Naltrexone does not attenuate the acute behavioral effects of ethanol or pentobarbital in humans

The aim of the present study was to determine whether naltrexone, an opioid antagonist, attenuates the acute subject-rated, performance-impairing and physiological effects of ethanol or pentobarbital. To accomplish this aim, two separate experiments were conducted. In Experiment 1, eight volunteers (one female, seven males) received ethanol (0, 0.5 and 1.0 g/kg) alone and in combination with naltrexone (0, 50 and 100 mg). In Experiment 2, eight different volunteers (five females, three males) received pentobarbital (0, 150 and 300 mg), alone and in combination with naltrexone (0, 50 and 100 mg). Subjects received one of the nine possible drug-naltrexone combinations under double-blind conditions during each of nine experimental sessions. Order of drug administration was mixed, and at least 48 h separated all sessions. In Experiment 1, subjects orally ingested ethanol 1 h after naltrexone. In Experiment 2, subjects ingested naltrexone 1 h after pentobarbital. The timing of drug administration was arranged so that the peak behavioral effects of ethanol or pentobarbital occurred so that across peak plasma levels of naltrexone. Drug effects were assessed before drug administration and periodically afterwards for 5 h using a battery of subject-rated drug-effect questionnaires and performance measures previously shown to be sensitive to the acute effects of ethanol. Ethanol and pentobarbital produced prototypical subject-rated drug effects (e.g. increased subject ratings of Drunk, Drug Liking, Elated and Good Effects) and impaired performance. Naltrexone did not produce significant effects on these measures. In other words, naltrexone did not attenuate the acute subject-rated and performance-impairing effects of ethanol or pentobarbital. The mechanism by which naltrexone exerts its clinical effect in the treatment of alcohol abuse/dependence remains unclear.