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

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 (CB1Rs; the primary target for {Delta}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 CB1R manipulation with a CB1R agonist, CB1R antagonist, and FAAH inhibitor (which increases overall endocannabinoid tone) did not alter overt risk-taking in the RDT. Interestingly, direct CB1R agonism, but not indirect CB1R stimulation or CB1R blockade, resulted in reduction in latency to make risky choices while not altering safe choice latency. Our findings suggest that CB1R 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.