1. ¹Center for the Study of Addictions, Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA
2. ²Mental Illness Research, Educational, and Clinical Center (MIRECC) at the Philadelphia VA Medical Center, USA
3. ³Section of Geriatric Psychiatry, Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA
4. ⁴Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA
5. ⁵Alcohol Research Center, Department of Psychiatry, University of Connecticut School of Medicine, USA
6. ⁶Department of Psychiatry, Yale University School of Medicine and Psychiatry Service, VA Connecticut Healthcare System, USA

Correspondence: Dr D Oslin, University of Pennsylvania, 3535 Market Street, Room 3002, Philadelphia, PA 19104, USA. Tel: +1 215 615-3083; Fax: +1 215 349-8389; E-mail: oslin@mail.med.upenn.edu

Received 8 January 2003; Revised 3 April 2003; Accepted 16 April 2003; Published online 18 June 2003.

Abstract

This study examined the association between two specific polymorphisms of the gene encoding the -opioid receptor and treatment outcomes in alcohol-dependent patients who were prescribed naltrexone or placebo. A total of 82 patients (71 of European descent) who were randomized to naltrexone and 59 who were randomized to placebo (all of European descent) in one of three randomized, placebo-controlled clinical trials of naltrexone were genotyped at the A₊₁₁₈G (Asn40Asp) and C₊₁₇T (Ala6Val) SNPs in the gene encoding the -opioid receptor (OPRM1). The association between genotype and drinking outcomes was measured over 12 weeks of treatment. In subjects of European descent, individuals with one or two copies of the Asp40 allele treated with naltrexone had significantly lower rates of relapse (p=0.044) and a longer time to return to heavy drinking (p=0.040) than those homozygous for the Asn40 allele. There were no differences in overall abstinence rates (p=0.611), nor were there differences in relapse rates or abstinence rates between the two genotype groups among those assigned to placebo. These preliminary results are consistent with prior literature demonstrating that the opioid system is involved in the reinforcing properties of alcohol and that allelic variation at OPRM1 is associated with differential response to a -receptor antagonist. If replicated, these results would help to identify alcohol-dependent individuals who may be most likely to respond to treatment with naltrexone.