Intravenous Cocaine Discrimination in Humans

人类静脉注射可卡因歧视

• 批准号: 6612678
• 负责人: CHRIS-ELLYN JOHANSON
• 金额: $ 34.65万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-15 至 2005-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6612678
• 关键词: amphetamines; behavior therapy; behavioral /social science research tag; clinical research; cocaine; dosage; drug abuse chemotherapy; drug screening /evaluation; human subject; intravenous drug abuse; pentobarbital; pharmacokinetics; psychological reinforcement; psychopharmacology; sensory feedback; substance abuse related behavior

DESCRIPTION (provided by applicant): Cocaine abuse/dependence remains a major social and public health problem. There are a significant number of cocaine dependent individuals for whom current behavioral treatment interventions are ineffective. Finding a successful pharmacological treatment for cocaine abuse/dependence continues to be an important yet elusive goal. Several compounds have been shown in pre-clinical studies to attenuate the discriminative stimulus and reinforcing effects of intravenous cocaine but when these medications have been tested in clinical trials, none have proven effective. It is not clear whether the lack of concordance is a function of the behavioral procedures that are used in these models or to a species difference. One strategy to answer this question is to conduct similar studies in humans to assess the validity of the animal models. Although there are established methods for studying the subjective, physiological, and reinforcing effects of intravenous cocaine in humans, drug discrimination methods with intravenous cocaine have not been developed. The potential advantage of studying the discriminative stimulus effects of drugs is that this procedure is particularly well suited for studying mechanisms underlying the dependence-related effects of drugs and has the potential to be relatively efficient, allowing several candidate medications to be evaluated over a relatively short period of time. The goal of this application is to establish the validity of an intravenous cocaine discrimination paradigm in humans. In the first study, human participants will be trained to discriminate the effects of intravenous cocaine injections. Dose-response functions will then be generated with cocaine doses higher and lower than the training dose and generalization tests will be conducted with doses of a drug similar pharmacologically to cocaine (d-amphetamine) and a drug different from cocaine (pentobarbital) to determine the specificity of the paradigm. The second study will determine whether oral cocaine can attenuate the subjective, physiological, and discriminative stimulus effects of intravenous cocaine injections. Although oral cocaine would be an unlikely medication for cocaine dependence, studies of the reinforcing effects of cocaine have demonstrated that they are blocked following the administration of oral cocaine and that this approach functions as a proof of concept in the absence of established blocking agents. These studies as a whole will investigate a promising new strategy for developing treatment medications for cocaine abuse/dependence. If successful, this will be an efficient paradigm for examining the ability of compounds to attenuate the effects of cocaine in humans and may lead to a successful pharmacological treatment for cocaine abuse/dependence.

描述（由申请人提供）：可卡因滥用/依赖仍然是一个主要的社会和公共卫生问题。当前的行为治疗干预措施无效。为可卡因滥用/依赖而成功的药理学治疗仍然是一个重要但难以捉摸的目标。在临床前研究中已经显示了几种化合物，以减轻静脉可卡因的歧视性刺激和增强作用，但是当在临床试验中测试这些药物时，没有证明有效。目前尚不清楚缺乏一致性是这些模型中使用的行为程序还是物种差异的函数。回答这个问题的一种策略是在人类中进行类似的研究以评估动物模型的有效性。尽管有一些既定的方法来研究静脉可卡因在人类中的主观，生理和增强作用，但尚未开发静脉可卡因的药物歧视方法。研究药物的歧视性刺激作用的潜在优势在于，该过程特别适合研究药物依赖性作用的基础机制，并且有可能相对有效，从而可以在相对较短的时间内评估几种候选药物一段时间。该应用的目的是确定人类静脉可卡因歧视范式的有效性。在第一项研究中，将对人类参与者进行培训，以区分静脉可卡因注射的作用。然后，将使用与训练剂量高和低的可卡因剂量生成剂量反应功能，并将用与可卡因（D-苯丙胺）相似的药物（与可卡因（Pentobarbital）相似的药物相似的药物进行概述和概括测试，以确定范式的特异性。第二项研究将确定口服可卡因是否可以减轻静脉可卡因注射的主观，生理和歧视性刺激作用。尽管口服可卡因是可卡因依赖性的不太可能的药物，但对可卡因的增强作用的研究表明，在口服可卡因的给药后，它们被阻止，并且在没有确定的阻止剂的情况下，这种方法是概念的证明。这些研究整体将调查一种有希望的新策略，用于开发可卡因滥用/依赖的治疗药物。如果成功，这将是检查化合物减弱可卡因对人类影响的能力的有效范式，并可能导致成功的药理学治疗可卡因滥用/依赖性。