds, a city of 700,000 people in the North of England, dihydrocodeine is the detoxification agent of choice. Sublingual buprenorphine, however, is being introduced. The comparative value of these two drugs for helping people successfully and comfortably withdraw from heroin has never been compared in a randomised trial. Additionally, there is a paucity of research evaluating interventions among drug users in the primary care setting. This study seeks to address this by randomising drug users presenting in primary care to receive either dihydrocodeine or buprenorphine.
The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS) project is a pragmatic randomised trial which will compare the open use of buprenorphine with dihydrocodeine for illicit opiate detoxification, in the UK primary care setting. The LEEDS project will involve consenting adults and will be run in specialist general practice surgeries throughout Leeds. The primary outcome will be the results of a urine opiate screening at the end of the detoxification regimen. Adverse effects and limited data to three and six months will be acquired.
An accumulating body of research suggests that former heroin abusers in methadone maintenance therapy (MMT) exhibit deficits in cognitive function. Whether these deficits are present in former methadone maintained patients following discontinuation of MMT is unknown. This study tests the hypothesis that former heroin users who have detoxified from methadone maintenance therapy and are drug-free have less pronounced cognitive impairment than patients continuing long-term MMT.
A series of neuropsychological tests were administered to three groups of subjects: 29 former heroin addicts receiving methadone maintenance treatment, 27 former heroin addicts withdrawn from all opiates, and 29 healthy controls without a history of drug dependence. Testing included Wechsler Adult Intelligence Scale-Revised Vocabulary Test, the Stroop Color-Word Test, the Controlled Oral Word Association Test, the Benton Visual Retention Test, and a Substance Use Inventory.
Both methadone-maintained and abstinent subject groups performed worse than controls on tasks that measured verbal function, visual-spatial analysis and memory, and resistance to distractibility. Abstinent subjects performed worse than their methadone maintained counterparts on tests measuring visual memory and construct formation. Cognitive impairment did not correlate with any index of drug use.
We confirmed previous findings of neuropsychological impairment in long-term MMT recipients. Both patients receiving MMT and former heroin users in prolonged abstinence exhibited a similar degree of cognitive impairment. Cognitive dysfunction in patients receiving methadone maintenance may not resolve following methadone detoxification.
Methadone; Opiates; Dependence; Abstinence; Neuropsychological; Cognitive
To test whether a combination of contingency management and methadone dose increase would promote abstinence from heroin and cocaine, we conducted a randomized controlled trial using a 2 X 3 (Dose X Contingency) factorial design in which dose assignment was double-blind. Participants were 252 heroin- and cocaine-abusing outpatients on methadone maintenance. They were randomly assigned to methadone dose (70 or 100 mg/day, double blind) and voucher condition (noncontingent, contingent on cocaine-negative urines, or “split”). The “split” contingency was a novel contingency that reinforced abstinence from either drug while doubly reinforcing simultaneous abstinence from both: the total value of incentives was “split” between drugs to contain costs. The main outcome measures were percentages of urine specimens negative for heroin, cocaine, and both simultaneously; these were monitored during a 5-week baseline of standard treatment (to determine study eligibility), a 12-week intervention, and a 10-week maintenance phase (to examine intervention effects in return-to-baseline conditions). DSM-IV criteria for ongoing drug dependence were assessed at study exit. Urine-screen results showed that the methadone dose increase reduced heroin use but not cocaine use. The Split 100mg group was the only group to achieve a longer duration of simultaneous negatives than its same-dose Noncontingent control group. The frequency of DSM-IV opiate and cocaine dependence diagnoses decreased in the active intervention groups. For a split contingency to promote simultaneous abstinence from cocaine and heroin, a relatively high dose of methadone appears necessary but not sufficient; an increase in overall incentive amount may also be required.
contingency management; polydrug dependence; methadone dose; DSM diagnoses
This study examined the effectiveness of methadone maintenance initiated prior to or just after release from prison at 6 months post-release.
A three-group randomized controlled trial was conducted between September 2003 and June 2005.
A Baltimore pre-release prison.
Two hundred and eleven adult pre-release inmates who were heroin-dependent during the year prior to incarceration.
Participants were assigned randomly to the following: counseling only: counseling in prison, with passive referral to treatment upon release (n = 70); counseling + transfer: counseling in prison with transfer to methadone maintenance treatment upon release (n = 70); and counseling + methadone: methadone maintenance and counseling in prison, continued in a community-based methadone maintenance program upon release (n = 71).
Addiction Severity Index at study entry and follow-up. Additional assessments at 6 months post-release were treatment record review; urine drug testing for opioids, cocaine and other illicit drugs.
Counseling + methadone participants were significantly more likely than both counseling only and counseling + transfer participants to be retained in drug abuse treatment (P = 0.0001) and significantly less likely to have an opioid-positive urine specimen compared to counseling only participants (P = 0.002). Furthermore, counseling + methadone participants reported significantly fewer days of involvement in self-reported heroin use and criminal activity than counseling only participants.
Methadone maintenance, initiated prior to or immediately after release from prison, increases treatment entry and reduces heroin use at 6 months post-release compared to counseling only. This intervention may be able to fill an urgent treatment need for prisoners with heroin addiction histories.
Heroin addiction; methadone maintenance; prisoners; randomized clinical trial; substance abuse treatment
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.
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.
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.
