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.