Psilocybin desynchronizes the human brain.
Joshua S. Siegel, Subha Subramanian, Demetrius Perry, Benjamin P. Kay, Evan M. Gordon, Timothy O. Laumann, Travis 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 (opens in new tab)
Study at a glance
AI-extracted from the abstract| 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 |
| Topics | Psilocybin |
| Keywords | Psychedelics Brain connectivity Consciousness Mental health |
| Citations | 241 |
| Key findings | 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.
Comparable studies
Other observational and cohort studies on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms. Patients with treatment-resistant depression | 2017 | Observational cohort | n = 19 |
| Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels Healthy volunteers | 2019 | Observational cohort | n = 8 |
| Increased spontaneous MEG signal diversity for psychoactive doses of ketamine, LSD and psilocybin Humans | 2017 | Observational study | |
| Classic psychedelic use is associated with reduced psychological distress and suicidality in the United States adult population. USA adult respondents from the National Survey on Drug Use and Health (2008-2012) | 2015 | Observational cohort | n = 190,000 |
| Prediction of Psilocybin Response in Healthy Volunteers Healthy volunteers | 2012 | Observational cohort | n = 409 |
Citations in the library
Cited by 183
- Psychedelic-Induced Neural Plasticity: A Comprehensive Review and a Discussion of Clinical Implications. Brain Sciences January 25, 2025
- Structural neural plasticity evoked by rapid-acting antidepressant interventions. Nature Reviews Neuroscience February 1, 2025
- The role of the psychedelic experience in psilocybin treatment for treatment-resistant depression. Journal of Affective Disorders March 1, 2025
- Psychedelic-assisted therapy for treating anxiety, depression, and existential distress in people with life-threatening diseases Cochrane Database of Systematic Reviews September 11, 2024
- Psychedelics in neuroinflammation: Mechanisms and therapeutic potential Progress in Neuro-Psychopharmacology and Biological Psychiatry January 31, 2025
and 178 more in the library
Cites 49
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Journal of Psychopharmacology November 30, 2016
- Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance Psychopharmacology July 7, 2006
- Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
and 44 more in the library