title: Understanding naltrexone mechanism of action and pharmacogenetics in Asian Americans via behavioral economics: a preliminary study.
abstract: A behavioral economic approach to understanding the relative value of alcohol may be useful for advancing medication development for alcoholism. Naltrexone is a heavily researched and moderately effective treatment for alcohol dependence making it a good candidate for a proof-of-concept study of behavioral economics and alcoholism pharmacotherapy. This study examines naltrexone efficacy and pharmacogenetics in terms of the relative value of alcohol, assessed via demand curve analysis. Participants were 35 heavy drinking (AUDIT ≥8) Asian Americans. A within-subjects cross-over medication design was used along with an intravenous alcohol challenge completed after 4 days of both naltrexone and placebo. At baseline and BrAC = 0.06g/dl, participants completed an Alcohol Purchase Task, which assessed estimated alcohol consumption along escalating prices. Behavioral economic demand curve analysis yielded measures of intensity, elasticity, maximum expenditure (O(max)), proportionate price insensitivity (P(max)) and breakpoint. Compared to placebo, naltrexone significantly reduced intensity, O(max) and breakpoint. There were also trend-level medication effects on P(max). BrAC was associated with increases in P(max) and breakpoint. A significant naltrexone × OPRM1 genotype interaction was observed for intensity of demand. The present study extends the literature on naltrexone's mechanisms through the application of a novel behavioral economic paradigm. These results indicate that naltrexone reduces several indices of demand for alcohol. This preliminary report provides further evidence for the effectiveness of naltrexone and supports the utility of a behavioral economic approach to alcoholism pharmacotherapy development.
authors.affiliation: Department of Psychology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Spencer
authors.initials: S
authors.lastname: Bujarski
authors.forename: James
authors.initials: J
authors.lastname: MacKillop
authors.forename: Lara A
authors.initials: LA
authors.lastname: Ray
mesh_terms: D000328:Adult; D000428:Alcohol Drinking / Q000188:drug therapy / Q000235:genetics / Q000523:psychology*; D001213:Asian / Q000235:genetics* / Q000523:psychology; D016739:Behavior, Addictive / Q000188:drug therapy; D004311:Double-Blind Method; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005838:Genotype; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D018803:Models, Economic; D009271:Naltrexone / Q000494:pharmacology* / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D017450:Receptors, Opioid, mu / Q000235:genetics*
chemical_list: D009292:Narcotic Antagonists; C485764:OPRM1 protein, human; D017450:Receptors, Opioid, mu; D000431:Ethanol; D009271:Naltrexone