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The phenomenology of psilocybin's experience mediates subsequent persistent psychological effects independently of sex, previous experience, or setting.

Tereza Klučková, Marek Nikolič, Filip Tylš, Vojtěch Viktorin, Čestmír Vejmola, Michaela Viktorinová, Anna Bravermanová, Renáta Androvičová, Veronika Andrashko, Jakub Korčák, Peter Zach, Kateřina Hájková, Martin Kuchař, Marie Balíková, Martin Brunovský, Jiří Horáček, Tomáš Páleníček

Pharmacological Reports June 16, 2025 DOI: 10.1007/s43440-025-00742-5 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Double-blind, placebo-controlled, cross-over study Peer reviewed
Sample size 40
Population Healthy individuals
Intervention Psilocybin
Dose 0.26 mg/kg
Topics Psilocybin Philosophy of mind
Keywords Healthy population Previous experience Repeated administration Sex Significant Favorable long-term outcomes Benefits Psilocybin's safety Acute sessions All participants Repeated use
Citations 4
Key points Psilocybin produces lasting positive effects in healthy individuals irrespective of previous experience, repeated use, setting, sex, or occupation, with challenging experiences in controlled settings not causing adverse outcomes.

Abstract

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. 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. 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. 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.

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

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Explore topics

Psilocybin Philosophy of mind Altered states of consciousness Ego dissolution Mystical experience