Spatiotemporal mapping of brain organisation following the administration of 2C-B and psilocybin

2C-B and psilocybin cause distinct acute changes in human brain organization, measured with 7 Tesla resting-state fMRI. In a within-subject, double-blind, placebo-controlled crossover study with 22 healthy volunteers, matched doses of 2C-B (20 mg) and psilocybin (15 mg) selectively reduced intranetwork static functional connectivity, while broadly increasing between-network and subcortical-cortical connectivity. Compared to psilocybin, 2C-B showed less pronounced reductions in between-network dynamic functional connectivity and instead produced elevations in transmodal static connectivity. Both compounds increased global connectivity and produced spatially divergent patterns but similar increases in brain complexity. PET density modeling linked where neural effects occurred to differences in monoaminergic transporter and serotonergic receptor binding profiles beyond 5-HT2A, suggesting pharmacology shapes functional dynamics. Behavioral psychedelic markers were associated with decoupling of the transmodal axis of functional brain organization, supporting 2C-B as a useful next-generation probe for psychedelic neuroscience.