Efficacy of Psilocybin in OCD: a Double-Blind, Placebo-Controlled Study.
- Study HIC#:2000020355
- Last Updated:12/22/2022
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.
- Age21 years - 55 years
- Start Date09/13/2017
- End Date07/31/2023
Trial Purpose and 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 all assessment points.
Aim 2: To explore the relationship between the psilocybin-induced brain connectivity changes and neuronal activation following symptom provocation in OCD. Resting-state brain connectivity will be assessed before and 48 hours after treatment. Neuronal activation induced by OCD-relevant provocative stimuli will be assessed 48 hours after the treatment. Hypothesis: We hypothesize that (i) psilocybin will normalize abnormal fronto-striatal functional connectivity in patients with OCD; (ii) psilocybin will decrease activation of anterior cingulate cortices, amygdala, and putamen in response to symptom-provoking stimuli, and normalization of one or more 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.
- DSM-5 diagnosis of OCD established by a trained clinician interview and confirmed by Mini International Neuropsychiatric Interview MINI (edition 7).
- YBOCS score of 18 or greater at evaluation
- Patients must have failed at least one medication and/or therapy trial of standard care treatment for OCD.
- English speaking - able to understand the process of consent and the risk and benefits associated with the study, and able to give written informed consent
- Must be willing to sign a medical release for the investigators to communicate directly with their therapist and doctors to confirm a medication and/or medical history. This is decided on a case by case basis upon the discretion of the PI.
- Must be medically cleared by the PI or another medical doctor before they can drive home the morning after the experimental sessions, after the 48-hour post-session assessments. They can also be driven home by a driver arranged by the subject or by the site personnel or taxi.
- Has been off selective serotonin inhibitors for five half-lives of the drug plus 2 weeks.
- Must avoid starting a new psychiatric medication during the study. Should participant's doctor recommend starting a new psychiatric medication, participant will be required to notify the study team.
- Must provide a contact (relative, spouse, close friend or other caregiver) who is willing and able to be reached by the Clinical Investigators in the event of a participant becoming suicidal.
- Are willing to refrain from taking any psychiatric medications during the study period.
- Must have a negative pregnancy test at study entry and prior to each experimental session if able to bear children, and must agree to use adequate birth control
- Are willing to commit to medication dosing, experimental sessions, follow-up sessions, to complete evaluation
- Personal or immediate family history of schizophrenia, bipolar affective disorder, delusion disorder, paranoid disorder, or schizoaffective disorder.
- Active suicidal intent
- Unremitted Tourette syndrome
- Pervasive developmental disability
- Current substance abuse disorder (except in the case of mild alcohol use disorder).
- Anxiolytic, neuroleptic and SRI medications
- Unstable neurological or medical condition; history of seizure, chronic/severe headaches.
- Any contraindications to undergoing an MRI scan, including having metal implants or metal fragments in the body. With participants who may have been exposed to metal fragments and who wish to participate in the MRS scans, a plain film X-ray may be order to clarify their eligibility status. Women of childbearing potential who elected not to have the pregnancy test, will be excluded from MRI.
- Any history of head injury with loss of consciousness for more than 30 minutes
- Positive urine pregnancy test at the time of screening
- Any use of psychedelic drugs within the prior 12 months.
- Any unstable medical condition that my render study procedures unsafe.