Δ⁹-Tetrahydrocannabinol Alters Limbic and Frontal Functional Brain Connectomes Among Young Adult Cannabis Users

Cannabis use among young adults has reached the highest levels ever recorded. Evidence indicates that acute Δ⁹-tetrahydrocannabinol (THC) disrupts brain connectivity. Few studies have examined this on a whole-brain level. We examined the effects of a single moderate dose of THC on resting-state functional brain networks among young adult cannabis users.

In a within-subject, double-blind, randomized study, 33 healthy occasional cannabis users received THC (7.5 mg, oral) and placebo before completing resting-state functional magnetic resonance imaging (rs-fMRI) during peak intoxication. Group-information-guided independent component analysis was performed on resting-state brain data to identify whole-brain networks associated with each scan. Within-samples t tests assessed for differences in intrinsic network functional connectivity and between-network functional connectivity after THC versus placebo. Additional linear models examined relationships between brain connectivity, subjective drug effects, and past-month cannabis use.

THC reduced within-network intrinsic connectivity in corticostriatal circuits and other networks associated with sensory systems, interoceptive experiences, and spatial reasoning. THC reduced connectivity between 2 networks characterized by the anterior cingulate cortex and dorsal insula regions as well as the ventral insula and lingual gyrus, respectively. Network connectivity during THC (vs. placebo) was not related to subjective measures of drug effect or recent cannabis use.

Our findings add to a growing literature showing that THC decreases rs-fMRI throughout the brain, impacting networks linked to the many behavioral and perceptual changes associated with THC. Future work is needed to extend these findings to clinical samples and to assess the extent to which these networks are associated with negative outcomes of chronic THC use.