Efficacy of Psilocybin in OCD: a Double-Blind, Placebo-Controlled Study.

NCT03356483 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: 20000203551K23MH122777-01A1
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to investigate the effects of oral psilocybin on OCD symptomatology and provide the first evidence of the neural mechanism that may mediate psilocybin's purported therapeutic effects on OCD.

Conditions

Obsessive-Compulsive Disorder

Keywords

Psilocybin

Outcome Measures

Primary Outcomes (4)

• Changes in severity of OCD symptoms, which will be measured by The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). The Primary Outcome Measure will be collected at baseline and 48 hours, assessing change from baseline at 48 hours.

  Assesses severity and types of OCD symptoms over the past seven days. Consists of two parts: 1- symptom checklist, 2- symptom severity scale. The most prominent obsessions and compulsions are identified by the checklist and then rated by the symptom severity scale. The symptom severity scale consists of 11 items (3 items are not included in the total score) and uses a 0 to 4 severity scale. Total Y-BOCS scores range from 0 to 40, with higher scores indicating greater severity of OCD symptoms.

  Baseline, 48 hours post-drug, weeks: 1, 2, 4, 12 post-drug

• Changes in severity of OCD symptoms, measured by Acute Yale-Brown Obsessive-Compulsive Scale (A-YBOCS)

  A clinician-administered measure of specific participant OCD symptoms over prior 24 hours. The most prominent obsessions and compulsions that were previously identified by the checklist are rated by the symptom severity scale. The symptom severity scale consists of 11 items (3 items are not included in the total score) and uses a 0 to 4 severity scale. Total A-YBOCS scores range from 0 to 40, with higher scores indicating greater severity of OCD symptoms.

  Baseline, 24 hours post-drug, 48 hours post-drug

• Changes in severity of OCD symptoms, measured by Visual Analog Scale (VAS) for OCD symptoms

  A self-report measure of severity of and distress related to OCD symptoms over the past 24 hours. Consists of 5 items assessing compulsive urges, obsessions, anxiety, mood, and discomfort, each on a 0-100 VAS, with higher scores on each item indicating greater severity.

  Baseline, 24 hours post-drug, 48 hours post-drug

• Changes in suicidality, measured by the Columbia-Suicide Severity Rating Scale (C-SSRS) Since Last Visit version

  A clinician-administered measure of suicidality since the last visit. Consists of 5 items assessing suicidal ideation and 6 items assessing suicidal and non-suicidal self-injurious behaviors. Higher scores on either scale indicate more severe suicidal ideation and suicidal or non-suicidal behaviors since the last study visit.

  Up to 12 weeks post-drug

Secondary Outcomes (32)

• Changes in brain connectivity, which will be measured with functional Magnetic Imaging Resonance (fMRI).

  Baseline & 48 hours post-drug

• Changes in depression symptoms, which will be measured by The Montgomery-Asberg Depression Scale (MADRS).

  Baseline, 2 days post-drug, weeks: 1, 2, 4, 12, post-drug

• Changes in depression symptoms, which will be measured by the Beck Depression Inventory (BDI).

  Baseline, 1 day post-drug, weeks: 2 & 12 post-drug

• Changes in dysfunctional beliefs, which will be measured by The Obsessive Beliefs Questionnaire (OBQ-44).

  Baseline & 2 weeks post-drug

• Changes in OCD symptoms, which will be measured by The Obsessive-Compulsive Inventory - Revised (OCI-R).

  Baseline & 2 weeks post-drug

Study Arms (2)

Psilocybin

EXPERIMENTAL

Psilocybin (0.25mg/kg)

Drug: Psilocybin (0.25mg/kg)

Niacin

PLACEBO COMPARATOR

Niacin (250mg)

Drug: Niacin (250mg)

Interventions

Psilocybin (0.25mg/kg) DRUG

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.

Also known as: "Magic Mushrooms"

Psilocybin

Niacin (250mg) DRUG

A medication used to treat high cholesterol, triglyceride levels, and niacin deficiency.

