Peer-reviewed articleOpen access

Psilocybin desynchronizes the human brain.

Siegel JS iD, Subramanian S, Perry D, Kay BP iD, Gordon EM iD, Laumann TO iD, Reneau TR iD, Metcalf NV, Chacko RV, Gratton C iD, Horan C, Krimmel SR, Shimony JS, Schweiger JA, Wong DF iD, Bender DA, Scheidter KM, Whiting FI, Padawer-Curry JA, Shinohara RT, Chen Y, Moser J iD, Yacoub E, Nelson SM, Vizioli L, Fair DA iD, Lenze EJ, Carhart-Harris R iD, Raison CL, Raichle ME, Snyder AZ iD, Nicol GE iD, Dosenbach NUF iD

NatureJul 17, 2024License: open accessUnited States, Israel, United Kingdom231 citationsDOI: 10.1038/s41586-024-07624-5

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 trials<sup>1-4</sup>. In animal models, psilocybin induces neuroplasticity in cortex and hippocampus<sup>5-8</sup>. 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.

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Psilocybin

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