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Effects of naltrexone on alcohol sensitivity and genetic moderators of medication response: a double-blind placebo-controlled study.
Arch Gen Psychiatry. 2007 Sep; 64(9):1069-77.AG

Abstract

CONTEXT

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.

OBJECTIVES

(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.

DESIGN

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

SETTING

Participants were recruited from the community.

PARTICIPANTS

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.

MAIN OUTCOME MEASURES

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.

CONCLUSION

This study advances the knowledge of mechanisms of action of naltrexone and genetic moderators of response to this pharmacotherapy.

Authors+Show Affiliations

Department of Psychology, University of Colorado at Boulder, Boulder, Colorado, USA. lara_ray@brown.eduNo affiliation info available

Pub Type(s)

Clinical Trial
Comparative Study
Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

17768272

Citation

Ray, Lara A., and Kent E. Hutchison. "Effects of Naltrexone On Alcohol Sensitivity and Genetic Moderators of Medication Response: a Double-blind Placebo-controlled Study." Archives of General Psychiatry, vol. 64, no. 9, 2007, pp. 1069-77.
Ray LA, Hutchison KE. Effects of naltrexone on alcohol sensitivity and genetic moderators of medication response: a double-blind placebo-controlled study. Arch Gen Psychiatry. 2007;64(9):1069-77.
Ray, L. A., & Hutchison, K. E. (2007). Effects of naltrexone on alcohol sensitivity and genetic moderators of medication response: a double-blind placebo-controlled study. Archives of General Psychiatry, 64(9), 1069-77.
Ray LA, Hutchison KE. Effects of Naltrexone On Alcohol Sensitivity and Genetic Moderators of Medication Response: a Double-blind Placebo-controlled Study. Arch Gen Psychiatry. 2007;64(9):1069-77. PubMed PMID: 17768272.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of naltrexone on alcohol sensitivity and genetic moderators of medication response: a double-blind placebo-controlled study. AU - Ray,Lara A, AU - Hutchison,Kent E, PY - 2007/9/5/pubmed PY - 2007/9/29/medline PY - 2007/9/5/entrez SP - 1069 EP - 77 JF - Archives of general psychiatry JO - Arch Gen Psychiatry VL - 64 IS - 9 N2 - CONTEXT: 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. OBJECTIVES: (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. DESIGN: A within-subject, double-blind, placebo-controlled laboratory trial of naltrexone. SETTING: Participants were recruited from the community. PARTICIPANTS: 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. MAIN OUTCOME MEASURES: 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. CONCLUSION: This study advances the knowledge of mechanisms of action of naltrexone and genetic moderators of response to this pharmacotherapy. SN - 0003-990X UR - https://www.unboundmedicine.com/medline/citation/17768272/Effects_of_naltrexone_on_alcohol_sensitivity_and_genetic_moderators_of_medication_response:_a_double_blind_placebo_controlled_study_ L2 - https://jamanetwork.com/journals/jamapsychiatry/fullarticle/10.1001/archpsyc.64.9.1069 DB - PRIME DP - Unbound Medicine ER -