Add-On Selective Estrogen Receptor Modulators for Methadone Maintenance Treatment.

Methadone maintenance treatment (MMT) remains the cornerstone for the management of opiate abuse. However, MMT can be associated with complex factors, including complications during the tolerance phase, the inability of some patients to maintain treatment effects during the tapering or abstinence phases, and the development of methadone dependence. Previous studies have revealed a sex disparity in MMT efficacy, showing that women undergoing MMT experiencing an increase in psychological symptoms compared with men and suggesting a link between disparate responses and the effects of estrogen signaling on methadone metabolism.

Dextromethorphan Dampens Neonatal Astrocyte Activation and Endoplasmic Reticulum Stress Induced by Prenatal Exposure to Buprenorphine.

Prenatal exposure to buprenorphine renders offspring vulnerable to cerebral impairments. In this study, our data demonstrate, for the first time, that prenatal exposure to buprenorphine escalates astrocyte activation concurrent with indications of endoplasmic reticulum (ER) stress in the hippocampi of neonates, and this can be prevented by the coadministration of dextromethorphan with buprenorphine. Furthermore, dextromethorphan can inhibit the accumulation of GPR37 in the hippocampus of newborns caused by buprenorphine and is accompanied by the proapoptotic ER stress response that involves the procaspase-3/CHOP pathway.

Reduced mortality in patients with extended duration of methadone maintenance treatment: a five-year retrospective nationwide study.

Background: The retention of patients under methadone maintenance treatment (MMT) is an indication for the effectiveness of the therapy. We aimed to explore the relation between mortality and the cumulative MMT duration.

Methods: A retrospective cohort analysis was performed using Taiwan Illicit Drug Issue Database (TIDID) and National Health Insurance Research Database (NHIRD) during 2012-2016.

Risk Assessment for Heroin Use and Craving Score Using Polygenic Risk Score.

Addiction is characterized by drug-craving, compulsive drug-taking, and relapse, and results from the interaction between multiple genetic and environmental factors. Reward pathways play an important role in mediating drug-seeking and drug-taking behaviors, and relapse. The objective of this study was to identify heroin addicts who carry specific genetic variants in their dopaminergic reward systems.

Augmentation in Healthcare Utilization of Patients with Opioid Use Disorder After Methadone Maintenance Treatment: A Retrospective Nationwide Study.

Introduction: The health benefits of entering methadone maintenance treatment (MMT) for opioid-dependent persons may not be merely limited to therapy of opioid use disorder. We aimed to compare the healthcare utilization of MMT patients before and after MMT.

Methods: A retrospective analysis was performed using the Taiwan Illicit Drug Issue Database and the National Health Insurance Research Database (NHIRD) between 2014 and 2016.

The roles of lumbar load thresholds in cumulative lifting exposure to predict disk protrusion in an Asian population.

Background: The purpose of this study was to determine whether a specific threshold per lifting movement, the accumulation above which best predicts lumbar disk protrusion, exists or the total lifting load should be considered.

Methods: This was a retrospective study. Subjects with various lifting exposures were recruited.

Corrigendum to "Effects of Electroacupuncture on Methamphetamine-Induced Behavioral Changes in Mice".

[This corrects the article DOI: 10.1155/2017/5642708.].

Reduced dosing and liability in methadone maintenance treatment by targeting oestrogen signal for morphine addiction.

Methadone maintenance treatment (MMT) is the major tapering therapy for morphine addictive patients. There have gender differences reported in response to MMT. This study discovered that the estrogen-response element single nucleotide polymorphism (ERE-SNP; rs16974799, C/T) of cytochrome 2B6 gene (cyp2b6; methadone catabolic enzyme) responded differently to MMT dosing.

Effects of Electroacupuncture on Methamphetamine-Induced Behavioral Changes in Mice.

Methamphetamine (METH) is a major drug of abuse worldwide, and no efficient therapeutic strategies for treating METH addiction are currently available. Continuous METH use can cause behavioral upregulation or psychosis. The dopaminergic pathways, particularly the neural circuitry from the ventral tegmental area to the nucleus accumbens (NAc), have a critical role in this behavioral stage.

Genome-Wide Pharmacogenomic Study on Methadone Maintenance Treatment Identifies SNP rs17180299 and Multiple Haplotypes on CYP2B6, SPON1, and GSG1L Associated with Plasma Concentrations of Methadone R- and S-enantiomers in Heroin-Dependent Patients.

Methadone maintenance treatment (MMT) is commonly used for controlling opioid dependence, preventing withdrawal symptoms, and improving the quality of life of heroin-dependent patients. A steady-state plasma concentration of methadone enantiomers, a measure of methadone metabolism, is an index of treatment response and efficacy of MMT. Although the methadone metabolism pathway has been partially revealed, no genome-wide pharmacogenomic study has been performed to identify genetic determinants and characterize genetic mechanisms for the plasma concentrations of methadone R- and S-enantiomers.

Buprenorphine-elicited alteration of adenylate cyclase activity in human embryonic kidney 293 cells coexpressing κ-, μ-opioid and nociceptin receptors.

Buprenorphine, a maintenance drug for heroin addicts, exerts its pharmacological function via κ- (KOP), μ-opioid (MOP) and nociceptin/opioid receptor-like 1 (NOP) receptors. Previously, we investigated its effects in an in vitro model expressing human MOP and NOP receptors individually or simultaneously (MOP, NOP, and MOP+NOP) in human embryonic kidney 293 cells. Here, we expanded this cell model by expressing human KOP, MOP and NOP receptors individually or simultaneously (KOP, KOP+MOP, KOP+NOP and KOP+MOP+NOP).

