Search Results (32)

Background/Objectives: Methadone maintenance treatment (MMT) is widely used in opioid use disorder (OUD). Its efficacy is influenced by its metabolism, primarily mediated by Cytochrome P450 (CYP450) enzymes in the liver. Genetic polymorphisms in CYP450 genes and other factors, such as age, sex, and concomitant treatments, contribute to interindividual variability in methadone response. This article addresses the relevance of pharmacokinetic biomarkers in methadone metabolism and its impact on treatment outcomes in European populations over the past 25 years. Methods: A systematic review was conducted using four databases (PsycINFO, PubMed, Scopus, and Web of Science) for studies published between 2000 and 2024 following the PRISMA 2020 guidelines (CRD42025641373 in PROSPERO). Two independent reviewers screened and assessed the study quality using NHLBI tools. Discrepancies were solved through consensus. Relevant data including sample size, genetic biomarkers, and key findings were extracted for each study. Data were synthesized and described in detail. Results: Fourteen studies on pharmacogenetic biomarkers influencing methadone metabolism in European populations were analyzed, encompassing a total of 3180 subjects. CYP2B6*6 was identified as a key variant associated with increased (S)-methadone plasma levels, potentially leading to cardiac complications, while the role of other pharmacokinetic genes, including ABCB1 and CYP2D6, was inconclusive. Conclusions: Genetic polymorphisms significantly influence methadone metabolism, with the CYP2B6*6 allele playing a key role in (S)-methadone metabolism and associated with cardiac risks. Pharmacogenetic studies integrating co-mediation—the principal cause of phenoconversion—as a potential variable alongside gender differences and encompassing adequate sample sizes could improve outcomes and establish the basis for personalized medicine of MMT. Full article

The main objective of this study was to assess the positive emotions and the quality of life among patients on methadone maintenance therapy (MMT) as well as their associated factors. This is a cross-sectional survey study. Participants undergoing MMT in two major Malaysian hospitals responded to the sociodemographic and clinical information sheet, the Positive Emotion Rating Scale (PERS), and the World Health Organization Quality of Life (WHOQOL)-BREF. Most of the participants (N = 154; mean age = 43.8 ± 9.0 years) were male (97.4%) and Malays (75.3%). Slightly more than half (50.6%) scored above 30 on the Positive Emotion Rating Scale. There was a significant association between being ethnically Malay, married, and employed and positive emotions. After adjusting for potential confounding factors, having positive emotions predicted a better overall, physical, and psychological quality of life. Being non-diabetic also significantly predicted a better quality of life in the overall domain, whilst not being married and family history of mental illness significantly predicted a lower overall and psychological quality of life. Positive emotions significantly improve patients’ quality of life in the MMT program, suggesting the inclusion of positive emotions in a holistic treatment approach. Full article

This study investigates the impact of methadone maintenance treatment (MMT) on the brain glymphatic system (GS) in opioid addiction in China. A total of 51 male MMT patients, 48 demographically matched healthy controls (HCs), and 20 heroin dependents (HDs) were recruited for this study. The GS functioning was assessed using diffusion-tensor-imaging analysis along perivascular spaces (DTI-ALPS index) and the bilateral ALPS divergency (DivALPS). Group differences were analyzed utilizing ANOVA and two-sample t-tests. The relationship between DivALPS and relapse rate was explored using regression analysis. The DTI-ALPS index was significantly higher for the left-side brain than the right side in all three groups. There was a significant difference for the right side (p = 0.0098) between the groups. The MMT and HD groups showed significantly higher DTI-ALPS than the HC group (p = 0.018 and 0.016, respectively). The DivALPS varied significantly among the three groups (p = 0.04), with the HD group showing the lowest and the HC group the highest values. Significant negative relationships were found between relapse count, DivALPS (p < 0.0001, Exp(B) = 0.6047), and age (p < 0.0001, Exp(B) = 0.9142). The findings suggest that MMT may contribute to promoting brain GS recovery in heroin addicts, and modulation of the GS may serve as a potential biomarker for relapse risk, providing insights into novel therapeutic strategies. Full article

