Psilocybin desynchronizes the human brain

Joshua S. Siegel (), Subha Subramanian, Demetrius Perry, Benjamin P. Kay, Evan M. Gordon, Timothy O. Laumann, T. Rick Reneau, Nicholas V. Metcalf, Ravi V. Chacko, Caterina Gratton, Christine Horan, Samuel R. Krimmel, Joshua S. Shimony, Julie A. Schweiger, Dean F. Wong, David A. Bender, Kristen M. Scheidter, Forrest I. Whiting, Jonah A. Padawer-Curry, Russell T. Shinohara, Yong Chen, Julia Moser, Essa Yacoub, Steven M. Nelson, Luca Vizioli, Damien A. Fair, Eric J. Lenze, Robin Carhart-Harris, Charles L. Raison, Marcus E. Raichle, Abraham Z. Snyder, Ginger E. Nicol and Nico U. F. Dosenbach
Additional contact information
Joshua S. Siegel: Washington University School of Medicine
Subha Subramanian: Beth Israel Deaconess Medical Center
Demetrius Perry: Washington University School of Medicine
Benjamin P. Kay: Washington University School of Medicine
Evan M. Gordon: Washington University School of Medicine
Timothy O. Laumann: Washington University School of Medicine
T. Rick Reneau: Washington University School of Medicine
Nicholas V. Metcalf: Washington University School of Medicine
Ravi V. Chacko: Advocate Christ Health Care
Caterina Gratton: Florida State University
Christine Horan: Miami VA Medical Center
Samuel R. Krimmel: Washington University School of Medicine
Joshua S. Shimony: Washington University School of Medicine
Julie A. Schweiger: Washington University School of Medicine
Dean F. Wong: Washington University School of Medicine
David A. Bender: Washington University School of Medicine
Kristen M. Scheidter: Washington University School of Medicine
Forrest I. Whiting: Washington University School of Medicine
Jonah A. Padawer-Curry: Washington University in St Louis
Russell T. Shinohara: University of Pennsylvania
Yong Chen: University of Pennsylvania
Julia Moser: University of Minnesota
Essa Yacoub: University of Minnesota
Steven M. Nelson: University of Minnesota
Luca Vizioli: University of Minnesota
Damien A. Fair: University of Minnesota
Eric J. Lenze: Washington University School of Medicine
Robin Carhart-Harris: University of California
Charles L. Raison: Usona Institute
Marcus E. Raichle: Washington University School of Medicine
Abraham Z. Snyder: Washington University School of Medicine
Ginger E. Nicol: Washington University School of Medicine
Nico U. F. Dosenbach: Washington University School of Medicine

Nature, 2024, vol. 632, issue 8023, 131-138

Abstract: Abstract A single dose of psilocybin, a psychedelic that acutely causes distortions of space–time perception and ego dissolution, produces rapid and persistent therapeutic effects in human clinical trials1–4. In animal models, psilocybin induces neuroplasticity in cortex and hippocampus5–8. It remains unclear how human brain network changes relate to subjective and lasting effects of psychedelics. Here we tracked individual-specific brain changes with longitudinal precision functional mapping (roughly 18 magnetic resonance imaging visits per participant). Healthy adults were tracked before, during and for 3 weeks after high-dose psilocybin (25 mg) and methylphenidate (40 mg), and brought back for an additional psilocybin dose 6–12 months later. Psilocybin massively disrupted functional connectivity (FC) in cortex and subcortex, acutely causing more than threefold greater change than methylphenidate. These FC changes were driven by brain desynchronization across spatial scales (areal, global), which dissolved network distinctions by reducing correlations within and anticorrelations between networks. Psilocybin-driven FC changes were strongest in the default mode network, which is connected to the anterior hippocampus and is thought to create our sense of space, time and self. Individual differences in FC changes were strongly linked to the subjective psychedelic experience. Performing a perceptual task reduced psilocybin-driven FC changes. Psilocybin caused persistent decrease in FC between the anterior hippocampus and default mode network, lasting for weeks. Persistent reduction of hippocampal-default mode network connectivity may represent a neuroanatomical and mechanistic correlate of the proplasticity and therapeutic effects of psychedelics.

Date: 2024
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DOI: 10.1038/s41586-024-07624-5

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