This observational study (n=83) examines factors influencing the effects of individual psilocybin-assisted therapy (PAT) on depression, anxiety, PTSD, and personality traits. Results show that a single high dose of psilocybin reduces symptoms of anxiety, depression, and PTSD over three months while increasing openness and conscientiousness. Mystical experiences, emotional breakthroughs, and personal growth, along with demographic factors, moderate these positive changes.
Abstract of Moderating factors in psilocybin-assisted treatment affecting mood and personality
“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.”
Authors: Mona Irrmischer, Drew Puxty, Barış Onur Yıldırım, Jan Berend Deijen & Hessel Engelbregt
Summary of Moderating factors in psilocybin-assisted treatment affecting mood and personality
Psychedelic-assisted therapy is a growing area of mental health treatment, with substances such as psilocybin, LSD, ketamine, and MDMA being studied for their therapeutic potential. These treatments have shown promise in addressing PTSD, anxiety, depression, and personality traits, offering larger effects than conventional psychopharmacological or psychotherapy interventions. Psilocybin, in particular, has demonstrated robust reductions in depressive and anxiety symptoms, often sustained for months beyond the acute effects. Additional research has highlighted the potential of psychedelics to alter personality traits like neuroticism, openness, and extraversion.
The rationale behind these therapies lies in their ability to enhance neural plasticity, emotional processing, and the therapeutic relationship. Moreover, extra-pharmacological factors such as the subjective experience during dosing sessions—often influenced by the “set” (mental state) and “setting” (environment)—play a significant role in treatment outcomes. Mystical-type experiences and emotional breakthroughs have been identified as mediators of long-term improvements in mental health. This study explores factors moderating these effects, focusing on demographics, subjective experiences, and personal growth post-treatment.
Methods
Participants
Find this paper
https://doi.org/10.1007/s00213-024-06733-3
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Cite this paper (APA)
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, 1-16.
Study details
Compounds studied
Psilocybin
Topics studied
Personality
Depression
Anxiety
PTSD
Study characteristics
Observational
Participants
83
Humans
Compound Details
The psychedelics given at which dose and how many times
Psilocybin 25 mg | 1x