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Background: Injection opioid use is associated with more severe health and psychosocial consequences relative to non-injection use, but few studies have examined whether injection use is associated with methadone maintenance treatment outcomes. The present study examined differential MMT outcomes among opioid injectors and non-injectors.Methods: Data were extracted from the clinic charts of opioid-dependent MMT patients (N = 290; n = 115 injectors) enrolled in a university-affiliated, urban MMT clinic. Injection status was examined as a predictor of short- (3-month opioid, cocaine, benzodiazepine and cannabis urine drug screens) and long- (days retained in treatment) term MMT outcomes.Results: Bivariate analyses revealed injection users were less likely to be African American and to have completed high school, were more likely to have started heroin use before age 21, to report having hepatitis C, to report a baseline cocaine use disorder, and had higher methadone doses at 3-months into treatment. Injection status significantly predicted a greater proportion of cocaine-positive urine drug screens in the first 3 months of treatment, but did not significantly predict opioid, benzodiazepine or cannabis drug screens, or length of treatment retention.Conclusion: This is one of a handful of studies to examine injection status as a predictor of MMT outcomes. Injection status is associated with cocaine use early in treatment, which has implications for the focus of treatment. [ABSTRACT FROM AUTHOR]

Background. Methadone maintenance treatment (MMT) is recognized as a reference treatment for opioid dependence. According to Italian Law, at the beginning of the treatment patients must receive medication under the supervision of a physician, to avoid overdose. After a period of stability, patients could be allowed to take methadone at home in pre-arranged and personalized concentrations, in order to empower their self-responsibility. The aim of the present investigation is to underline the presence of a “glitch in the system” of the MMT. Methods. In the last three years, 7 forensic autopsies and toxicological analysis on corpses of regular opioid users were performed into the Institute of Legal Medicine of Bari. Results. In all these cases very high methadone concentration in blood were found. All the 7 subjects were following a MMT in a Public Health Institute and the cause of death was respiratory depression by overdose of methadone in 6 cases. Conclusion. Therefor an improvement of the MMT’s guideline is needed to reduce methadone overdose deaths in future. [ABSTRACT FROM AUTHOR]

Quality of life (QoL) is found to be lower in heroin addicts; however, few studies examine detailed QoL performance and related factors in heroin patients attending a methadone maintenance treatment program (MMTP). The study thus aimed to explore QoL and its determinants for publicly-funded and self-paid patients attending an MMTP. Methods: Participants were recruited in Jianan Psychiatric Center, Tainan, Taiwan, during their first clinic visit for the MMTP. Age-, sex-, education-, and municipality-matched referents were collected from the 2001 Taiwan National Health Interview Survey database. The participants had a mean age of 38.29 years [standard deviation (SD) = 7.65 years] for publicly-funded (n = 129) and 37.97 years (SD = 7.16 years) for self-paid (n = 105) MMTP patients. Matched referents (n = 217) were 37.74 years (SD = 7.44 years). All participants were measured with the brief version of the World Health Organization's Quality of Life (WHOQOL-BREF) assessment. MMTP patients additionally went through tests for the hepatitis B virus, hepatitis C virus, and human immunodeficiency virus (HIV). Results: Both publicly-funded and self-paid MMTP patients had lower QoL scores than their matched counterparts in the physical and psychological domains (p

Abstract Background The rapid expansion of methadone maintenance treatment (MMT) services has significantly improved health status and quality of life of patients. However, little is known about its impacts on addiction-related stigma and associated factors. Methods A cross-sectional survey was conducted in 2013 in Vietnam’s capital, Hanoi, and Nam Dinh province among 1016 methadone maintenance patients; 26.6 % at provincial AIDS centers (PAC) and 73.4 % at district health centers (DHC), respectively. Drug addiction history and related stigma, health status, MMT-related covariates, and sociodemographic characteristics were interviewed. Results More than one-sixth of the sample reported experiencing felt or enacted stigma, including Blame or Judgement (17.2 %), Shame (19.9 %), or Others’ fear of HIV transmission (17.1 %). These proportions were higher in PACs than in DHCs, which are integrated with other HIV or general health care services. Very few patients reported being discriminated at the workplace (2.5 %) or at health care services (1.7 %); however, 15.6 % of patients at PACs and 10.6 % of patients at DHCs reported discrimination in their communities. Drug users taking MMT for longer periods were less likely to report felt stigma. Other factors associated with stigma against MMT patients included the lack of comprehensive services, higher education, presence of pain/discomfort, and anxiety/depression, self-reported HIV positive, and number of previous drug rehabilitation episodes. Conclusion The study shows a high level of stigma against MMT patients and emphasizes the necessity to integrate MMT with comprehensive health and support services. Mass communication campaigns to reduce stigma against people with drug addiction and HIV/AIDS, as well as vocational trainings and jobs referrals for MMT patients, are needed to maximize the benefits of MMT programs in Vietnam.