Long-acting buprenorphine formulations have been recently marketed for the Opioid Agonist Treatment (OAT) of opioid use disorder (OUD) associated with medical, social, and psychological support. Their duration of action ranges from one week up to 6 months. The non-medical use of opioids is increasing with a parallel rise in lethal overdoses. Methadone and buprenorphine are the standard treatment for opioid dependence. Methadone Maintenance Treatment (MMT) is widely recognized as one of the most effective ways of reducing the risks of overdose, crime, and transmission of HIV (Human Immunodeficiency Virus) in people who use opioids; however, its effectiveness has been hindered by low rates of uptake and retention in treatment. Furthermore, both methadone and buprenorphine are widely diverted and misused. Thus, a crucial aspect of treating OUD is facilitating patients’ access to treatment while minimizing substance-related harm and improving quality of life. The newly developed long-acting buprenorphine formulations represent a significant change in the paradigm of OUD treatment, allowing an approach individualized to patients’ needs. Strengths of this individualized approach are improved adherence (lack of peaks and troughs in blood concentrations) and a reduced stigma since the patient doesn’t need to attend their clinic daily or nearly daily, thus facilitating social and occupational integrations as the quality of life. However, less frequent attendance at the clinic should not affect the patient–physician relationship. Therefore, teleconsulting or digital therapeutic services should be developed in parallel. In addition, diversion and intravenous misuse of buprenorphine are unlikely due to the characteristics of these formulations. These features make this approach of interest for treating OUD in particular settings, such as subjects staying or when released from prison or those receiving long-term residential treatment for OUD in the therapeutic communities. The long-lasting formulations of buprenorphine can positively impact the OUD treatment and suggest future medical and logistic developments to maximize their personalized management and impact. Full article

Methadone treatment reduces the use of heroin and withdrawal symptoms; however, methadone is an expensive medication with a narrow safety margin. We compared the retention rates, persistence of heroin use, and quality of life of a group of patients undergoing conventional Methadone Maintenance Treatment (MMT) with a group for whom the CYP2B6 516G>T polymorphism was used in addition to the MMT to calculate the required methadone dose. Over 12 weeks, the retention rate, heroin usage, and quality of life of patients under conventional treatment (n = 34) were compared with those of patients for whom we used genetic markers to calculate methadone dosage (n = 38). At the end of the study, 26.4% of patients abandoned the program, and neither demographic nor clinical variables were associated with treatment adherence. Of the remaining patients, 16% of the control group and 8% of patients in the pharmacogenetic group reported heroin use, while both groups showed a 64% reduction in the use of cocaine/crack (no significant differences between the groups were found). Starting in the second week, the methadone dosage was lower among the patients for whom methadone was prescribed based on genotype. Although there were six individuals in the control group and three in the pharmacogenetic group with QTc intervals > 450 ms (a threshold that is considered dangerous), we did not find a relationship between the QTc interval and methadone dosage. There were no differences in the perception of quality of life between the two groups. The results of this pilot study suggest that concerning methadone therapy, the CYP2B6 genotype contributes to reduced effective doses and treatment costs. Full article

Chronic opioid use disorder patients often also use other substances such as amphetamines. The gene-based analysis method was applied in the genomic database obtained from our previous study with 343 methadone maintenance treatment (MMT) patients. We found that the gene encoding gamma-aminobutyric acid type A receptors (GABA-A receptor) delta subunit isoforms (GABRD) was associated with amphetamine use in heroin dependent patients under MMT in Taiwan. A total of 15% of the 343 MMT patients tested positive for amphetamine in the urine toxicology test. Two genetic variants in the GABRD, rs2889475 and rs2376805, were found to be associated with the positive urine amphetamine test. They are located in the exon 1 of the splice variant and altered amino acid compositions (T126I, C/T, for rs2889475, and R252Q, G/A, for rs2376805). The CC genotype carriers of rs2889475 showed a four times higher risk of amphetamine use than those with TT genotype. The GG genotype carriers of rs2376805 showed a three times higher risk of amphetamine use than the AA genotype carriers. To our knowledge, this is the first report that demonstrated an association of the delta splice variant isoform in the GABA-A receptor with an increased risk of amphetamine use in MMT patients. Our results suggest that rs2889475 and rs2376805 may be indicators for the functional role and risk of amphetamine use in MMT patients. Full article

