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Mystical but Not Challenging Experiences Predict Symptom Improvement After Psilocybin for Treatment-Resistant OCD

Sarah Shnayder, Gabrielle Agin-Liebes, Troy Hubert, Terence H. W. Ching, Jamila Hokanson, Christopher Pittenger, Benjamin Kelmendi, Thomas G. Adams

February 11, 2026 preprint DOI: 10.31234/osf.io/d94hb_v1 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Exploratory analysis of data from a randomized, double-blind, placebo-controlled trial and subsequent open-label phase
Sample size 27
Population Participants with treatment-resistant obsessive-compulsive disorder (OCD)
Intervention Psilocybin
Dose 0.25 mg/kg
Duration Single dosing session with 1- and 12-week follow-up
Topics Anxiety Psilocybin Mystical experience
Keywords Obsessive compulsive Mood Exploratory research Clinical trial Severity of illness Hallucinogen Clinical psychology Psychotherapist Anhedonia Depressive symptoms Depression economics
Key findings Greater mystical-type experiences during psilocybin sessions were associated with lower OCD symptom severity at 1- and 12-week follow-up.

Abstract

Background: Psilocybin treatment has shown promise across a range of psychiatric conditions. Mystical-type experiences during dosing sessions have been shown to predict the clinical effects of psilocybin treatment in depression, anxiety, and addiction. However, no studies have examined whether acute subjective experiences predict treatment response in obsessive-compulsive disorder (OCD).

Methods: Exploratory analyses were conducted using data from participants with treatment-resistant OCD who received psilocybin as part of a randomized, double-blind, placebo-controlled trial and subsequent open-label phase. Twenty-seven participants who received psilocybin (0.25 mg/kg) completed the Mystical Experience Questionnaire (MEQ) and Challenging Experience Questionnaire (CEQ) the day following their session. OCD severity was assessed using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) at baseline and at 1- and 12-week follow-up.Results: Greater mystical-type experiences during psilocybin were associated with lower OCD symptom severity at 1- and 12-week follow-up, even after controlling for baseline OCD symptom severity and treatment condition. The Mystical subscale demonstrated the strongest and most consistent associations at both time points, while the Space–Time subscale was only associated with lower Y-BOCS at 12 weeks. The Positive Mood and Ineffability subscales were not significantly associated with post-treatment OCD symptom severity after correction for multiple comparisons. Challenging experiences were not significantly associated with post-treatment OCD severity.

Conclusions: Mystical experiences – particularly experiences of unity, sacredness, and transcendence – during psilocybin sessions are associated with greater OCD symptom reduction. These findings support attention to experiential quality in psilocybin-assisted therapy and have implications for optimizing treatment through dosing, set, setting, and integration practices.

Comparable studies

Other randomized controlled trials on psilocybin for anxiety, most cited first.

Study Year Design Participants
Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Cancer patients with life-threatening diagnoses and symptoms of depression and/or anxiety 2016 Randomized controlled trial n = 51
Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Patients with cancer-related anxiety and depression 2016 Double-blind, placebo-controlled, crossover trial n = 29
Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance Hallucinogen-naïve adults reporting regular participation in religious or spiritual... 2006 Double-blind study n = 36
Pilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer Adults with advanced-stage cancer and anxiety 2010 Double-blind, placebo-controlled study n = 12
Acute, subacute and long-term subjective effects of psilocybin in healthy humans: a pooled analysis of experimental studies Healthy human subjects 2010 Pooled analysis of double-blind placebo-controlled experimental studies n = 110

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