Epigenetic Moderators of Naltrexone Efficacy in Reducing Heavy Drinking in Alcohol Use Disorder: a Randomized Trial

Overview

Journal Pharmacogenomics J

Specialties Genetics
Molecular Biology
Pharmacology

Date 2021 Aug 12

PMID 34381173

Citations 1

Authors

Joseph P Schacht

Michaela Hoffman

Brian H Chen

Raymond F Anton

Affiliations

Soon will be listed here.

Abstract

Polymorphisms in genes associated with opioid signaling and dopamine reuptake and inactivation may moderate naltrexone efficacy in Alcohol Use Disorder (AUD), but the effects of epigenetic modification of these genes on naltrexone response are largely unexplored. This study tested interactions between methylation in the μ-opioid receptor (OPRM1), dopamine transporter (SLC6A3), and catechol-O-methyltransferase (COMT) genes as predictors of naltrexone effects on heavy drinking in a 16-week randomized, placebo-controlled trial among 145 treatment-seeking AUD patients. OPRM1 methylation interacted with both SLC6A3 and COMT methylation to moderate naltrexone efficacy, such that naltrexone-treated individuals with lower methylation of the OPRM1 promoter and the SLC6A3 promoter (p = 0.006), COMT promoter (p = 0.005), or SLC6A3 3' untranslated region (p = 0.004), relative to placebo and to those with higher OPRM1 and SLC6A3 or COMT methylation, had significantly fewer heavy drinking days. Epigenetic modification of opioid- and dopamine-related genes may represent a novel pharmacoepigenetic predictor of naltrexone efficacy in AUD.

Citing Articles

Can Epigenetics Predict Drug Efficiency in Mental Disorders?.

David G, Amir Y, Salalha R, Sharvit L, Richter-Levin G, Atzmon G Cells. 2023; 12(8).

PMID: 37190082 PMC: 10136455. DOI: 10.3390/cells12081173.

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