(1) Background: Internet gaming disorder (IGD) shares many similarities with substance use disorder (SUD), contributing to its recognition as an addictive disorder. Nevertheless, no study has compared IGD to other addictive disorders in terms of personality traits established as highly co-occurring with SUDs. (2) Methods: We recruited a sample of gamers (massively multiplayer online role-playing games) (MMORPGs) via online in-game forums. We compared 83 individuals with IGD (MMORPG-IGD group) to 47 former heroin addicts under methadone maintenance treatment (MMT; MMT group) with regard to alexithymia, impulsivity, sensation seeking and aggressiveness assessed through self-administered scales, being TAS-20, BIS-10, Z-SSS and BDHI, respectively. (3) Results: Our results draw a relatively similar personality profile between groups but indicate that the subject traits are generally more pronounced in the MMT cohort. The overall lesser intensity of these traits in the MMORPG-IGD group might reflect the greater variability in the severity of the IGD. (4) Conclusions: IGD shares personality traits with MMT, and intensity may be influenced by the severity of the addiction or by certain direct environmental factors, and might also influence the propensity towards one behavior rather than another. Full article

Although hepatitis C virus (HCV) prevails in patients receiving methadone maintenance treatment (MMT), most do not receive anti-HCV therapy. This single-center observational study aimed to achieve HCV micro-elimination at an MMT center during the COVID-19 pandemic using a collaborative referral model, which comprised a referral-for-diagnosis stage (January 2020 to August 2020) and an on-site-diagnosis stage (September 2020 to January 2021). A multidisciplinary team was established and all MMT center patients were enrolled. HCV micro-elimination was defined as >90% of HCV-infected patients diagnosed and >80% of HCV-viremic patients treated. A total of 305 MMT patients, including 275 (90.2%) anti-HCV seropositive patients, were enrolled. Among 189 HCV-infected patients needing referral, the accumulative percentage receiving HCV RNA testing increased from 93 (49.2%) at referral-for-diagnosis stage to 168 (88.9%) at on-site-diagnosis stage. Among 138 HCV-viremic patients, the accumulative percentage receiving direct-acting antiviral (DAA) therapy increased from 77 (55.8%) at referral-for-diagnosis stage to 129 (93.5%) at on-site-diagnosis stage. We achieved an HCV RNA testing rate of 92.4% (254/275), an HCV treatment rate of 95.8% (203/212) and a sustained virological response rate of 94.1% (191/203). The collaborative referral model is highly effective in HCV RNA testing and HCV treatment uptake among MMT patients, achieving HCV micro-elimination. Full article

Methadone maintenance therapy (MMT) is a well-established and effective treatment for heroin use disorders. Whether frontal lobe function and demoralization serve as suitable prognostic and outcome assessment factors remains unknown. A quasi-experimental study was conducted with a single-group repeated-measures design at a medical center and mental hospital in Taiwan. We enrolled 70 participants (39 completed treatments and 31 dropped out). Frontal lobe function, demoralization, depression, and craving at three time points were analyzed. There were differences between patients who completed the treatment (n = 39) and those who did not (n = 31). Thirty-nine patients completed the treatment (average age, 45.5 years; 89.7% men; average duration of heroin use, 27.21 years; MMT, 38.18 mg/day). Post-MMT (6 months), frontal lobe function, demoralization, depression, and craving significantly improved. Dropouts had higher frontal lobe function, lower demoralization, higher craving, younger age, and earlier onset age than patients who completed the pretest treatment. Clinicians should be aware of the severity of demoralization. Clinicians may select suitable patients for MMT by assessing frontal lobe function, demoralization, craving, age, and onset age. A 6-month course of MMT improved demoralization, frontal lobe function, depression, and addiction. Six months of treatment was more effective than 3 months. Suitable patient identification and continuous treatment are important in MMT. Full article

