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:

Low dose (100 µg/kg) psilocybin, High dose (300 µg/kg) psilocybin, or 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.