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

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.