Effects of Repeated Psilocybin Dosing in OCD

Inclusion Criteria:

1. Primary DSM-5 diagnosis of OCD, with Y-BOCS-II score of 26 or greater at screening

2. Failed at least one medication and/or therapy trial of standard care treatment forOCD

3. English fluency

4. Agree to sign a medical release for investigators to communicate directly withparticipants' providers to confirm medication and psychotherapy histories or arrangecontingencies in event of crises.

5. Agree to provide an adult contact (relative, spouse, close friend or othercaregiver) who is willing and able to be reached by the PI and/or study personnel inthe event of an emergency, and who can provide transportation for study visits andindependently comment on any changes in the participant's mood or behavior aftereach administration of psilocybin.

6. Agree to commit to all study procedures.

7. Ability to orally ingest pills for psilocybin dosing visits.

8. Agree to adhere to lifestyle and medication modifications.

9. Must not be on psychotropic medications for OCD or comorbid psychiatric conditionsfor at least 8 weeks at the time of randomization, and agree to refrain from takingor starting any psychiatric medications until after 4 weeks post-second dose.

10. Must not be in current psychotherapy (CBT or ERP) and must not start new course ofpsychotherapy (CBT or ERP) for OCD or comorbid psychiatric conditions until after 4weeks post-second dose.

11. If participant is of childbearing potential, must have a negative pregnancy test atstudy entry and prior to each dosing session.

12. If participant is of childbearing potential, agree to use adequate birth control andnot attempt to become pregnant during study up to 4 weeks post-second dose.

Exclusion Criteria:

1. Personal or immediate (first-degree relative) family history of formally diagnosedschizophrenia or other psychotic disorders, or bipolar I/II disorder

2. Lack of knowledge about biological families' medical history, due to adoption orother circumstance

3. Active suicidal intent or suicidal or non-suicidal self-injurious behaviors

4. Unremitted Tourette syndrome

5. Lifetime diagnosis of autism spectrum disorder

6. Current substance use disorder (except for mild alcohol use disorder)

7. Any neurological condition, including history of seizure(s) or chronic/severeheadaches

8. Any history of head injury with loss of consciousness for more than 30 min

9. Any use of classic psychedelic substances within the prior 12 months

10. Unwillingness to abstain from use of classic psychedelics outside of the study up to 4 weeks post-second dose.

11. Use of tobacco products or a THC-containing product more than 2 times per week onaverage over the past 30 days at screening.

12. Unwilingness or inability to abstain from use of tobacco or THC-containing productsfrom 1 week prior to randomization up to 4 weeks post-second dose.

13. Positive urine drug test for any prohibited substance at screening or days ofdosing, or positive breathalyzer test for alcohol on days of dosing

14. Unwillingness or inability to abstain from alcohol use at least 24 hours prior tothe days of dosing, up to 24 hours after each dosing day (or corresponding intervalsfor waitlist group).

15. Any medical conditions that may render study procedures unsafe, includinghypertension, history of cardiovascular disease, moderate-to-severe hepatic or renalimpairment, diabetes, and hypo- or hyperthyroidism.