D-Cyloserine to Enhance Extinction to Alcohol Cues

描述(申请人提供)：酒精依赖的基于消退的治疗有很强的理论和经验基础，但在临床试验中只取得了有限的积极结果。最近的基础和人类研究表明，D-环丝氨酸(DC)可以增强对恐惧线索的消退，而且有几条证据表明，DC也可以增强对酒精线索的消退。因此，DCs可能是AUDS消退治疗的一种有用的药理学辅助手段。这项拟议的研究是一项概念验证性测试，目的是确定dcs是否能增强对酒精信号的消退。66名酒精依赖的成年人将参加一项双盲、安慰剂对照的两组(DCS[50 mg]/安慰剂)受试者间人类实验室研究。受试者将接受对酒精暗示的反应的初步测试，两次急性注射DC或安慰剂的消退会议，以及一周和一个月后的后续酒精线索反应性测试。我们假设DCs将增强对酒精线索的消退，这在第二次消退会议、一周的随访期和一个月的随访期得到了证明。第二个目的是调查DCs对酒精线索消退的影响是否会转化为日常生活中渴望的变化。此外，我们还将研究dcs对觉醒的影响以及对酒精暗示的反应。确认了DCs增强酒精提示消退的概念，将为后续关于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，拟议的研究将采用翻译性实验范式，有可能在未来的研究中研究其他可能增强酒精线索消退的药物。 与公共卫生相关：基于消退的治疗是治疗酒精滥用的一种有前途的方法，但在临床试验中仅显示了温和的积极结果。D-环丝氨酸已被证明在动物和人类对焦虑的研究中可以增强消退，也可以增强对酒精线索的消退。这项拟议的研究将实证测试D-环丝氨酸是否能增强酒精的消退，这是改善酒精滥用基于消退的治疗的线索。

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.