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

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

This study will test the effects of psilocybin on memory and cognition in healthy participants using computerized tasks and magnetic resonance imaging (MRI).

In a double-blind, placebo-controlled, repeated measures design in healthy participants, this study will test the effects of psilocybin on memory and cognition in healthy individuals using computerized tasks and magnetic resonance imaging (MRI). A better understanding of the basic neurocognitive effects of psilocybin may allow for minimizing potential harms and maximizing potential benefits of psilocybin therapy.

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).