Background‎: The relationship between substance use and sleep is bidirectional. Substance use directly causes sleep disturbances, and sleep problems are a critical factor in substance-use relapse. Methods: This study evaluated sleep disorders in 65 methadone maintenance treatment (MMT) patients, and 61 opium-dependent patients who did not receive any treatment between September 2011 and July 2012 in Kermanshah, Iran. Both groups filled out the Pittsburgh Sleep Quality Index (PSQI) and Global Sleep Assessment Questionnaire (GSAQ).Findings: Sleep disorders were remarkably similar in both groups: 78.5% of MMT patients and 87.7% of opium-dependent patients suffered from sleep problems. Sleep disorders in the opium-dependent group were remarkably higher and more prominent.Conclusion: Compared to opium, MMT does not have as many negative effects on sleep and is more effective in mitigating sleep problems.

Objective: To explore the association between methadone dosage, plasma drug concentration, SNPs of μ-opioid receptor gene (OPRM1), ATP-binding cassette subfamily B member 1 gene (ABCB1), and methadone maintenance treatment (MMT) response.Method: A total of 240 Chinese Han participants receiving MMT were recruited from Shanghai. Nine single nucleotide polymorphisms (SNPs) of the OPRM1 gene and three SNPs of the ABCB1 gene were genotyped, plasma methadone concentration was detected, and a morphine urine test was taken from all subjects.Results: Methadone dosage, plasma methadone concentration, and negative rate of morphine urine test of retention participants were significantly higher, although the addiction severity index (ASI) was not significantly different between the two groups. A allele and AA genotype carriers of rs562859 (OPRM1 gene) had better compliance of MMT, and AA genotype carriers had a higher negative rate of morphine urine test. However, the difference was not significant after adjusting influence factors (age, sex, and methadone dosage). GG genotype carriers of rs3192723 (OPRM1 gene) had a significantly lower negative rate of morphine urine test, and the difference was still significant after adjusting influence factors. Logistic regression analysis showed that methadone-free trough concentration (OR = 0.910, p = 0.023) and AA genotype of rs526859 (OR = 0.580, p = 0.037) were associated with better compliance of MMT. After Bonferroni correction, only free trough concentration of methadone was negatively correlated with MMT compliance. The SNPs rs6912029 (OR = 0.021, p = 0.066) and rs6902403 (OR = 0.910, p = 0.007) of the OPRM1 gene, age at first use (OR = 1.118, p = 0.005), and average methadone dosage (OR = 1.033, p = 0.045) were associated with MMT effect. After Bonferroni correction, average methadone dosage was no longer correlated with MMT effect.Conclusion: Dosage of methadone, plasma methadone concentration, several SNPs (rs3192723, rs6912029, rs6902403) of the OPRM1 gene, and age of first drug use were associated with better MMT outcomes.

