Examining mystical experiences as a predictor of psilocybin-assisted psychotherapy for treatment-resistant depression
In a clinical sample of 31 people with treatment‑resistant major depressive disorder or Bipolar II disorder who received one to three 25 mg psilocybin‑assisted psychotherapy sessions, greater mystical experiences during the first dosing session predicted larger reductions in depressive symptoms at two weeks, whereas this relationship was not observed for second or third doses. These findings provide preliminary support that mystical‑type experiences may contribute to the therapeutic effects of psilocybin‑assisted psychotherapy for treatment‑resistant depression.
Authors
- Roger McIntyre
- Jonathan Rosenblat
- Shokouh Meshkat
Published
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.
Research Summary of 'Examining mystical experiences as a predictor of psilocybin-assisted psychotherapy for treatment-resistant depression'
Introduction
Psilocybin-assisted psychotherapy (PAP) has shown promise for treatment-resistant depression and other psychiatric conditions, but the psychological and biological mechanisms that produce therapeutic benefit remain uncertain. Prior studies have identified acute subjective phenomena during psychedelic sessions—such as emotional breakthrough, ego dissolution, and mystical-type experiences—as candidate predictors or mediators of clinical improvement. However, evidence is mixed: some human studies find mystical-type experiences associated with enduring positive outcomes, while other trials have not observed a predictive relationship. Measurement and conceptual questions also persist, including whether mystical experience should be treated as a continuous dimension or dichotomised into a ‘complete mystical experience’. Brudner and colleagues sought to examine whether mystical experiences, as measured by the Mystical Experience Questionnaire-30 (MEQ-30), predict antidepressant response in a clinical sample with treatment-resistant depression (including major depressive disorder and Bipolar II disorder). Using data from a previously reported waitlist-controlled feasibility trial, the investigators tested whether MEQ-30 scores collected after dosing predicted clinician-rated depressive symptoms two weeks post-dose. The study additionally described frequencies of dichotomised complete mystical experiences across up to three fixed 25 mg psilocybin dosing sessions, since the prevalence of such experiences at this dose in a treatment-resistant clinical sample had not been clearly reported.
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Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
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- APA Citation
Brudner, R. M., Kaczmarek, E., Blainey, M. G., Schulz-Quach, C., Meshkat, S., Doyle, Z., Lipsitz, O., Offman, H., Sethi, R., Weiglein, G., McIntyre, R. S., & Rosenblat, J. D. (2025). Examining mystical experiences as a predictor of psilocybin-assisted psychotherapy for treatment-resistant depression. Journal of Psychopharmacology, 39(9), 950-956. https://doi.org/10.1177/02698811251346697
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