THE EFFECTS OF ACUTE CANNABIS WITH AND WITHOUT CANNABIDIOL ON NEURAL REWARD ANTICIPATION IN ADULTS AND ADOLESCENTS

Abstract Background Cannabis, and its main psychoactive compound tetrahydrocannabinol (THC), may alter the brain’ s reward system both acutely and over time. The endocannabinoid and reward systems mature during adolescence and adolescents may therefore respond differently to acute cannabis exposure compared with adults. Despite this, no previous functional magnetic resonance imaging (fMRI) study has examined the acute effects of cannabis in this age group. Aims & Objectives. The aims of this study were to investigate the neural correlates of reward anticipation after acute exposure to THC with and without cannabidiol (CBD), and whether the effect of cannabis differed in adolescents and adults.

Method: This double-blind, placebo-controlled, randomised, crossover design used data from the 'CannTeen’ study, collected between March 11, 2019, and June 16, 2021. Twenty-three adults (26-29 years) and 24 adolescents (16-17 years), matched on gender and cannabis use frequency (0.5-3 days/week) performed the Monetary Incentive Delay task after inhaling cannabis with 0.107 mg/kg THC ('THC’) (8 mg THC for a 75-kg person) or with THC plus 0.320 mg/kg CBD ('THC+CBD’) (24 mg CBD for a 75-kg person), or placebo cannabis. We investigated neural responses to reward anticipation with whole-brain analyses and region of interest analyses in the right and left ventral striatum, right and left anterior cingulate cortex, and right insula. All analyses and hypotheses were pre-registered to the Open Science Framework.

Results: THC acutely reduced reward anticipation activity in the right (p =.005, d = 0.49) and left (p =.003, d = 0.50) ventral striatum and the right insula (p =.01, d = 0.42) compared with placebo. THC+CBD also reduced activity in the right ventral striatum (p =.01, d = 0.41) and the right insula (p =.002, d = 0.49) compared with placebo. The effects of active cannabis were the same in adolescents and adults and there were no differences between the THC and THC+CBD conditions. Bayesian analyses supported these null findings. There were no significant effects in the whole-brain analyses. Discussion & Conclusion In weekly cannabis users, cannabis suppresses the brain’ s anticipatory reward response to money and CBD does not moderate this effect. Furthermore, the adolescent reward circuitry is not differentially sensitive to acute effects of cannabis on reward anticipation. This is the first study to investigate the acute effects of cannabis on the adolescent brain using fMRI and future studies of other cognitive and psychological processes are needed.