Abstract
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. More specifically, estradiol levels are positively associated with MMT dosing, and the expression of a single-nucleotide polymorphism (SNP) associated with estrogen receptor (ER) regulation is also associated with MMT dosing. In addition to performing mechanistic dissections of estrogen signaling in the presence of methadone, past studies have also proposed the targeting of estrogen signaling during MMT. The present report provides an overview of the relevant literature regarding sex effects, including differences in sex hormones and their potential impacts on MMT regimens. Moreover, this article provides a pharmacological perspective on the targeting of estrogen signals through the use of selective ER modulators (SERMs) during MMT. Preliminary preclinical experiments were also performed to evaluate the potential effects of targeting estrogen signaling with tamoxifen on methadone metabolism.
Highlights
The use of illicit opioids remains an ongoing issue for both individuals and society at large [1]
All experimental procedures for human studies were approved by the China Medical University Hospital (CMUH) Institutional review board (DMR94-IRB-007), and informed consent was obtained from each subject
The results showed excellent tolerance behavior, and the addition of TMX to maintenance treatment (MMT) enhanced the conditioned place preference (CPP) retention time, indicating that TMX has the potential to relieve stress-induced cravings for opioids during the tolerance phase of MMT programs, which could prevent the chances of a methadone overdose
Summary
The use of illicit opioids remains an ongoing issue for both individuals and society at large [1]. Individuals who develop opioid dependency often experience personal or social problems and often engage in opioid abuse. Opioid abuse patients present with behavioral changes, such as social withdrawal [2]; increased risk of contracting human immunodeficiency virus (HIV); and greater. Methadone maintenance treatment (MMT) consists of the administration of methadone over a prolonged period of time to treat an individual addicted to opioids, such as heroin. MMT is typically used to treat individuals who experience relapse following typical detoxification regimens or admission to a substance abuse treatment facility that requires complete abstinence [7]. MMT facilitates “social rehabilitation” by allowing people with addiction to avoid the uncomfortable withdrawal symptoms associated with complete abstinence. MMT has been used to treat opioid abuse patients for decades and has long served as the standard treatment for opiate dependence. MMT is associated with complications, including differential efficacies, and some patients experience difficulty during the transition from MMT to abstinence [8]
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