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对酒精中毒的治疗最有希望。纳曲酮(NAL)可以改善治疗结果，但还没有关于100毫克剂量对饮酒冲动或反应等机制的影响的研究。昂丹西酮(OND)显示出相当大的前景，但对其作用机制知之甚少。OND和NAL的结合减少了饮酒，但从未单独针对每种药物进行过测试。某些个体差异变量已显示出缓解某些药物效果的希望。这项研究的目的是评估OND(0.5毫克/天)、NAL(100毫克/天)以及两者一起在几种机制以及几个假设的调节变量上的价值。具体目的是调查：(1)在戒酒治疗中，这些剂量的OND、NAL或它们的组合是否导致戒酒患者对酒精线索的反应减少(研究1)；(2)OND和/或NAL是否导致非寻求治疗的酒鬼饮酒后快感和渴望减少(研究2)；(3)OND和/或NAL是否导致在酒吧和自然环境中饮酒的减少(研究2)；(4)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在多大程度上缓解了上述目标的影响。我们会进行两项研究。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，调查每种药物7天对正在治疗的新近戒酒的酒精者对酒精提示反应的影响。第二项研究将采用2X2受试者内安慰剂对照的交叉设计，调查每种药物在酒吧实验室对酒精摄取的反应以及对不寻求治疗的酗酒者在酒吧实验室和家庭环境中的饮酒量的影响。结果将为这些药物单独和联合使用在与复发和饮酒严重程度相关的措施上的相对前景提供证据。还将提供关于更有可能从每种药物中受益的亚群的证据。

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.