Human Lab Model of Behavioral/Pharmacological Treatment for Cocaine Dependence

描述(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，过去一个月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的数据，可卡因仍然是急诊室入院时最常提到的药物。由于对公共健康的担忧和与滥用可卡因相关的成本，确定治疗可卡因依赖的药物疗法是国家药物滥用研究所(NIDA)的优先事项。尽管进行了密集的研究，但还没有确定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审查。具体地说，针对可卡因依赖的行为治疗寻求加强与药物无关的行为。例如，应急管理使用货币奖励措施来减少可卡因的使用，并与长期戒除可卡因的高比率有关。考虑到行为疗法对可卡因依赖的有效性，但相对成本也很高，一些人认为药物疗法可能能够增强行为疗法的有效性，并降低与提供这些疗法相关的成本。事实上，药物疗法(即地昔帕明和安非他酮)已被证明能提高行为疗法对可卡因依赖的有效性。本申请中提出的实验的目的是使用已经存在的、经过验证的应急管理模型--可卡因与金钱的选择范式，对可卡因依赖的药物和行为联合治疗的人体实验室模型进行反向工程。本申请中提出的研究有两个具体目标。第一个具体目标是调整对药物预处理敏感的可卡因与金钱选择范式的模型(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名寻求可卡因依赖的非治疗受试者将在一系列鼻内可卡因剂量和货币价值之间进行选择。这些数据将被用来指导实验2中将使用哪些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式的敏感性。在实验2中，8名寻求可卡因依赖的非治疗受试者将在安慰剂或300毫克安非他酮维持7天后，在鼻内注射一系列剂量的可卡因和货币价值之间进行选择。这项申请中提出的研究将有助于开发一种有效和有效的人体实验室可卡因依赖药物筛选。项目简介本申请中提出的研究旨在开发一种联合行为和药物治疗可卡因依赖的模式。通过这个模型，我们希望更有效地筛选可能增强应急管理有效性的药物，应急管理是一种成功地控制可卡因依赖的行为治疗方法。

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.