OPIATE ANTAGONIST--ALCOHOL REACTIVITY AND CONSUMPTION

尽管已经进行了一些关于各种药物的功效的研究， 治疗酒精中毒的药物，阿片拮抗剂化合物 似乎是最有希望的。 越来越多的证据表明， 内源性阿片系统参与了酒精效应的体验 以及维持酒精消费。 几种阿片拮抗剂 据报道可用于治疗酒精中毒的药物 不同的阿片受体结合特性。 虽然纳洛酮 和纳美芬主要是μ阿片拮抗剂，纳美芬结合到 δ受体的亲和力是纳洛酮的2倍。 鉴于这种 差异和临床前报告的更大效力的δ拮抗作用， 饮酒，纳美芬可能对急性 酒精对人体的影响 虽然酒精中毒的前瞻性药物治疗试验是唯一的 评估药物治疗的效用的确定性方法 治疗这种情况，这些试验是昂贵的，耗时的， 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的影响， 饮酒者的消费量可能能够识别出 在治疗试验中最有效的方法。 拟定的研究将是一项随机安慰剂对照比较， 两种阿片拮抗剂药物纳洛酮和纳美芬 改变酗酒者和社交饮酒者对急性 饮酒和饮酒的“自由选择” 限制访问模式。 不寻求治疗的酗酒者 滥用或依赖（N = 135）和社交饮酒者（N=135）将被随机 被分配服用安慰剂、纳洛酮或纳美芬7天。 上 第八天，每名受试者将接受他们的研究药物， 实验室设置，并将摄入固定剂量的饮料， 在有限的酒精消费期内选择。 反应 酒精呈现（预期）、消费（药理学），以及 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。 受试者将因其参与而获得报酬， 将在2015年年底接受一个简短的动机咨询会议， 议定书，教育他们关于大量饮酒的风险， 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.