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. 2025 Sep;39(9):950-956.
doi: 10.1177/02698811251346697. Epub 2025 Jul 1.

Examining mystical experiences as a predictor of psilocybin-assisted psychotherapy for treatment-resistant depression

Ryan M Brudner  1   2 , Erica Kaczmarek  3 , Marc G Blainey  4 , Christian Schulz-Quach  5 , Shakila Meshkat  1 , Zoe Doyle  1   2 , Orly Lipsitz  6 , Hilary Offman  2 , Rickinder Sethi  1   2 , Geneva Weiglein  2 , Roger S McIntyre  3   5   7 , Joshua D Rosenblat  1   3   5
Affiliations

Examining mystical experiences as a predictor of psilocybin-assisted psychotherapy for treatment-resistant depression

Ryan M Brudner et al. J Psychopharmacol. 2025 Sep.

Abstract

Background: Psilocybin-assisted psychotherapy (PAP) is a promising treatment for various psychiatric disorders. However, the exact biological and psychological mechanisms of action of PAP remain to be determined. Examining predictors of PAP outcomes may help identify necessary processes for positive treatment outcomes. Mystical experiences are considered a key aspect of the subjective effects of ingesting psilocybin. Mystical experiences have been observed to be possibly predictive of positive outcomes in psilocybin treatments. Therefore, some argue that mystical-type experiences are necessary to achieve therapeutic benefits.

Aims: The current study examines mystical experiences as a predictor of antidepressant treatment outcomes in PAP, in a complex clinical sample.

Methods: Participants included 31 individuals with a primary diagnosis of major depressive disorder (MDD) or Bipolar II Disorder (BDII), with treatment resistance to symptoms of their disorder. Participants had one, two, or three PAP treatments with a fixed dose of 25 mg of psilocybin. Depressive symptoms were measured at baseline, at a pre-dose visit and at 2 weeks post-dosing. The presence of mystical experiences was measured on the dosing day after the acute effects had resolved.

Results: For the first psilocybin dose, participants with greater levels of mystical experiences exhibited a greater antidepressant effect from PAP. This effect was not found at the second or third doses.

Conclusion: These results provide preliminary support for the hypothesis that mystical experiences have therapeutic importance in PAP and extend the literature to include a clinical sample of individuals with treatment-resistant depression in the context of MDD or BDII.

Keywords: Major depressive disorder; bipolar disorder; mystical experiences; psilocybin-assisted psychotherapy; treatment-resistant depression.

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Conflict of interest statement

Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Zoe Doyle is a Clinical Project Lead at Braxia Scientific Corp. Orly Lipsitz has received research grant support from the Canadian Psychological Association, the University of Toronto, and the Canadian Institutes of Health Research, and scholarship support from the Social Sciences and Humanities Research Council, Canadian Institutes of Health Research, and the Ontario Graduate Scholarship. Christian Schulz-Quach has received education scholarship support from the Academic Scholars Award, Department of Psychiatry, University of Toronto, and Young Leaders Programme and Cancer Experience Programme, Princess Margaret Cancer Centre, University Health Network. He is on the board of directors for the Canadian Academy for Consultation and Liaison Psychiatry. Roger S McIntyre has received research grant support from CIHR/GACD/National Natural Science Foundation of China (NSFC) and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Neurawell, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Viatris, Abbvie and Atai Life Sciences. Dr Roger S McIntyre is the CEO of Braxia Scientific Corp. All other authors have no declarations of interest or funding. Dr. Joshua D Rosenblat has received research grant support from the Canadian Institute of Health Research (CIHR), Physician Services Inc (PSI) Foundation, Labatt Brain Health Network, Brain and Cognition Discovery Foundation (BCDF), Canadian Cancer Society, Canadian Psychiatric Association, Academic Scholars Award, American Psychiatric Association, American Society of Psychopharmacology, University of Toronto, University Health Network Centre for Mental Health, Joseph M. West Family Memorial Fund, Inagene and Timeposters Fellowship and industry funding for speaker/consultation/research fees from iGan, Boehringer Ingelheim, Abbvie, Braxia Health (Canadian Rapid Treatment Centre of Excellence), Braxia Scientific, Janssen, Allergan, Lundbeck, Sunovion and COMPASS.

Figures

Figure 1.
Figure 1.
Dose 1 MEQ-30 total scores and MADRS scores 2 weeks post-dose. The Y-axis shows actual MADRS scores measured 2 weeks after dose 1. The regression line represents the predictive relationship from the hierarchical regression model, with MEQ-30 total scores and baseline MADRS scores as predictors (β = −0.387, p = 0.026).
See this image and copyright information in PMC

References

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