Effects of Psilocybin in Obsessive Compulsive Disorder

NCT05546658 | Active Not Recruiting Early Phase 1 DMC FDA Drug

• 1 other identifier: IRB00284207
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

This study will test the feasibility, safety, and evidence for efficacy of psilocybin administration in participants with obsessive compulsive disorder (OCD). This will serve as a preliminary proof of concept study for future larger studies aimed to investigate the utility, cognitive mechanisms, and neural correlates of this intervention.

Conditions

Obsessive-Compulsive Disorder

Keywords

Obsessive-Compulsive Disorder; Psilocybin

Outcome Measures

Primary Outcomes (4)

• Change in The Yale Brown Obsessive Compulsive Scale (Y-BOCS) score

  The 10 Y-BOCS items are each scored on a four-point scale from 0 = "no symptoms" to 4 = "extreme symptoms". The sum of the first five items is a severity index for obsessions, and the sum of the last five an index for compulsions. Total score is used as a measure of severity.

  1 week post session 1, 1 week post session 2

• State-Trait Anxiety Inventory (STAI)

  The State-Trait Anxiety Inventory -State Version (STAI-S) has 20 items on a 4-point scale. Responses for the S-Anxiety scale assess intensity of current feelings "at this moment": 1) not at all, 2) somewhat, 3) moderately so, and 4) very much so. Item scores are added to obtain subtest total scores. Scoring should be reversed for anxiety-absent items (19 items of the total 40). Range of scores for each subtest is 20-80, the higher score indicating greater anxiety.

  1 month post session 2

• Beck Depression Inventory II (BDI-II)

  The BDI-II is a self-report inventory of depressive symptoms, consisting of 21-items. Each of the 21 items corresponding to a symptom of depression is summed to give a single score for the Beck Depression Inventory-II (BDI-II). There is a four-point scale for each item ranging from 0 to 3. On two items (16 and 18) there are seven options to indicate either an increase or decrease of appetite and sleep. Higher scores indicate higher levels of depression.

  1 month post session 2

• Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q)

  The Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) is a 16-item self-report questionnaire that captures life satisfaction over the past week. Each question is scored on a 5-point scale from 1 (Very Poor) to 5 (Very Good) that indicates the degree of enjoyment or satisfaction achieved during the past week relative to the particular activity or feeling described in the item. Total score indicates higher quality of life.

  1 month post session 2

Study Arms (2)

Immediate Psilocybin

EXPERIMENTAL

This arm will receive two sessions of psilocybin first (20mg in first session and then, if well tolerated, 30mg).

Drug: Psilocybin

Delayed Psilocybin

ACTIVE COMPARATOR

Waitlist control. This arm will receive psilocybin after the waiting period is over (20mg in first session and then, if well tolerated, 30mg).

Drug: Psilocybin

Interventions

Psilocybin DRUG

Psilocybin administration under supportive conditions

Delayed Psilocybin; Immediate Psilocybin

Eligibility Criteria

• Age: 21 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have given written informed consent
• Currently meet criteria for a DSM-5 diagnosis of OCD and report a history of OCD for at least 1 year prior to screening
• Have a Y-BOCS score of 18 or more
• Have at least one prior attempt at treatment, either ERP or pharmacotherapy
• No antidepressant medications for approximately five half-lives prior to acceptance in treatment phase of study
• Women who are of childbearing potential and sexually active who are not practicing an effective means of birth control must agree to practice an effective means of birth control throughout the duration of the study
• Be judged by study team clinicians to be at low risk for suicidality
• Concurrent psychotherapy is allowed if the type and frequency of the therapy has been stable for at least two months prior to screening and is expected to remain stable during participation in the study
• Be otherwise medically stable as determined by screening for medical problems via a personal interview, a medical questionnaire, a physical examination, an electrocardiogram (ECG), and routine medical blood and urinalysis laboratory tests (CBC, CMP, urine beta-HCG, urine toxicology screen)
• Agree to consume approximately the same amount of caffeine-containing beverage (e.g., coffee, tea) that he/she consumes on a usual morning, before arriving at the research unit on the mornings of drug session days. If the participant does not routinely consume caffeinated beverages, he/she must agree not to do so on session days
• Agree to refrain from using any psychoactive drugs, including alcoholic beverages, within 24 hours of each drug administration. The exceptions are caffeine and nicotine
• Agree not to take any PRN medications on the mornings of drug sessions
• Agree not to take sildenafil (Viagra®), tadalafil, or similar medications within 72 hours of each drug administration
• Agree that for one week before each drug session, he/she will refrain from taking any nonprescription medication, nutritional supplement, or herbal supplement except when approved by the study investigators. Exceptions will be evaluated by the study investigators and will include acetaminophen, non-steroidal anti-inflammatory drugs, and common doses of vitamins and minerals.
• Have limited lifetime use of hallucinogens (the following criteria are preferred: no use in the past 5 years; total hallucinogen use less than 10 times)

You may not qualify if:

• Clinically significant transaminitis (AST or ALT greater than two times normal value)
• Women who are pregnant (as indicated by a positive urine pregnancy test assessed at intake and before each drug session) or nursing
• Women who are of childbearing potential and sexually active who are not practicing an effective means of birth control
• Cardiovascular conditions: coronary artery disease, stroke, angina, uncontrolled hypertension, a clinically significant ECG abnormality (e.g., atrial fibrillation), prolonged QTc interval (i.e., QTc \> 450 msec), heart valve, or transient ischemic attack (TIA) in the past year
• Epilepsy with history of seizures
• Type 1 diabetes
• BMI \< 18
• Currently taking on a regular (e.g., daily) basis any psychoactive prescription medication or any medications having a primary centrally-acting serotonergic effect, or MAOIs. For individuals who have intermittent or PRN use of such medications, psilocybin sessions will not be conducted until approximately five half-lives of the agent have elapsed after the last dose.
• Current (severe) migraine or other recurring severe headaches
• Current or past history of meeting DSM-5 criteria for schizophrenia spectrum or other psychotic disorders (except substance-/medication-induced or due to another medical condition), or bipolar I disorder
• Current or history within one year of meeting DSM-5 criteria for a moderate or severe alcohol, or other drug use disorder (excluding tobacco and caffeine)
• Nicotine dependence that would be incompatible with an individual to be nicotine free for 8-10 hours on a psilocybin session day
• Have a first degree relative with schizophrenia or other psychotic disorders (except substance/medication-induced or due to another medical condition), or bipolar I disorder

Sponsors & Collaborators

• Johns Hopkins University: lead
• Usona Institute: collaborator

Study Sites (1)

Johns Hopkins University School of Medicine

Baltimore, Maryland, 21224, United States

Location

Related Publications (15)

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• Guy, W. (1976). ECDEU assessment manual for psychopharmacology-revised (DHEW publ no ADM 76-338). rockville, MD, US department of health, education, and welfare. Public Health Service, Alcohol, Drug Abuse, and Mental Health Administration, NIMH Psychopharmacology Research Branch, Division of Extramural Research Programs, 1076, 534-537.

  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

• David B Yaden, PhD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Open-label, wait-list control, cross-over study

Study Record Dates

• First Submitted: September 15, 2022
• First Posted: September 21, 2022
• Study Start: November 28, 2022
• Primary Completion (Estimated): September 12, 2026
• Study Completion (Estimated): September 12, 2027
• Last Updated: April 2, 2026

Record last verified: 2026-04

Locations

US (1)