The most promising pharmacogenetic evidence in alcohol interventions concerns the OPRM1 A118G polymorphism as a moderator of clinical response to naltrexone (NTX). An initial retrospective analysis of NTX trials found that OPRM1 influenced treatment response, such that individuals with the Asp40 variant (G allele) receiving NTX had a longer time until the first heavy drinking day and were half as likely to relapse compared to those homozygous for the Asn40 variant (A allele) [92]. This finding was later extended in the COMBINE study, such that G carriers showed a greater proportion of days abstinent and a lower proportion of heavy drinking days compared in response to NTX versus placebo, whereas participants homozygous for the A allele did not show a significant medication response [93]. Moreover, 87.1% of G allele carriers who received NTX were classified as having a good clinical outcome at study endpoint, versus 54.5% of Asn40 homozygotes who received NTX. (Moderating effects of OPRM1 were specific to participants receiving medication management without the cognitive-behavioral intervention [CBI] and were not evident in participants receiving NTX and CBI). A smaller
