This project will investigate the effectiveness of the opiate antagonist naltrexone in decreasing alcohol intoxication and preventing relapse during alcoholism treatment. Animal research has demonstrated that both opiate agonists and antagonists modulate alcohol consumption and effects. Recently, human trials have suggested naltrexone's effectiveness in decreasing relapse of abstinent alcoholics during ongoing rehabilitation services. Two methodologically distinct studies will be conducted concurrently during this 3-year project. The first study will use clinical pharmacology laboratory methodology to examine naltrexone effects on alcohol reinforcement and intoxication in community-recruited, heavy drinking subjects. Subjects will be randomized and maintained on one of three naltrexone doses (0, 50 or 100 mg). Each subject then will receive three alcohol doses (0, 0.5 g/kg, 1.0 g/kg) in randomized order. Comprehensive subjective, psychomotor, autonomic and neuroendocrine measures will be collected at baseline and repeatedly over a 3-hour post-ingestion period. This study will provide suggestive evidence for potential mechanisms of naltrexone's efficacy in preventing relapse in abstinent alcoholics. Additional data on drug safety will be provided by examining naltrexone effects on alcohol pharmacodynamics. The second study will utilize a randomized, double-blind, placebo controlled clinical trial to determine a dose-effect function for naltrexone in preventing alcohol relapse in recently abstinent treatment patients. Subjects will be randomized and maintained for 6 months on one of three naltrexone doses (0, 50 or 100 mg). A variety of measures of alcohol and drug use, psychosocial adjustment and physical status will be collected regularly during the 6-month medication period and a 6-month follow-up period. Also, detailed measures of psychosocial treatment participation and retention will be obtained in order to examine the impact of pharmacotherapy on treatment compliance. Subjects will be stratified -on the basis of alcohol vs. alcohol + opiate dependence to provide important information for future patient-treatment matching efforts. This clinical trial will evaluate the effectiveness of naltrexone for preventing relapse and decreasing alcohol consumption in recently abstinent alcohol-dependent patients when administered in combination with psychochosocial treatment interventions.
| McCaul, M E; Wand, G S; Stauffer, R et al. (2001) Naltrexone dampens ethanol-induced cardiovascular and hypothalamic- pituitary-adrenal axis activation. Neuropsychopharmacology 25:537-47 |
| McCaul, M E; Wand, G S; Eissenberg, T et al. (2000) Naltrexone alters subjective and psychomotor responses to alcohol in heavy drinking subjects. Neuropsychopharmacology 22:480-92 |
| McCaul, M E; Wand, G S; Rohde, C et al. (2000) Serum 6-beta-naltrexol levels are related to alcohol responses in heavy drinkers. Alcohol Clin Exp Res 24:1385-91 |