Drug addiction, or substance use disorder (SUD), is a chronic, relapsing disorder in which compulsive drug-seeking and drug-taking behaviour persist despite serious negative consequences. Drug abuse represents a problem that deserves great attention from a social point of view, and focuses on the importance of genetic studies to help in understanding the genetic basis of addiction and its medical treatment. Despite the complexity of drug addiction disorders, and the high number of environmental variables playing a role in the onset, recurrence, and duration of the symptoms, several studies have highlighted the non-negligible role of genetics, as demonstrated by heritability and genome-wide association studies. A correlation between the relative risk of addiction to specific substances and heritability has been recently observed, suggesting that neurobiological mechanisms may be, at least in part, inherited. All these observations point towards a scenario where the core neurobiological factors of addiction, involving the reward system, impulsivity, compulsivity, stress, and anxiety response, are transmitted, and therefore, genes and mutations underlying their variation might be detected. In the last few years, the development of new and more efficient sequencing technologies has paved the way for large-scale studies in searching for genetic and epigenetic factors affecting drug addiction disorders and their treatments. These studies have been crucial to pinpoint single nucleotide polymorphisms (SNPs) in genes that affect the reaction to medical treatments. This is critically important to identify pharmacogenomic approaches for substance use disorder, such as OPRM1 SNPs and methadone required doses for maintenance treatment (MMT). Nevertheless, despite the promising results obtained by genome-wide association and pharmacogenomic studies, specific studies related to population genetics diversity are lacking, undermining the overall applicability of the preliminary findings, and thus potentially affecting the portability and the accuracy of the genetic studies. In this review, focusing on cannabis, cocaine and heroin use, we report the state-of-the-art genomics and pharmacogenomics of SUDs, and the possible future perspectives related to medical treatment response in people that ask for assistance in solving drug-related problems. Full article

Cannabis and opioids are substances that affect reproductive health. Opioids suppress testosterone and studies have shown that cannabis may increase testosterone. However, there is minimal research describing the endocrine effects of concurrent cannabis and opioid use. We hypothesize that cannabis use improves opioid-induced testosterone suppression. To test this hypothesis, we used cross-sectional data from a prospective cohort study including 122 men enrolled in methadone maintenance treatment (MMT). We measured serum testosterone with an enzyme-linked immunosorbent assay at study enrolment. Urine drug screens were collected for 15 months and identified 52.5% of participants (n = 64) as cannabis users. The association between cannabis use and testosterone level was examined using regression models with serum testosterone as the dependent variable. In our multivariable regression, methadone dose was associated with lower serum testosterone (β = −0.003, 95% CI-0.005, −0.001, p = 0.003). However, neither cannabis use as a dichotomous variable nor the percentage of cannabis-positive urine drug screens were significantly associated with serum testosterone (β = 0.143, 95% CI −0.110, 0.396, p = 0.266, and β = 0.002, 95% CI > −0.001, 0.005, p = 0.116, respectively). Therefore, it does not appear that cannabis has an association with testosterone levels in men on MMT. Full article