Also known as: Nicotinic acid

Niacin

Eligibility Criteria

• Age: 21 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
• Y-BOCS score of 19 or greater
• Failure of at least one trial of standard care treatment (medication and/or psychotherapy \[CBT/ERP\]) for OCD
• English proficiency and fluency, and ability to understand the consent process and provide written informed consent
• Willingness to sign a medical release for direct communication between research staff and external provider(s) about the participant's treatment and medical histories
• Non-consumption of SSRIs for at least 8 weeks at the time of randomization
• Willingness to refrain from psychiatric medications (e.g., antidepressants, first- and second-generation antipsychotics, mood stabilizers) during the study period, as well as certain other medications (e.g., anti-seizure medications, cardiovascular medications, and aldomet specifically) during the day of dosing
• Willingness to abstain from THC-containing products for study duration. A negative urinary drug screen is also required at baseline and the day of dosing.
• A negative urinary pregnancy screen at study entry and day of dosing if of childbearing potential, and willingness to use adequate birth control for study duration
• Having a contact person who is willing and able to be reached by the study team in the event of an emergency/crisis, and who is able to transport the participant home at the end of the inpatient stay/dosing week
• Willingness to commit to all study procedures and visits, including inpatient stay, assessments and self-reports, neuroimaging, and being medically cleared to be discharged and transported home at the end of the dosing week

You may not qualify if:

• Personal or immediate family history of schizophrenia spectrum and other psychotic disorders, bipolar I or II disorder, or major depressive disorder with psychotic features
• Active suicidal intent
• Unremitted Tourette syndrome
• Autism spectrum disorder
• OCPD or BPD
• Current substance use disorder (except mild alcohol use disorder)
• Unstable neurological or medical condition(s) that may render study procedures unsafe, including poorly managed diabetes, hypertension, or cardiovascular conditions, or history of seizure(s) or chronic/severe headaches
• Any history of head injury with loss of consciousness for more than 30 minutes
• Any contraindications to undergoing an MRI scan, including having metal implants or metal fragments in the body
• Any use of psychedelic substances within the prior 12 months

Sponsors & Collaborators

• Yale University: lead
• Heffter Research Institute: collaborator
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

Connecticut Mental Health Center

New Haven, Connecticut, 06519, 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

• 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

• Carhart-Harris RL, Erritzoe D, Williams T, Stone JM, Reed LJ, Colasanti A, Tyacke RJ, Leech R, Malizia AL, Murphy K, Hobden P, Evans J, Feilding A, Wise RG, Nutt DJ. Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin. Proc Natl Acad Sci U S A. 2012 Feb 7;109(6):2138-43. doi: 10.1073/pnas.1119598109. Epub 2012 Jan 23.

  PMID: 22308440 BACKGROUND

• Ching THW, Grazioplene R, Bohner C, Kichuk SA, DePalmer G, D'Amico E, Eilbott J, Jankovsky A, Burke M, Hokanson J, Martins B, Witherow C, Patel P, Amoroso L, Schaer H, Pittenger C, Kelmendi B. Safety, tolerability, and clinical and neural effects of single-dose psilocybin in obsessive-compulsive disorder: protocol for a randomized, double-blind, placebo-controlled, non-crossover trial. Front Psychiatry. 2023 Apr 25;14:1178529. doi: 10.3389/fpsyt.2023.1178529. eCollection 2023.

  PMID: 37181888 DERIVED

MeSH Terms

Conditions

Obsessive-Compulsive Disorder

Interventions

Psilocybin; Niacin

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; Nicotinic Acids; Acids, Heterocyclic; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Benjamin Kelmendi, MD

  Yale University

  PRINCIPAL INVESTIGATOR

• Christopher Pittenger, MD, PhD

  Yale University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Research Scientist

Model Details: In the study, half of the participants will be randomized to receive psilocybin (n=15) or the active-placebo-control, niacin (n=15). Following the first treatment session of either the active agent or active-placebo-control, participants who were randomized to receive active-placebo-control will be offered the option to receive open-label psilocybin. The blind will be broken at 48-hours to make this determination.

Study Record Dates

• First Submitted: November 6, 2017
• First Posted: November 29, 2017
• Study Start: November 13, 2018
• Primary Completion: July 25, 2024
• Study Completion: July 25, 2024
• Last Updated: November 20, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)