Genetic moderators of naltrexone's effects on alcohol cue reactivity.

Full Abstract

BACKGROUND:
Naltrexone (NTX) reduces drinking and craving in alcoholic individuals in treatment and also in heavy drinkers. Polymorphisms in the D4 dopamine receptor (DRD4) gene and mu-opiate receptor gene (OPRM1) may moderate NTX's effects on craving. This study examined these candidate genes as moderators of the effects of NTX on cue-elicited urge to drink in non-treatment-seeking heavy drinkers.

METHOD:
Data from the subset of 93 participants who consented for genetic testing in a larger study of medication effects were used to examine pharmacogenetic hypotheses. The non-treatment-seeking male and female heavy drinkers (62% alcohol dependent) were genotyped for the variable number of tandem repeats polymorphism in the DRD4 gene [L=7 or more (n=34), S=less than 7 (n=56)] and Asn40Asp single-nucleotide polymorphism in the OPRM1 gene [29 aspartate (Asp) carriers and 59 asparagine (Asn) homozygotes]. Ten days after randomization to NTX (50 mg) or placebo, participants completed an alcohol cue reactivity assessment.

RESULTS:
Any medication effects were all accounted for by interaction with genotype. Naltrexone increased urge for alcohol in Asp carriers across alcohol and neutral beverage cue trials and had no effect on homozygous Asn carriers. Asp40 carriers on either medication had greater decreases (from resting baseline) in mean arterial blood pressure across all beverage cue trials compared with Asn carriers. For DRD4, no differential medication effects by DRD4 polymorphism were found. Alcohol dependence diagnosis did not moderate the effects of gene and medication on cue-elicited measures.

DISCUSSION:
The differential responses to NTX due to variation in the OPRM1 gene may help explain conflicting results in clinical trials and suggest directions for patient-treatment matching.

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Author information

Author/s: McGeary, John E (JE); Monti, Peter M (PM); Rohsenow, Damaris J (DJ); Tidey, Jennifer (J); Swift, Robert (R); Miranda, Robert (R);

Affiliation: Center for Alcohol and Addiction Studies, Brown University, Providence, Rhode Island 02906, USA. John_McGeary(-atsign-)brown.edu

Grants: R01-AA-007850-15 (Agency:NIAAA NIH HHS) ; T32AA007459 (Agency:NIAAA NIH HHS)

Journal and publication information

Publication Type: Comparative Study; Journal Article; Randomized Controlled Trial; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.

Journal: Alcoholism, clinical and experimental research (Alcohol Clin Exp Res), published in United States. (Language: eng)

Reference: 2006-Aug; vol 30 (issue 8) : pp 1288-96

Dates: Created 2006/08/10; Completed 2006/09/29; Revised 2008/11/21;

PMID: 16899031, status: MEDLINE (last retrieval date: 12/26/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Adolescent
Adult
Alcohol Drinking - drug therapy; genetics; psychology
Alcoholism - drug therapy; genetics; psychology
Analysis of Variance
Chi-Square Distribution
Cues
Ethanol - administration & dosage

Female
Genetic Variation - drug effects; genetics
Genotype
Humans
Male
Naltrexone - pharmacology; therapeutic use
Receptors, Dopamine D4 - genetics
Receptors, Opioid, mu - genetics

Associated Chemicals: DRD4 protein, human (0) ; OPRM1 protein, human (0) ; Receptors, Opioid, mu (0) ; Receptors, Dopamine D4 (137750-34-6) ; Naltrexone (16590-41-3) ; Ethanol (64-17-5)

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