Psilocybin shapes the slow, global propagation of brain activity over the cortical layout of 5HT2a receptors
Veronica Mäki-marttunen
Communications Biology March 26, 2026 DOI: 10.1038/s42003-026-09912-4 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational study using existing dataset Peer reviewed |
|---|---|
| Population | Healthy adults (open dataset) |
| Interventions | Psilocybin Methylphenidate |
| Topics | Psilocybin Serotonin |
| Keywords | Neural activity Premovement neuronal activity Human brain Central nervous system Brain mapping |
| Citations | 1 |
| Key findings | Psilocybin increases propagation speed of infraslow cortical activity, which is associated with increased functional connectivity and contraction of the principal gradient, potentially mediated by 5HT2a receptor distribution. |
Abstract
Uncovering the neural basis of psychedelics’ potent effects on brain activity and conscious experience has great potential for understanding their therapeutic effects. Numerous studies using functional magnetic resonance imaging (fMRI) uncovered a strong effect of psychedelics on global properties of fMRI signal, but how they map to underlying neural phenomena remains to be further explored. In this article, we aimed to relate commonly reported findings from functional connectivity studies of psychedelics to changes in the spatio-temporal propagation of activity over the unimodal-transmodal cortical axis. We used data from an openly available dataset including baseline sessions, a control session with administration of methylphenidate, and psilocybin, a 5HT2a agonist. We found that faster propagation speed was related to increased total functional connectivity and a contraction of the principal gradient. The results support the view that these functional connectivity indices obtained from entire signal time courses reflect the modulation of specific global events of propagation. Furthermore, we found that the cortical distribution of 5HT2a receptors could contribute to the modulation of travelling wave propagation by psilocybin. These findings provide a link between macroscopic signatures of neuromodulatory activity, global brain events and receptor action, with relevance for understanding the mechanisms of psychedelic effects. The psychedelic substance psilocybin modifies the temporo-spatial aspects of global infraslow cortical activity across the serotonin receptor landscapes. These findings provide a link between macroscopic signatures of neuromodulatory activity, global brain events and receptor action, with relevance for understanding the mechanisms of psychedelic 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
Cites 30
- REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics Pharmacological Reviews June 20, 2019
- Validation of the revised Mystical Experience Questionnaire in experimental sessions with psilocybin Journal of Psychopharmacology October 6, 2015
- Increased Global Functional Connectivity Correlates with LSD-Induced Ego Dissolution. Current Biology April 13, 2016
- Psychedelics promote plasticity by directly binding to BDNF receptor TrkB Nature Neuroscience June 1, 2023
- Changes in global and thalamic brain connectivity in LSD-induced altered states of consciousness are attributable to the 5-HT2A receptor Elife October 25, 2018
and 25 more in the library