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

项目摘要

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.