A critical point to be highlighted in this review is how fast the empirical data are accumulating on the effect of the Asn40Asp variation on alcoholism-related phenotypes, including responses to opioid antagonists. This growing body of research underscores the enthusiasm in the field for finding specific genes and endophenotypes that might better predict the risk for developing alcohol dependence and better identify treatment responders. Despite this enthusiasm, it must be recognized that many clinical and laboratory studies are small in size and that some have not randomized individuals to conditions (such as naltrexone or placebo medication) based on a priori ascertainment of OPRM1 genotypes. As clearly noted in Table 1, samples at different stages of alcohol use and misuse have been tested across studies (e.g., social drinkers, at risk drinkers, nontreatment-seeking alcoholics, etc.). Differences in the gender and ethnic composition of the sample pose yet another obstacle to replication, as the genetic effects may be small and moderated by gender and/or ethnicity. And, while animal studies have been creative, technically demanding, and highly promising, some of the preclinical models lend
