Additional studies have examined the Asn40Asp SNP and naltrexone pharmacogenetics. A controlled laboratory study of naltrexone found that Asp40 carriers reported greater naltrexone-induced blunting of alcohol “high,” as compared to placebo and to individuals who were homozygous for the Asn40 allele (Ray and Hutchison, 2007). This study suggested a biobehavioral mechanism by which naltrexone may be differentially effective among Asp40 carriers, such that these individuals may be more sensitive to the reinforcing effects of alcohol and in turn more responsive to the dampening of the alcohol “high” afforded by naltrexone. Secondary analyses from this laboratory study found that naltrexone selectively elevated GABAergic neurosteroid levels among Asp40 carriers, indicating a potential neurosteroid contribution to the differential effects of naltrexone among Asp40 carriers (Ray et al., 2010a). A recent placebo-controlled study has replicated the naltrexone-induced blunting of alcohol “euphoria” among Asp40 carriers after a priming dose of alcohol in a sample of social drinkers (Setiawan et al., 2011). These effects were only seen in women and were not extended to a progressive ratio paradigm, such that naltrexone did not decrease motivation to work for additional alcoholic beverages.
