Effects of Repeated Psilocybin Dosing in OCD

NCT05370911 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 2000032623
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

This study aims to investigate the effects of repeated dosing of oral psilocybin on obsessive-compulsive disorder (OCD) symptomatology in a randomized, waitlist-controlled design with blinded independent ratings, and assess psychological mechanisms that may mediate psilocybin's therapeutic effects on OCD.

Conditions

Obsessive-Compulsive Disorder

Keywords

Psilocybin

Outcome Measures

Primary Outcomes (1)

• Change in Yale-Brown Obsessive-Compulsive Scale-Second Edition (Y-BOCS-II) Severity Scale total score from baseline at 4 days post-second dose

  Clinician-administered assessment of severity of OCD symptoms over the past seven days. The most prominent obsessions and compulsions are rated on the Severity Scale from 0 to 4. Total Y-BOCS-II scores range from 0 to 40, with higher scores indicating greater severity of OCD symptoms.

  Baseline & 4 days post-second dose

Secondary Outcomes (29)

• Change in Montgomery-Asberg Depression Scale (MADRS) total score from baseline at 4 days post-second dose

  Baseline & 4 days post-second dose

• Change in Dimensional Obsessive-Compulsive Scale (DOCS) total score from baseline at 4 days post-second dose

  Baseline & 4 days post-second dose

• Change in Obsessive Beliefs Questionnaire-44 (OBQ-44) total score from baseline at 4 days post-second dose

  Baseline & 4 days post-second dose

• Change in Acceptance and Action Questionnaire for Obsessions and Compulsions (AAQ-OC) total score from baseline at 4 days post-second dose

  Baseline & 4 days post-second dose

• Change in Tolerance of Uncontrollability Questionnaire (TOUQ) total score from baseline at 4 days post-second dose

  Baseline & 4 days post-second dose

Study Arms (2)

Immediate Treatment

EXPERIMENTAL

Participants randomized to this condition will receive treatment immediately, facilitated by two study staff members, and which consists of two preparatory sessions, followed by the first dosing session and two integration sessions, then the second dosing session and two integration sessions. This is followed by follow-up and long-term follow-up visits up to 12 months post-second dose.

Drug: Psilocybin

Waitlist Control/Delayed Treatment

NO INTERVENTION

Participants randomized to this condition will first enter a waitlist phase that lasts for 7 weeks, after which rater unblinding will occur, and participants will be rescreened. If participants remain eligible at this time, they will begin their treatment phase. During their treatment phase, participants in this condition will receive the same treatment as described for participants in the immediate treatment group. This is followed by follow-up and long-term follow-up visits up to 12 months post-second dose.

Interventions

Psilocybin DRUG

The first oral dose will be 25 mg, and the second dose will be either 25 mg or 30 mg, depending on response to first dose. Psilocybin is a naturally occurring hallucinogenic ingredient found in some varieties of mushrooms that can be produced synthetically. It is considered to be a serotonergic psychedelic. We will use synthetically produced oral psilocybin in this study. Other Names: "Magic Mushrooms"

Immediate Treatment

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Primary DSM-5 diagnosis of OCD, with Y-BOCS-II score of 26 or greater at screening
• Failed at least one medication and/or therapy trial of standard care treatment for OCD
• English fluency
• Agree to sign a medical release for investigators to communicate directly with participants' providers to confirm medication and psychotherapy histories or arrange contingencies in event of crises.
• Agree to provide an adult contact (relative, spouse, close friend or other caregiver) who is willing and able to be reached by the PI and/or study personnel in the event of an emergency, and who can provide transportation for study visits and independently comment on any changes in the participant's mood or behavior after each administration of psilocybin.
• Agree to commit to all study procedures.
• Ability to orally ingest pills for psilocybin dosing visits.
• Agree to adhere to lifestyle and medication modifications.
• Must not be on psychotropic medications for OCD or comorbid psychiatric conditions for at least 8 weeks at the time of randomization, and agree to refrain from taking or starting any psychiatric medications until after 4 weeks post-second dose.
• Must not be in current psychotherapy (CBT or ERP) and must not start new course of psychotherapy (CBT or ERP) for OCD or comorbid psychiatric conditions until after 4 weeks post-second dose.
• If participant is of childbearing potential, must have a negative pregnancy test at study entry and prior to each dosing session.
• If participant is of childbearing potential, agree to use adequate birth control and not attempt to become pregnant during study up to 4 weeks post-second dose.

