Pharmacogenetic Effects of Naltrexone in Individuals of East Asian Descent: Human Laboratory Findings from a Randomized Trial.

BACKGROUND: Genetic variation in the endogenous opioid system has been identified as 1 potential source of individual variability in naltrexone treatment outcomes. The majority of naltrexone pharmacogenetic studies have focused on a particular single nucleotide polymorphism (SNP) of the mu-opioid receptor gene (OPRM1; rs1799971; commonly known as the Asn40Asp SNP) in Caucasian samples with decidedly mixed results. The goal of this study was to test the pharmacogenetic effects of naltrexone on subjective response to alcohol and self-administration of alcohol in individuals of East Asian descent. We hypothesized that naltrexone, compared with placebo, would potentiate the aversive and sedative effects of alcohol and reduce alcohol self-administration to a greater extent in Asp40 carriers. METHODS: Participants (N = 77; Asn40Asn, n = 29; Asn40Asp, n = 34, and Asp40Asp, n = 14) completed 2 double-blinded and counterbalanced experimental sessions: one after taking naltrexone (50 mg/d) for 5 days and one after taking matched placebo for 5 days. In each experimental session, participants received a priming dose of intravenous alcohol up to the breath alcohol concentration target of 0.06 g/dl which was immediately followed by an alcohol self-administration period (1 hour). RESULTS: There were no pharmacogenetic effects observed for alcohol-induced stimulation, sedation, craving for alcohol, or alcohol self-administration in the laboratory. During the self-administration period, Asp40 carriers consumed fewer drinks and had a longer latency to first drink as compared to Asn40 homozygotes. CONCLUSIONS: These findings in East Asians add to the mixed literature on naltrexone pharmacogenetics from predominantly Caucasian samples and highlight the complexity of these effects and their overall limited replicability. It is plausible that a consistent pharmacogenetic effect in tightly controlled preclinical and experimental medicine models "fades" in more complex and heterogeneous settings and samples.

The relationship between methamphetamine and alcohol use in a community sample of methamphetamine users.

BACKGROUND: While methamphetamine (MA) and alcohol are often used in combination, little is known about the pattern of co-use between these substances. The goal of the present study is to examine the relationship between MA use and alcohol use in a community sample of non-treatment seeking regular MA users. METHODS: Participants completed a face-to-face assessment battery, which included a diagnostic interview for MA dependence and the timeline follow-back interview for both alcohol and MA use over the past 30 days. Sixty regular MA and alcohol users supplied data for 1800 person-days. RESULTS: Compared with non-drinking days, drinking days and binge drinking days increased the odds of same day MA use by 4.22 and 4.50 times, respectively (p's<0.0001). Further, binge drinking incrementally increased risk for MA use above and beyond the effects of drinking itself (p<0.0001). Lagged models revealed previous day MA use to predict following day MA use (p<0.0001), yet, after controlling for this relationship, neither previous day alcohol use nor previous day binge drinking predicted following-day MA use. Finally, the effect of binge drinking on MA use was stronger among individuals with lower MA dependence severity or higher alcohol problem severity (p's<0.05). CONCLUSIONS: These results suggest that alcohol and MA are co-used in predictable patterns, and in particular, that binge drinking may be incrementally associated with the likelihood of MA use. Future studies are needed to explore the temporal relationship between alcohol and MA use within a given episode.