Psilocybin for Amblyopia - Targeting Critical Periods in Humans

Inclusion Criteria:

* 18 to 65 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, medical history and physical examination, an electrocardiogram (ECG), and routine medical blood and urinalysis laboratory tests
* Women who are of child-bearing potential and sexually active agree to use highly effective means of birth control (i.e. implants, injectables, combined oral contraceptives, progestin-containing intrauterine device (IUD) or vasectomized partner) for the duration of this study
* 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 morning of the drug session day. If the participant does not routinely consume caffeinated beverages, he/she must agree not to do so on the session day.
* 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.
* Have a clinical diagnosis of amblyopia, with best-corrected visual acuity in the range of 0.2 - 1.0 LogMAR (approximately equivalent to 20/30 to 20/200)
* Has undergone an eye exam and prescription assessment within a recent period
* Has been wearing current spectacle correction for a minimum of six weeks prior to enrollment

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 highly effective means of birth control (i.e. those that result in \<1% failure rate per year; note that condoms alone are not considered highly effective)
* Cardiovascular conditions: coronary artery disease, stroke, angina, uncontrolled hypertension, a clinically significant ECG abnormality (e.g. atrial fibrillation), artificial heart valve, or transient ischemic attack (TIA) in the past year
* Epilepsy with history of seizures
* Insulin-dependent diabetes; if taking oral hypoglycemic agent, then no history of hypoglycemia
* Currently taking on a regular (e.g. daily) basis any medications having a primary centrally-acting serotonergic effect, including monoamine oxidase inhibitor (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.
* Current or past history of meeting DSM-5 criteria for schizophrenia spectrum or other psychotic disorders (except substance/medication-induced or due to another medical condition)
* Current or past history within the last five years of meeting DSM-5 criteria for a severe alcohol or drug use disorder (excluding caffeine and nicotine)
* Have a first-degree relative with bipolar I disorder, schizophrenia spectrum, or other psychotic disorders (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
* Explanation for visual acuity loss other than amblyopia, including cataracts, corneal disease, optic neuropathy, retinopathy, glaucoma, history of eye trauma or intraocular surgery, or any other ocular pathology as determined by study ophthalmologist