Neural and computational markers of reward processes as longitudinal risk markers of cannabis use escalation in young adults with anhedonia

About This Grant

Chronic cannabis use is linked to poor physical and mental health. Young adults (age 18-21) with anhedonia, defined as deficient processing and experiencing of pleasure and rewards, are especially at risk for escalating their cannabis use. Anhedonia is a key transdiagnostic feature of many disabling conditions that have high rates of cannabis use and cannabis use disorder. Examining mechanisms of cannabis use escalation in young adults with elevated anhedonia is therefore highly significant as it would inform targeted prevention efforts for individuals who are at elevated risk. One reason young adults with anhedonia may be at risk for chronic cannabis use is because they abnormally process delta-9-tetrahydrocannabinol (D9-THC), the psychoactive ingredient in cannabis linked to the rewarding and reinforcing properties of cannabis. The few studies on the acute effects of D9-THC on reward processing have yielded mixed results, potentially due to not taking individual differences in anhedonia into account. Indeed, our preliminary study suggests that an individual’s level of anhedonia impacts how acute administration of D9-THC (relative to placebo) affects one’s neural response to rewards. Given that sensitivity to acute effects of other drugs (e.g., stimulants, alcohol) is a known risk factor for chronic use of those drugs, D9- THC’s effect on reward processing may be a mechanism for escalation to chronic cannabis use among young adults with anhedonia. The first goal of this project is therefore to examine how an acute laboratory administration of D9-THC (vs. placebo) impacts two aspects of reward processing: how individuals (a) anticipate receiving rewards (reward anticipation) and (b) learn associations between their actions and rewarding outcomes (reward-based reinforcement learning [RBRL]). Deficits in reward anticipation and RBRL have been robustly linked with anhedonia, but only examined in a handful of small D9-THC administration studies. The second goal of this study is to test if sensitivity to D9-THC’s effects on reward processes serves as a biomarker for escalation to chronic cannabis use in young adults with anhedonia. We will recruit 144 young adult (aged 18-21) occasional to regular cannabis users (who use less than daily) with a clinically significant range of anhedonia. At baseline, participants will undergo two double-blind, within-subject, drug-challenge visits (placebo vs. D9-THC), during which they will complete the reward anticipation and RBRL tasks in a fMRI scanner. All participants will then be followed for 2 years to assess future cannabis use and cannabis use disorder symptoms. A unique feature of this novel study is the assessment of two types of reward responses to acute D9-THC, as well as a longitudinal follow-up among a clinically-relevant sample. In sum, the present proposal has the potential to identify novel biomarkers for escalation to chronic cannabis use in an understudied, clinically relevant population – work that will ultimately inform targeted intervention and prevention efforts among young adult cannabis users at risk for chronic use.