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History of Changes for Study: NCT05370911
Effects of Repeated Psilocybin Dosing in OCD
Latest version (submitted November 21, 2022) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 May 6, 2022 None (earliest Version on record)
2 May 12, 2022 Outcome Measures, Eligibility and Study Status
3 June 7, 2022 Study Status, Eligibility, Outcome Measures and Arms and Interventions
4 August 24, 2022 Study Status and Eligibility
5 September 20, 2022 Study Status, Eligibility and Outcome Measures
6 September 25, 2022 Eligibility and Study Status
7 October 4, 2022 Contacts/Locations and Study Status
8 November 2, 2022 Study Status
9 November 21, 2022 Study Status
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Study NCT05370911
Submitted Date:  May 6, 2022 (v1)

Open or close this module Study Identification
Unique Protocol ID: 2000032623
Brief Title: Effects of Repeated Psilocybin Dosing in OCD
Official Title: Effects of Repeated Dosing of Psilocybin on Obsessive-Compulsive Disorder: A Randomized, Waitlist-Controlled Study
Secondary IDs:
Open or close this module Study Status
Record Verification: May 2022
Overall Status: Not yet recruiting
Study Start: November 2022
Primary Completion: November 2025 [Anticipated]
Study Completion: November 2026 [Anticipated]
First Submitted: April 19, 2022
First Submitted that
Met QC Criteria:
May 6, 2022
First Posted: May 12, 2022 [Actual]
Last Update Submitted that
Met QC Criteria:
May 6, 2022
Last Update Posted: May 12, 2022 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Yale University
Responsible Party: Principal Investigator
Investigator: Benjamin Kelmendi, MD
Official Title: Assistant Professor of Psychiatry
Affiliation: Yale University
Collaborators: Steven & Alexandra Cohen Foundation
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
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.
Detailed Description:

Aim 1: To examine the effects of two doses of psilocybin on OCD symptoms among participants in the immediate treatment condition, compared to participants in the waitlist control/delayed treatment condition. The investigators hypothesize that participants in the immediate treatment group will report statistically significantly greater symptom improvement from baseline 4 days post-second dose, compared to participants in the waitlist control/delayed treatment group at the same interval during their waitlist phase.

Aim 2: To examine the effects of two doses of psilocybin on OCD symptoms, compared to one dose. The investigators hypothesize that two doses of oral psilocybin will reduce OCD symptoms to a statistically significantly greater extent than one dose.

This study aims to investigate the effects of repeated dosing of oral psilocybin on OCD symptomatology and assess psychological mechanisms that may mediate psilocybin's therapeutic effects on OCD. This study will employ a randomized, waitlist-controlled design with blinded independent ratings, with participants randomized to receive either immediate treatment (two doses oral psilocybin separated by one week) or delayed treatment (7 weeks post-randomization). An adaptive dose selection strategy will be implemented, with the first dose being standardized at 25 mg of psilocybin, and the second dose being either the same or a higher dosage (i.e., 30 mg) on the basis of a clinically significant response from baseline or not, respectively, 4 days post-first dose.

This study is conducted entirely on an outpatient basis with the possibility of remote/virtual follow-up visits after each dosing session. The dosing sessions last the entire day, and participants will be medically cleared prior to being permitted to return home with assistance (e.g., driven by a family member or friend, or ride share).

Open or close this module Conditions
Conditions: Obsessive-Compulsive Disorder
Keywords: Psilocybin
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 1
Interventional Study Model: Parallel Assignment
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).
Number of Arms: 2
Masking: Single (Outcomes Assessor)
Allocation: Randomized
Enrollment: 30 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Immediate Treatment
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.
Drug: Psilocybin

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"

No Intervention: Waitlist Control/Delayed Treatment
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 then 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.
Open or close this module Outcome Measures
Primary Outcome Measures:
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
[ Time Frame: Baseline & 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.
Secondary Outcome Measures:
1. Change in Montgomery-Asberg Depression Scale (MADRS) total score from baseline at 4 days post-second dose
[ Time Frame: Baseline & 4 days post-second dose ]

Clinician-administered assessment of severity of depressive symptoms over past month. Total scores range from 0 to 60, with higher scores indicating greater severity of depressive symptoms.
2. Change in Dimensional Obsessive-Compulsive Scale (DOCS) total score from baseline at 4 days post-second dose
[ Time Frame: Baseline & 4 days post-second dose ]

Self-report measure of various OCD symptoms over the modified time frame of the past week. Total scores range from 0 to 140, with higher scores indicating greater severity of OCD symptoms.
3. Change in Obsessive Beliefs Questionnaire-44 (OBQ-44) total score from baseline at 4 days post-second dose
[ Time Frame: Baseline & 4 days post-second dose ]

