Impact of Cannabinoid Type 1 Receptor Modulation on Risky Decision-Making

ABSTRACT Recent changes in policy regarding cannabis in the U.S. have been accompanied by an increase in the prevalence of cannabis use and a reduction in the perceived harms associated with consumption. However, little is understood regarding the effects of cannabinoids on cognitive processes. Given that deficient risk-taking is commonly observed in individuals suffering from substance use disorders (SUDs), we assessed the impact of manipulating cannabinoid type 1 receptors (CB 1 Rs; the primary target for Δ 9 -tetrahydrocannabinol in the brain) on punishment-based risk-taking using the risky decision-making task (RDT) in male Long-Evans rats. The RDT measures preference for small, safe rewards over large, risky rewards associated with an escalating chance of foot shock. Systemic bidirectional CB 1 R manipulation with a CB 1 R agonist, CB 1 R antagonist, and FAAH inhibitor (which increases overall endocannabinoid tone) did not alter overt risk-taking in the RDT. Interestingly, direct CB 1 R agonism, but not indirect CB 1 R stimulation or CB 1 R blockade, resulted in reduction in latency to make risky choices while not altering safe choice latency. Our findings suggest that CB 1 R activation expedites engagement in punishment based risk-taking without affecting overall preference for risky vs. safe options. This indicates that risk preference and rate of deliberation for risk-taking are influenced by distinct neural substrates, an important consideration for development of precise treatments targeting the aberrant risk-taking typical of SUD symptomology.