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

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 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, (3) extend and apply his existing expertise in neuroimaging research to these new areas, and enhance/develop his (4) knowledge of the responsible conduct of research, (5) skills for scientific communication and grant writing, and (6) 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), Director of the Brain Stimulation Laboratory at the Medical University of South Carolina, 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) to provide in-house safety oversight and medical supervision at UK, and Dr. Terry Lohrenz (External Preceptor) to provide guidance with advanced statistical analyses of neuroimaging data. In addition, Dr. Wesley will 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 a strong scientific premise, is innovative, and will use rigorous methods. This research will combine the acute administration of Ä9-tetrahydrocannabinol (THC), the main psychoactive ingredient in cannabis, with brain stimulation and neuroimaging methods to examine the role of the prefrontal cortex and connected brain regions of interest in cannabis-impaired decision-making in emerging adults. Specifically, high-definition transcranial direct current stimulation (HD-tDCS) will be used to raise or lower intrinsic regional brain activity during administration of THC in randomized, double-blind, placebo- and sham-controlled experiments. Aim 1 will test the hypotheses that increasing activity (Exp. 1) will attenuate, whereas lowering activity (Exp.2) will enhance, the impairing effects of THC. Aim 2 will test the hypothesis that individual differences in brain structure and function predict the effects of THC and HD-tDCS. Results from this project will improve our understanding of the mechanisms involved in cannabis-