Self-report measure of various obsessive beliefs implicated in OCD in general. Total scores range from 44 to 308, with higher scores indicating greater severity of obsessive beliefs.
4. Change in Acceptance and Action Questionnaire for Obsessions and Compulsions (AAQ-OC) total score from baseline at 4 days post-second dose
[ Time Frame: Baseline & 4 days post-second dose ]

Self-report measure of experiential avoidance and psychological flexibility in the context of OCD symptoms in general. Total scores range from 13 to 91, with higher scores indicating greater psychological inflexibility.
5. Change in Tolerance of Uncontrollability Questionnaire (TOUQ) total score from baseline at 4 days post-second dose
[ Time Frame: Baseline & 4 days post-second dose ]

Self-report measure of ability to tolerate uncontrollability (or inversely need for control) in general. Total scores range from 19 to 133, with higher scores indicating greater tolerance of uncontrollability.
6. Change in White Bear Suppression Inventory (WBSI) total score from baseline at 4 days post-second dose
[ Time Frame: Baseline & 4 days post-second dose ]

Self-report measure of thought suppression tendencies in general. Total scores range from 15 to 75, with higher scores indicating stronger thought suppression tendencies.
7. Change in Difficulties in Emotion Regulation Scale (DERS) total score from baseline at 4 days post-second dose
[ Time Frame: Baseline & 4 days post-second dose ]

Self-report measure of emotion regulation difficulties in general. Total scores range from 36 to 180, with higher scores indicating greater difficulties with regulating emotions.
8. Change in Southampton Mindfulness Questionnaire (SMQ) total score from baseline at 4 days post-second dose
[ Time Frame: Baseline & 4 days post-second dose ]

Self-report measure of trait mindfulness in regards to distressing thoughts and images. Total scores range from 0 to 96, with higher scores indicating greater trait mindfulness.
9. Toronto Mindfulness Scale (TMS)
[ Time Frame: Up to 3 weeks for immediate treatment condition, and up to 10 weeks for waitlist condition ]

Self-report measure of state mindfulness during dosing session. Total scores range from 0 to 52, with higher scores indicating greater state mindfulness.
10. Set, Setting, and Intentions (SSI) Scale
[ Time Frame: Up to 3 weeks for immediate treatment condition, and up to 10 weeks for waitlist condition ]

Self-report measure of set, setting, and clarity of intentions just prior to dosing session. Total mean scores range from 0 to 100 (after reverse-scoring two items), with higher scores indicating greater preparedness for the dosing session.
11. Mystical Experience Questionnaire (MEQ)
[ Time Frame: Up to 3 weeks for immediate treatment condition, and up to 10 weeks for waitlist condition ]

Self-report measure of acute mystical experiences during dosing. Total mean scores range from 0 to 5, with higher scores indicating greater mystical experiences.
12. Psychological Insight Questionnaire (PIQ)
[ Time Frame: Up to 3 weeks for immediate treatment condition, and up to 10 weeks for waitlist condition ]

Self-report measure of acute psychological insights during dosing. Total mean scores range from 0 to 5, with higher scores indicating greater insightful experiences.
13. Challenging Experience Questionnaire (CEQ)
[ Time Frame: Up to 3 weeks for immediate treatment condition, and up to 10 weeks for waitlist condition ]

Self-report measure of acute challenging experiences during dosing. Total mean transformed scores range from 0 to 1, with higher scores indicating greater challenging experiences.
14. Ego Dissolution Inventory (EDI)
[ Time Frame: Up to 3 weeks for immediate treatment condition, and up to 10 weeks for waitlist condition ]

Self-report measure of acute experiences of ego dissolution during dosing. Total mean scores range from 0 to 100, with higher scores indicating greater ego dissolution.
15. Emotional Breakthrough Inventory (EBI)
[ Time Frame: Up to 3 weeks for immediate treatment condition, and up to 10 weeks for waitlist condition ]

Self-report measure of different experiences of emotional breakthroughs during dosing. Total mean scores range from 0 to 100, with higher scores indicating greater emotional breakthrough.
16. Change in Self-Compassion Scale (SCS) total mean score from baseline at 4 days post-second dose
[ Time Frame: Baseline & 4 days post-second dose ]

Self-report measure of self-compassion in general. Total mean scores range from 1 to 5 (after reverse-scoring 13 items), with higher scores indicating greater self-compassion.
17. Change in Ten-Item Personality Inventory (TIPI) total score from baseline at 4 days post-second dose
[ Time Frame: Screening, 4 days and 12 months post-second dose ]

Brief self-report measure of Big Five personality dimensions. Total scores range from 10 to 70 (after reverse-scoring 5 items), with higher scores indicating more positive personality traits.
18. Change in Persisting Effects Questionnaire (PEQ) subscale scores from 4 weeks post-second dose at 12 months post-second dose
[ Time Frame: 4 weeks post-second dose & 12 months post-second dose ]

