Feasibility, Clinical Effects, and Safety of Psilocybin-assisted Psychotherapy for Treatment-resistant OCD

NCT06299319 | Enrolling By Invitation Phase 1

• 1 other identifier: 149-2021
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Psilocybin, the chemical component of "magic mushrooms", has been administered with psychotherapy in several randomized clinical trials (RCTs) showing large and sustained antidepressant effects. There is interest to see if similar effects may be provided in those with obsessive compulsive disorder (OCD). The purpose of this study is to evaluate the safety, feasibility, and clinical effects of psilocybin administration in those with OCD. Ten participants with treatment-resistant OCD will receive two doses of 25mg of psilocybin under supportive conditions, two weeks apart. The investigators hypothesize that two sessions of psilocybin 25mg administered under supportive conditions to participants with treatment-resistant OCD will lead to significant reductions in OCD symptoms.

Conditions

Obsessive-Compulsive Disorder

Keywords

psilocybin; psychedelics; obsessive-compulsive disorder; clinical trial

Outcome Measures

Primary Outcomes (3)

• Feasibility of administering psilocybin (25 mg) in adults with treatment-resistant OCD

  Percentage of participants recruited and retained

  Screening Period, Intervention (2 weeks), Follow-up after 2nd dosing session (up to 10 weeks after 2nd dose)

• Incidence of adverse events (Safety and Tolerability)

  Frequency of dropouts attributed to adverse effects or serious adverse events

  Screening Period, Intervention (2 weeks), Follow-up after 2nd dosing session (up to 10 weeks after 2nd dose)

• Change in the Yale-Brown Obsessive-Compulsive Scale (YBOCS) total score from baseline

  The Yale-Brown Obsessive-Compulsive Scale is a test to rate the severity of obsessive-compulsive disorder symptoms. It is a 10-item scale, with questions 1-5 regarding obsessions, and questions 6-10 regarding compulsions. Each item is scored from 1-4, for a total possible score of 40. Higher scores represent a more severe condition.

  Baseline (Day -1) to Week 3 (Day 21)

Secondary Outcomes (7)

• Proportion of participants who respond to treatment

  Baseline (Day -1) to Week 3 (Day 21)

• Changes in Patient Health Questionnaire (PHQ-9) from Baseline to Week 3

  Baseline (Day -1) to Week 3 (Day 21)

• Change in the Clinical Global Impression (CGI) scale from Baseline to Week 3

  Baseline (Day -1) to Week 3 (Day 21)

• Change in the World Health Organization Quality of Life Short Version (WHOQOL-BREF) score from Baseline to Week 3

  Baseline (Day -1) to Week 3 (Day 21)

• Change in World Health Organization Disability Assessment Schedule (WHODAS 2.0) from Baseline to Week 3

  Baseline (Day -1) to Week 3 (Day 21)

Study Arms (1)

Experimental: Psilocybin 25 mg

EXPERIMENTAL

Participants will receive a 25 mg dose of psilocybin, twice throughout the trial, with two weeks in between doses.

Drug: Psilocybin

Interventions

Psilocybin DRUG

The psilocybin used in this study meets quality specifications suitable for human research use. The active drug is encapsulated using a hydroxypropyl methylcellulose (HPMC) capsule and contains 25 mg of psilocybin. The psilocybin will be administered twice during the trial, in conjunction with supportive therapy.

Also known as: PEX010

Experimental: Psilocybin 25 mg

Eligibility Criteria

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

You may qualify if:

• Adults 18 to 65 years old;
• Are outpatients
• Must be deemed to have capacity to provide informed consent;
• Must sign and date the informed consent form;
• Stated willingness to comply with all study procedures;
• Ability to read and communicate in English, such that their literacy and comprehension is sufficient for understanding the consent form and study questionnaires, as evaluated by study staff obtaining consent;
• Primary The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnosis of obsessive compulsive disorder (OCD) based on medical records and assessment using the Structured Clinical Interview for DSM-5 (SCID-5) administered at the first screening visit;
• Participants diagnosed with treatment-resistant OCD defined as individuals with a score of ≥ 16 on the YBOCS (i.e. moderate symptom severity) and that have not responded to two or more separate pharmacological interventions and one or more trials of cognitive behavioural therapy (CBT); there is no upper limit on the number of treatment failures;
• Individuals with an estimated glomerular filtration rate (eGFR) above 40mL/min/1.73m2 and all blood work within normal limits as assessed by clinical laboratory tests at Screening (V1)
• Ability to take oral medication;
• Individuals who are capable of becoming pregnant: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation;
• Individuals who are willing to and have tapered off current OCD medications for a minimum of 2-weeks prior to Baseline (V2) and whose physician confirms that it is safe for them to do so;
• Individuals who are willing to and have tapered off current inhibitors of 5'-diphospho-glucuronosyltransferase (UGT)1A9 and 1A10, aldehyde dehydrogenase inhibitors (ALDHs) and alcohol dehydrogenase inhibitors (ADHs) for a minimum of 2-weeks (or more depending on the medication) prior to Baseline (V2) and for the duration of the study and whose physician confirms that it is safe for them to do so; and
• Agreement to adhere to Lifestyle Considerations (section 4.5) throughout study duration.

