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

Phase

Condition

Anxiety Disorders

Panic Disorders

Obsessive-compulsive Disorder

Treatment

Psilocybin

Clinical Study ID

NCT06299319

149-2021

Ages 18-65
All Genders

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

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 andcomprehension is sufficient for understanding the consent form and studyquestionnaires, 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 recordsand 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 ascore of ≥ 16 on the YBOCS (i.e. moderate symptom severity) and that have notresponded to two or more separate pharmacological interventions and one or moretrials of cognitive behavioural therapy (CBT); there is no upper limit on the numberof 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 clinicallaboratory tests at Screening (V1)
Ability to take oral medication;
Individuals who are capable of becoming pregnant: use of highly effectivecontraception for at least 1 month prior to screening and agreement to use such amethod during study participation;
Individuals who are willing to and have tapered off current OCD medications for aminimum of 2-weeks prior to Baseline (V2) and whose physician confirms that it issafe 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 dehydrogenaseinhibitors (ALDHs) and alcohol dehydrogenase inhibitors (ADHs) for a minimum of 2-weeks (or more depending on the medication) prior to Baseline (V2) and for theduration of the study and whose physician confirms that it is safe for them to doso; and
Agreement to adhere to Lifestyle Considerations (section 4.5) throughout studyduration.

Exclusion

Exclusion Criteria:

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 ofScreening (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 prescribedopioids 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 5of the C-SSRS;
Any DSM-5 lifetime diagnosis of a schizophrenia-spectrum disorder; psychoticdisorder (unless substance induced or due to a medical condition), bipolar I or IIdisorder, paranoid personality disorder, borderline personality disorder, orneurocognitive disorder as determined by medical history and the SCID-5 clinicalinterview;
Any first-degree relative with a diagnosis of schizophrenia-spectrum disorder;psychotic disorder (unless substance-induced or due to a medical condition); orbipolar I or II disorder as determined by the family medical history form anddiscussions with the participant;
Have contraindications to transcranial magnetic stimulation (TMS) as determined bythe transcranial magnetic stimulation adult safety screen (TASS) questionnaire;
Have a history of seizures;
Are taking anticonvulsants or benzodiazepines (Lorazepam up to 2mg/day isacceptable);
Presence of a relative or absolute contraindication to psilocybin, including a drugallergy, recent stroke history, uncontrolled hypertension, low or labile bloodpressure, recent myocardial infarction, cardiac arrhythmic, severe coronary arterydisease, 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 infectiousdiseases or any other major concurrent illness that, in the opinion of theinvestigator, may interfere with the interpretation of the study results orconstitute a health risk for the participant if they take part in the study.

Study Design

Psilocybin

September 01, 2024

October 31, 2025

Study Description

Literature suggests that up to 40 percent of individuals with OCD do not respond to conventional treatment and experience treatment resistant OCD (TROCD) (1, 2). Psilocybin, the chemical component of "magic mushrooms", has been administered with psychotherapy in several randomized clinical trials (RCTs) showing large and sustained antidepressant effects (3). Results of these trials have led to growing calls for transition to clinical use, as well as increased research for other mental health disorders. It is presumed that psilocybin's therapeutic effects are induced by the psychedelic "trip", which is dependent on serotonin 2A receptor (5-HT2AR) activation (4, 5). All studies have used psilocybin in conjunction with psychotherapy involving two therapists present during full-day dosing sessions. There is a need for more data in the TROCD population as there is only one clinical trial published for this specific population, followed by various case reports.

Using a proof-of-concept, open-label, clinical trial approach, 10 participants with TROCD will receive 2 doses of 25mg of psilocybin, with two weeks between each dosing day. The objectives of this study are as follows:

To assess the safety, and feasibility, of psilocybin, administered with psychological support to adult participants with TROCD. Hypothesis 1: The investigators will be able to recruit and retain ten participants with TROCD for the duration of the trial and that psychedelic-assisted psychotherapy for obsessive compulsive disorder (PAP-OCD) will be safe in those with TROCD, as measured by monitoring adverse events and using the Columbia Suicide Severity Rating Scale (C-SSRS).
To assess the clinical effects of PAP in those with TROCD. Hypothesis 2: Two sessions of psilocybin (25mg) administered under supportive conditions to participants with TROCD will lead to significant reductions in OCD symptoms as measured by the Yale-Brown Obsessive Compulsive Scale (YBOCS) when comparing baseline to Week 3.
Provide pilot data on the effect of psilocybin and supportive therapy on TROCD in preparation of a future larger RCT.

Overview of Study Design:

All 10 participants will follow the same study design. Each participant will undergo a screening assessment where they will complete lab tests, and clinical and psychiatric assessments to determine eligibility. Following the screening visit, participants will undergo a washout period where they will be tapered off concomitant medications over a medication the participant is being tapered off (based on the half-life of the medication) and the participant's preference for the length of the tapering period. All medications will require a minimum of a 2-week tapering period with the exception of fluoxetine which will require a minimum of 4-weeks. Additional time may be added at the discretion of the study investigator. During this period, there will be weekly check-ins with the study physician.

At study Visit 2 (Baseline, V2), participants will complete a series of questionnaires and assessments, preparatory therapy with trained study therapists, and undergo a brain functional magnetic resonance imaging (fMRI). The preparatory therapy sessions will build a therapeutic alliance, and provide psychoeducation about, and set intentions for, the psilocybin session. To reduce participant burden, baseline can be broken up into multiple days, however all assessments must be completed within 7-days of the first dose. At study Visit 3 (V3), neurophysiological measurements will be performed.

Upon completion of V2 and V3, participants will undergo the first psilocybin dosing session at Visit 4 (V4) where they will receive an active dose (25mg) of psilocybin in conjunction with supportive therapy. The psilocybin session will last 5 to 6 hours and will be conducted in the existing psychedelic treatment suite developed at the Centre for Addiction and Mental Health (CAMH). Two trained study therapists will be supporting each participant during the dosing session. After 5 hours of dose administration, participants will be evaluated for safety by the study psychiatrist and discharged home in the company of a caregiver or a family member.

On the day after the dosing session (Visit 5, V5) and one-week after the dosing session (Visit 6, V6), participants will be asked to complete the same questionnaires that were done at Baseline (V2) and will undergo an integrative therapy session with the trained study therapist. At Visit 7 (V7), 2-weeks after the first psilocybin dose, participants will undergo the second psilocybin dosing session where they will receive an active dose (25mg) of psilocybin in conjunction with supportive therapy.

On the day after the second dosing session (Visit 8, V8) and one-week after the second dosing session [3-weeks after dose 1] (Visit 10, V10), participants will be asked to complete the same questionnaires that were done at Baseline (V2) and will undergo an integrative therapy session with the trained study therapist. Between Visit 8 (V8) and Visit 10 (V10), during study Visit 9 (V9), the same neurophysiological measurements will be performed as during Visit 3 (V3). Follow-up assessments will also occur at 6, 9, and 12 weeks (Visit 11, 12, and 13) after the second psilocybin dosing session. The same questionnaires administered at Baseline (V2) will be repeated at each of these study visits.

Connect with a study center

Centre for Addiction and Mental Health
Toronto, Ontario M6J 1H1
Canada
Active - Recruiting

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