Acute and Post-Dosing Effects of Single-Dose Psilocybin for Obsessive-Compulsive Disorder in a Randomized, Double-Blind, Placebo-Controlled Trial: An Interpretative Phenomenological Analysis

Terence H. W. Ching^1*Brittany Stahnke²Sarah Shnayder¹Gabrielle Agin-Liebes¹Thomas Grover Adams¹Lucia Amoroso¹Olivia Baiz¹Alexander Belser³Calvin Bohner¹Michelle Burke¹Elizabeth D'Amico¹Giuliana DePalmer¹Jeffrey Eilbott¹Geena Fram¹Rachael Grazioplene¹Jamila Hokanson¹Anastasia Jankovsky¹Stephen A. Kichuk¹Bradford Martins¹Prerana Purohit¹Henry Schaer¹Yania P. Sierra¹Chelsea Witherow¹Christopher Pittenger^1,4,5,6,7,8Benjamin Kelmendi¹

• ¹Department of Psychiatry, Yale University School of Medicine, New Haven, CT, United States
• ²Department of Social Work, Eastern Tennessee State University, Johnson City, TN, United States
• ³New York University Postdoctoral Program in Psychoanalysis and Psychotherapy, New York, NY, United States
• ⁴Department of Psychology, Yale University, New Haven, CT, United States
• ⁵Center for Brain and Mind Health, Yale University School of Medicine, New Haven, CT, United States
• ⁶Child Study Center, Yale University School of Medicine, New Haven, CT, United States
• ⁷Department of Neuroscience, Yale University School of Medicine, New Haven, CT, United States
• ⁸Wu-Tsai Institute, Yale University, New Haven, CT, United States

Introduction: The subjective effects of psilocybin on obsessive-compulsive disorder (OCD) are under-explored. Therefore, we conducted a qualitative study of participant experiences from the first randomized placebo-controlled trial of single-dose psilocybin combined with unstructured and non-directive support for individuals with treatment-refractory OCD. Our research explored how participants experienced acute and post-dosing effects, the interrelationships between these effects, and participants' perspectives on therapeutic change. Materials and Methods: We conducted qualitative interviews with 12 participants approximately one month after psilocybin dosing; (six who received psilocybin in the initial randomized placebo-controlled phase, six who received open-label psilocybin following unblinding). We analyzed interview transcripts via interpretative phenomenological analysis (IPA) and engaged in consensus decision-making to arrive at 100% intercoder agreement in the process of abstracting codes into higher-order themes. Results: Four major themes (and several subthemes) emerged from our analysis: 1) Influences on Psilocybin Experience (i.e., Set, Setting); 2) Acute Effects (i.e., Acute perceptual effects, Acute [meta]cognitive effects, Acute emotional effects, Acute impact of OCD, Other acute effects); 3) Post-Dosing Changes in OCD (i.e., Post-dosing changes in symptoms, Post-dosing changes in perceptions of OCD); as well as 4) Post-Dosing Changes Beyond OCD Symptoms (i.e., Post-dosing [meta]cognitive changes, Other post-dosing changes). Meaningful interrelationships among codes, subthemes, and themes were the norm. Discussion: Our findings highlight the moderate to strong influences of set and setting in the nature and trajectory of participants' psilocybin experiences. We also uncovered acute, synergistic visual/perceptual, emotional/psychological, and physiological/somatic effects that map onto those commonly reported in prior psilocybin trials for other closely related indications. However, these acute effects tended to occur at lower intensities (i.e., 'partial' experiences) potentially due to acute interference by OCD symptoms. Certain acute and post-dosing (meta)cognitive and behavioral effects also map onto putative mechanisms of action in evidence-based psychotherapy for OCD (e.g., exposure and response prevention [ERP] and acceptance and commitment therapy [ACT]). These findings yielded hypotheses for future investigation, and point toward potential integration of psilocybin with structured psychotherapy approaches for OCD.