D-Cyloserine to Enhance Extinction to Alcohol Cues

D-环丝氨酸可增强酒精线索的消除

• 批准号: 7903862
• 负责人: JAMES MACKILLOP
• 金额: $ 18.84万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7903862
• 关键词: Acute; Adult; Affect; Alcohol dependence; Alcohols; Animals; Anxiety; Arousal; Attenuated; Clinical Research; Clinical Trials; Consumption; Cues; Cycloserine; Development; Double-Blind Method; Enrollment; Extinction (Psychology); Fright; Future; Glucuronides; Hour; Human; Individual; Laboratories; Laboratory Study; Life; Measures; Nature; Outcome; Outpatients; Patient Self-Report; Persons; Pharmaceutical Preparations; Placebo Control; Placebos; Prevention; Process; Public Health; Reaction; Reporting; Research; Research Project Grants; Sampling; Testing; Translating; Visit; alcohol abstinence; alcohol cue; alcohol exposure; alcohol misuse; alcohol response; alcohol use disorder; base; biobehavior; craving; cue reactivity; design; follow-up; human subject; improved; public health relevance; response; treatment duration; urinary

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.

描述（由申请人提供）：基于消除的酒精依赖治疗具有强大的理论和经验基础，但在临床试验中仅取得了适度的积极结果。最近的基础和人类研究表明，D-环丝氨酸 (DCS) 会增强对恐惧线索的消退，并且一些证据表明 DCS 也可能会增强对酒精线索的消退。因此，DCS 可能是 AUDS 的基于消退治疗的有用药理学辅助手段。拟议的研究是一项概念验证测试，旨在验证 DCS 是否会增强酒精线索的消除。 66 名酒精依赖成年人将参加一项双盲安慰剂对照两组（DCS [50 毫克]/安慰剂）受试者间人类实验室研究。受试者将接受对酒精提示反应的初步测试、两次快速施用 DCS 或安慰剂的消退疗程，以及一周和一个月后的后续酒精提示反应测试。我们假设 DCS 将增强对酒精线索的消退，第二次消退阶段、一周随访和一个月随访中提示引起的渴望减弱就证明了这一点。第二个目的是调查 DCS 对酒精线索消除的影响是否会转化为日常生活中渴望的变化。还将检查 DCS 对酒精暗示反应的唤醒和情感的影响。 DCS增强酒精线索消退概念验证的确认，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，拟议的研究将采用转化实验范式，该范式有可能在未来的研究中研究可能增强酒精线索消除的其他药物。 公共卫生相关性：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出有限的积极结果。在动物和人类的焦虑研究中，D-环丝氨酸已被证明可以增强消退作用，也可能增强对酒精暗示的消退作用。拟议的研究将根据经验测试 D-环丝氨酸是否增强酒精线索的消退，从而改善酒精滥用的基于消退的治疗。