Yale Program for Psychedelic Science (YPPS) Manual for Psilocybin Combined with Non-Directive Support in the Treatment of OCD
Terence H. W. Ching, Rachael Grazioplene, Christopher Pittenger, Benjamin Kelmendi
March 17, 2023 preprint DOI: 10.31234/osf.io/ba42z (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized, waitlist-controlled study with blinded ratings |
|---|---|
| Population | Participants with obsessive-compulsive disorder (OCD) |
| Intervention | Psilocybin |
| Dose | 25 mg; second dose 25 mg or 30 mg |
| Duration | Two doses separated by one week; delayed treatment at 7 weeks post-randomization |
| Topics | Psilocybin |
| Keywords | Dosing Obsessive compulsive Hallucinogen Randomized controlled trial Clinical psychology Psychotherapist Pharmacology |
| Citations | 6 |
| Registration | NCT05370911 |
| Key points | The study will investigate whether repeated psilocybin dosing, with non-directive support, reduces OCD symptoms and explore psychological mechanisms mediating therapeutic effects. |
Abstract
The Yale Program for Psychedelic Science (YPPS) supports a multi-disciplinary research community dedicated to investigating the effects of psychedelic substances on brain function, cognition, and behavior, including their therapeutic potential in treating neuropsychiatric conditions. In support of this mission, YPPS is testing the safety and efficacy of psilocybin, administered in conjunction with non-directive psychological support, as a treatment for certain neurological and psychiatric conditions. The current study, “Effects of repeated dosing of psilocybin on obsessive-compulsive disorder: A randomized, waitlist-controlled study” (NCT05370911), will investigate the effects of repeated dosing of oral psilocybin on obsessive-compulsive disorder (OCD) symptomatology and assess psychological mechanisms that may mediate psilocybin’s therapeutic effects on OCD. The study will employ a randomized, waitlist-controlled design with blinded ratings, with participants randomized to receive either immediate treatment (two doses of oral psilocybin separated by one week) or delayed treatment (7 weeks post-randomization). An adaptive dose selection strategy will be implemented; the first dose will be fixed at 25 mg of psilocybin, and the second dose will be 25 mg or 30 mg, depending on whether or not a clinically significant response is detected after the first dose. This manual provides background and details for facilitator-related activities at various phases – pre-dosing preparation sessions, dosing sessions, and post-dosing integration sessions. The approach for psychological support by facilitators is unstructured and non-directive. In other words, facilitators do not provide any structured therapy, but rather collaborate and support participants as they prepare for psilocybin dosing sessions, ensure their psychological safety during dosing sessions, and provide them with an unstructured, non-directive context in which to process and consolidate their experiences during and after each dosing at defined time points. In doing so, while no structured therapy program is implemented, the presence and accompaniment by facilitators throughout all study sessions in the treatment phase may be experienced as supportive or even therapeutic by participants. This manual shares several features with a previous YPPS protocol-specific session monitor manual for single-dose psilocybin paired with psychological support for OCD (Ching et al., 2022), including the primary focus on a non-directive approach for preparatory, dosing, and integration sessions. Distinctive additions in this manual include a discussion of psychological processes in OCD that serve as a context for responsive facilitation of study visits, as well as updated facilitator checklists for preparatory, dosing, and integration sessions specific to the current two-dose protocol.
Comparable studies
Other randomized controlled trials on psilocybin, 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 |
| Trial of Psilocybin versus Escitalopram for Depression Selected group of patients with depression | 2021 | Randomized controlled trial | |
| Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder Adults aged 21 to 75 years with major depressive disorder, not currently using... | 2020 | Randomized controlled trial | n = 24 |
Citations in the library
Cited by 6
- Psychedelic-assisted psychotherapy: where is the psychotherapy research? Psychopharmacology August 1, 2024
- A primer for culturally attuned psychedelic clinical trials Journal of Psychedelic Studies May 15, 2025
- 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 Frontiers in Psychiatry December 10, 2025
- “Skin contains land and birds”: Understanding inner healing intelligence through critical vitalism and Indigenous thought Journal of Psychedelic Studies July 28, 2025
- Integration in classic psychedelic-assisted therapies for mental health conditions: a scoping review Psychedelics July 1, 2026
and 1 more in the library
Cites 15
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Journal of Psychopharmacology November 30, 2016
- Human hallucinogen research: guidelines for safety. Journal of Psychopharmacology July 1, 2008
- Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects. Psychopharmacology December 1, 2011
- Mystical experiences occasioned by the hallucinogen psilocybin lead to increases in the personality domain of openness Journal of Psychopharmacology September 28, 2011
and 10 more in the library