Effects of Psilocybin on Electrophysiology and the Dynamic Content of Thought

In this double-blind, placebo-controlled, within-subject, full cross-over study in healthy volunteers, computerized, electroencephalography (EEG), and magnetic resonance imaging (MRI) measures will be assessed to test the acute effects of a moderate dose of psilocybin (10 mg/70 kg) on creativity, the contents and dynamics of thought, memory, and shared vs individual brain response while viewing naturalistic stimuli. Understanding the acute psychological and neural effects of psychedelic drugs such as psilocybin may allow for future optimization of psychedelic medicine, as well as a deeper and more refined understanding of consciousness itself.

Inclusion criteria

• 18 to 75 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 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" 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 used a psychedelic drug (e.g. lysergic acid diethylamide(LSD)/acid, psilocybin mushrooms, ayahuasca) at least five times in their lifetime.
• Proof of COVID-19 vaccination

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 fibrilation), artificial heart valve, or heart attack in the past year
• Epilepsy with history of seizures
• 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
• Currently taking on a regular (e.g. daily) basis any medications having a primary centrally-acting serotonergic effect, including mono-amine oxidase inhibitors (MAOIs). For individuals who have intermittent or "as needed" 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
• Current or past history of meeting Diagnostic and Statistical Manual, version 5 (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 moderate or severe alcohol or drug use disorder (excluding caffeine and nicotine)
• Have a first or second-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
• Has history of migraine, tension, or other recurring headaches.
• Head trauma, traumatic brain injury, or concussion with loss of consciousness for >2 minutes
• Contraindications for magnetic resonance imaging (MRI) (e.g. claustrophobia incompatible with MRI scanning, medical device or implant incompatible with MRI, prior history as a metal worker and/or certain metallic objects in the body)
• Left-handedness (assessed by the Edinburgh Handedness Inventory)