Moderating factors in psilocybin-assisted treatment affecting mood and personality: A naturalistic, open-label investigation
In a naturalistic, open‑label study a single high dose of psilocybin with psychotherapy produced sustained reductions in depression, anxiety, PTSD symptoms and neuroticism, and increases in openness and conscientiousness at three months. The size of these benefits was moderated by participants’ subjective dosing experiences (mystical‑type experiences, emotional breakthrough and post‑treatment growth) and demographic factors, highlighting variables that may help optimise psilocybin‑assisted treatment.
Authors
- Irrmischer, M.
- Puxty, D. J.
- Deijen, J. B.
Published
Abstract
Rationale
Psychedelic-assisted therapy is increasingly applied within mental health treatment.
Objectives
This study focused on factors moderating changes in the acute and long-term effects of an individual psilocybin-assisted program on depression, anxiety, PTSD and personality structures by including demographic factors, subjective experience and degree of mystical type experiences during the dosing, as well as emotional breakthrough and personal growth after the program.
Methods
At baseline, 1 week and 3 months after the psilocybin program participants completed the Generalized Anxiety Disorder Assessment (GAD-7), Patient Health Questionnaire (PHQ-9), PTSD Checklist for DSM-5 (PCL-5) and NEO Five-Factor Inventory-3 (NEO-FFI-3). In addition, after the dosing the Mystical Experiences Questionnaire (MEQ-30), Posttraumatic Growth Inventory (PTGI) and Emotional Breakthrough Inventory (EBI) were administered. Moderation effects were established using linear mixed-model analysis.
Results
A single high dose of psilocybin in combination with therapy was found to lower symptoms of anxiety, depression, PTSD and neuroticism over a period of 3-months. Scores on openness and conscientiousness increased after the treatment only. Participants reported mystical type experiences, emotional breakthrough and personal growth. These subjective experiences together with demographic factors were moderating the observed positive changes.
Conclusions
Findings indicate that individual psilocybin-assisted therapy has the potential for beneficial effects on mood and personality characteristics. Moreover, the study highlights the importance of subjective experiences and demographic factors in moderating this effect. This study adds to the ongoing research on psilocybin-assisted therapy by investigating contributing factors for optimizing this evolving type of therapy.
Research Summary of 'Moderating factors in psilocybin-assisted treatment affecting mood and personality: A naturalistic, open-label investigation'
Introduction
Psychedelic-assisted therapy, using agents such as psilocybin alongside psychological support, has re-emerged as a potentially effective adjunct for mood and trauma-related disorders. Earlier clinical work showed rapid and sometimes durable reductions in depression and anxiety after one or two psilocybin sessions, and some studies reported shifts in personality traits such as reduced neuroticism and increased openness. Investigators have also highlighted the likely importance of extra‑pharmacological factors—'set', 'setting', and the subjective quality of the acute experience (for example mystical-type experiences or emotional breakthrough)—in shaping longer-term outcomes. This study, led by Irrmischer and colleagues, set out to examine which demographic and subjective factors moderate acute and longer-term changes in depression, anxiety, PTSD and selected personality traits following an individual, naturalistic psilocybin-assisted treatment programme. The primary aim was exploratory: to test whether baseline characteristics, facets of the acute mystical experience, measures of emotional breakthrough and post‑session interpretations of growth were associated with changes on standard clinical and personality measures over time.
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Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
- APA Citation
Irrmischer, M., Puxty, D., Yıldırım, B. O., Deijen, J. B., & Engelbregt, H. (2025). Moderating factors in psilocybin-assisted treatment affecting mood and personality: A naturalistic, open-label investigation. Psychopharmacology, 242(4), 725-740. https://doi.org/10.1007/s00213-024-06733-3
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