Examining mystical experiences as a predictor of psilocybin-assisted psychotherapy for treatment-resistant depression
Ryan M Brudner, Erica Kaczmarek, Marc G Blainey, Christian Schulz-Quach, Shakila Meshkat, Zoe Doyle, Orly Lipsitz, Hilary Offman, Rickinder Sethi, Geneva Weiglein, Roger S McIntyre, Joshua D. Rosenblat
Journal of Psychopharmacology July 1, 2025 DOI: 10.1177/02698811251346697 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 31 |
| Population | Individuals with treatment-resistant major depressive disorder or bipolar II disorder |
| Intervention | Psilocybin-assisted psychotherapy |
| Dose | 25 mg |
| Duration | 2-week follow-up |
| Topics | Altered states of consciousness Depression Psychedelic-assisted therapy Mystical experience Psilocybin |
| Keywords | Bipolar disorder Mystical experiences Psilocybin-assisted psychotherapy Hallucinogen therapy Entheogen therapy Spiritual experiences Profound experiences Peak experiences Refractory depression Chronic depression Severe depression Difficult-to-treat depression |
| Citations | 3 |
| Key findings | Greater levels of mystical experiences after the first psilocybin dose predicted greater antidepressant effects, but this effect was not found at the second or third doses. |
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.
Comparable studies
Other observational and cohort studies on psilocybin and psychedelic-assisted therapy, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Acute subjective effects in LSD- and MDMA-assisted psychotherapy Patients with psychiatric disorders (posttraumatic stress disorder and major... | 2020 | Observational study | n = 18 |
| Natural speech algorithm applied to baseline interview data can predict which patients will respond to psilocybin for treatment-resistant depression. 17 patients with treatment-resistant depression and 18 untreated age-matched healthy... | 2018 | Observational cohort with machine learning classification | n = 35 |
| Predicting the outcome of psilocybin treatment for depression from baseline fMRI functional connectivity. Patients with treatment-resistant depression or moderate-to-severe major depression | 2024 | Observational cohort | n = 38 |
| The Promise of Therapeutic Psilocybin: An Evaluation of the 134 Clinical Trials, 54 Potential Indications, and 0 Marketing Approvals on ClinicalTrials.gov. Psilocybin clinical trials listed on ClinicalTrials.gov | 2024 | Observational study | n = 134 |
| Naturalistic psychedelic therapy: The role of relaxation and subjective drug effects in antidepressant response 28 PAT patients and 28 healthy volunteers | 2024 | Observational cohort with comparison group | n = 56 |