You may not qualify if:

• Pregnant as assessed by a urine pregnancy test at Screening (V1) and Baseline (V2) or individuals that intend to become pregnant during the study or are breastfeeding;
• Treatment with another investigational drug or other intervention within 30 days of Screening (V1);
• Have initiated psychotherapy in the preceding 12 weeks prior to Screening (V1);
• Have a DSM-5 diagnosis of substance use disorder (use of tobacco and prescribed opioids are permitted) within the preceding 6 months;
• Have active suicidal ideation as determined by the C-SSRS and/or clinical interview. Significant suicide risk is defined by suicidal ideation as endorsed by items 4 or 5 of the C-SSRS;
• Any DSM-5 lifetime diagnosis of a schizophrenia-spectrum disorder; psychotic disorder (unless substance induced or due to a medical condition), bipolar I or II disorder, paranoid personality disorder, borderline personality disorder, or neurocognitive disorder as determined by medical history and the SCID-5 clinical interview;
• Any first-degree relative with a diagnosis of schizophrenia-spectrum disorder; psychotic disorder (unless substance-induced or due to a medical condition); or bipolar I or II disorder as determined by the family medical history form and discussions with the participant;
• Have contraindications to transcranial magnetic stimulation (TMS) as determined by the transcranial magnetic stimulation adult safety screen (TASS) questionnaire;
• Have a history of seizures;
• Are taking anticonvulsants or benzodiazepines (Lorazepam up to 2mg/day is acceptable);
• Presence of a relative or absolute contraindication to psilocybin, including a drug allergy, recent stroke history, uncontrolled hypertension, low or labile blood pressure, recent myocardial infarction, cardiac arrhythmic, severe coronary artery disease, or moderate to severe renal or hepatic impairment;
• Use of classic psychedelic drugs within the previous 12 months; OR
• Any other clinically significant physical illness including chronic infectious diseases or any other major concurrent illness that, in the opinion of the investigator, may interfere with the interpretation of the study results or constitute a health risk for the participant if they take part in the study.

Sponsors & Collaborators

• Centre for Addiction and Mental Health: lead

Study Sites (1)

Centre for Addiction and Mental Health

Toronto, Ontario, M6J 1H1, Canada

Location

Related Publications (5)

• Bloch MH, Landeros-Weisenberger A, Kelmendi B, Coric V, Bracken MB, Leckman JF. A systematic review: antipsychotic augmentation with treatment refractory obsessive-compulsive disorder. Mol Psychiatry. 2006 Jul;11(7):622-32. doi: 10.1038/sj.mp.4001823. Epub 2006 Apr 4.

  PMID: 16585942 BACKGROUND

• Pallanti S, Quercioli L. Treatment-refractory obsessive-compulsive disorder: methodological issues, operational definitions and therapeutic lines. Prog Neuropsychopharmacol Biol Psychiatry. 2006 May;30(3):400-12. doi: 10.1016/j.pnpbp.2005.11.028. Epub 2006 Feb 28.

  PMID: 16503369 BACKGROUND

• Perkins D, Sarris J, Rossell S, Bonomo Y, Forbes D, Davey C, Hoyer D, Loo C, Murray G, Hood S, Schubert V, Galvao-Coelho NL, O'Donnell M, Carter O, Liknaitzky P, Williams M, Siskind D, Penington D, Berk M, Castle D. Medicinal psychedelics for mental health and addiction: Advancing research of an emerging paradigm. Aust N Z J Psychiatry. 2021 Dec;55(12):1127-1133. doi: 10.1177/0004867421998785. Epub 2021 Mar 21.

  PMID: 33745287 BACKGROUND

• Halberstadt AL, Koedood L, Powell SB, Geyer MA. Differential contributions of serotonin receptors to the behavioral effects of indoleamine hallucinogens in mice. J Psychopharmacol. 2011 Nov;25(11):1548-61. doi: 10.1177/0269881110388326. Epub 2010 Dec 8.

  PMID: 21148021 BACKGROUND

• Madsen MK, Fisher PM, Burmester D, Dyssegaard A, Stenbaek DS, Kristiansen S, Johansen SS, Lehel S, Linnet K, Svarer C, Erritzoe D, Ozenne B, Knudsen GM. Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels. Neuropsychopharmacology. 2019 Jun;44(7):1328-1334. doi: 10.1038/s41386-019-0324-9. Epub 2019 Jan 26.

  PMID: 30685771 BACKGROUND

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

• Gwyneth Zai, MD, MSc, PhD

  Centre for Addiction and Mental Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 15, 2024
• First Posted: March 7, 2024
• Study Start: September 1, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: May 18, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)