Variation in Mu-Opioid Receptor Gene (OPRM1) as a Moderator of Naltrexone Treatment to Reduce Heavy Drinking in a High Functioning Cohort.

BACKGROUND It is well known that naltrexone, an FDA-approved medication for treatment of alcohol dependence, is effective for only a subset of individuals. Recent studies have examined the utility of a functional A118G single nucleotide polymorphism (SNP) of the mu-opioid receptor gene (OPRM1) as a predictor of naltrexone treatment response. Although the findings to date have generally been consistent with a moderating effect of the SNP, further evaluation of this hypothesis is warranted. OBJECTIVE To evaluate whether problem drinkers with one or two copies of the 118G allele respond better to naltrexone treatment. The treatment goal in this cohort of high functioning men who have sex with men (MSM) was to reduce heavy drinking, rather than to promote abstinence. METHOD 112 subjects of European ancestry from a randomized clinical trial of naltrexone and behavioral therapy for problem drinking MSM were included in the analysis. Subjects were treated for 12 weeks with 100 mg/day of oral naltrexone hydrochloride. All participants received medical management with a modified version of the Brief Behavioral Compliance Enhancement Treatment (BBCET), alone or in combination with Modified Behavioral Self-control Therapy (MBSCT). RESULTS Naltrexone-treated subjects with one or two 118G alleles had a significantly greater percentage of non-hazardous drinking (NoH) (p < 0.01) than those treated with placebo or A118 homozygotes in either medication group. CONCLUSIONS These results are consistent with a modest moderating effect of the OPRM1 118G allele on the reduction of heavy drinking by naltrexone treatment.