OPIATE ANTAGONIST--ALCOHOL REACTIVITY AND CONSUMPTION

尽管已经进行了一些关于各种功效的研究

Although a number of studies have been conducted on the efficacy of various medications in the treatment of alcoholism, opiate antagonist compounds appear to show the most promise. There is increasing evidence that the endogenous opiate system is involved in the experience of alcohol effects and in the maintenance of alcohol consumption. Several opiate antagonist drugs which have reported utility in the treatment of alcoholism have different opiate receptor binding characteristics. While both naltrexone and nalmefene are predominantly mu opiate antagonists, nalmefene binds to the delta receptor with 2 times the affinity of naltrexone. Given this difference and preclinical reports of grater potency of delta antagonism on alcohol consumption, nalmefene may have more pronounced affects on acute alcohol reactivity in humans. While prospective pharmacologic treatment trials in alcoholism are the only definitive method for evaluating the utility of medications for the treatment of this condition, these trials are costly, time consuming, and put patients at risk for adverse events. Laboratory paradigms which examine the effect of medications on acute alcohol reactivity and consumption in alcoholics may be able to identify compounds which would be the most efficacious to employ in treatment trials. The proposed study will be a randomized placebo controlled comparison of the ability of two opiate antagonist drugs, naltrexone and nalmefene, to alter the reactivity of alcoholics and social drinkers to an acute administration of alcohol and to consumption of alcohol in a "free choice" limited access paradigm. Non-treatment seeking individuals with alcohol abuse or dependence (N-135) and social drinkers (N=135) will be randomly assigned to take placebo, naltrexone, or nalmefene for 7 days. On the eighth day each individual will receive their study medication in a laboratory setting and will ingest a fixed dose of the beverage of their choice followed by a limited access alcohol consumption period. Reactions to alcohol presentation (anticipatory), consumption (pharmacologic), and free choice ingestion (cognitive control and craving), will be measured utilizing subjective, cognitive, physiologic and biologic assessments. Subjects will be paid for their participation and alcoholic individuals will undergo a brief motivational counseling session at athe end of the protocol to educate them about the risks of heavy alcohol consumption and motivate them to seek treatment.