Effects of Psilocybin in Obsessive Compulsive Disorder

Inclusion Criteria:

• Have given written informed consent

• Currently meet criteria for a DSM-5 diagnosis of OCD and report a history of OCD forat least 1 year prior to screening

• Have a Y-BOCS score of 18 or more

• Have at least one prior attempt at treatment, either ERP or pharmacotherapy

• No antidepressant medications for approximately five half-lives prior to acceptancein treatment phase of study

• Women who are of childbearing potential and sexually active who are not practicingan effective means of birth control must agree to practice an effective means ofbirth control throughout the duration of the study

• Be judged by study team clinicians to be at low risk for suicidality

• Concurrent psychotherapy is allowed if the type and frequency of the therapy hasbeen stable for at least two months prior to screening and is expected to remainstable during participation in the study

• Be otherwise medically stable as determined by screening for medical problems via apersonal interview, a medical questionnaire, a physical examination, anelectrocardiogram (ECG), and routine medical blood and urinalysis laboratory tests (CBC, CMP, urine beta-HCG, urine toxicology screen)

• Agree to consume approximately the same amount of caffeine-containing beverage (e.g., coffee, tea) that he/she consumes on a usual morning, before arriving at theresearch unit on the mornings of drug session days. If the participant does notroutinely consume caffeinated beverages, he/she must agree not to do so on sessiondays

• Agree to refrain from using any psychoactive drugs, including alcoholic beverages,within 24 hours of each drug administration. The exceptions are caffeine andnicotine

• Agree not to take any PRN medications on the mornings of drug sessions

• Agree not to take sildenafil (Viagra®), tadalafil, or similar medications within 72hours of each drug administration

• Agree that for one week before each drug session, he/she will refrain from takingany nonprescription medication, nutritional supplement, or herbal supplement exceptwhen approved by the study investigators. Exceptions will be evaluated by the studyinvestigators and will include acetaminophen, non-steroidal anti-inflammatory drugs,and common doses of vitamins and minerals.

• Have limited lifetime use of hallucinogens (the following criteria are preferred: nouse in the past 5 years; total hallucinogen use less than 10 times)

Exclusion Criteria:

• Clinically significant transaminitis (AST or ALT greater than two times normalvalue)

• Women who are pregnant (as indicated by a positive urine pregnancy test assessed atintake and before each drug session) or nursing

• Women who are of childbearing potential and sexually active who are not practicingan effective means of birth control

• Cardiovascular conditions: coronary artery disease, stroke, angina, uncontrolledhypertension, a clinically significant ECG abnormality (e.g., atrial fibrillation),prolonged QTc interval (i.e., QTc > 450 msec), heart valve, or transient ischemicattack (TIA) in the past year

• Epilepsy with history of seizures

• Type 1 diabetes

• BMI < 18

• Currently taking on a regular (e.g., daily) basis any psychoactive prescriptionmedication or any medications having a primary centrally-acting serotonergic effect,or MAOIs. For individuals who have intermittent or PRN use of such medications,psilocybin sessions will not be conducted until approximately five half-lives of theagent have elapsed after the last dose.

• Current (severe) migraine or other recurring severe headaches

• Current or past history of meeting DSM-5 criteria for schizophrenia spectrum orother psychotic disorders (except substance-/medication-induced or due to anothermedical condition), or bipolar I disorder

• Current or history within one year of meeting DSM-5 criteria for a moderate orsevere alcohol, or other drug use disorder (excluding tobacco and caffeine)

• Nicotine dependence that would be incompatible with an individual to be nicotinefree for 8-10 hours on a psilocybin session day

• Have a first degree relative with schizophrenia or other psychotic disorders (exceptsubstance/medication-induced or due to another medical condition), or bipolar Idisorder