LICIT AND ILLICIT ABUSED DRUGS--BEHAVIORAL INTERACTIONS

申请人摘要： 在正常人和受试者中进行了一系列研究。 有吸毒史来调查几个主要的行为- 咖啡因与经典药物咖啡因的药理作用 虐待：身体依赖/容忍、歧视性刺激效应、 和增强效果。研究将在两个非 住宅和住宅实验室研究环境。毒品会 以胶囊形式给药或双倍剂量静脉注射给药 盲目情况与给药或终止用药的影响 将使用主观、行为和/或 生理指标。一系列三项研究将延长 研究人员对咖啡因身体依赖的研究。前三名 其中将提供有关药理特异性和 利用变异在药物歧视中的作用机制 比较咖啡因与茶碱、d-苯丙胺和 三氮肥。其中一项研究将调查 对咖啡因和其他物质的区别作用的敏感性 化合物。另外两项研究将描述 受过歧视训练的受试者的概括性 小剂量咖啡因与安慰剂或低剂量D-苯丙胺与安慰剂。 其他研究将使用歧视程序作为基线 咖啡因耐受性的特征和提高咖啡因的尝试 增援。最终的歧视研究将包括申请 调查人员的低剂量咖啡因辨别程序 建立低剂量口服可卡因辨别模型 有吸毒史。最后一组三项研究将描述 主观性、精神运动表现、生理学和强化 静脉注射咖啡因的效果。两项关于受试者的研究 有药物滥用史的人将调查咖啡因的影响 剂量和静脉注射持续时间，并将咖啡因与 其他精神运动兴奋剂可卡因，d-苯丙胺和 尼古丁。最终的研究将使用相同的程序来比较 正常人静脉注射咖啡因和尼古丁。 这项研究使用了咖啡因和其他经典的精神运动兴奋剂 应该促进对行为-药理学机制的理解 潜在的药物滥用/依赖。鉴于广泛合法地使用 咖啡因，这个项目也将在临床上具有重要意义 确定咖啡因身体依赖易感性的决定因素 以及在普通人群中的强化和开发咖啡因- 使用减少或戒烟计划以及最大限度地减少 与咖啡因相关的健康风险。

APPLICANT'S ABSTRACT: A series of studies is proposed in normal human subjects and in subjects with histories of drug abuse to investigate several major behavioral- pharmacological effects that caffeine shares with classic drugs of abuse: physical dependence/tolerance, discriminative stimulus effects, and reinforcing effects. Studies will be conducted in both non- residential and residential laboratory research settings. Drugs will be administered in capsules or by intravenous injection under double- blind conditions and the effects of drug administration or termination of chronic dosing will be assessed using subjective, behavioral and/or physiological measures. A series of three studies will extend the investigators' work on caffeine physical dependence. The first three of these will provide information about pharmacological specificity and mechanisms of action by using variations on drug discrimination procedures to compare caffeine with theophylline, d-amphetamine and triazloam. One study will investigate individual differences in sensitivity to the discriminative effects of caffeine and these other compounds. Two other studies will characterize the profiles of generalization in subjects trained on discriminations involving either low-dose caffeine vs. placebo or low-dose d-amphetamine vs. placebo.Two other studies will use discrimination procedures as a baseline for characterizing caffeine tolerance and for attempting to enhance caffeine reinforcement. The final discrimination study will involve application of the investigators' low-dose caffeine discrimination procedures to develop a low-dose oral cocaine discrimination model in subjects with histories of drug abuse. A final set of three studies will characterize subjective, psychomotor performance, physiological and reinforcing effects of intravenously administered caffeine. Two studies in subjects with histories of drug abuse will investigate the effects of caffeine dose and intravenous injection duration, and will compare caffeine with the other psychomotor stimulant drugs cocaine, d-amphetamine and nicotine. A final study will use identical procedures to compare the intravenous administration of caffeine and nicotine in normal subjects. This research with caffeine and other classic psychomotor stimulants should advance understanding of behavioral-pharmacological mechanisms underlying drug abuse/dependence. Given the widespread licit use of caffeine, this project will also be of clinical importance in identifying determinants of vulnerability to caffeine physical dependence and reinforcement in the general population and to developing caffeine- use reduction or cessation programs as well as programs for minimizing caffeine-associated health risks.