You may not qualify if:

• Personal or immediate (first-degree relative) family history of formally diagnosed schizophrenia or other psychotic disorders, or bipolar I/II disorder
• Lack of knowledge about biological families' medical history, due to adoption or other circumstance
• Active suicidal intent or suicidal or non-suicidal self-injurious behaviors
• Unremitted Tourette syndrome
• Lifetime diagnosis of autism spectrum disorder
• Current substance use disorder (except for mild alcohol use disorder)
• Any neurological condition, including history of seizure(s) or chronic/severe headaches
• Any history of head injury with loss of consciousness for more than 30 min
• Any use of classic psychedelic substances within the prior 12 months
• Unwillingness to abstain from use of classic psychedelics outside of the study up to 4 weeks post-second dose.
• Use of tobacco products or a THC-containing product more than 2 times per week on average over the past 30 days at screening.
• Unwilingness or inability to abstain from use of tobacco or THC-containing products from 1 week prior to randomization up to 4 weeks post-second dose.
• Positive urine drug test for any prohibited substance at screening or days of dosing, or positive breathalyzer test for alcohol on days of dosing
• Unwillingness or inability to abstain from alcohol use at least 24 hours prior to the days of dosing, up to 24 hours after each dosing day (or corresponding intervals for waitlist group).
• Any medical conditions that may render study procedures unsafe, including hypertension, history of cardiovascular disease, moderate-to-severe hepatic or renal impairment, diabetes, and hypo- or hyperthyroidism.

Sponsors & Collaborators

• Yale University: lead
• Steven & Alexandra Cohen Foundation: collaborator

Study Sites (2)

Enact Research Collaborative (40 Temple St, 4th Floor)

New Haven, Connecticut, 06510, United States

Location

Yale Program for Psychedelic Research

New Haven, Connecticut, 06510, United States

Location

Related Publications (5)

• Moreno FA, Wiegand CB, Taitano EK, Delgado PL. Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder. J Clin Psychiatry. 2006 Nov;67(11):1735-40. doi: 10.4088/jcp.v67n1110.

  PMID: 17196053 BACKGROUND

• Davis AK, Barrett FS, May DG, Cosimano MP, Sepeda ND, Johnson MW, Finan PH, Griffiths RR. Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2021 May 1;78(5):481-489. doi: 10.1001/jamapsychiatry.2020.3285.

  PMID: 33146667 BACKGROUND

• Ross S, Bossis A, Guss J, Agin-Liebes G, Malone T, Cohen B, Mennenga SE, Belser A, Kalliontzi K, Babb J, Su Z, Corby P, Schmidt BL. Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. J Psychopharmacol. 2016 Dec;30(12):1165-1180. doi: 10.1177/0269881116675512.

  PMID: 27909164 BACKGROUND

• Griffiths RR, Johnson MW, Carducci MA, Umbricht A, Richards WA, Richards BD, Cosimano MP, Klinedinst MA. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial. J Psychopharmacol. 2016 Dec;30(12):1181-1197. doi: 10.1177/0269881116675513.

  PMID: 27909165 BACKGROUND

• Ching THW, Amoroso L, Bohner C, D'Amico E, Eilbott J, Entezar T, Fitzpatrick M, Fram G, Grazioplene R, Hokanson J, Kichuk SA, Martins B, Patel P, Schaer H, Shnayder S, Witherow C, Pittenger C, Kelmendi B. Safety, feasibility, tolerability, and clinical effects of repeated psilocybin dosing combined with non-directive support in the treatment of obsessive-compulsive disorder: protocol for a randomized, waitlist-controlled trial with blinded ratings. Front Psychiatry. 2024 Jan 9;14:1278823. doi: 10.3389/fpsyt.2023.1278823. eCollection 2023.

  PMID: 38264632 DERIVED

MeSH Terms

Conditions

Obsessive-Compulsive Disorder

Interventions

Psilocybin

Condition Hierarchy (Ancestors)

Anxiety Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines

Study Officials

• Benjamin Kelmendi, MD

  Yale University

  PRINCIPAL INVESTIGATOR

• Terence Ching, PhD

  Yale University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Only the independent rater for each participant will be blinded to their condition; blind will be broken at the end of week 7 (i.e., 4 weeks post-second dosing), after which participants in the waitlist/delayed treatment group will begin their treatment phase.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Psychiatry

Model Details: In the study, participants will be randomized to receive either immediate treatment with two doses of oral psilocybin separated by one week (n = 15) or enter a waitlist control/delayed treatment group and receive the same treatment 7 weeks post-randomization (n = 15).

Study Record Dates

• First Submitted: April 19, 2022
• First Posted: May 12, 2022
• Study Start: July 20, 2023
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2027
• Last Updated: February 13, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)