Sexual dysfunction has been extensively studied in methadone maintenance treatment (MMT) patients. However, little data is available regarding sexual inactivity in the MMT patient population. The objectives of this study were to determine the prevalence and putative risk factors for sexual inactivity in the MMT patient population. This cross-sectional study involved 25–71 year old MMT patients recruited from six methadone clinics. Two hundred and seventy-one patients were interviewed for demographic characteristics, comorbidities, concurrent medications used, and sexual activity. The prevalence of sexual inactivity in the MMT population was found to be 47.6%. Increasing age (p < 0.01) and being single/divorced (p < 0.01) were significantly associated with sexual inactivity. In subgroup analysis, increasing age was significantly associated with sexual inactivity in both single/divorced (p < 0.05) and married (p < 0.05) subgroups, while unemployment (p < 0.05) was only significantly associated with sexual inactivity in the earlier subgroup. Our results suggest that sexual inactivity is common in the MMT patient population. The putative risk factors are related to biological and sociocultural factors. Having specific comorbidities or being on certain medications were not correlated with sexual inactivity in the MMT population. Routine assessment of sexual problems is essential, and proper management should be performed for MMT patients. Full article

In this work, we investigate differences in gut microbial diversity driven by drug use or by the widely used methods for drug cessation: methadone maintenance treatment (MMT) and compulsory detention (CD). Methods: 99 participants (28 CD participants, 16 MMT patients, 27 drug users, and 28 healthy controls) were selected using strict inclusion criteria. Nutritional intake and gut microbial diversity were analyzed with bioinformatics tools and SPSS 20.0. Results: Alpha diversity was not significantly different among groups, whereas beta diversity of gut microbiota and nutrient intake were significantly higher among MMT patients. Taxa were unevenly distributed between groups, with drug users having the highest proportion of Ruminococcus and MMT patients having the highest abundance of Bifidobacterium and Lactobacillus. Conclusion: Drug use, cessation method, and diet contribute to shaping human gut communities. High beta diversity among MMT patients is likely driven by methadone use and high nutrient intake, leading to increased orexin A and enrichment for beneficial bacteria, while diversity in CD participants is largely influenced by diet. Full article

The quality of family relationships is important for individual and family well-being. Improving family relationships is also an important goal in methadone maintenance treatment (MMT). Little is known about factors associated with the improvement of family relationships among MMT clients. This study aimed to identify factors associated with family relationship improvement in MMT. We retrospectively analyzed existing data from 2006 to 2014 at 15 MMT clinics in Guangdong, China, including 2171 subjects with 4691 follow-ups. Generalized estimating equations were used to investigate the association between living status transitions, behavior changes and family relationship improvement, with covariates controlled for. Family relationship improvement was found in 23.1% of all follow-up intervals. Participants who began living with family, living on a regular wage, and gained employment were more likely to have improved family relationships. The quality of family relationships also improved among participants who ceased contact with drug-addicted fellows, ceased drug use, and those who were sexually active. These results suggest that improvement in living status, positive changes in drug use, and sexual activity are associated with family relationship improvement and corresponding interventions may be developed to facilitate clients’ recovery. Full article

We aimed to evaluate the status and barriers related to hepatitis C virus (HCV) treatment among Chinese methadone maintenance treatment (MMT) clients, and the willingness and barriers of patients to accept directly observed treatment (DOT) service and oral direct-acting antivirals (DAAs). We conducted a cross-sectional survey from July to October 2017 in Guangdong Province, China, involving 678 HCV antibody-positive MMT patients. If they reported being infected with HCV, then their HCV treatment experience, willingness to use DOT and DAAs, along with any barriers, were collected. Logistic regression analysis was used to identify the correlates of initiating HCV treatment. Among those reporting HCV infection (54%, 366/678), 39% (144/366) initiated treatment; however, 38% (55/144) interrupted and 55% (79/135) delayed treatment for 15 months. Seventy-five percent (273/366) and 53% (195/366) were willing to use DOT and DAAs, respectively. Unaffordable medical costs and insignificant symptoms were the major barriers to HCV treatment and accepting DOT or DAAs. The lack of a stable residence, being a woman, and having ever injected drugs were all associated with a low probability of initiating treatment (p < 0.05). This study highlights a limited uptake of HCV treatment among MMT patients, and a need to strengthen the popularity of DOT and DAAs and integrate them into Chinese MMT clinics. Full article