Brain-Behavior Markers of Reward and Cannabis Abuse Risk in Young Adults

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The overarching goal of the study is to obtain the necessary training to better understand the neural mechanisms underlying the rewarding, reinforcing properties of cannabis. The proposed study aims to characterize individual differences in subjective reward response and neural reward processing to delta-9- tetrahydrocannabinol (THC), the main psychoactive ingredient in cannabis, among healthy young adults who may be at-risk for problematic cannabis use. Individuals differ in their subjective response to THC on self- report measures of drug reward. Few studies have examined how THC impacts brain reward circuitry in humans. As cannabis becomes increasingly available in the U.S. there is serious concern about negative outcomes related to problematic use. To minimize the adverse impact of increased use, it is critical to identify risk factors that make certain individuals more vulnerable to problematic cannabis use. One factor implicated in risk for drug use and abuse is the sensitivity and function of brain reward circuitry, especially in response to early drug use. Preliminary evidence indicates that THC activates brain reward circuitry, especially the ventral striatum (VS) and medial prefrontal cortex (mPFC), which might be linked to individual differences in rewarding effects of cannabis. To date, little is known about the neural mechanisms underlying the rewarding, reinforcing properties of cannabis and how these may contribute to individual differences in subjective reward response to THC, a marker of drug abuse liability. In the current K23 application, I propose to examine the affective reward mechanisms that identify individuals who may be at risk for cannabis use and abuse. In the proposed study, 80 healthy young adults (aged 18-25), who report occasional cannabis use (≥10x in life, but use ≤1x a week), will undergo two double-blind, within-subject, drug-challenge visits (placebo, 7.5mg THC). During these visits, participants will complete neural measures of reward during electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI), as well as subjective measures of drug reward. By combining neural and behavioral measures with an acute drug administration design, I will (a) determine if THC enhances brain reward reactivity; (b) examine if THC-induced alterations in neural reward reactivity are related to subjective reward response; and (c) determine if “baseline” neural reward reactivity (i.e., during the placebo session) predicts subjective reward response to THC. This study concurrently provides an excellent opportunity to receive mentor-directed, hands-on training in several key areas necessary to refine my knowledge and skill- sets. Specifically, the proposed training plan will focus on four new domains: 1) EEG, 2) Addiction and drug administration studies, 3) Biostatistics, and 4) Professional development. This study, coupled with completion of the training goals will launch my independent career in the translational affective neuroscience of drug abuse and will lay the foundation for future, high impact R01 studies focused on behavioral-brain risk phenotypes and intervention targets for Substance Use Disorders, including Cannabis Use Disorder.