Background: Topiramate facilitates gamma aminobutyric acid (GABA) transference and an ideal candidate for reducing cocaine use in methadone patients. The present study evaluated topiramate in Dual dependence on opiate and cocaine. Methods: This placebo-controlled study (Clinical Trial Registration Code: TCTR20170201001) conducted during the period 2013–2014, Cocaine-dependent individuals maintained on methadone (n=50) were randomized to receive topiramate or identical placebo capsules. Participants' dosage ranged between 25-300 mg/day (12 wk) in escalating doses. Methadone Doses started at 30 mg/day (median 100 mg/day; range 20 –140 mg/day). In addition, all subjects received brief behavioral compliance enhancement treatment (BBCET). The data were analyzed by Chi-square Test, generalized estimating equations (GEE) models, linear mixed effects (LME) model and Analysis of covariance (ANCOVA). Primary outcome measures included twelve weekly urine drug screens (cocaine abstinence, detection of benzoylecgonine) and treatment retention. Secondary outcome measures included correlation between cocaine craving with cocaine urine samples and Side effects of depression. Results: Topiramate was not better than placebo in reducing cocaine use. The secondary outcome showed that Topiramate was better than placebo in reducing cocaine craving. The mean [99% confidence interval (CI)] scores of cocaine craving were 24.31 (18.61–30.01) in experimental group and 21.84 (16.86–26.81) in control group (all P > 0.01). Retention and correlation between cocaine craving and cocaine urine samples were not significantly different between the groups. Topiramate usage was not associated with increase in depression symptoms as a side effect (P>0.05). Conclusion: The efficacy of topiramate in cocaine treatment is limited and needs the similar controlled clinical trials and can be used as a complementary intervention.

IntroductionMethadone maintenance treatment (MMT) programs have been rapidly scaled up nationwide in China in recent years, and psychosocial intervention measures, including counseling, were recommended for improving the outcomes of MMT. However, the effectiveness of counseling in MMT programs remains controversial. This study investigated the efficacy of educational and behavioral counseling (EBC) mode in an MMT program in China.MethodsA total of 125 eligible participants were randomized to EBC or a control group. Patients in the EBC group received weekly, manual-guided, group educational counseling for 8 weeks and individual behavioral counseling for the next 8 weeks. Patients in the control group received standard methadone maintenance treatment as usual (TAU).ResultsDuring the 16-week trial, the EBC group showed better treatment attendance (P = 0.022) and a greater increase in knowledge regarding heroin addiction (P = 0.001) and MMT (P = 0.005) than did the TAU group. Between the two groups, there were no significant differences regarding drug abstinence and reduction of risky behaviors.ConclusionEBC affiliated with MMT improved patients’ cognition and adherence to treatment, facilitating their successful recovery.Clinical Trial RegistrationChiCTR-IOR-15006673: http://www.chictr.org.cn.

Objective: Frequent use of opioids produces reactive oxygen species, upregulates inflammatory factors, and contributes to opiate dependence. In this study, we examined perturbations of plasma oxidative and inflammatory markers in patients with opioid use disorder in two phases. In the first phase, we compared the oxidative status in patients with opioid use disorders and in healthy controls; and in the second phase, we examined oxidative changes before and after methadone maintenance treatment. Method: To explore whether oxidative changes were associated with opioid use disorder, we compared plasma oxidative and inflammatory markers in patients with opioid use disorder and in smoking and non-smoking healthy participants. All participants completed measures of catalase (CAT), glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), matrix metalloproteinase (MMP-9), and TNF-α at baseline. Baseline measures were compared using Kruskal-Wallis test. In the second phase, to explore oxidative changes during transition from opium use to methadone, blood and urine samples of patients with opioid use disorder were re-evaluated on Days 3, 7, and 14 after methadone therapy. Repeated measures analysis was used to determine the relative contribution of intervention to changes in CAT, GSH, MDA, SOD, MMP-9, and TNF-α level over time. Results: We observed lower SOD and catalase activities, and higher TNF-α and MMP-9 level in patients compared to the two comparison groups. Opioids exacerbated the oxidative imbalance and superimposed the underlying oxidative injury in smoker comparison group. Methadone therapy was associated with lower MMP-9 and TNF-α level, and higher SOD and catalase activities two weeks after therapy; showing an improvement in oxidative profile. Conclusion: This was an investigation indicating an oxidative imbalance before methadone therapy and during early days of transition from opium use to methadone. Being aware of redox status is crucial for determining an appropriate antioxidant therapy in opioid use disorder.

