Pharmacogenetic effects were also observed for a tSNP in the OPRD1 gene (^4, rs4654327) on dampening self-reported alcohol stimulation and craving for alcohol in the laboratory. Specifically, GG homozygotes showed no effect of naltrexone, versus placebo, on alcohol-induced stimulation and alcohol craving, while for A carriers, naltrexone blunted alcohol’s stimulant effects and attenuated alcohol craving. These results may be clinically meaningful as naltrexone’s purported mechanisms of action include dampening the rewarding effects of alcohol and reductions in craving (Anton et al., 2004, King et al., 1997, Swift et al., 1994). Taken together, these findings suggest that variation in delta and kappa opioid receptor genes may further explain variation in the effects of naltrexone on subjective responses to alcohol and alcohol craving. Further, these results suggest that the biobehavioral mechanisms underlying the treatment efficacy of naltrexone for alcohol dependence may extend beyond mu opioid receptors.