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.
heroin abuse; Brief Symptom Rating Scale; World Health Organization questionnaire on quality of life
Addictions to illicit drugs are among the nation’s most critical public health and societal problems. The current opioid prescription epidemic and the need for buprenorphine/naloxone (Suboxone®; SUBX) as an opioid maintenance substance, and its growing street diversion provided impetus to determine affective states (“true ground emotionality”) in long-term SUBX patients. Toward the goal of effective monitoring, we utilized emotion-detection in speech as a measure of “true” emotionality in 36 SUBX patients compared to 44 individuals from the general population (GP) and 33 members of Alcoholics Anonymous (AA). Other less objective studies have investigated emotional reactivity of heroin, methadone and opioid abstinent patients. These studies indicate that current opioid users have abnormal emotional experience, characterized by heightened response to unpleasant stimuli and blunted response to pleasant stimuli. However, this is the first study to our knowledge to evaluate “true ground” emotionality in long-term buprenorphine/naloxone combination (Suboxone™). We found in long-term SUBX patients a significantly flat affect (p<0.01), and they had less self-awareness of being happy, sad, and anxious compared to both the GP and AA groups. We caution definitive interpretation of these seemingly important results until we compare the emotional reactivity of an opioid abstinent control using automatic detection in speech. These findings encourage continued research strategies in SUBX patients to target the specific brain regions responsible for relapse prevention of opioid addiction.
In the US, methadone maintenance is restricted by federal and state regulations to large specialized clinics that serve fewer than 20% of the heroin-dependent population. In Europe, Canada, and Australia, primary health care providers already are utilized widely as methadone prescribers. In preparation for a limited study of office-based methadone treatment in New York City, 71 providers from 11 sites were surveyed about their willingness to prescribes methadone in their office-based pratices. Of the 71, 85% had methadone-maintained patients who came to their practice for other care. One-third felt knowledgeable enough to prescribes methadone, and 66% said they would if given proper training and support (88% among AIDS care providers). Half expressed concern that they might be unable to meet the multiple needs of these patients. With additional training and ancillary support, the 47 providers willing to become methadone providers could serve, at 10–20 patients each, 470–940 patients, a population the size of 3–5 average methadone clinics.
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.
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.
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.
Findings suggest that providing MMT within detoxification centers promotes successful referral of heroin addicts to community-based MMT upon their release.
Heroin addiction; Detoxification; Methadone maintenance treatment; HIV; China
The μ-opioid receptor is the site of action of opiates and opioids. We examined whether there are differences in CpG dinucleotide methylation in the OPRM1 promoter between former heroin addicts and controls. We analyzed methylation at sixteen CpG dinucleotides in DNA obtained from lymphocytes of 194 Caucasian former severe heroin addicts stabilized in methadone maintenance treatment and 136 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.
Methylation; addiction; gene; heroin; methadone; CpG
Opioid addiction is a chronic disease with high genetic contribution and a large inter-individual variability in therapeutic response. The goal of this study was to identify pharmacodynamic factors that modulate methadone dose requirement. The neurotrophin family is involved in neural plasticity, learning memory and behavior and deregulated neural plasticity may underlie the pathophysiology of drug addiction. BDNF was shown to affect the response to methadone maintenance treatment. This study explores the effects of polymorphisms in the nerve growth factor (beta polypeptide) gene, NGFB, on the methadone doses required for successful maintenance treatment for heroin addiction. Genotypes of 14 NGFB polymorphisms were analyzed for association with the stabilizing methadone dose in 72 former severe heroin addicts with no major co-medications. There was significant difference in methadone doses required by subjects with different genotypes of the NGFB intronic SNP rs2239622 (P = 0.0002). These results may have clinical importance.
methadone; opioid addiction; nerve growth factor; NGFB; heroin addiction
Interim methadone (with emergency counseling only) (IM), is an effective, but highly restricted alternative to Methadone Treatment Program (MTP) waiting lists. However, it is not known whether IM disadvantages patients as compared to standard methadone treatment (SM). In this clinical trial, conducted in two MTPs, 230 newly-admitted patients were randomly assigned to: IM, SM and “Restored” Methadone treatment (SM with a counselor with a reduced case load) (RM). Data were analyzed using generalized estimating equations and generalized linear modeling. There were no significant differences among Conditions in: days in treatment or of heroin or cocaine use and heroin or cocaine positive urine drug tests. The IM as compared to the SM group had significantly fewer self-reported days of criminal activity and lower amounts of money spent on drugs and illegal income. These findings suggest that when SM is unavailable, IM should be more widely used and less restricted. These findings suggest that when SM is unavailable IM should be more widely utilized and less restricted.
Interim methadone; methadone treatment; waiting lists; opioid dependence; counseling
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.
The study examined concurrent illicit heroin use among methadone maintenance clients in China and its association with clients’ demographic characteristics, treatment experience, and personal social network.
Face-to-face surveys were conducted with 178 clients randomly recruited from six methadone maintenance treatment (MMT) clinics in Sichuan, China. Concurrent heroin use was measured based on self-report of heroin use during the past 30 days and a confirmatory urine morphine test. The participants’ demographic characteristics and treatment factors were measured and examined. The drug use status of their family members and friends was also assessed.
A total of 80 participants (44.9%) who either reported illicit heroin use in the past 30 days or had a positive urine test were defined as using heroin concurrently. Having drug-using friends was significantly associated with increased concurrent heroin use. Longer length of treatment (2 years or longer) was associated with increased concurrent heroin use. Among those who had both drug-using family members and friends, more women (71.4%) than men (50.0%) used heroin. For those who had no drug-using family members or friends, more men (34.8%) than women (20.8%) used heroin.
Study findings indicate an urgent need to address concurrent illicit heroin use among MMT clients. Further examination of the influence of social networks on concurrent drug abuse behavior is encouraged. Results also highlight the importance of understanding gender differences in treatment seeking and behavioral changes, which is crucial to the development of gender-specific treatment strategies.
Drug use; Methadone maintenance therapy; China
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.
heroin addiction; prisoners; methadone maintenance