Receptor-enriched analysis of functional connectivity (REACT) for understanding cannabinoid neuropsychopharmacology
bioRxiv (Cold Spring Harbor Laboratory) June 5, 2025 Ekaterina Shatalina, Natalie Ertl, Kat Petrilli et al. 1 citation preprint
Inhaling cannabis with THC alone or THC plus CBD reduces resting-state functional connectivity in brain networks that are rich in CB1 and CB2 cannabinoid receptors. Co-administering CBD with THC produced more widespread reductions than THC alone, affecting regions involved in cognition and emotion such as the prefrontal cortex, cingulate cortex, insula, hippocampus, amygdala, and putamen. Higher THC levels in the blood were linked to greater connectivity decreases when CBD was also present. Subjective drug effects correlated with connectivity changes in a region-specific way. The findings suggest that CBD may enhance rather than dampen THC's effects on brain connectivity, contrary to some earlier expectations.