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

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dc.creatorGirn, Manesh
dc.creatorDoss, Manoj K
dc.creatorRoseman, Leor
dc.creatorPreller, Katrin H
dc.creatorPalhano-Fontes, Fernanda
dc.creatorPasquini, Lorenzo
dc.creatorBarrett, Frederick S
dc.creatorMallaroni, Pablo
dc.creatorMason, Natasha L
dc.creatorTimmermann, Christopher
dc.creatorMcCulloch, Drummond E
dc.creatorFisher, Patrick M
dc.creatorWinston, Brian S
dc.creatorMoujaes, Flora
dc.creatorMuller, Felix
dc.creatorLiechti, Matthias E
dc.creatorVollenweider, Franz X
dc.creatorRamaekers, Johannes G
dc.creatorKuypers, Kim
dc.creatorAraujo, Draulio B
dc.creatorSporns, Olaf
dc.creatorSiegel, Joshua
dc.creatorDosenbach, Nico
dc.creatorNutt, David J
dc.creatorCarhart-Harris, Robin L
dc.creatorStamatakis, Emmanuel A
dc.creatorBzdok, Danilo
dc.date2026-04-22T15:17:12Z
dc.date2026-04
dc.date2025-03-25
dc.date2026-04-22T15:17:11Z
dc.date.accessioned2026-08-03T04:38:37Z
dc.descriptionAcknowledgements: We thank R. McPhedrain for carefully reviewing and offering feedback on the analysis code and assisting with figure creation. D.B. was supported by the Brain Canada Foundation, through the Canada Brain Research Fund, with the financial support of Health Canada, National Institutes of Health (NIH R01 AG068563A, NIH R01 DA053301-01A1, NIH R01 MH129858-01A1), the Canadian Institute of Health Research (CIHR 438531, CIHR 470425), the Healthy Brains Healthy Lives initiative (Canada First Research Excellence fund), the IVADO R3AI initiative (Canada First Research Excellence fund) and by the CIFAR Artificial Intelligence Chairs program (Canada Institute for Advanced Research).
dc.descriptionPsychedelic drugs are re-emerging as promising scientific and clinical tools. However, despite a rapidly expanding literature on their therapeutic value, the neural mechanisms underlying psychedelic effects remain unclear. Resting-state functional magnetic resonance imaging studies of acute psychedelic effects, conducted independently by several research groups, have so far yielded fragmented and sometimes inconsistent findings. Here, to help facilitate greater convergence, we conducted a 'mega-analysis' integrating 11 independent resting-state functional magnetic resonance imaging datasets across five psychedelic drugs (psilocybin, lysergic acid diethylamide, mescaline, N,N-dimethyltryptamine and ayahuasca) from research groups spanning three continents and five countries. By applying a uniform preprocessing pipeline and a Bayesian hierarchical modeling framework, we discovered several common features in the induced alterations to brain function across drugs and sites. Most prominently, we identified a core signature of increased functional connectivity between transmodal (default, frontoparietal and limbic) and unimodal networks (visual and somatomotor), with subnetwork specificity. Furthermore, key subcortical regions (thalamus, caudate and putamen) and the cerebellum exhibited altered coupling with sensorimotor networks. In contrast to several single-site reports, Bayesian modeling revealed weak-to-moderate and selective reductions in within-network functional connectivity, with substantial variability across drugs and networks. Together, these findings extend past work by demonstrating that psychedelics reconfigure large-scale cortical organization while selectively engaging subcortical circuitry. This study provides the most comprehensive synthesis of psychedelic brain action to date, helping resolve inconsistencies and offering a probabilistic map of how psychedelics alter large-scale brain organization. We hereby provide a cornerstone to benchmark and shepherd future psychedelic neuroimaging research.
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dc.identifier1078-8956
dc.identifiers41591-026-04287-9
dc.identifier4287
dc.identifierhttps://www.repository.cam.ac.uk/handle/1810/402009
dc.identifier1546-170X
dc.identifier.urihttps://repo.dare.co.zw/handle/123456789/191987
dc.languageen
dc.languageeng
dc.publisherSpringer Nature
dc.publisherhttps://doi.org/10.1038/s41591-026-04287-9
dc.subjectHallucinogens
dc.subjectHumans
dc.subjectMagnetic Resonance Imaging
dc.subjectBrain
dc.subjectLysergic Acid Diethylamide
dc.subjectBayes Theorem
dc.subjectPsilocybin
dc.subjectN,N-Dimethyltryptamine
dc.subjectBanisteriopsis
dc.subjectBrain Mapping
dc.subjectNerve Net
dc.titleAn international mega-analysis of psychedelic drug effects on brain circuit function.
dc.typeArticle

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