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，但在临床试验中仅具有适度的阳性结果。最近的基本和人类研究表明，D-胞丝烯（DC）增强了对恐惧提示的灭绝，几条证据表明，DC也可能增强对酒精提示的灭绝。因此，DC可能是基于灭绝的AUD处理的有用的药理辅助手段。拟议的研究是对DC是否增强酒精提示灭绝的概念验证测试。六十六名酒精依赖的成年人将参加双盲安慰剂对照的两组（DC [50 mg]/安慰剂）人类实验室研究。受试者将对酒精提示的反应进行初步测试，两次急性给药DC或安慰剂的灭绝课程，然后在一个星期和一个月后进行后续酒精提示反应性测试。我们假设DC将增强对酒精提示的灭绝，这是在第二次灭绝会议，一周的随访和一个月的随访中所证明的。第二个目的是研究DC对酒精提示的影响是否转化为日常生活中渴望的变化。还将检查DC对唤醒和对酒精提示的影响的影响。肯定概念证明DC会增强对酒精提示的灭绝将为DC是否增强基于灭绝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实验范式，该范式有可能研究其他药物，以增强未来研究中酒精提示的灭绝。 公共卫生相关性：基于灭绝的治疗是治疗酒精滥用的一种有前途的方法，但在临床试验中仅表现出适度的积极结果。已证明D-胞菌素可以增强动物和人类焦虑研究的消失，并且还可能增强对酒精提示的灭绝。拟议的研究将在经验上测试D-胞丝烯是否增强了对酒精提示的灭绝，以改善基于灭绝的酒精滥用治疗方法。