Background: Methadone maintenance treatment (MMT) has been implemented in China for nearly two decades, with a significant decrease in the number of participants in recent years. However, there is a lack of comprehensive research focusing on the long-term effectiveness in the context of this decline, especially from the perspectives of MMT participants themselves. This study aims to address this gap by examining the benefits and challenges experienced by long-term MMT participants in China, to uncover potential causes of the decrease in participant numbers and to improve the effectiveness of the program., Methods: We conducted semi-structured interviews with 21 long-term MMT participants (treatment duration ≥ 5 years) recruited through purposive sampling from 6 MMT clinics in the Guangdong Province, China, between December 2021 and August 2022. Thematic analysis was employed to analyze the transcribed interviews. Two analysts independently coded the data, and a third researcher double-coded 20% of transcripts to ensure intercoder reliability., Results: Overall, participants corroborated the notable decline in MMT participants during their long-term MMT, citing death, arrest, and self-perceived abstinence from heroin, as their perceived driving factors. They reported positive changes in their health, family relationships, and social functioning. However, they identified economic hardship as their greatest challenge associated with MMT, further exacerbated by other barriers including the conflict of clinic opening hours and working schedules, discrimination from employers, and COVID-19-related restrictions. Additionally, participants identified issues with dose adjustment and emergency treatment continuation., Conclusions: This study outlines the overall improvement in the quality of life of long-term MMT participants. However, it highlights the need for official guidelines for dose adjustment and emergency treatment continuation as well as the provision of health education, job referrals, and flexibility of clinic opening times to facilitate the return to society receiving participants. Establishing a follow-up mechanism for those receiving MMT is also recommended to prevent relapses to heroin and other illicit substances., (© 2023. The Author(s).)

Elevated impulsivity has been frequently reported in individuals with opioid addiction receiving methadone maintenance therapy (MMT), but the underlying neural mechanisms and cognitive subprocesses are not fully understood. We acquired functional magnetic resonance imaging (fMRI) data from 37 subjects with heroin addiction receiving long-term MMT and 33 healthy controls who performed a probabilistic reversal learning task, and measured their resting-state brain glucose using fluorine-18-fluorodeoxyglucose positron emission tomography ( 18 F-FDG PET). Subjects receiving MMT exhibited significantly elevated self-reported impulsivity, and computational modeling revealed a marked impulsive decision bias manifested as switching more frequently without available evidence. Moreover, this impulsive decision bias was associated with the dose and duration of methadone use, irrelevant to the duration of heroin use. During the task, the switch-related hypoactivation in the left rostral middle frontal gyrus was correlated with the impulsive decision bias while the function of reward sensitivity was intact in subjects receiving MMT. Using prior brain-wide receptor density data, we found that the highest variance of regional metabolic abnormalities was explained by the spatial distribution of μ-opioid receptors among 10 types of neurotransmitter receptors. Heightened impulsivity in individuals receiving prolonged MMT is manifested as atypical choice bias and noise in decision-making processes, which is further driven by deficits in top-down cognitive control, other than reward sensitivity. Our findings uncover multifaceted mechanisms underlying elevated impulsivity in subjects receiving MMT, which might provide insights for developing complementary therapies to improve retention during MMT., Competing Interests: Declaration of Competing Interest The authors report no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Methamphetamine use threatens positive treatment outcomes in substance use and HIV, for people with opioid use disorders (POUD) in many countries. This paper describes the adaptation of four evidence-based interventions (EBI) (motivational interviewing, contingency management, Matrix group model and SMS text messaging) for treating methamphetamine use among POUD receiving methadone maintenance therapy in Vietnam., Methods: Following the ADAPT-ITT (Assessment-Decision-Administration-Production-Topical experts-Training-Testing) framework, we conducted 16 focus group discussions with POUD (n = 25) and providers (n = 22) at four methadone clinics in two largest cities (Hanoi in the North, Ho Chi Minh City in the South) to assess patterns of methamphetamine use and to get feedback on proposed EBIs. The proposed EBIs were properly adapted and used to train providers in two of the four methadone clinics. The revised EBIs were tested over 12 weeks among 42 POUD on methadone who use methamphetamine. Post-intervention feedback served to fine-tune the revised EBIs., Results: Insights about patterns of methamphetamine use suggested that EBIs should focus on different triggers to methamphetamine use among POUD receiving methadone treatment in the two cities. All EBIs should emphasise family-related topics to build a strong motivation for treatment. Participants suggested when, where and how each EBI should be delivered. Most participants were satisfied with the adapted EBIs. Limited human resources at methadone clinics might hinder implementation of the adapted EBIs., Discussion and Conclusions: We successfully completed the adaptation of EBIs for POUD who use methamphetamine on methadone in Vietnam. The pilot testing of the adapted EBIs demonstrated feasibility and acceptability., Trial Registration: NCT04706624. Registered 13 January 2021. https://clinicaltrials.gov/ct2/show/NCT04706624., (© 2023 Australasian Professional Society on Alcohol and other Drugs.)

