The goal of this study was to assess for interactions between tag single nucleotide polymorphisms (tSNPs) in the genes encoding kappa and delta opioid receptors and naltrexone on subjective responses to alcohol and craving in the laboratory. Results revealed a significant interaction between OPRK1 genotype at one locus (OPRK1^2, rs997917) and medication (naltrexone vs. placebo), demonstrating differential naltrexone-induced changes in alcohol sedation. Specifically, among TT homozygotes, naltrexone dampened feelings of sedation compared to placebo, while among C-allele carriers naltrexone enhanced alcohol-induced sedation. OPRK1^2 has been previously tested for association with alcohol, opiate, or other drug dependence, but was not a significant predictor of drug or alcohol problems (Zhang et al., 2008). Interestingly, a nearby marker in OPRK1 (rs963549) showed marginal significance in predicting relapse rates and time to relapse in a naltrexone treatment study (Gelernter et al, 2007). However, this marginal effect was limited to a main effect of genotype in that study, as this marker did not significantly interact with medication treatment (naltrexone vs. placebo). As ascertained through publicly available data from HapMap analyzed through Haploview, these two OPRK1
