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

In healthy individuals, psilocybin produces lasting positive effects regardless of previous psychedelic experience, repeated use, setting, sex, or occupation. In a double-blind, placebo-controlled crossover study with 40 participants (20 females, mean age 38), each received two doses of psilocybin (0.26 mg/kg) at least 56 days apart. Acute effects were moderate on the Altered States of Consciousness Scales, with mostly pleasant or fluctuating experiences and only one unpleasant session; all sessions ended positively or neutrally. Long-term effects, assessed by the Persisting Effects Questionnaire, were positive across all domains with negligible negative effects. Peak experiences ending in a positive mood strongly predicted favorable long-term outcomes, while challenging experiences did not cause adverse outcomes. These findings support psilocybin's psychological safety and repeated use in clinical trials.

Study at a glance

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.