INNOVATIVE APPROACHES FOR COCAINE PHARMACOTHERAPY

此应用程序是一个药物开发单位（MDU），这将补充我们现有的研究计划，寻找有效的治疗药物成瘾。该MDU在宾夕法尼亚州/弗吉尼亚州成瘾研究中心的总体保护伞内的紧密整合，使我们能够以最少的新资源提出大量的研究（两项大规模临床试验，一项实验室研究和试点项目）。具体而言，该中心的主题侧重于使用创新策略，以找到有效的药物疗法来治疗可卡因依赖。核心设施包括数据管理单元、重要的计算机支持（包括促进中心通信的广域网）、人体实验室和尿液检测实验室。该中心提案包括一个核心项目和三个项目，以及一系列关于GABA能药物的试点研究。核心将具有一般行政职能，并帮助进行整体科学指导、数据管理、常见临床服务、受试者招募、药房服务、实验室职能和单个项目的协调。此外，该中心还将对与增强GABA能活性有关的有前景的可卡因依赖性药理学药物进行试点研究，为临床试验创造新的方向。项目l研究了金刚烷胺和普萘洛尔单独或联合使用，在恢复早期阶段的受试者中，这些受试者最近尿液中可卡因呈阳性，并且在可卡因选择性严重程度评估中得分较高。我们的初步数据表明，药物治疗对这一亚组患者特别有帮助。项目2将测试纳洛酮和双硫仑单独和联合使用治疗可卡因依赖合并酒精依赖的情况。这项研究试图复制和扩展最近的发现，双硫仑减少可卡因和酒精依赖患者的可卡因和酒精的使用。此外，它扩展了我们早期的纳洛酮对酒精滥用可卡因依赖受试者的初步研究。这两种化合物的组合可能特别有助于增强治疗保留和减少可卡因和酒精的使用。项目3评估了各种药物对线索反应性的影响以及线索反应性对临床结果的预测有效性。通过从项目1、2和核心试点项目中随机抽取受试者，受试者将在接受研究药物前接受提示筛选，并在临床试验开始后约4周接受研究药物治疗。除了测试特定的药物，该中心将利用一系列综合项目，以提高我们对可卡因治疗的理解，因为它涉及稳定和戒毒作为治疗目标，而不是减少可卡因复发的数量和强度。此外，我们将研究使用线索反应，因为它预测治疗结果，并作为一个可能的筛选工具，为新的药物。

This application is for a Medication Development Unit (MDU) which will complement our existing program of research in finding effective treatments for drug addiction. The tight integration of this MDU within the general umbrella of the Penn/VA Center for Studies of Addiction, allows us to propose a substantial amount of research (two large scale clinical trials, a laboratory study, and pilot projects) with minimal new resources. Specifically, the theme of this center focuses on the use of innovative strategies to find effective pharrnacotherapies to treat cocaine dependence. The core facilities Include a data management unit, significant computer support including a wide area network to facilitate Center communication, human labs, and a urine testing lab. This Center proposal includes a core and three projects plus a series of pilot studies on GABAergic agents. The core will have general administrative functions and help with the overall scientific direction, data management, common clinical services, subject recruitment, pharmacy services, laboratory functions, and coordination of the individual projects. In addition, the core will conduct pilot studies of promising pharmacological agents for cocaine dependence related to enhancing GABAergic activity, creating new directions for clinical trials. Project l investigates the use of amantadine and propranolol, alone or in combination, in subjects in the early stages of their recovery who have recently had a positive urine for cocaine and a high score on the Cocaine Selective Severity Assessment. Our preliminary data suggest that pharmacotherapy is particularly helpful for this subgroup of patients. Project 2 will test the use of naltrexone and disulfiram, alone and in combination, in the treatment of cocaine dependence complicated by alcohol dependence. This study attempts to replicate and extend recent findings that disulfiram reduces both cocaine and alcohol use in cocaine- alcohol dependent patients. In addition, it extends our earlier pilot study of naltrexone on alcohol abusing cocaine dependent subjects. The combination of these two compounds may be particularly helpful in enhancing treatment retention and reducing cocaine and alcohol use. Project 3 evaluates the effects of various medications on cue reactivity and the predictive validity of cue reactivity on clinical outcome. By taking subjects randomized from Project 1, 2 and the core pilot projects, subjects will be administered cue screening prior to receiving study medications, and again about 4 weeks into the clinical trial while on study medications. In addition to testing specific medications, the Center will utilize an integrated series of projects to improve our understanding of cocaine treatment as it relates to stabilization and detoxification as treatment goals versus reducing the number and intensity of cocaine relapses. In addition we will investigate the use of cue reactivity as it predicts treatment outcome and as a possible screening tool for new medications.