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

Background: Cannabis use among young adults has reached the highest levels ever recorded. Evidence indicates acute delta-9-tetrahydrocannabinol (THC) disrupts brain connectivity. Few studies examine 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.

Methods: In a within-subject, double-blind, randomized study, 33 healthy occasional cannabis users received THC (7.5mg, oral) and placebo before completing rsfMRI 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 vs. placebo. Additional linear models related brain connectivity, subjective drug effects, and past-month cannabis use.

Results: 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 two 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.

Conclusions: Our findings add to a growing literature showing THC decreases rsfMRI 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.