Psilocybin for Treatment of Obsessive Compulsive Disorder

The study seeks to improve our ability to treat and improve the lives of people who have
obsessive-compulsive disorder (OCD) by exploring the benefits of psilocybin, a mind-altering
drug that changes activity in brain areas believed to be involved in OCD. Anecdotal reports
and results from previous research support this idea. This two-phase study will enroll
patients with symptomatic OCD who are not taking mind-altering medications or street drugs.

During Phase One, neither participants nor the investigators will know which drugs or doses
are administered. This information will be available if it is medically necessary to reveal
which drugs and doses were administered. Five subjects in each group will receive study drug
a total of four times, separated by one week. During Phase Two, participants will not know
which drugs or doses they receive, but the investigators will know. All participants will
receive psilocybin at some point during study participation.

Participants will be randomly assigned to one of the following groups:

1. Low dose (100 µg/kg) psilocybin,

2. High dose (300 µg/kg) psilocybin, or

3. Lorazepam (1 mg), a calming medication. Lorazepam is used often for anxiety and will be
used to mask which drug participants receive.

Participants will spend approximately 12 hours at the research site under observation during
each visit, until they are free of the mind-altering effects of the drug and are determined
by the psychiatrist to be safe to go home accompanied by a responsible adult. The effects of
low versus high doses, and the additive effects of repeated doses will be analyzed and will
be compared to the effects of lorazepam.

Inclusion Criteria:

- Have moderate to severe OCD (DSM-5) after diagnostic interview using the Structured
Clinical Interview for DSM-5 Research Version (SCID-R).

- Failed at least one adequate attempted routine care treatment.

- Considered safe for independent living

Exclusion Criteria:

- Concurrent psychosis, active substance use disorder, or a personal history of
psychosis.

- Medical illness based on physical examination and routine blood testing that may
complicate cardiovascular safety or drug metabolism or excretion, such as uncontrolled
hypertension, severe cardiac disease, or kidney or liver failure.

- Unstable Chronic Obstructive Pulmonary Disease (COPD) or severe sleep apnea

- Psychiatric comorbidity that may represent an acute risk to their own or others'
safety.

- Subjects may not be using antidepressant medication for OCD for at least two weeks
before receiving study drug, and they cannot require any sedative, narcotic, or
neuroleptic medications on a regular basis. Any of these medications they have taken
should have been stopped long enough in the past to allow for their elimination and
safe withdrawal prior to starting administration of the study drug. The specific time
required will be dependent on the medication the patient was previously receiving.

- Women who are pregnant, breastfeeding, or unwilling/unable to practice medically
acceptable birth control during the study.

- Allergy to lorazepam.