Inclusion Criteria:
* 21 to 60 years old
* Have given written informed consent
* Have at least a high-school level of education or equivalent (e.g. GED) and be fluent in English
* Be healthy and psychologically stable as determined by screening for medical and psychiatric problems via a personal interview, a medical questionnaire, a physical examination, an electrocardiogram (ECG), and routine medical blood and urinalysis laboratory tests
* Agree to refrain from using any psychoactive drugs, including alcoholic beverages and nicotine, within 24 hours of each drug administration. The exception is caffeine.
* Agree not to take any as needed (PRN) medications on the mornings of drug sessions
* Agree not to take sildenafil (Viagra®), tadalafil, or similar medications within 72 hours of each drug administration.
* Agree that for one week before each drug session, he/she will refrain from taking any nonprescription medication, nutritional supplement, or herbal supplement except when approved by the study investigators. Exceptions will be evaluated by the study investigators and will include acetaminophen, non-steroidal anti-inflammatory drugs, and common doses of vitamins and minerals.
* Licensed to drive (for driving simulator test).
Exclusion Criteria:
* Women who are pregnant (as indicated by a positive urine pregnancy test assessed at intake and before each drug session) or nursing; women who are of child-bearing potential and sexually active who are not practicing an effective means of birth control.
* Cardiovascular conditions: coronary artery disease, stroke, angina, uncontrolled hypertension, a clinically significant ECG abnormality (e.g. atrial fibrillation, corrected QT interval (QTc) \> 450 msec), artificial heart valve, or transient ischemic attack (TIA) in the past year
* Epilepsy
* Insulin-dependent diabetes; if taking oral hypoglycemic agent, then no history of hypoglycemia
* Currently taking psychoactive drugs (prescribed or not) on a daily basis. This includes nicotine but excepts caffeine.
* Currently taking on a regular (e.g. daily) basis any medications having a centrally-acting serotonergic effect, including monoamine oxidase inhibitors (MAOIs). For individuals who have intermittent or PRN use of such medications, psilocybin sessions will not be conducted until at least five half-lives of the agent have elapsed after the last dose.
* More than 20% outside the upper or lower range of ideal body weight according to Metropolitan Life height and weight table
* History of schizophrenia spectrum disorder
* History of bipolar I disorder
* History of substance induced psychotic disorder
* Current history of meeting Diagnostic and Statistical Manual (DSM)-5 criteria for a moderate or severe alcohol or drug use disorder (excluding caffeine and nicotine)
* Have a first degree relative with bipolar I disorder, or schizophrenia spectrum disorder.
Cardiovascular screening: To qualify for the study, blood pressure at screening will be less than 130 mmHg systolic, 80 mmHg diastolic, and 90 beats per minute; mean heart rate must also be no less than 40 beats per minute. Blood pressure will be taken while subjects are at rest and have been seated or supine for at least 5 minutes.
