Human Lab Model of Behavioral/Pharmacological Treatment for Cocaine Dependence

描述（由申请人提供）：可卡因依赖仍然是一个重大的公共卫生问题。来自全国药物使用和健康调查的数据表明，自2002年以来，在过去一个月里使用可卡因的美国人数量保持相对稳定，根据药物滥用警告网络，可卡因仍然是急诊室入院时最常提到的药物。由于与可卡因滥用有关的公共卫生问题和费用，确定治疗可卡因依赖的药物疗法是国家药物滥用研究所的一个优先事项。尽管进行了大量的研究，但尚未找到一种被广泛接受的治疗可卡因依赖的药物。对可卡因依赖的一些非药物治疗也进行了研究。具体地说，对可卡因依赖的行为治疗寻求加强与毒品无关的行为。例如，应急管理使用金钱奖励来减少可卡因的使用，这与长期戒断可卡因的高比率有关。鉴于对可卡因依赖的行为治疗的有效性，但也相对较高的成本，一些人认为药物治疗可能能够提高行为治疗的有效性，并降低与这些治疗相关的成本。事实上，药物疗法（即地西帕明和安非他酮）已被证明可以提高对可卡因依赖的行为疗法的有效性。本申请中提出的实验目的是“逆向工程”一个人类实验室模型，利用一个已经存在的和经过验证的应急管理模型，可卡因与金钱选择范式，对可卡因依赖进行药物和行为联合治疗。本申请中提出的研究有两个具体目的。第一个具体目标是采用对药理学预处理敏感的可卡因与货币选择范式模型（Higgins等人，1996年），并确定最佳参数（即可卡因剂量、货币价值）。在实验1中，8名寻求非治疗可卡因依赖的受试者将在鼻内可卡因和货币价值之间做出选择。这些数据将用于指导在实验2中使用何种可卡因剂量和货币价值。第二个具体目标是验证可卡因与金钱选择范式作为药物和行为联合治疗模型的敏感性。在实验2中，8名寻求可卡因依赖治疗的受试者在服用安慰剂或300毫克安非他酮维持7天后，将在一系列剂量的鼻内可卡因和货币价值之间做出选择。在本申请中提出的研究将有助于开发一种有效的人类实验室筛选可卡因依赖药物。本申请中提出的研究旨在开发一种结合行为和药物治疗可卡因依赖的模型。有了这个模型，我们希望更有效地筛选可能提高应急管理效果的药物，这是一种成功管理可卡因依赖的行为治疗。

DESCRIPTION (provided by applicant): Cocaine dependence continues to be a significant public health concern. Data from the National Survey on Drug Use and Health indicate that the number of Americans who had used cocaine in the past month has remained relatively stable since 2002 and cocaine remains the most frequently mentioned drug in emergency-room admissions according to the Drug Abuse Warning Network. Because of the public-health concerns and costs associated with its abuse, identifying a pharmacotherapy for the treatment of cocaine dependence is a priority for the National Institute on Drug Abuse (NIDA). Despite intense research efforts, a widely accepted medication for cocaine dependence has not yet been identified. A number of non-pharmacological treatments for cocaine dependence have also been examined. Specifically, behavioral treatments for cocaine dependence seek to reinforce non- drug related behaviors. For example, contingency management uses monetary incentives to decrease cocaine use and is associated with high rates of prolonged cocaine abstinence. Given the effectiveness, but also high relative cost, of behavioral treatments for cocaine dependence, some have theorized that pharmacotherapies may be able to enhance the effectiveness of behavioral therapies and decrease costs associated with delivery of these therapies. Indeed, pharmacotherapies (i.e., desipramine and bupropion) have been shown to enhance the effectiveness of behavioral therapies for cocaine dependence. The purpose of the experiments proposed in this application is to "reverse engineer" a human laboratory model of combined pharmacological and behavioral treatments for cocaine dependence using an already existing and validated model of contingency management, the cocaine versus money choice paradigm. The research proposed in this application has two specific aims. The first specific aim is to adapt a model of the cocaine versus money choice paradigm that is sensitive to pharmacological pretreatment (Higgins et al., 1996) and determine optimal parameters (i.e., cocaine dose, monetary values). In Experiment 1, eight non-treatment seeking cocaine-dependent subjects will choose between a range of doses of intranasal cocaine and monetary values. These data will be used to guide which cocaine dose and monetary values will be used in Experiment 2. The second specific aim is to validate the sensitivity of the cocaine versus money choice paradigm as a model of combined pharmacological and behavioral treatment. In Experiment 2, eight non-treatment seeking cocaine-dependent subjects will choose between a range of doses of intranasal cocaine and monetary values following maintenance for seven days on placebo or 300 mg bupropion. The research proposed in this application will serve to develop an efficient and valid human laboratory screen of medications for cocaine dependence. Project Narrative The research proposed in this application seeks to develop a model of combined behavioral and pharmacological treatment for cocaine dependence. With this model, we hope to more efficiently screen medications that might enhance the efficacy of contingency management, a behavioral treatment that is successful in managing cocaine dependence.