Neural Mechanisms of Cannabinoid-Impaired Decision-Making in Emerging Adults

项目摘要 这项指导职业发展奖(K01)将使迈克尔·韦斯利博士能够实现他的长期 成为临床神经科学研究项目的独立研究员的目标 新兴成年人的大麻使用障碍(CUD)，这是目前NIDA的资金优先事项。卫斯理博士是一个新的 肯塔基大学(英国)医学院助理教授。本报告中提议的活动 该奖项以韦斯利博士在神经成像和药物滥用研究方面的背景专业知识为基础，并将使他 完成以下短期目标：成为(1)临床药理学和(2)方面的专家 新发成人CUD患者的无创性脑刺激研究及HIS的增强/发展 (3)负责任地进行研究的知识；(4)科学交流和拨款撰写的技能； 以及(5)管理独立研究项目的能力。 英国有许多专注于药物滥用研究的教师和项目，是一个理想的环境 卫斯理博士完成这个奖项。韦斯利博士组建了一支由乔什博士组成的明星指导团队 Lile(导师)，他在英国有一个由NIH资助的成功的临床药理学研究项目，Mark博士 乔治(共同导师)，他率先使用非侵入性脑刺激治疗抑郁症。在……里面 此外，Lumy Sawaki博士(内部P受体)和Lon Hays博士(研究医生)将提供局部安全 监督和医疗监督，Terry Lohrenz博士(外部P受体)将提供指导 高级神经影像数据统计分析。韦斯利博士还将参加一系列正式课程， 实验室交流和研究研讨会/会议，以帮助他实现该奖项的目标。 拟议的研究项目是基于大麻损害决策过程的前提 而这些损害效应增加了新兴成年人患CUD的风险。这 研究将结合∆9-四氢大麻酚(Thc)的急性给药，主要精神活性物质 大麻成分，带有高清晰度经颅直流电刺激(HD-tDC)和神经成像， 使用严格的方法，检查大麻受损的前额叶皮质感兴趣区的作用 初出茅庐的成年人的决策。目标1将检验提高固有PFC活性(Exp.1) 将减弱，而降低活性(Exp2)将增强THC对以下措施的损害影响 新兴成年人的决策和相关的神经认知过程。目标2将检验这一假设 基线任务执行期间的大脑活动和连通性与随后的 对THC和HD-TDC做出反应。这一极具创新性的项目将提高我们对 参与大麻有损决策的机制，这将向禁毒办管理层提供信息并解决 这是一个日益严重的公共卫生问题。

PROJECT ABSTRACT This mentored career development award (K01) will enable Dr. Michael Wesley to achieve his long-term goal of becoming an independent investigator with a clinical neuroscience research program examining cannabis use disorder (CUD) in emerging adults, which is a current NIDA funding priority. Dr. Wesley is a new Assistant Professor in the University of Kentucky (UK) College of Medicine. The activities proposed in this award build on Dr. Wesley’s background expertise in neuroimaging and drug abuse research and will allow him to accomplish the following short-term objectives: Become an expert in (1) clinical pharmacology and (2) non-invasive brain stimulation research in an emerging adult population with CUD, and enhance/develop his (3) knowledge of the responsible conduct of research, (4) skills for scientific communication and grant writing, and (5) ability to manage an independent research program. UK has numerous faculty and projects focused on drug abuse research and is an ideal environment for Dr. Wesley to complete this award. Dr. Wesley has assembled a stellar mentoring team consisting of Dr. Josh Lile (Mentor), who has a successful NIH-funded clinical pharmacology research program at UK and Dr. Mark George (Co-Mentor), who pioneered the use of non-invasive brain stimulation for treating depression. In addition, Dr. Lumy Sawaki (Internal Preceptor) and Dr. Lon Hays (Study Physician) will provide local safety oversight and medical supervision, and Dr. Terry Lohrenz (External Preceptor) will provide guidance with advanced statistical analysis of neuroimaging data. Dr. Wesley will also engage in a series of formal classes, lab exchanges, and research seminars/meetings to assist him in accomplishing the objectives of this award. The proposed research project is based on the premise that cannabis impairs decision-making processes and these impairing effects contribute to an increased risk of developing CUD in emerging adults. This research will combine the acute administration of ∆9-tetrahydrocannabinol (THC), the main psychoactive ingredient in cannabis, with high-definition transcranial direct current stimulation (HD-tDCS) and neuroimaging, using rigorous methods, to examine the role of prefrontal cortex regions of interest in cannabis-impaired decision-making in emerging adults. Aim 1 will test the hypotheses that raising intrinsic PFC activity (Exp. 1) will attenuate, whereas lowering activity (Exp.2) will enhance, the impairing effects of THC on measures of decision-making and associated neurocognitive processes in emerging adults. Aim 2 will test the hypothesis that brain activity and connectivity during baseline task performance is associated with the subsequent response to THC and HD-tDCS. This highly innovative project will improve our understanding of the mechanisms involved in cannabis-impaired decision-making, which will inform CUD management and address a growing public health concern.