Psilocybin alters brain activity related to sensory and cognitive processing in a time-dependent manner
Marek Nikolič, Pedro A. M. Mediano, Tom Froese, David Reydellet, Tomáš Páleníček
medRxiv September 11, 2024 preprint DOI: 10.1101/2024.09.09.24313316 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Placebo-controlled crossover study |
|---|---|
| Sample size | 20 |
| Population | Healthy individuals |
| Intervention | Psilocybin |
| Dose | 0.26 mg/kg |
| Duration | 24-hour monitoring with EEG at baseline and 1, 1.5, 3, 6, and 24 hours after administration |
| Topics | Psilocybin |
| Keywords | Cognition Sensory system Sensory processing Cognitive psychology Hallucinogen |
| Citations | 6 |
| Key points | Psilocybin acutely decreases alpha and beta power, increases delta and gamma power, reduces alpha global connectivity, and raises signal complexity, with opposing complexity changes in the Default Mode Network and visual network linked to self-perception. |
Abstract
Abstract Psilocybin is a classic psychedelic and a novel treatment for mood disorders. Psilocybin induces dose-dependent transient (4-6 hours) usually pleasant changes in perception, cognition, and emotion by non-selectively agonizing the 5-HT 2A receptors and negatively regulating serotonin reuptake, and long-term positive antidepressant effect on mood and well-being. Long-term effects are ascribed to the psychological quality of the acute experience, increase in synaptodensity and temporary (1-week) down-regulation of 5-HT 2A receptors. Electroencephalography, a non-invasive neuroimaging tool, can track the acute effects of psilocybin; these include the suppression of alpha activity, decreased global connectivity, and increased brain entropy (i.e. brain signal diversity) in eyes-closed resting-state. However, few studies investigated how these modalities are affected together through the psychedelic experience. The current research aimed to evaluate the psilocybin intoxication temporal EEG profile. 20 healthy individuals (10 women) underwent oral administration of psilocybin (0.26 mg/kg ) as part of a placebo-controlled cross-over study, resting-state 5-minute eyes closed EEG was obtained at baseline and 1, 1.5, 3, 6, and 24 hours after psilocybin administration. Absolute power, relative power spectral density (PSD), power envelope global functional connectivity (GFC), Lempel-Ziv complexity (LZ), and a Complexity via State-Space Entropy Rate (CSER) were obtained together with measures of subjective intensity of experience. Absolute power decreased in alpha and beta band, but increased in delta and gamma frequencies. 24h later was observed a broadband decrease. The PSD showed a decrease in alpha occipitally between 1 and 3 hours and a decrease in beta frontally at 3 hours, but power spectra distribution stayed the same 24h later. The GFC showed decrease acutely at 1, 1.5, and 3 hours in the alpha band. LZ and showed an increase at 1 and 1.5 hours. Decomposition of CSER into functional bands shows a decrease in alpha band but increase over higher frequencies. Further, complexity over a source space showed opposing changes in the Default Mode Network (DMN) and visual network between conditions, suggesting a relationship between signal complexity, stimulus integration, and perception of self. In an exploratory attempt, we found that a change in gamma GFC in DMN correlates with oceanic boundlessness. Psychological effects of psilocybin may be wrapped in personal interpretations and history unrelated to underlying neurobiological changes, but changes to perception of self may be bound to perceived loss of boundary based on whole brain synchrony with the DMN in higher frequency bands.
Comparable studies
Other randomized controlled trials on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Cancer patients with life-threatening diagnoses and symptoms of depression and/or anxiety | 2016 | Randomized controlled trial | n = 51 |
| Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Patients with cancer-related anxiety and depression | 2016 | Double-blind, placebo-controlled, crossover trial | n = 29 |
| Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance Hallucinogen-naïve adults reporting regular participation in religious or spiritual... | 2006 | Double-blind study | n = 36 |
| Trial of Psilocybin versus Escitalopram for Depression Selected group of patients with depression | 2021 | Randomized controlled trial | |
| Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder Adults aged 21 to 75 years with major depressive disorder, not currently using... | 2020 | Randomized controlled trial | n = 24 |
Citations in the library
Cited by 6
- How to set up a psychedelic study: Unique considerations for research involving human participants. Neuroscience & Biobehavioral Reviews July 1, 2026
- The entropic brain today Brain December 12, 2025
- LSD Reconfigures Cortical Dynamics Through Faster Brain Rhythms and Increased Fractal Dimension bioRxiv (Cold Spring Harbor Laboratory) January 29, 2026
- Effects of psychedelics on human oscillatory brain activity. International review of neurobiology 2025
- EEG microstate dynamics during psilocybin intoxication relate to acute experience and persisting psychological changes bioRxiv (Cold Spring Harbor Laboratory) June 12, 2026
and 1 more in the library
Cites 41
- 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
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
- Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder JAMA Psychiatry November 4, 2020
- Human hallucinogen research: guidelines for safety. Journal of Psychopharmacology July 1, 2008
- REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics Pharmacological Reviews June 20, 2019
and 36 more in the library