An international mega-analysis of psychedelic drug effects on brain circuit function

Psychedelic drugs are linked to consistent changes in large-scale brain circuit function, according to an international mega-analysis of resting-state fMRI studies. The team integrated 11 independent rsfMRI datasets collected across five psychedelic drugs (psilocybin, LSD, mescaline, DMT, and ayahuasca) from research groups in five countries. Using a uniform preprocessing pipeline and Bayesian hierarchical modeling, they synthesized data across 273 participants and over 550 connectomes to reduce fragmentation and reconcile inconsistent prior findings. Across drugs and sites, the clearest shared pattern was increased functional connectivity between transmodal networks (default, frontoparietal, limbic) and unimodal networks (visual, somatomotor), with additional subnetwork specificity. Key subcortical regions (thalamus, caudate, putamen) and the cerebellum also showed altered coupling with sensorimotor networks, while within-network functional connectivity showed weak-to-moderate and selective reductions with substantial variability. The results provide a probabilistic “map” for benchmarking future psychedelic neuroimaging work.