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

Summary

A research study examined how psilocybin experiences affect long-term mental health and well-being in healthy volunteers. Participants received two doses of psilocybin in controlled medical settings while undergoing brain imaging. The study found that psilocybin consistently produced positive, lasting improvements in mood, well-being, and spiritual outlook, regardless of whether people had used psychedelics before, their sex, or the specific imaging setting used.

Background

Psilocybin has shown promise as a rapid-onset antidepressant, but the relationship between acute phenomenological experiences and long-term psychological effects remains underexplored. Variables such as sex, previous psychedelic experience, and setting may influence these outcomes.

Objective

To examine the correlation between acute phenomenological experiences of psilocybin and persistent psychological effects in healthy subjects, while controlling for previous psychedelic experience, repeated administration, and sex.

Results

All results were independent of sex, previous experience, and setting. Psilocybin produced moderate acute effects and lasting positive effects across all PEQ domains with negligible negative effects. Oceanic Boundlessness and Visionary Restructuralization correlated with positive outcomes; peak experiences ending in positive mood were strongly associated with favorable 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 rationale for repeated use in clinical trials.
  • Published in:Pharmacological Reports,
  • Study Type:Clinical Trial,
  • Source: PMID: 40522607, DOI: 10.1007/s43440-025-00742-5
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