Effect of Δ9-Tetrahydrocannabinol on Frontostriatal Resting State Functional Connectivity and Subjective Euphoric Response in Healthy Young Adults

Background: Few studies have examined how Δ9-Tetrahydrocannabinol (THC), the main psychoactive component of cannabis, impacts brain reward circuitry in humans. In this study, we examined if an acute dose of THC altered resting state functional connectivity between the striatum and prefrontal cortex among healthy young adults with limited cannabis use.

Methods: Participants received THC (n=24) or placebo (n=22) in a double-blind, randomized, between-subject design. Participants completed self-report measures of euphoria and drug-liking throughout the visit. Approximately 120 minutes after drug administration, participants completed an 8-minute resting state functional MRI (rs-fMRI) scan. We utilized seed-based connectivity of the striatum (bilateral putamen, caudate, and NAcc seeds) to the frontal cortex.

Results: Individuals who received THC demonstrated greater rs-fMRI connectivity between the right NAcc and regions of the medial prefrontal cortex (mPFC) (p-values<0.05, corrected) and higher subjective euphoria ratings p=.03) compared to compared to individuals who received placebo. Higher ratings of euphoria were related to greater right NAcc-dorsal mPFC (dmPFC) connectivity for the THC group (p=.03), but not for the placebo group (p=.98).

Conclusions: This is one of the first studies to examine rs-fMRI connectivity in healthy young non-users after THC administration. We found individuals receiving THC show greater rs-fMRI connectivity between the NAcc and mPFC, regions implicated in reward, compared to individuals receiving placebo. In addition, individuals receiving THC reported higher subjective euphoria ratings, which were positively associated with NAcc-dmPFC connectivity. Overall, our findings suggest THC may produce subjective and neural reward responses that contribute to the rewarding, reinforcing properties of cannabis.