A Polymorphism of the μ-Opioid Receptor Gene (OPRM1) and Sensitivity to the Effects of Alcohol in Humans


  • This research was supported by NIAAA Grants F31 AA14847 (LAR) and R01 AA12238 (KEH) and by Grant M01 RR00051 from the General Clinical Research Center Program of the National Center for Research Resources, National Institutes of Health.

Reprint requests: Kent E. Hutchison, PhD, University of Colorado, Department of Psychology, Muenzinger Psychology Building, Campus Box 345, Boulder, CO 80309-0345; Fax: 303-492-2967; E-mail: kenth@psych.colorado.edu.


Background: Recent research has implicated the endogenous opioid system in the development of alcohol use disorders. The A118G polymorphism of the OPRM1 gene has been shown to confer functional differences to μ-opioid receptors, such that the G variant binds β-endorphin three times more strongly than the A variant. The goal of this study was to test whether the A118G polymorphism is associated with sensitivity to the effects of alcohol.

Methods: Participants who were either homozygous for the A allele (n= 23) or heterozygous (n= 15) received intravenous doses of alcohol designed to reach three target levels of breath alcohol concentration: 0.02, 0.04, and 0.06. The testing procedure consisted of measures of subjective intoxication, stimulation, sedation, and mood states at baseline and at each of the three target breath alcohol concentrations.

Results: The results suggested that individuals with the G allele reported higher subjective feelings of intoxication, stimulation, sedation, and happiness across trials as compared with participants with the A allele. Furthermore, participants with the G allele were almost three times more likely to report a positive family history of alcohol use disorders than participants with the A allele.

Conclusions: These findings may help to explain previous research suggesting that naltrexone is more effective among individuals with the G allele. A medication that reduces feelings of euphoria after alcohol consumption may be more successful among individuals with a genetic predisposition to greater feelings of euphoria after consuming alcohol.