EEG microstate dynamics during psilocybin intoxication relate to acute experience and persisting psychological changes
Nikola Jajcay, Čestmír Vejmola, Jakub Korčák, Filip Tylš, Michaela Viktorinová, Vojtěch Viktorin, Anna Bravermanová, Renáta Androvičová, Marie Balíková, Jiřı́ Horáček, Martin Brunovský, Jaroslav Hlinka, Tomáš Páleníček
bioRxiv (Cold Spring Harbor Laboratory) June 12, 2026 preprint DOI: 10.64898/2026.06.09.731183 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Double-blind, randomized, placebo-controlled crossover study |
|---|---|
| Sample size | 15 |
| Population | Healthy volunteers |
| Intervention | Psilocybin |
| Duration | Single session with EEG at five time points spanning pre-drug baseline, peak intoxication, and recovery; follow-up at 28 days post-administration |
| Topics | Default mode network Psilocybin |
| Keywords | Ministate Electroencephalography Hallucinogen Tryptamines Consciousness Local field potential Neuroimaging Anhedonia Human brain Dynamics music Delta wave Audiology |
| Key points | Psilocybin accelerates transitions between brain states (increased GFP peaks, reduced microstate lifespan, increased frequency of occurrence) while largely preserving microstate coverage, and individual differences in these dynamics correlate with acute subjective experience and persisting psychological changes at 28 days. |
Abstract
Abstract Psilocybin and other serotonergic psychedelics show therapeutic promise for psychiatric disorders, yet objective neural correlates linking the acute psychedelic state to persisting psychological outcomes remain limited. Electroencephalography (EEG) microstate analysis characterizes the rapid spatiotemporal organization of large-scale brain activity, offering a millisecond-resolution window into neural dynamics. Here, we examined resting-state EEG microstates in 15 healthy volunteers who participated in a double-blind, randomized, placebo-controlled crossover study of psilocybin, using both data-driven (three-microstate) and canonical (four-microstate) analysis solutions. EEG was recorded at five time points spanning pre-drug baseline, peak intoxication, and recovery. Psilocybin significantly increased the number of global field power (GFP) peaks and reduced microstate lifespan while increasing frequency of occurrence during peak intoxication (50–100 min post-administration), consistent with accelerated transitions between brain states. Notably, microstate coverage was largely preserved, with only a transient difference at peak intoxication in the 2–20 Hz band-width, suggesting that access to the repertoire of canonical brain states is broadly maintained despite altered temporal dynamics. Critically, individual differences in microstate dynamics during peak intoxication correlated with both acute subjective experience intensity and self-reported psychological changes measured 28 days post-administration, providing exploratory evidence for a link between acute neural dynamics and longer-term experiential outcomes in healthy volunteers. These findings suggest that psilocybin is associated with altered temporal organization of large-scale brain dynamics with largely preserved microstate coverage, and identify EEG microstates as candidate neural markers for psychedelic-induced alterations in consciousness with potential relevance to therapeutic research.
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
Cites 42
- 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
- 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
- The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs Frontiers in Human Neuroscience 2014
- Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder JAMA Psychiatry November 4, 2020
and 37 more in the library