Psilocybin Desynchronizes Brain Networks
Joshua S. Siegel, Subha Subramanian, Nico U.f. Dosenbach, Ginger E. Nicol
Biological Psychiatry April 29, 2024 DOI: 10.1016/j.biopsych.2024.02.132 (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 |
| Duration | Up to 3 weeks post-dose, with follow-up at 6+ months |
| Topics | Psilocybin |
| Keywords | Hallucinogen Pharmacology |
| Citations | 14 |
| Key findings | Psilocybin disrupts connectivity across cortical networks and subcortical structures, driven by desynchronization of brain activity, with persistent decrease in hippocampal-DMN connectivity lasting weeks but normalizing after six months. |
Abstract
1 Summary The relationship between the acute effects of psychedelics and their persisting neurobiological and psychological effects is poorly understood. Here, we tracked brain changes with longitudinal precision functional mapping in healthy adults before, during, and for up to 3 weeks after oral psilocybin and methylphenidate (17 MRI visits per participant) and again 6+ months later. Psilocybin disrupted connectivity across cortical networks and subcortical structures, producing more than 3-fold greater acute changes in functional networks than methylphenidate. These changes were driven by desynchronization of brain activity across spatial scales (area, network, whole brain). Psilocybin-driven desynchronization was observed across association cortex but strongest in the default mode network (DMN), which is connected to the anterior hippocampus and thought to create our sense of self. Performing a perceptual task reduced psilocybin-induced network changes, suggesting a neurobiological basis for grounding , connecting with physical reality during psychedelic therapy. The acute brain effects of psilocybin are consistent with distortions of space-time and the self. Psilocybin induced persistent decrease in functional connectivity between the anterior hippocampus and cortex (and DMN in particular), lasting for weeks but normalizing after 6 months. Persistent suppression of hippocampal-DMN connectivity represents a candidate neuroanatomical and mechanistic correlate for psilocybin’s pro-plasticity and anti-depressant effects.
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 3
- Clinical utility of fMRI in evaluating of LSD effect on pain-related brain networks in healthy subjects. Heliyon August 15, 2024
- Psilocybin Attenuates Cortical Representations of Aversion in the Mouse Auditory Cortex. bioRxiv : the preprint server for biology March 27, 2026
- The therapeutic use of psychedelic drugs: Legal, policy, and neuroscientific perspectives. Pharmacology, Biochemistry, and Behavior November 1, 2025