OPIATE ANTAGONIST--ALCOHOL REACTIVITY AND CONSUMPTION

虽然已经对各种不同的药物的疗效进行了一些研究 治疗酒精中毒的药物、阿片类拮抗剂化合物 似乎展现了最有希望的一面。越来越多的证据表明， 内源性阿片系统参与酒精效应的体验 以及在维持酒精消费方面。几种阿片类拮抗剂 据报道在治疗酒精中毒方面有效的药物有 不同的阿片受体结合特性。虽然纳曲酮和纳曲酮 和纳美芬是主要的MU阿片类拮抗剂，纳美芬与 受体的亲和力是纳曲酮的2倍。鉴于此， 德尔塔拮抗剂的药效差异及临床前报道 饮酒、纳美芬对急性发作的影响可能更明显 人类的酒精反应。 而酒精中毒的前瞻性药物治疗试验是唯一 评价药物治疗的有效性的确定方法 这种情况的治疗，这些试验是昂贵的，耗时的，和 使患者面临不良事件的风险。实验室范例 检查药物对急性酒精反应性和 酗酒者的饮酒可能会辨别出 在治疗试验中使用的最有效的。 这项拟议的研究将是一项随机的安慰剂对照比较 两种阿片类拮抗剂纳曲酮和纳美芬的作用 将酗酒者和社交饮酒者的反应性改变为急性 对酒精的管理和“自由选择”的酒精消费 有限访问模式。未接受治疗的酗酒者 滥用或依赖(N-135)和社交饮酒者(N=135)将随机 被分配服用安慰剂、纳曲酮或纳美芬7天。论 第八天，每个人将在一年内接受他们的学习药物 实验室设置，并将摄取固定剂量的饮料 选择之后是一个有限的酒精消费期。反作用 酒精呈现(预期性)、消费(药理学)和 自由选择摄入(认知控制和渴望)，将被测量 利用主观、认知、生理和生物评估。 受试者将根据他们的参与和酗酒的个人获得报酬 将在课程结束时接受一次简短的激励辅导课程 协议，教育他们大量饮酒的风险，并 鼓励他们寻求治疗。

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.