A Pharmacological Analysis of Delta 9-THC in Humans

描述(由申请人提供)： 里尔博士的研究生和博士后研究重点是兴奋剂成瘾的神经药理学基础，以及如何将调节兴奋剂效应的神经递质系统作为药物开发的靶点。申请书中提出的职业发展和研究计划概述了使他能够将以前的经验以及新的方法应用于一个新兴的研究领域--大麻相关疾病的治疗--的培训。尽管大麻的使用比任何其他非法药物更为普遍，并可能发展为滥用和依赖，但目前还没有针对这些疾病的药物疗法，为此目的进行的临床研究也很少。这里描述的实验旨在识别参与大麻主要活性成分Delta 9-THC对人类影响的神经递质系统。这些实验的主要结果变量是Delta9-THC产生的内感线索。Delta9-THC的相互感觉效应将通过药物辨别程序来衡量，这是一种药理学上的特异性和敏感的手段，以表征药物的特征。由于大麻相关障碍与行为和认知的不良适应变化有关，还将采取额外的实验措施来评估强化、主观评级、冲动、精神运动表现、学习和记忆。将调查大麻、阿片、GABA和多巴胺系统的作用，这将揭示未来研究工作的目标。Lile博士将由人体大麻研究专家凯利博士赞助。这些实验和本提案中描述的培训将在肯塔基大学进行，该大学拥有广泛的科学家社区，从事与药物成瘾有关的基础和临床研究。这一奖项将允许Lile博士发展成为一名独立的研究员，并建立一个专注于大麻相关疾病的人类研究计划。

DESCRIPTION (provided by applicant): Dr. Lile's graduate and post-doctoral research focused on the neuropharmacological basis of stimulant addiction and how the neurotransmitter systems that mediate the effects of stimulants could be targeted for medications development. The career development and research plan proposed in this application outlines the training that will enable him to apply his previous experience, along with new methodolgies, to an emerging area of research, the treatment of cannabis-related disorders. Despite the fact that cannabis use is more prevalent than for any other illicit drug and can progress to abuse and dependence, there are no pharmacotherapies for these disorders and little clinical research has been conducted to this end. The experiments described here were designed to identify the neurotransmitter systems that are involved in the effects of the primary active constituent of cannabis, delta 9-THC, in humans. The primary outcome variable for these experiments is the interoceptive cue produced by delta 9-THC. The interoceptive effects of delta 9- THC will be measured using the drug-discrimination procedure, which is a pharmacologically specific and sensitive means to characterize the profile of a drug. Because cannabis-related disorders are associated with maladaptive changes in behavior and cognition, additional experimental measures to assess reinforcement, subjective ratings, impulsivity, psychomotor performance, learning and memory will also be taken. The role of the cannabinoid, opioid, GABA and dopamine systems will be investigated, which will reveal targets for future research efforts. Dr. Lile will be sponsored by Dr. Kelly, an expert in cannabis research in humans. The conduct of these experiments and the training described in this proposal will occur at the University of Kentucky, which has an extensive community of scientists engaged in basic and clinical research related to drug addiction. This award will allow Dr. Lile to develop as an independent investigator and to establish a program of human research concentrated on cannabis-related disorders.