Self-report measure of persisting effects from dosing in general. Subscale scores range from a minimum of 0 to a maximum of 5 to 85, with higher scores indicating greater positive or negative persisting changes since dosing.
19. Change in Alcohol Use Disorders Identification Test (AUDIT) total score from baseline at 4 weeks post-second dose
[ Time Frame: Baseline & 4 weeks post-second dose ]

Self-report measure of alcohol use severity. Total scores range from 0 to 40, with higher scores indicating greater alcohol use severity.
20. Change in Drug Use Disorders Identification Test (DUDIT) total score from baseline at 4 weeks post-second dose
[ Time Frame: Baseline & 4 weeks post-second dose ]

Self-report measure of illicit substance use. Total scores range from 0 to 44, with higher scores indicating greater illicit substance use severity.
21. Change in Fagerstrom Test for Nicotine Dependence (FTND) total score from baseline at 4 weeks post-second dose
[ Time Frame: Baseline & 4 weeks post-second dose ]

Self-report measure of nicotine use. Total scores range from 0 to 10, with higher scores indicating greater nicotine use severity.
22. Change in Sheehan Disability Scale (SDS) total score from baseline at 4 days post-second dose
[ Time Frame: Baseline & 4 weeks post-second dose ]

Self-report measure of symptom-related functional impairment in general. Total scores range from 0 to 30, with higher scores indicating greater functional impairment.
23. Change in Quality of Life Enjoyment & Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) percentage maximum score from baseline at 4 days post-second dose
[ Time Frame: Baseline & 4 weeks post-second dose ]

Self-report measure of life satisfaction over the past week. Percentage maximum scores range from 0% to 100%, with higher percentages indicating greater life satisfaction.
24. Approach-Avoidance Task (AAT)
[ Time Frame: Baseline & 4 days post-second dose ]

Computerized behavioral measure of approach and avoidance tendencies in regards to standardized OCD-relevant pictorial stimuli
25. PACT Anagram Task (PAT)
[ Time Frame: Baseline & 4 days post-second dose ]

Online anagram task developed as a behavioral assessment of intolerance of uncertainty
26. Writing task
[ Time Frame: Baseline & 4 days post-second dose ]

Online writing task in which participants describe their perceptions of their OCD symptoms with a short written essay
27. Columbia Suicide Severity and Risk Scale (C-SSRS) Since Last Visit version
[ Time Frame: Every study visit through study completion, an average of 12 months and 3 weeks for immediate treatment condition, and an average of 12 months and 10 weeks for waitlist condition ]

Clinician-administered assessment of suicidal ideation and behaviors since the last study visit
28. Theoretical Orientation Profile Scale-Revised (TOPS-R)
[ Time Frame: Baseline ]

Clinician-reported measure of theoretical orientation over eight subscales, each corresponding to a different theoretical orientation. Subscale scores range from 1 to 30, with higher scores indicating greater affiliation with a particular theoretical orientation.
29. Working Alliance Inventory-Short Revised (WAI-SR)
[ Time Frame: 4 days post-second dose ]

Self-report measure of perceived working alliance with study clinicians. Total scores range from 0 to 60, with higher scores indicating stronger perceived working alliance.
Open or close this module Eligibility
Minimum Age: 21 Years
Maximum Age: 65 Years
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  1. Primary DSM-5 diagnosis of OCD
  2. Patients must have failed at least one medication and/or therapy trial of standard care treatment for OCD
  3. English fluency
  4. Agree to refrain from taking or starting any psychiatric medications during the study period.
  5. Agree to pause current or not initiate new course of psychotherapy for OCD during the study period.
  6. If participant is a female of childbearing potential, must have a negative pregnancy test at study entry and prior to each dosing session.
  7. Must agree to use adequate birth control throughout study duration.

Exclusion Criteria:

  1. Unremitted Tourette syndrome
  2. Pregnant or lactating women
  3. Unable or unwilling to adhere to contraceptive measures
  4. Positive urine drug test for any prohibited substance, or positive breathalyzer test for alcohol, at screening or day of dosing
  5. Any unstable medical condition that my render study procedures unsafe
Open or close this module Contacts/Locations
Central Contact Person: Yale OCD Clinic Psychedelic Research
Telephone: 203-623-3023
Email: psychedelicresearch@yale.edu
Study Officials: Benjamin Kelmendi, MD
Principal Investigator
Yale University
Christopher Pittenger, MD, PhD
Study Director
Yale University
Locations: United States, Connecticut
Connecticut Mental Health Center
New Haven, Connecticut, United States, 06519
Contact:Contact: Yale OCD Clinic Psychedelic Research 203-623-3023 psychedelicresearch@yale.edu
Contact:Principal Investigator: Benjamin Kelmendi, MD
Contact:Sub-Investigator: Terence Ching, PhD
Open or close this module IPDSharing
Plan to Share IPD: No
Open or close this module References
Citations: 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. PubMed 17196053
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. Erratum In: JAMA Psychiatry. 2021 Feb 10;: PubMed 33146667
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. PubMed 27909164
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. PubMed 27909165
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