D-Cyloserine to Enhance Extinction to Alcohol Cues

描述（由申请人提供）：基于灭绝的酒精依赖治疗具有强大的理论和经验基础，但在临床试验中只有适度的积极结果。最近的基础研究和人体研究表明，d -环丝氨酸（DCS）增强了对恐惧线索的消失，一些证据表明DCS也可能增强对酒精线索的消失。因此，DCS可能是AUDS基于消失治疗的有用药理学辅助手段。这项提议的研究是一项概念验证测试，目的是验证DCS是否会增强对酒精线索的消失。66名酒精依赖的成年人将被纳入一项双盲安慰剂对照两组（DCS [50 mg]/安慰剂）受试者之间的人类实验室研究。受试者将接受对酒精提示反应的初始测试，在急性给予DCS或安慰剂的情况下进行两次消退测试，并在一周和一个月后进行后续酒精提示反应测试。我们假设DCS会增强对酒精线索的消退，正如在第二次消退阶段、一周随访和一个月随访中线索引发的渴望减弱所证明的那样。第二个目的是调查DCS对酒精线索的消退作用是否转化为日常生活中渴望的变化。DCS对酒精提示的唤醒和影响的影响也将被检查。确认DCS增强对酒精线索的消退的概念证明，将为后续DCS是否增强基于消退的治疗的临床研究提供经验基础。此外，拟议的研究将采用一种转化实验范式，有可能在未来的研究中研究可能增强对酒精线索的消除的其他药物。

DESCRIPTION (provided by applicant): Extinction-based treatment for alcohol dependence has a strong theoretical and empirical basis, but only modest positive outcomes in clinical trials. Recent basic and human research has revealed that D-cycloserine (DCS) enhances extinction to fear cues and several lines of evidence suggest that DCS may also enhance extinction to alcohol cues. Thus, DCS may be a useful pharmacological adjunct to extinction-based treatment for AUDS. The proposed study is a proof-of-concept test of whether DCS enhances extinction to alcohol cues. Sixty-six alcohol dependent adults will be enrolled in a double-blind placebo-controlled two-group (DCS [50 mg]/placebo) between-subjects human laboratory study. Subjects will undergo an initial test of reactions to alcohol cues, two extinction sessions with acute administration of DCS or placebo, and follow-up alcohol cue reactivity tests one-week and one-month later. We hypothesize that DCS will enhance extinction to alcohol cues, as evidenced by attenuated cue-elicited craving at the second extinction session, the one-week follow- up, and the one-month follow-up. A secondary aim is to investigate whether the effects of DCS on extinction to alcohol cues translate into changes in craving in daily life. Effects of DCS on arousal and affect in response to alcohol cues will also be examined. Affirmation of the proof-of-concept that DCS enhances extinction to alcohol cues will provide the empirical basis for subsequent clinical research on whether DCS enhances extinction- based treatment. Furthermore, the proposed study will employ a translational experimental paradigm that has the potential for investigating additional medications that may enhance extinction to alcohol cues in future studies. PUBLIC HEALTH RELEVANCE: Extinction-based treatment is a promising approach for treating alcohol misuse but has demonstrated only modest positive outcomes in clinical trials. D-Cycloserine has been demonstrated to enhance extinction in animal and human research on anxiety and may also enhance extinction to alcohol cues. The proposed study will empirically test whether D-Cycloserine enhances extinction to alcohol cues toward improving extinction- based treatment for alcohol misuse.