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Mystical Experiences Mediate the Effects of Psilocybin-Assisted Psychotherapy + Mindfulness-Based Stress Reduction on Trait Mindfulness and Depression Symptoms: Mechanistic Results from a Randomized Controlled Trial

Kevin Byrne, Madeleine Odette, Eric L Garland, Benjamin R. Lewis

Journal of Affective Disorders Reports October 1, 2026 DOI: 10.1016/j.jadr.2026.101187 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Randomized controlled trial Peer reviewed
Sample size 25
Population Frontline physicians and nurses with COVID-related depression
Interventions Psilocybin Mindfulness Based Stress Reduction (MBSR)
Dose 25mg
Duration 8-week intervention, 2-week primary endpoint, 6-month follow-up for FFMQ-15
Measures FFMQ-15, BSI, NADA-trait, MEQ-30
Topics Depression Meditation Mystical experience Psilocybin Psychedelic-assisted therapy
Key findings Adding group psilocybin-assisted therapy (25 mg) to an 8-week MBSR program produced greater mindfulness gains than MBSR alone at 2 weeks, on the FFMQ-15 and BSI. Exploratory mediation analyses found significant indirect effects of mystical experience intensity on both trait mindfulness and depressive symptom change; the authors say these findings require confirmation in larger samples.

Abstract

ABSTRACT Background Healthcare workers experienced amplified depression and burnout during COVID-19. Both Mindfulness Based Stress Reduction (MBSR) and psilocybin have been shown to reduce depressive symptoms in this population, however the psychological mechanisms by which adding psilocybin to mindfulness training improves depression and trait mindfulness remain incompletely characterized. Drawing on the Mindfulness-to-Meaning Theory (MMT), we hypothesized that psilocybin-occasioned mystical experiences would serve as the primary mechanism linking psilocybin-assisted therapy to improvements in trait mindfulness and depressive symptoms.

Methods: Frontline physicians and nurses (N=25) with COVID-related depression were randomized 1:1 to 8-week MBSR alone or MBSR plus group psilocybin-assisted therapy (25mg). Trait mindfulness (FFMQ-15), savoring capacity (BSI), and nondual awareness (NADA-trait) were assessed at baseline and 2 weeks. FFMQ-15 was also assessed at 6 months post intervention. Mystical experience intensity (MEQ-30) was assessed post-dosing session or post MBSR mindfulness retreat. Mediation analyses tested whether MEQ-30 mediated treatment effects on mindfulness and depression changes.

Results: Twenty-two participants completed 2-week assessments. ANCOVA showed significant between group effects favoring the MBSR + psilocybin treatment arm on mindfulness gains as measured by the FFMQ-15 (F(1,19)= 5.53, FDR-corrected p=0.045) and the BSI (F(1,19)=9.08, FDR-corrected p= 0.02) at the 2 week primary endpoint. In exploratory mediation analyses, intensity of mystical experience showed significant indirect effects on both change in trait mindfulness and depressive symptoms.

Conclusions: Adding group psilocybin intervention to an MBSR curriculum augmented mindfulness gains. Exploratory mediation analyses identified significant indirect effects of mystical experience intensity on both trait mindfulness and depressive symptom change; these findings require confirmation in larger samples.

In the evidence

This study is part of the evidence base for 3 syntheses in the library. Here is how each one recorded it.

  • State of the evidence: Psilocybin and meditation Supports

    Adding psilocybin-assisted therapy to MBSR produced greater mindfulness gains than MBSR alone at two weeks, with mystical experience intensity showing indirect effects on mindfulness and depression change.

    Synthesized

  • State of the evidence: Psilocybin and psychedelic-assisted therapy Supports

    Adding psilocybin-assisted therapy to MBSR produced greater mindfulness gains than MBSR alone at 2 weeks, with mystical experience intensity mediating effects; authors call for larger samples.

    Synthesized

  • State of the evidence: Depression Supports

    MBSR plus group psilocybin-assisted therapy showed significant between-group effects favoring the psilocybin arm on mindfulness gains, with mystical experience proposed as the mediating mechanism.

    Synthesized

Comparable studies

Other randomized controlled trials on psilocybin and meditation, most cited first.

Study Year Design Participants
Psilocybin-occasioned mystical-type experience in combination with meditation and other spiritual practices produces enduring positive changes in psychological functioning and in trait measures of prosocial attitudes and behaviors Healthy participants 2017 Randomized controlled trial n = 75
Psilocybin-assisted mindfulness training modulates self-consciousness and brain default mode network connectivity with lasting effects. Participants following a single administration of psilocybin during a 5-day mindfulness... 2019 Randomized, double-blind, placebo-controlled study n = 38
Characterization and prediction of acute and sustained response to psychedelic psilocybin in a mindfulness group retreat. Meditators participating in a 5-day mindfulness group retreat 2019 Randomized controlled trial n = 39
Clinical Interpretations of Patient Experience in a Trial of Psilocybin-Assisted Psychotherapy for Alcohol Use Disorder Participants in an ongoing trial of psilocybin-assisted treatment for alcohol use disorder 2018 Double-blind placebo-controlled clinical trial n = 3
Meditating on psychedelics. A randomized placebo-controlled study of DMT and harmine in a mindfulness retreat Experienced meditators 2024 Randomized controlled trial n = 40

Citations in the library

Cites 38

and 33 more in the library

Related reading

Explore topics

Depression Meditation Mystical experience Psilocybin Psychedelic-assisted therapy Mysticism

By condition and practice

Psilocybin and meditation Psilocybin and psychedelic-assisted therapy Psilocybin for depression