Clinical Laboratory Evaluations of Aprepitant for the Treatment of Opioid Depende

目前阿片类药物依赖的治疗将受益于添加非阿片类药物为基础的治疗药物。最近的临床前研究表明，NK1受体参与阿片类药物的奖励和戒断。本研究旨在探讨一种临床上可用的NK 1拮抗剂阿瑞匹坦在阿片类药物依赖患者中的应用。基于阿片类药物成瘾的独特行为和药理学特征，以及目前采用的治疗方法，我们建议任何潜在的阿片类药物成瘾治疗药物的治疗机制必须包括减少阿片类药物戒断的能力。这在治疗开始时尤为重要（例如，解毒）。此外，对于长期治疗和复发预防，重要的是管理药物渴望，改善压力的影响，并抑制阿片类药物的奖励作用，如果患者确实经历了滑倒。因此，我们建议在临床实验室中研究阿瑞匹坦，使用急性阿片类药物奖励，强化和戒断模型，以及压力和线索暴露反应。

Project Summary Current treatments for opioid dependence would benefit by the addition of a non-opioid based treatment medication. Recent pre-clinical studies have demonstrated the involvement of the NK1 rector in opioid reward and withdrawal. This study proposes to investigate a clinically available the NK1 antagonist, aprepitant, in opioid dependent patients. Based on the unique behavioral and pharmacological characteristics of opioid addiction, and what is known of the currently employed treatments, we propose that the therapeutic mechanism of any potential opioid addiction treatment medication must include the ability to reduce opioid withdrawal. This is of particular importance during treatment initiation (eg. detoxification). In addition, for longterm treatment and relapse prevention it is important to manage drug craving, to ameliorate the effects of stress, and inhibit the rewarding effects of opioids if patients do experience a slip. Therefore, we propose to study aprepitant in the clinical laboratory, using models of acute opioid reward, reinforcement and withdrawal, as well as stress- and cue-exposure responding.