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。目前的行为治疗干预措施对大量可卡因依赖者无效。寻找可卡因滥用/依赖的成功药物治疗仍然是一个重要但难以实现的目标。临床前研究表明，几种化合物可以减弱静脉注射可卡因的辨别刺激和增强作用，但当这些药物在临床试验中进行测试时，没有一种药物被证明有效。目前尚不清楚缺乏一致性是这些模型中使用的行为程序的函数还是物种差异的函数。回答这个问题的一个策略是在人类身上进行类似的研究，以评估动物模型的有效性。尽管已经建立了研究静脉注射可卡因对人类的主观、生理和增强作用的方法，但尚未开发出静脉注射可卡因的药物辨别方法。研究药物的区别性刺激作用的潜在优势在于，该程序特别适合研究药物依赖性相关作用的机制，并且具有相对有效的潜力，允许在相对较短的时间内评估几种候选药物。一段时间。该应用的目标是建立人类静脉注射可卡因辨别范式的有效性。在第一项研究中，人类参与者将接受培训以区分静脉注射可卡因的效果。然后，使用高于和低于训练剂量的可卡因剂量生成剂量反应函数，并使用药理学上与可卡因相似的药物（d-安非他明）和不同于可卡因的药物（戊巴比妥）的剂量进行泛化测试，以确定范式的特殊性。第二项研究将确定口服可卡因是否可以减弱静脉注射可卡因的主观、生理和歧视性刺激作用。尽管口服可卡因不太可能是治疗可卡因依赖的药物，但对可卡因增强作用的研究表明，口服可卡因后可卡因的增强作用会被阻断，并且在没有确定的阻断剂的情况下，这种方法可以作为概念证明。这些研究作为一个整体将调查一种有前途的新策略，用于开发可卡因滥用/依赖的治疗药物。如果成功，这将成为检查化合物减弱可卡因对人类影响的能力的有效范例，并可能导致对可卡因滥用/依赖的成功药物治疗。