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

新兴成年人大麻素决策受损的神经机制

• 批准号: 10190873
• 负责人: Michael J Wesley
• 金额: $ 15.79万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-15 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10190873
• 关键词: Acute; Address; Anodes; Attenuated; Award; Behavior; Behavioral Mechanisms; Brain; Cannabinoids; Cannabis; Cathodes; Chemicals; Clinical; Clinical Pharmacology; Communication; Data; Decision Making; Development; Disease Management; Dorsal; Drug Use Disorder; Drug abuse; Drug usage; Environment; Faculty; Functional Magnetic Resonance Imaging; Funding; Genetic; Goals; Grant; Impairment; Individual; Individual Differences; Intervention; Intoxication; K-Series Research Career Programs; Kentucky; Knowledge; Lateral; Lesion; Link; Maps; Measures; Medial; Medical; Medicine; Membrane Potentials; Mental Depression; Mentors; Methodology; Methods; National Institute of Drug Abuse; Nature; Neurocognitive; Neurons; Neurosciences Research; Neurotransmitters; Perception; Pharmaceutical Preparations; Physicians; Physiological; Population; Predisposition; Prefrontal Cortex; Process; Public Health; Research; Research Personnel; Research Project Grants; Research Training; Rest; Risk; Role; Safety; Series; Short-Term Memory; Site; Statistical Data Interpretation; Substance abuse problem; Supervision; Task Performances; Techniques; Testing; Tetrahydrocannabinol; Tissues; Training; United States National Institutes of Health; Universities; Writing; base; career development; college; disorder prevention; emerging adult; emerging adulthood; endogenous cannabinoid system; experimental study; frontal lobe; improved; individual response; innovation; interest; marijuana use; marijuana use disorder; marijuana user; meetings; neuroimaging; neuromechanism; noninvasive brain stimulation; preclinical study; professor; programs; relating to nervous system; response; responsible research conduct; skills; social; success

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.

项目摘要 这个修订的职业发展奖（K01）将使迈克尔·卫斯理博士能够实现他的长期 成为临床神经科学研究计划的独立研究者的目标 新兴成年人的大麻使用障碍（CUD）是当前的NIDA资金优先级。卫斯理博士是新的 肯塔基大学（英国）医学院的助理教授。提出的活动 以卫斯理博士在神经影像学和药物滥用研究方面的背景专业知识为基础上的奖项，并将允许他 要实现以下短期目标：成为（1）临床药理学专家和（2） 在患有CUD的新兴成年人口中，非侵入性大脑刺激研究，并增强/发展他的 （3）了解负责任的研究的知识，（4）科学交流和授予写作的技能， （5）管理独立研究计划的能力。 英国有众多的教职员工，专注于药物滥用研究，是理想的环境 韦斯利博士完成了这个奖项。韦斯利博士组建了一支由乔什博士组成的出色的心理团队 Lile（导师），他在英国拥有成功的NIH资助的临床药理学研究计划和Mark博士 乔治（联合学），他率先使用非侵入性大脑刺激来治疗抑郁症。在 此外，Lumy Sawaki博士（内部受体）和Lon Hays博士（学习医师）将提供当地安全 监督和医疗监督，特里·洛伦兹（Terry Lohrenz）博士（外部主持人）将提供指导 神经影像数据的高级统计分析。卫斯理博士还将参加一系列正规课程， 实验室交流和研究中心/会议，以帮助他完成该奖项的目标。 拟议的研究项目基于大麻损害决策过程的前提 这些损害效应有助于增加新兴成年人发展CUD的风险。 研究将结合Δ9-四氢大麻酚（THC）的急性给药，主要的精神活性 大麻中的成分，具有高清经颅直流刺激（HD-TDC）和神经影像学， 使用严格的方法，检查大麻损伤中感兴趣的前额叶皮层区域的作用 新兴成年人的决策。 AIM 1将测试提高内在PFC活性的假设（Exp。1） 将减弱，而降低活动（EXP.2）将增强，THC对测量的损害影响 新兴成年人的决策和相关的神经认知过程。 AIM 2将检验假设 基线任务性能期间的大脑活动和连通性与随后的 对THC和HD-TDC的响应。这个高度创新的项目将提高我们对 大麻障碍决策涉及的机制将为CUD管理和地址提供信息 越来越多的公共卫生问题。