Background: The prevalence of addiction is increasing in the world. Methadone Maintenance Treatment (MMT) can be associated with severe stress and mild to moderate depressive symptoms. Vitamins and minerals are commonly found in multivitamins seem to improve mood. Therefore, the aim of this study was to evaluate the effect of multivitamins on anxiety and depression in patients undergoing MMT in a double-blind randomized controlled trial., Methods: The study was designed as a double-blind, randomized controlled trial and involved 70 male MMT patients over the age of 18. Participants were randomized to one of two groups, either those receiving multivitamins or those receiving a placebo for 12 weeks. The multivitamin capsule included vitamin E, B1, B2, B3, B5, B6, B12, C, biotin, folic acid, and zinc. Anxiety and depression were measured using standard questionnaires, before and after the intervention., Results: The between-group comparison (i.e., intervention vs. placebo) indicated there was no significant difference in anxiety scores; however, there was a significant between-group difference in depression scores, favoring the intervention group., Conclusions: Multivitamin supplementation improved depression but did not have a significant impact on anxiety in patients undergoing MMT., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Heroin users are vulnerable and represent a highly-infected reservoir for hepatitis C virus (HCV) infection. This study investigated HCV prevalence and genotypes distribution among heroin users who received methadone maintenance treatment (MMT) in Jiangsu.Methods: From June to December in 2016, a total of 534 patients among nine MMT clinics in six regions of Jiangsu were enrolled, with their demographic characteristics collected and serum samples tested for HCV antibody. 395 samples were seropositive and furthered to RNA extraction. HCV NS5B region fragments were amplified and subsequently sequenced.Results: Among HCV seropositive samples, 240 were characterized by NS5B partial sequences and classified into four genotypes (GPs) and eight subtypes. HCV GP3 predominated and accounted for 66.3%, followed by GP1 (27.5%), GP6 (4.2%) and GP2 (2.1%). HCV subtypes 3b (41.7%) and 3a (24.6%) were the most common subtypes. None of the demographic characteristics showed a significant difference when comparing with HCV genotypes. The geographic feature shown GPs in six regions were the same, but the frequency of subtypes exhibited regional divergence. Phylogenetic analyses demonstrated that 3b had become a local endemic in Jiangsu.Conclusion: The distribution of HCV subtypes among heroin users in Jiangsu province was complex. The data could provide more precise estimates for HCV prevalence and genotype distribution as well as heroin users of Jiangsu province. [ABSTRACT FROM AUTHOR]

Background: Service providers including doctors, nurses, and other healthcare professionals play an essential role in methadone maintenance treatment (MMT). This study evaluated the impact of an intervention targeting MMT providers on their clients' treatment retention.Methods: This study was conducted in 68 MMT clinics in five provinces of China with 36 clients randomly selected from each clinic. The clinics were randomized to intervention or control condition. The MMT CARE intervention started with group sessions to enhance providers' communication skills. The trained providers were encouraged to conduct individual sessions with clients to promote treatment engagement. The outcomes, which include client retention (main outcome) and their reception of provider-delivered individual sessions (process outcome), were measured over a 24-month period.Results: Significantly fewer intervention clients dropped out from MMT than control clients during the study period (31% vs. 41%; p < 0.0001). Dropout hazard was significantly lower in the intervention condition compared to the control condition (HR = 0.71, 95% CI: 0.57, 0.89). More intervention clients had individual sessions than control clients (93% vs. 70%; p < 0.0001). Having individual sessions was associated with a significantly lower dropout hazard (HR = 0.30, 95% CI: 0.23, 0.40). The intervention clients had a significantly lower dropout hazard than the control clients if they started the individual sessions during the first six months (HR = 0.68, 95% CI: 0.51, 0.90).Conclusions: The MMT CARE intervention focusing on provider capacity building has demonstrated efficacy in reducing clients' treatment dropout. This study sheds light on MMT service improvement in China and other global community-based harm reduction programs. [ABSTRACT FROM AUTHOR]

