An increasing number of studies now indicate that the prophylactic administration of naltrexone is of benefit to some alcoholics to control alcohol abuse. The exact ways in which naltrexone alters ethanol intoxication in humans is not clear yet. The proposed study will investigate how subjective effects of the GABA-benzodiazepine receptor complex (GBRC) activation are affected by naltrexone pretreatment in alcoholic patients, and what aspect of the induced change is predictive of favorable response on subsequent rehabilitation with naltrexone. The philosophy of this approach is that the GBRC is the primary site of action where alcohol intoxication initiates the mobilization of the opiate system in alcoholics. The main hypothesis to be tested is that naltrexone reduces the euphorigenic (and/or increases the dysphoric) properties of lorazepam, and patients with greater change in euphorigenic (and/or dysphoric effects will show reduced alcohol drinking during the follow up period. The project will examine twenty-six subjects who meet DSM-IV and Cloniger's Type 2 criteria for the alcohol dependence over a 2-year period. After detoxification, subjects will undergo a naltrexone/placebo trial with lorazepam challenge to determine the way naltrexone blocks intoxication experience mediated by the GBRC. The prognostic quality of the subjective measures for the subsequent therapeutic responses to naltrexone will be examined. Subjects will be receiving naltrexone therapy for a six (6) month trial. Drinking behavior during this period will be monitored by the study team with the verification of a collateral informant. At the end of the follow-up phase, the subjects will be evaluated using the Treatment Outcome Scale of alcoholism. It is predicted that those patients which show the greatest naltrexone attenuation of lorazepam-induced intoxication will also be those who benefit most from the naltrexone therapy.
