Effects of THC on Alcohol Consumption and Neural Correlates of Reward - PROJECT SUMMARY / ABSTRACT Cannabis is commonly co-used by individuals who drink alcohol, such that their intoxicating effects overlap (known as `simultaneous use'). Simultaneous use is known to be associated with experiencing increased negative consequences, however, evidence is conflicting regarding whether cannabis acutely increases or decreases alcohol consumption. The neural mechanism(s) underlying simultaneous use are also not well understood. Existing research suggests that overlapping neural mechanisms underlie the effects of alcohol and THC (Δ-9-tetrahydrocannabinol, the primary psychoactive substance in cannabis), and this circuitry may affect motivation for alcohol misuse and simultaneous use. Specifically, cannabinoid receptors (i.e., CB1, to which THC binds as a partial agonist) are distributed throughout the mesolimbic brain regions that underlie alcohol reward. Activation of CB1 is thought to influence neural circuitry underlying reward signaling, such that reward signaling may be amplified by THC, however it is unclear whether THC sates or primes reward-responses to alcohol. An important limitation of prior work is that most studies have used THC doses that are significantly below the level used in the real world. Legal-market cannabis products containing high levels of THC are increasingly popular and available, but their effects neural reward processing and acute alcohol self- administration have not been studied in the laboratory. We propose to test the effects of a 20mg oral dose of THC (i.e., a dronabinol capsule) vs 0 mg THC (placebo capsule) on reward processing during alcohol and cannabis cue-reactivity tasks in 25 adults who drink alcohol and use cannabis. Participants will complete a baseline session and 2 experimental laboratory sessions in this double-blind pharmaco-imaging study with a crossover design. At one experimental session, participants will consume THC before undergoing a brain scan and participating in an intravenous (IV) alcohol self-administration session. At the other experimental session, they will undergo the exact same study procedures after consuming the placebo capsule. Session order will be counterbalanced. We will also examine if neural responses to THC are associated with real-world co-use patterns as assessed by two weeks of daily-diary data collection. The pharmacokinetics of oral THC provide a long time period of elevated blood THC levels, allowing us to perform an MRI scan and IV-alcohol session while THC remains at peak blood levels. We hypothesize that individuals who experience stronger neural reward signaling or reduction in aversive signaling following 20mg dronabinol vs placebo will self-administer more IV alcohol and report more frequent simultaneous alcohol and cannabis use during the daily diary period. Aims include examining the effect of oral THC on neural response to reward (i.e., alcohol and cannabis cues), examining the effect of oral THC on alcohol self-administration, and examining the relationship between neural reward responses and alcohol consumption.
