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。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，可卡因仍然是急诊室入院时最常提到的药物。由于与滥用可卡因有关的公共健康问题和费用，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工作，但尚未确定一种被广泛接受的可卡因依赖药物。对可卡因依赖的一些非药物治疗也进行了研究。具体来说，可卡因依赖的行为治疗寻求加强非药物相关的行为.例如，应急管理利用金钱奖励来减少可卡因的使用，并与长期可卡因戒断率高有关。鉴于可卡因依赖行为治疗的有效性，但相对成本较高，一些人认为药物疗法可能能够提高行为疗法的有效性，并降低与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）已经显示出增强可卡因依赖行为疗法的有效性。本申请中提出的实验的目的是使用已经存在的和验证的应急管理模型，可卡因与金钱选择范例，对可卡因依赖的组合药理学和行为治疗的人类实验室模型进行“逆向工程”。本申请中提出的研究有两个具体目标。第一个具体目标是适应对药物预处理敏感的可卡因与金钱选择范例的模型（Higgins等人，1996）并确定最佳参数（即，可卡因剂量、货币价值）。在实验1中，8名非寻求治疗的可卡因依赖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。这些数据将用于指导实验2中使用的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治疗相结合的模型的敏感性。在实验2中，8名非寻求治疗的可卡因依赖性受试者将在安慰剂或300 mg安非他酮维持7天后在一系列鼻内可卡因剂量和货币价值之间进行选择。本申请中提出的研究将有助于开发一种有效和有效的可卡因依赖药物的人类实验室筛选。项目叙述本申请中提出的研究旨在开发一种可卡因依赖的行为和药理学联合治疗模型。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，应急管理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.