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, Nico U F Dosenbach
Nature August 1, 2024 DOI: 10.1038/s41586-024-07624-5 via PubMed
Summary
AI-generated from the abstractA single high dose of psilocybin (25 mg) massively disrupts functional connectivity in the human brain, causing more than threefold greater change than methylphenidate (40 mg). These changes are driven by desynchronization across spatial scales, dissolving network distinctions by reducing correlations within and anticorrelations between networks. The strongest effects occur in the default mode network, which is connected to the anterior hippocampus and is thought to create the sense of space, time, and self. Individual differences in connectivity changes are strongly linked to the subjective psychedelic experience. A persistent decrease in connectivity between the anterior hippocampus and default mode network lasts for weeks, suggesting a neuroanatomical correlate of the therapeutic and proplasticity effects of psychedelics.
Study at a glance
| Characteristics | Longitudinal precision functional mapping Peer reviewed |
|---|---|
| Population | Healthy adults |
| Interventions | Psilocybin Methylphenidate |
| Dose | 25 mg psilocybin, 40 mg methylphenidate |
| Duration | 3 weeks after high-dose psilocybin and methylphenidate, with an additional psilocybin dose 6-12 months later |
| Keywords | Psychedelics Neuroscience Brain connectivity Consciousness Mental health |
| Citations | 241 |
| Key finding | Psilocybin massively disrupts functional connectivity in cortex and subcortex, with the strongest and most persistent changes in the default mode network and its connection to the anterior hippocampus. |
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.