Highlights • History of childhood trauma showed a decreased ability to learn stimuli with a positive reward. • History of childhood trauma showed an increased ability to learn stimuli with a negative outcome. • Traumatic life events are correlated with negative reward fixation. • Difficulty of performance was observed mainly in drug-related (cue) context. • Results reflect the consistent need to compensate the attention when cue exist. Abstract Previously we showed that methadone maintenance treatment (MMT) patients displayed difficulties in generalization and reversal learning in the presence of drug-related context, compared to prolonged abstinence individuals. We now tested how history of childhood trauma, affects their reversal learning abilities. Fifty-one MMT patients were evaluated on a performance- based paradigm which assesses the ability to acquire and reverse stimulus–outcome associations in neutral and drug-related context. Patients with a history of childhood trauma (n = 32) as compared to patients without such a history showed decreased ability to learn associations with positive outcome, and had poorer performance in drug compare to neutral-related context. Most importantly, while individuals with childhood trauma history showed higher success rates in conditions of positive to negative reversals, an opposite pattern was observed in conditions of negative to positive reversal; whereas patients with trauma history preformed significantly worse than patients with no history. The results are in line with other studies which tested the effects of childhood trauma both in clinical and in healthy populations. Recognizing this trait that more disturbed by drug related context, may contribute to develop and improve personalized treatments which takes into account the difficulties as well as the strength associated with childhood trauma. [ABSTRACT FROM AUTHOR]

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Background: The US has the highest incarceration rate in the world and spends $40-$80 billion to house inmates per year. It is well-known that a significant correlation is present between substance use and crime, especially over recent years as opioid use disorder (OUD) has grown exponentially. To mitigate OUD, methadone maintenance treatment (MMT) has demonstrated effectiveness in numerous randomized and quasi-experimental studies. A potentially fruitful environment for MMT is correctional facilities, particularly short-term facilities, such as city and county jails. However, little is known about the economic implications of MMT within correctional facilities.Objective: The aim of the present study was to estimate the economic costs of jail-based MMT using data from a novel, established MMT program located within a large urban jail in New Mexico.Methods: Data were collected using administrative records and by interviewing program administrators using a modified version of the Drug Abuse Treatment Cost Analysis Program (DATCAP). Both sensitivity analysis and cost-structure analysis were conducted to gauge the robustness of the findings.Results: The average (per patient) weekly cost of MMT is $115 and the total treatment cost for an average treatment episode is $689. These costs are generally in-line with non-jail-based MMT programs of similar size. Weekly cost estimates range from $86 to $185 depending on the size of the treatment facility, with larger programs exhibiting lower per-patient costs.Conclusion: Results provide a valuable economic benchmark to policy makers, criminal justice officials, and program administrators considering establishing and/or expanding MMT in jail settings. [ABSTRACT FROM AUTHOR]

