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

Yale University

Status and phase: Active, not recruiting; Phase 1

Conditions: Obsessive-Compulsive Disorder

Treatments: Drug: Psilocybin (0.25mg/kg); Drug: Niacin (250mg)

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT03356483

1K23MH122777-01A1 (U.S. NIH Grant/Contract)

2000020355

Details and patient eligibility

About

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.

Full description

Aim 1: To investigate the effects of psilocybin on OCD symptomatology. OCD symptom severity will be assessed before treatment and 24 and 48 hours after treatment, one week after treatment, two weeks, one month, and three months after treatment. Hypothesis: We hypothesize that 0.25mg/kg of psilocybin will lead to greater symptom improvement than niacin (as the active-placebo-control agent) at the primary endpoint of 48 hours post-dosing and at all other assessment points.

Aim 2: To explore the relationship between the psilocybin-induced brain connectivity changes and symptom change in OCD. Resting-state brain connectivity will be assessed before and 48 hours after treatment. Hypothesis: We hypothesize that (i) psilocybin will normalize abnormal fronto-striatal functional connectivity in patients with OCD; and (ii) normalization of these abnormalities will correlate with improvement in symptomatology after psilocybin treatment.

This study will pilot a single-center, randomized, active-placebo-controlled, double-blind design to examine the clinical and neural effects on OCD, of either 0.25mg/kg of psilocybin or active placebo-control agent (niacin 250mg), given along with non-drug preparatory and follow-up support appointments to 30 study participants. The duration of the randomized study phase is from consent until two weeks after drug administration. Participants will be followed for 12 weeks (3 months) post-study drug administration.

Eligible participants will be admitted as an inpatient for at least 3 nights / 4 days surrounding the initial drug administration (or more, at the option of the subject and the investigator). Participants will be randomized into active medication and active-placebo-control groups, and will be blinded as to their study condition. This admission 2 nights prior to the drug administration will allow the participant to adjust to sleeping on the unit and allow them to settle in to the research unit routine. A return for an fMRI scan (48 hours after the administration session) will be scheduled. The participants who received active-placebo-control will be offered the option to receive open-label psilocybin.

Enrollment: 31 patients

Sex: All

Ages: 21 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Primary DSM-5 diagnosis of OCD
2. Y-BOCS score of 19 or greater
3. Failure of at least one trial of standard care treatment (medication and/or psychotherapy [CBT/ERP]) for OCD
4. English proficiency and fluency, and ability to understand the consent process and provide written informed consent
5. Willingness to sign a medical release for direct communication between research staff and external provider(s) about the participant's treatment and medical histories
6. Non-consumption of SSRIs for at least 8 weeks at the time of randomization
7. 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
8. 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.
9. 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
10. 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
11. 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

Exclusion criteria

1. Personal or immediate family history of schizophrenia spectrum and other psychotic disorders, bipolar I or II disorder, or major depressive disorder with psychotic features
2. Active suicidal intent
3. Unremitted Tourette syndrome
4. Autism spectrum disorder
5. OCPD or BPD
6. Current substance use disorder (except mild alcohol use disorder)
7. 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
8. Any history of head injury with loss of consciousness for more than 30 minutes
9. Any contraindications to undergoing an MRI scan, including having metal implants or metal fragments in the body
10. Any use of psychedelic substances within the prior 12 months

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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31 participants in 2 patient groups, including a placebo group

Psilocybin

Experimental group

Description:

Psilocybin (0.25mg/kg)

Treatment:

Drug: Psilocybin (0.25mg/kg)

Niacin

Placebo Comparator group

Description:

Niacin (250mg)

Treatment:

Drug: Niacin (250mg)