Autobiographically meaningful music with psilocybin to shape set and setting

Inclusion Criteria:

* • Fluent in English

  * No hearing impairment
  * Right-handed
  * Have a screening weight ≥ 40 kg (88.18 lbs) with BMI ≥16.
  * Be medically stable as determined by screening for medical problems via a personal interview, a medical history, a physical examination, an electrocardiogram (ECG), and routine medical blood and urinalysis laboratory tests
  * 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 the research unit on the mornings of drug session days. If the participant does not routinely consume caffeinated beverages, he/she must agree not to do so on session days.
  * Agree to refrain from using any psychoactive drugs within 24 hours of each drug administration. The exceptions are caffeine and nicotine, which can be consumed before arriving for drug administration sessions.
  * 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 not to use any hair conditioner 24-hours before EEG sessions (Visits 3, 4, and 7)
  * Females of child-bearing potential must agree to use highly effective methods of contraception (defined as use of an intrauterine device, vaginal ring, or implanted or oral hormonal contraceptives) during the study
  * 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.
  * Have limited lifetime use of hallucinogens, if any (the following criteria are preferred: no use in the past 5 years; total hallucinogen use less than 10 times)
  * Proof of COVID-19 vaccination.

Exclusion Criteria:

* • Unusually low reward response to music (defined as a majority of responses of "1" on the BMRQ)

  * 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 highly effective means of contraception
  * Cardiovascular conditions: coronary artery disease, stroke, angina, uncontrolled hypertension, a clinically significant ECG abnormality (e.g., atrial fibrillation), prolonged corrected QT interval (QTc) interval (i.e., QTc \> 450 msec), artificial heart valve, or transient ischemic attack (TIA) in the past year
  * Insulin-dependent diabetes; if taking oral hypoglycemic agent, then no history of hypoglycemia
  * Currently taking psychoactive prescription medication on a regular (e.g., daily) basis - exceptions may be made at the discretion of the study team physician for participants taking medications with short half-life if participants are able to abstain from taking the medication during session days (e.g. methylphenidate taken for attention or hyperactivity)
  * Currently taking on a regular (e.g., daily) basis any medications that have a primary 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 5 half-lives of the agent have elapsed after the last dose.
  * Current or past history of meeting Diagnostic and Statistical Manual (DSM-5) criteria for schizophrenia spectrum or other psychotic disorders (except substance/medication-induced or due to another medical condition), or Bipolar I Disorder
  * Current or history within one year of meeting DSM-5 criteria for a moderate or severe substance use disorder. If a nicotine user, consuming the equivalent of more than 10 cigarettes per day.
  * Have a first-degree relative with schizophrenia spectrum or other psychotic disorders, or bipolar disorder with mania (except substance/medication-induced or due to another medical condition)
  * Has a psychiatric condition judged to be incompatible with establishment of rapport or safe exposure to psilocybin
  * History of a medically significant suicide attempt as assessed by a study team clinician
  * Standard MRI contraindications: head trauma, claustrophobia incompatible with scanning, contraindicated medical devices, prior history as a metal worker and/or certain metallic objects in the body -- must complete MRI screening form and be approved by MRI technologist before each scan
  * History of migraine.
  * History of angiotensin-converting enzyme inhibitor (ACEi) angioedema