Introduction: Illicitly manufactured fentanyl (IMF) is a potent synthetic opioid that has been contributing to overdose deaths in the United States. This study examined intake toxicology and six-month treatment outcomes for patients newly admitted to a single methadone maintenance treatment program (MMTP) in Rhode Island with a high prevalence of illicit fentanyl.Methods: We conducted a retrospective chart review of patients admitted to a single MMTP between November 1st, 2016 and August 31st, 2017 followed for six months. Outcomes measured included: 1) retention in treatment at 6 months; 2) evidence of sustained abstinence; 3) relapse; 4) methadone dosage required to achieve sustained abstinence; and 5) the number of days required to achieve abstinence.Results: We observed 154 unique intake events (representing 147 patients). 80% (n = 123) tested positive for fentanyl at intake. During the six-month follow up period, 32% (n = 49) left treatment before six months, two individuals died within five weeks of discontinuation. No deaths were seen among those remaining in treatment. The majority (89%) who remained in treatment at six months achieved abstinence. No significant difference was seen for dose or time to achieve abstinence. Relapse was common (57%). Repeated exposure to fentanyl was seen frequently (71%) while in MMT before and after achieving abstinence.Conclusion: While there is concern that the potency of IMF may reduce the effectiveness of MAT, this study suggests that MMT is safe, abstinence achievable, and MMT is protective against death among fentanyl-exposed patients. [ABSTRACT FROM AUTHOR]

Objective: To explore the association between methadone dosage, plasma drug concentration, SNPs of μ-opioid receptor gene (OPRM1), ATP-binding cassette subfamily B member 1 gene (ABCB1), and methadone maintenance treatment (MMT) response. Method: A total of 240 Chinese Han participants receiving MMT were recruited from Shanghai. Nine single nucleotide polymorphisms (SNPs) of the OPRM1 gene and three SNPs of the ABCB1 gene were genotyped, plasma methadone concentration was detected, and a morphine urine test was taken from all subjects. Results: Methadone dosage, plasma methadone concentration, and negative rate of morphine urine test of retention participants were significantly higher, although the addiction severity index (ASI) was not significantly different between the two groups. A allele and AA genotype carriers of rs562859 (OPRM1 gene) had better compliance of MMT, and AA genotype carriers had a higher negative rate of morphine urine test. However, the difference was not significant after adjusting influence factors (age, sex, and methadone dosage). GG genotype carriers of rs3192723 (OPRM1 gene) had a significantly lower negative rate of morphine urine test, and the difference was still significant after adjusting influence factors. Logistic regression analysis showed that methadone-free trough concentration (OR = 0.910, p = 0.023) and AA genotype of rs526859 (OR = 0.580, p = 0.037) were associated with better compliance of MMT. After Bonferroni correction, only free trough concentration of methadone was negatively correlated with MMT compliance. The SNPs rs6912029 (OR = 0.021, p = 0.066) and rs6902403 (OR = 0.910, p = 0.007) of the OPRM1 gene, age at first use (OR = 1.118, p = 0.005), and average methadone dosage (OR = 1.033, p = 0.045) were associated with MMT effect. After Bonferroni correction, average methadone dosage was no longer correlated with MMT effect. Conclusion: Dosage of methadone, plasma methadone concentration, several SNPs (rs3192723, rs6912029, rs6902403) of the OPRM1 gene, and age of first drug use were associated with better MMT outcomes. [ABSTRACT FROM AUTHOR]

The objective of the present study was to determine whether methadone maintenance treatment (MMT) in heroin-dependent patients affects inhibitory control, whether any MMT-induced changes correlate with methadone dose and MMT duration, and whether these changes depend on the psychological characteristics of patients, such as depression, anxiety and impulsivity. Response inhibition in the GO/NO-GO test was combined with functional magnetic resonance imaging (fMRI) scanning data to examine whether MMT affects inhibitory control in 21 heroin-addicted patients who had already undergone at least three months of MMT. Patients were evaluated one year prior to and after the MMT period. Participants exhibited no difference in their GO/NO-GO reaction time and accuracy rate, or in their false alarm rate under NO-GO conditions. However, increased activation was detected in numerous brain regions in their 12-month fMRI scans, although these were not in the frontal-striatal loop. Increased fMRI activation in the left precentral gyrus and superior temporal gyrus were negatively correlated with the daily methadone dose and total methadone dose during the one-year study period. In conclusion, these results suggested that MMT over one year does not significantly change the behavioral indicators of inhibitory control function in heroin-dependent patients. The increase in activation leads to the hypothesis that MMT over one year may increase cognitive inhibitory control, which may be the result of the combined negative effect of methadone and the positive effect of functional recovery after withdrawal of heroin. [ABSTRACT FROM AUTHOR]