Effects of naltrexone on alcohol sensitivity and genetic moderators of medication response: a double-blind placebo-controlled study.
BACKGROUND
Clinical trials have suggested a modest effect of naltrexone as a pharmacotherapy for alcoholism, and a recent study has suggested that the effects may be moderated by variations in the mu-opioid receptor gene (OPRM1). However, the mechanism by which naltrexone may be differentially effective as a function of the OPRM1 genotype is unclear.


OBJECTIVE
(1) To replicate and expand on the association between the A118G single nucleotide polymorphism(SNP) of the OPRM1 gene and alcohol sensitivity, (2) to examine the effects of naltrexone on alcohol sensitivity, and (3) to test the A118G SNP of the OPRM1 gene as a moderator of the effects of naltrexone on alcohol sensitivity.


METHODS
A within-subject, double-blind, placebo-controlled laboratory trial of naltrexone.


METHODS
Participants were recruited from the community.


METHODS
Non-treatment-seeking heavy drinkers were enrolled in the study. Prospective genotyping was conducted to oversample for the genetic variant of interest. Intervention After taking naltrexone (50 mg) or placebo, participants completed an intravenous alcohol challenge session in which they were assessed at baseline and at each of the 3 target breath alcohol concentrations: 0.02, 0.04, and 0.06 mg/L.


METHODS
The Biphasic Alcohol Effects Scale, the Alcohol Urge Questionnaire, the Profile of Mood States, and the Alcohol Rating Scale were administered.


RESULTS
Individuals with at least 1 copy of the G allele reported lower alcohol craving and higher alcohol-induced "high" across rising breath alcohol concentrations. Naltrexone was found to blunt alcohol's effects on stimulation, positive mood, craving, and enjoyment. The effects of naltrexone on blunting alcohol-induced high were stronger among individuals with the G allele.


CONCLUSIONS
This study advances the knowledge of mechanisms of action of naltrexone and genetic moderators of response to this pharmacotherapy.
Ray
Lara A
LA
Department of Psychology, University of Colorado at Boulder, Boulder, Colorado, USA. lara_ray@brown.edu
Hutchison
Kent E
KE
D000328:Adult; D000428:Alcohol Drinking / Q000235:genetics / Q000523:psychology; D000437:Alcoholism / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*; D016739:Behavior, Addictive / Q000175:diagnosis / Q000517:prevention & control / Q000523:psychology; D001944:Breath Tests; D004311:Double-Blind Method; D004644:Emotions / Q000187:drug effects; D000431:Ethanol / Q000097:blood / Q000494:pharmacology; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D009271:Naltrexone / Q000494:pharmacology* / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D010597:Pharmacogenetics; D010919:Placebos; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000235:genetics*; D012201:Reward
D009292:Narcotic Antagonists; C485764:OPRM1 protein, human; D010919:Placebos; D017450:Receptors, Opioid, mu; D000431:Ethanol; D009271:Naltrexone