Health insurance coverage and healthcare utilization among infants of mothers in the national methadone maintenance treatment program in Taiwan.

Background: Children of heroin-using women have a higher risk of unfavorable health and developmental outcomes. Although methadone maintenance treatment (MMT) has been widely used to treat heroin-using pregnant women, potential effects on accessibility and utilization of healthcare service for their offspring are less explored.

Methods: We used four national registry and health insurance datasets in Taiwan from 2004 to 2009 to form a population-based matched retrospective cohort study.

Beneficial effects of co-treatment with dextromethorphan on prenatally methadone-exposed offspring.

Background: Heroin use among young women of reproductive age has drawn much attention around the world. Although methadone is widely used in maintenance therapy for heroin/morphine addiction, the long-term effects of prenatal exposure to methadone and preventative therapy remain unclear. For revealing this question, female pregnant Sprague-Dawley rats were sub-grouped to receive (1) vehicle, (2) methadone 5 mg/kg at embryonic day 3 (E3) and then 7 mg/kg from E4 to E20, (3) dextromethorphan (DM) 3 mg/kg, and (4) methadone + DM (the rats received methadone followed by DM treatment), subcutaneously, twice a day from E3 to E20.

Pharmacogenomics study in a Taiwan methadone maintenance cohort.

Pharmacogenomics is research to study the drug treatment responses in subgroups of patients according to their genetic variants or genetic expression information. Methadone maintenance treatment, which is usually prescribed for patients with heroin dependence, was launched in Taiwan by the government in 2006. In this study, 366 patients who had taken methadone continually in the previous 7 days were examined.

Comparison of adverse obstetric outcomes and maternity hospitalization among heroin-exposed and methadone-treated women in Taiwan.

Aims: To identify sociodemographic and clinical factors predicting the overall risk of adverse obstetric outcomes and the length of maternal hospital stay among heroin-exposed and methadone-treated women in Taiwan.

Methods: Using the retrospective matched cohort study design, 396 births to women on methadone treatment during pregnancy (the methadone-treated group) and 609 to women who started methadone treatment after childbirth (the heroin-exposed group) were identified in the National Methadone Maintenance Program. Adverse pregnancy outcomes were assessed by still birth, low birth weight and preterm delivery.

The dose-response relationship between cumulative lifting load and lumbar disk degeneration based on magnetic resonance imaging findings.

Background: Lumbar disk degeneration (LDD) has been related to heavy physical loading. However, the quantification of the exposure has been controversial, and the dose-response relationship with the LDD has not been established.

Objective: The purpose of this study was to investigate the dose-response relationship between lifetime cumulative lifting load and LDD.

Assessment of CYP450 genetic variability effect on methadone dose and tolerance.

Aim: Methadone dose is related to treatment success in individuals under methadone maintenance treatment (MMT). We constructed a gene matrix using previously identified genetic polymorphisms in CYP450 and determined their genetic influence on methadone dose or tolerance.

Materials & Methods: The allelic combinations of CYP450 genetic variants (two from CYP2C19, four from CYP2B6 and five from CYP3A4) were analyzed in 366 MMT heroin dependent patients as possible determinants of methadone dose and tolerance using analysis of covariance.

The association of genetic polymorphisms in the κ-opioid receptor 1 gene with body weight, alcohol use, and withdrawal symptoms in patients with methadone maintenance.

Methadone is a synthetic opioid that binds to the κ-opioid receptor with a low affinity. This study tested the hypotheses that the genetic polymorphisms in the κ-opioid receptor 1 (OPRK1) gene region are associated with methadone treatment responses in a Taiwan methadone maintenance treatment (MMT) cohort. Seventeen single nucleotide polymorphisms (SNPs) in OPRK1 were selected and genotyped on DNA of 366 MMT patients.

Effect of prenatal methadone on reinstated behavioral sensitization induced by methamphetamine in adolescent rats.

It has been known that methadone maintenance treatment is the standard treatment of choice for pregnant opiate addicts. However, there are few data on newborn outcomes especially in the cross talk with other addictive agents. The present study was to investigate the effect of prenatal exposure to methadone on methamphetamine (METH)-induced behavioral sensitization as an indicator of drug addiction in later life.

Functional genetic polymorphisms in CYP2C19 gene in relation to cardiac side effects and treatment dose in a methadone maintenance cohort.

Abstract Methadone maintenance therapy is an established treatment for heroin dependence. This study tested the influence of functional genetic polymorphisms in CYP2C19 gene encoding a CYP450 enzyme that contributes to methadone metabolism on treatment dose, plasma concentration, and side effects of methadone. Two single nucleotide polymorphisms (SNPs), rs4986893 (exon 4) and rs4244285 (exon 5), were selected and genotyped in 366 patients receiving methadone maintenance therapy in Taiwan.

Sex differences in opioid analgesia and addiction: interactions among opioid receptors and estrogen receptors.

Opioids are widely used as the pain reliever and also notorious for being addictive drugs. Sex differences in the opioid analgesia and addiction have been reported and investigated in human subjects and animal models. Yet, the molecular mechanism underlying the differences between males and females is still unclear.

Hepatitis C virus infection influences the S-methadone metabolite plasma concentration.

Background And Objectives: Heroin-dependent patients typically contract hepatitis C virus (HCV) at a disproportionately high level due to needle exchange. The liver is the primary target organ of HCV infection and also the main organ responsible for drug metabolism. Methadone maintenance treatment (MMT) is a major treatment regimen for opioid dependence.