Ondansetron and Naltrexone:Cue Reactivity and Drinking

描述（由申请人提供）：研究机制可以帮助确定哪种药物对酒精中毒治疗最有希望。纳曲酮（NAL）改善了治疗效果，但没有100毫克剂量对饮酒冲动或反应等机制的影响的研究。昂丹司琼（OND）显示出相当大的前景，但关于其机制的信息很少。OND和NAL的联合使用减少了饮酒量，但从未单独对每种药物进行过测试。某些个体差异变量显示出缓和某些药物效果的希望。本研究的目的是评估OND （0.5 mg/天），NAL （100 mg/天）以及两者在几种机制以及几种假设的调节变量上的价值。具体目的是调查：(1)这些剂量的OND、NAL或联合使用是否会减少戒酒者对酒精线索的线索诱发反应（研究1）；(2)在不寻求治疗的酗酒者中，OND和/或NAL是否会导致饮酒后愉悦效果和渴望减少（研究2）；(3)在酒吧和自然环境中，OND和/或NAL是否会导致饮酒量减少（研究2）；(4)上述目标的影响程度与早发性与晚发性酒精中毒、酗酒家族史或D4多巴胺受体7重复等位基因的存在有关。将进行两项研究。第一项研究将采用2 × 2 （NAL vs.安慰剂；OND vs.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酒精线索反应性的影响。第二项研究将采用2x2受试者安慰剂对照交叉设计，研究每种药物服用7天对酒吧实验室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使用和联合使用在与饮酒复发和严重程度相关的措施上的相对前景提供证据。还将提供更有可能从每种药物中受益的亚人群的证据。

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.