Psychedelic compounds such as psilocybin, LSD, mescaline, DMT and ayahuasca are attracting growing interest for their scientific and therapeutic potential. In this global collaboration, the team integrated 11 independent resting state fMRI datasets spanning three continents and five countries, covering 267 participants and more than 500 scanning sessions. By applying a unified preprocessing pipeline and a Bayesian hierarchical modelling framework, they were able to map, with unprecedented clarity, the shared neural signatures of acute psychedelic action across multiple substances.
A striking and highly consistent pattern emerged: psychedelics increase functional connectivity between high level transmodal networks (including the default mode, frontoparietal and limbic systems) and sensory networks involved in vision and somatomotor processing. This suggests that psychedelics loosen the brain’s usual hierarchical constraints, enabling information to flow more freely between systems that do not normally interact as strongly (see also: https://www.nature.com/articles/s41467-022-33578-1). At the same time, several key subcortical structures, including the thalamus, caudate, putamen and cerebellum, showed altered coupling with sensorimotor circuits, highlighting their active role in shaping the psychedelic state.
Interestingly, our large‑scale, harmonised analysis reveals a more nuanced picture than previously thought to be the case: reductions in within network connectivity are weaker, more selective and more variable across drugs, underscoring the importance of multi-site, multi-drug evidence when making claims about global network disruption.
Altogether, this work provides the most comprehensive synthesis of psychedelic brain action to date. It not only resolves longstanding inconsistencies but also offers a probabilistic map of how these substances reconfigure large scale cortical and subcortical organisation. Researchers’ hope is that this study becomes a foundational resource — a benchmark to guide and strengthen future psychedelic neuroimaging research as the field matures.
Reference: Girn, M., Doss, M.K., Roseman, L. et al. An international mega-analysis of psychedelic drug effects on brain circuit function. Nat Med 32, 1543–1554 (2026). https://doi.org/10.1038/s41591-026-04287-9
https://www.nature.com/articles/s41591-026-04287-9
Adapted from: Emmanuel Stamatakis LinedIn post
Posted on 29/04/2026
