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Genetic moderators of naltrexone's effects on alcohol cue reactivity

John E McGeary1, Peter M Monti, Damaris J Rohsenow

  • 1Center for Alcohol and Addiction Studies, Brown University, Providence, Rhode Island 02906, USA. John_McGeary@brown.edu

Alcoholism, Clinical and Experimental Research
|August 11, 2006
PubMed
Abstract

Insights

Naltrexone’s effect on alcohol craving differs based on OPRM1 gene variations. Asp40 carriers experienced increased urge, while Asn homozygotes showed no change, suggesting personalized naltrexone treatment for heavy drinkers.

Area of Science:

  • Pharmacogenetics
  • Neuroscience
  • Addiction Medicine

Background:

  • Naltrexone (NTX) is used to reduce alcohol consumption and craving.
  • Genetic variations in dopamine D4 receptor (DRD4) and mu-opiate receptor (OPRM1) genes may influence NTX efficacy.
  • This study investigated these genes' role in moderating NTX's effect on alcohol craving in heavy drinkers.

Purpose of the Study:

  • To examine if OPRM1 and DRD4 gene polymorphisms moderate the effects of naltrexone on alcohol cue-elicited urge.
  • To investigate potential patient-treatment matching strategies for naltrexone therapy.

Main Methods:

  • Utilized data from 93 participants in a larger medication study, focusing on those consenting to genetic testing.
  • Genotyped participants for DRD4 variable number tandem repeat and OPRM1 Asn40Asp single nucleotide polymorphism.
  • Assessed alcohol cue reactivity 10 days after randomization to naltrexone (50 mg) or placebo.

Main Results:

  • Naltrexone increased alcohol urge in OPRM1 Asp40 carriers but had no effect in Asn homozygotes.
  • Asp40 carriers showed greater decreases in blood pressure compared to Asn carriers.
  • No significant effects of DRD4 gene polymorphisms on naltrexone response were observed.

Conclusions:

  • OPRM1 gene variation significantly influences individual responses to naltrexone regarding alcohol craving.
  • These findings may help reconcile conflicting results from naltrexone clinical trials.
  • Highlights the potential for personalized medicine approaches in treating heavy drinking.

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