Trial PaperAnxiety DisordersDepressive DisordersPTSDPersonality & Trait FactorsPsilocybin

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

Psychopharmacology
individual Study

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.

Available with Blossom Pro

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.

Expert Research Summaries

Go Pro to access AI-powered section-by-section summaries, editorial takes, and the full research toolkit.

Full Text PDF

Full Paper PDF

Pro members can view the original manuscript directly in the browser.

Study Details

Related Clinical Trial

References (30)

Papers cited by this study that are also in Blossom

Prospective examination of the therapeutic role of psychological flexibility and cognitive reappraisal in the ceremonial use of ayahuasca

Agin-Liebes, G. I., Zeifman, R. J., Luoma, J. B. et al. · Journal of Psychopharmacology (2022)

Validation of the revised Mystical Experience Questionnaire in experimental sessions with psilocybin

Barrett, F. S., Johnson, M. W., Griffiths, R. R. · Journal of Psychopharmacology (2015)

MDMA-assisted psychotherapy using low doses in a small sample of women with chronic posttraumatic stress disorder

Bouso, J. C., Doblin, R., Farré, M. et al. · Journal of Psychoactive Drugs (2008)

REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics

Carhart-Harris, R. L., Friston, K. J. · Pharmacological Reviews (2019)

Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study

Carhart-Harris, R. L., Bolstridge, M., Rucker, J. et al. · Lancet Psychiatry (2016)

1174 cited
Psilocybin with psychological support for treatment-resistant depression: six-month follow-up

Carhart-Harris, R. L., Bolstridge, &. M., Day, C. M. J. et al. · Psychopharmacology (2017)

Trial of Psilocybin versus Escitalopram for Depression

Carhart-Harris, R. L., Giribaldi, B., Watts, R. et al. · New England Journal of Medicine (2021)

927 cited
Psychedelics and the essential importance of context

Carhart-Harris, R. L., Roseman, L., Haijen, E. C. H. M. et al. · Journal of Psychopharmacology (2018)

Psychological flexibility mediates the relations between acute psychedelic effects and subjective decreases in depression and anxiety

Davis, A. K., Barrett, F. S., Griffiths, R. R. · Journal of Contextual Behavioral Science (2020)

Show all 30 references
Psilocybin therapy increases cognitive and neural flexibility in patients with major depressive disorder

Doss, M. K., Považan, M., Rosenberg, M. D. et al. · Translational Psychiatry (2021)

249 cited
Effects of psilocybin therapy on personality structure

Erritzoe, D., Roseman, L., Nour, M. R. et al. · Acta Psychiatrica Scandinavica (2018)

219 cited
Psilocybin-occasioned mystical experiences in the treatment of tobacco addiction

Garcia-Romeu, A., Griffiths, R. R., Johnson, M. W. · Current Drug Abuse Reviews (2015)

Default Mode Network Modulation by Psychedelics: A Systematic Review

Gattuso, J. J., Perkins, D., Ruffell, S. G. D. et al. · International Journal of Neuropsychopharmacology (2022)

Posttraumatic Growth After MDMA-Assisted Psychotherapy for Posttraumatic Stress Disorder

Gorman, I., Belser, A. B., Jerome, L. et al. · Journal of Traumatic Stress (2020)

31 cited
Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer

Grob, C. S., Danforth, A. L., Chopra, G. S. et al. · JAMA Psychiatry (2011)

Predicting responses to psychedelics: a prospective study

Haijen, E. C. H. M., Kaelen, M., Roseman, L. et al. · Frontiers in Pharmacology (2018)

339 cited
The hidden therapist: evidence for a central role of music in psychedelic therapy

Kaelen, M., Giribaldi, B., Raine, J. et al. · Psychopharmacology (2018)

213 cited
Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized controlled trials

Krebs, T. S., Johansen, P. Ø. · Journal of Psychopharmacology (2012)

Reviewing the potential of psychedelics for the treatment of PTSD

Krediet, E., Bostoen, T., Breeksema, J. J. et al. · International Journal of Neuropsychopharmacology (2020)

Ketamine psychedelic therapy (KPT): a review of the results of ten years of research

Krupitsky, E. M., Grinenko, A. Y. · Journal of Psychoactive Drugs (1997)

A Meta-Analysis of Placebo-Controlled Trials of Psychedelic-Assisted Therapy

Luoma, J. B., Chwyl, C., Bathje, G. J. et al. · Journal of Psychoactive Drugs (2020)

168 cited
Mystical experiences occasioned by the hallucinogen psilocybin lead to increases in the personality domain of openness

Maclean, K. A., Johnson, M. W., Griffiths, R. R. · Journal of Psychopharmacology (2011)

Factor analysis of the mystical experience questionnaire: A study of experiences occasioned by the hallucinogen psilocybin

MacLean, K. A., Leoutsakos, J. S., Johnson, M. W. et al. · Journal for the Scientific Study of Religion (2012)

350 cited
Ego-dissolution and psychedelics: validation of the ego-dissolution inventory (EDI)

Nour, M. R., Evans, J., Nutt, D. J. et al. · Frontiers in Human Neuroscience (2016)

Quality of acute psychedelic experience predicts therapeutic efficacy of psilocybin for treatment-resistant depression

Roseman, L., Nutt, D. J., Carhart-Harris, R. L. · Frontiers in Pharmacology (2018)

Long-lasting subjective effects of LSD in normal subjects

Schmid, Y., Liechti, M. E. · Psychopharmacology (2017)

Cited By (1)

Papers in Blossom that reference this study

Your Personal Research Library

Go Pro to save papers, add notes, rate studies, and organize your research into custom shelves.

Moderating factors in psilocybin-assisted... — Research Summary & Context | Blossom