The phenomenology of psilocybin's experience mediates subsequent persistent psychological effects independently of sex, previous experience, or setting
Repeated administration of psilocybin in healthy adults produced persistent positive psychological effects, and the acute phenomenology—particularly Oceanic Boundlessness, Visionary Restructuralization and peak experiences ending in a positive mood—predicted these long-term benefits independently of sex, prior psychedelic experience, setting or repeat dosing. Challenging or mixed acute experiences in the controlled laboratory did not produce lasting negative outcomes, supporting psilocybin’s psychological safety for repeated use in clinical trials.
Authors
- Tomáš Páleníček
- František Tylš
- Martin Brunovský
Published
Abstract
Background
Recent studies intensively explore psilocybin’s antidepressant potential, but variables like previous experience, repeated use, setting, and sex remain underexplored. This study examines acute and long-term effects of psilocybin in healthy individuals.
Methods
A double-blind, placebo-controlled, cross-over study included 40 healthy participants (20 females, mean age 38). Each received two doses of psilocybin (0.26 mg/kg) at least 56 days apart (mean 488) in two neuroimaging study arms. Nearly half had previous psychedelic experience. Acute effects were measured using the Altered States of Consciousness Scales (ASCs) and a Visual Analogue Scale (VAS) for emotional valence. The Persisting Effects Questionnaire (PEQ) assessed long-term effects.
Results
All results were independent of observed variables such as previous psychedelic experience, repeated use, setting, sex and occupation. Acute effects were moderate on the ASCs, with VAS ratings showing mostly pleasant or fluctuating experiences and only one unpleasant session. All experiences resolved in a positive or neutral state by the session’s end. Psilocybin produced lasting positive effects across all PEQ domains, with negligible negative effects. Oceanic Boundlessness (OBN) and Visionary Restructuralization (VRS) correlated with positive outcomes, while Dread of Ego Dissolution (DED), typically associated with fear, did not predict negative effects. The nature of the acute experience (pleasant or mixed) was not linked to the direction or intensity of long-term outcomes. Peak experiences ending in a positive mood were strongly associated with favourable long-term effects.
Conclusion
Repeated psilocybin administration in healthy individuals induces positive, lasting effects, with challenging experiences in controlled settings not causing adverse outcomes. These findings support psilocybin’s psychological safety and its repeated use in clinical trials.
Research Summary of 'The phenomenology of psilocybin's experience mediates subsequent persistent psychological effects independently of sex, previous experience, or setting'
Introduction
Psilocybin, a serotonergic tryptamine psychedelic, has accumulating evidence for rapid antidepressant and enduring positive effects on well-being and attitudes in healthy and clinical populations. A central question addressed in recent research is the extent to which the subjective psychedelic experience — particularly peak or mystical-type states and features such as ego dissolution — mediates longer-term psychological benefits. At the same time, uncertainty remains about whether factors such as previous psychedelic experience, repeated dosing, sex, and the specific testing environment (for example EEG versus fMRI settings) influence either the acute phenomenology or the persistent outcomes. This study set out to test whether the acute phenomenological features of a psilocybin session predict persistent changes in mood, well-being and spirituality in healthy volunteers, while accounting for previous psychedelic experience, repeated administration, sex, and experimental setting. Tylš and colleagues used validated instruments for acute states (the Altered States of Consciousness scales, ASCs, and a time-course Visual Analogue Scale, VAS) and for persisting outcomes (the Persisting Effects Questionnaire, PEQ) to examine these relationships in a controlled, double-blind, placebo-controlled, crossover design embedded within a larger neuroimaging project. The investigators hypothesised that characteristics of the acute experience would drive long-term positive outcomes and treated the other variables as exploratory moderators.
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Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
- Authors
- APA Citation
Klučková, T., Nikolič, M., Tylš, F., Viktorin, V., Vejmola, Č., Viktorinová, M., Bravermanová, A., Androvičová, R., Andrashko, V., Korčák, J., Zach, P., Hájková, K., Kuchař, M., Balíková, M., Brunovský, M., Horáček, J., & Páleníček, T. (2025). The phenomenology of psilocybin's experience mediates subsequent persistent psychological effects independently of sex, previous experience, or setting. Pharmacological Reports, 77(4), 1024-1039. https://doi.org/10.1007/s43440-025-00742-5
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