The Acute Effects of Psilocybin on Cognition, Memory, and Brain Function

Inclusion Criteria:

* 21 to 45-years-old.
* 3-30 lifetime psychedelic uses.
* English as a first language.
* High school education (or equivalent)
* Psychiatrically healthy (as assessed by the SCID-5).
* Medically healthy (as assessed by a physical examination and ECG).
* Willingness to attend all study sessions and complete all procedures.
* BMI between 19 and 30.

Exclusion Criteria:

* Current or past diagnosis of psychiatric disorders except panic attacks, depressive disorder, or anxiety, or disorder from ≥1 year prior.
* Current or past medical conditions that might interfere with study participation or be contraindicated for psilocybin administration (e.g., hypertension, history of stroke, cardiovascular disease, etc.)
* Current daily medications except birth control (females).
* Pregnant, nursing, or planning to become pregnant (assessed with urine pregnancy test).
* Ingestion of a psychedelic \<2 months prior to an experimental session (with the exception of psilocybin administered in the context of the current study's repeated measures design).
* History of serious adverse event with a psychedelic and/or self-reported hypersensitivity to psychedelics.
* Inability to abstain from alcohol 48 hours prior to an experimental session.
* Use of other psychoactive drugs (other than caffeine or nicotine) 1 week prior to an experimental session.
* Positive urine drug screening for drugs of abuse during experimental sessions.
* Self-reported ferrous metal, metallic implants, or implanted medical devices that would preclude participation in MRI procedures, including but not limited to cochlear implants, implanted brain stimulators, and aneurysm clips.
* Self-reported past penetrating brain injury or any head injury resulting in a loss of consciousness for 30 minutes or more or post-concussive symptoms for more than seven days following a head injury.
* Self-reported claustrophobia (prohibiting MRI acquisition).
* Any other factors such as unstable housing or life-threatening circumstances, erratic behavior, etc. that are judged by the investigators to be a significant barrier to participation in the study protocol and/or to establishing rapport necessary for safe administration of psilocybin.
* Participant unwillingness to not ingest or use additional serotonergic psychedelics outside the context of study procedures for the duration of the study.
* Resting blood pressure \>140/90 mm hg at study entry.
* Lifetime history of cardiomyopathy, stroke, heart disease, heart attack, tachycardia, elongated QT-interval corrected by Friderichia (\> 450ms for men and \> 470ms for women); clinically significant cardiac arrhythmia within 1 year of study entry; and/or abnormal electrocardiogram on study entry.
* Left-handedness (given that functional lateralizations may differ from those of right-handed individuals).