Ondansetron and Naltrexone:Cue Reactivity and Drinking

描述（由申请人提供）： 调查机制可以帮助确定哪些药物最有希望治疗酒精中毒。纳洛酮（NAL）可改善治疗结果，但没有关于100 mg剂量对饮酒冲动或反应等机制的影响的研究。昂丹司琼（OND）显示出相当大的希望，其机制的信息很少。OND与NAL的组合减少了饮酒，但从未单独对每种药物进行过测试。某些个体差异变量已显示出缓和某些药物作用的希望。本研究的目的是评价OND（0.5 mg/天）、NAL（100 mg/天）以及两者联合使用对几种机制的价值，沿着几个假设的调节变量。具体的目的是调查：（1）这些剂量的OND、NAL或组合是否导致在治疗中的戒酒酗酒者中对酒精线索的减少的线索引发的反应（研究1）;（2）OND和/或NAL是否导致在非寻求治疗的酗酒者中摄入酒精后的减少的愉悦效果和渴望（研究2）;（3）OND和/或NAL是否导致酒吧和自然环境中的酒精消费减少（研究2）;（4）早发性与晚发性酒精中毒、酒精中毒家族史、或存在D4多巴胺受体的7-重复等位基因。将进行两项研究。第一项研究将采用2 × 2（NAL与安慰剂; OND与安慰剂）组间随机安慰剂对照设计，研究每种药物治疗7天对最近戒酒的酗酒者对酒精线索的反应性的影响。第二项研究将采用2 × 2受试者内安慰剂对照交叉设计，研究每种药物治疗7天对酒吧实验室中酒精摄入反应的影响，以及对非寻求治疗的重度饮酒者在酒吧实验室和家庭环境中饮酒量的影响。结果将为这些药物单独或联合使用与复发和饮酒严重程度相关的措施的相对承诺提供证据。 还将提供更有可能从每种药物中获益的亚群的证据。

DESCRIPTION (provided by applicant): Investigating mechanisms can help determine which medications show the most promise for alcoholism treatment. Naltrexone (NAL) results in improved treatment outcomes but there are no studies of the effects of 100 mg dose on mechanisms such as urges or responses to drinking. Ondansetron (OND) shows considerable promise with little information about its mechanisms. The combination of OND with NAL reduces drinking but has never been tested against each medication alone. Certain individual difference variables have shown promise for moderating the effects of some medications. The objective of this research is to evaluate the value of OND (0.5 mg/day), NAL (100 mg/day) and both together on several mechanisms along with several hypothesized moderating variables. The specific aims are to investigate: (1)whether these doses of OND, NAL or the combination results in reduced cue-elicited responses to alcohol cues among abstinent alcoholics in treatment (Study 1); (2) whether OND and/or NAL results in reduced pleasurable effects and craving after alcohol ingestion among non-treatment-seeking alcoholics (Study 2); (3) whether OND and/or NAL results in less alcohol consumption in a bar and in the natural environment (Study 2); (4) the extent to which the effects in the above aims are moderated by early vs. late-onset alcoholism, family history of alcoholism, or presence of the 7-repeat allele of the D4 dopamine receptor. Two studies will be conducted. The first will investigate the effects of 7 days on each medication on reactivity to alcohol cues among recently abstinent alcoholics in treatment, using a 2 X 2 (NAL vs. placebo; OND vs. placebo) between-groups randomized placebo-controlled design. The second will investigate the effects of 7 days on each medication on reactions to alcohol ingestion in a bar-lab and on amount consumed both in the bar-lab and the home environment among non-treatment-seeking heavy drinkers, using a 2 X 2 within-subject placebo-controlled cross-over design. Results will provide evidence for the relative promise of these medications separately and in combination on measures relevant to relapse and severity of drinking. Evidence will also be provided about subpopulations more likely to benefit from each medications.