Overview

The aim of this double-blind, placebo-controlled, within-subjects study is to determine whether other psychoactive substances can produce experiences akin to those seen with classic psychedelics. Screening involves a medical and psychiatric examination, including blood draw, history and physical, interviews, and questionnaires. Eligible participants will then be asked to complete up to 6 experimental drug administration session during which the participants will potentially receive and report on the subjective effects of 6 different psychoactive substances or inactive placebo. Drug assignment for some sessions will be randomized (like flipping a count or rolling a pair of dice), and both participants and study staff will be blind to the drug condition on any given day. Participants will also complete 2 preparation sessions (4 hours total) before the first experimental session, and follow-up visits after each session to discuss and debrief on the participants subjective experience.

Eligibility

Inclusion Criteria:

• Be 25 to 55 years old
• BMI between 18 and 34 kg/m2
• 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 subject does not usually consume caffeinated beverages, he or she must agree not to do so on session days
• Agree to refrain from using any psychoactive drugs, including alcoholic beverages, within 24 hours of each drug administration. Exceptions include daily use of caffeine and nicotine.
• Be healthy and psychologically stable as determined by screening for medical problems via a personal interview, a medical questionnaire, a physical examination, an electrocardiogram (ECG), and routine medical blood and urinalysis laboratory tests
• Agree not to take any PRN prescription medications on the mornings of the sessions unless deemed appropriate by study team.

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 (e.g. oral contraceptives, intrauterine device)
• Cardiovascular conditions-coronary artery disease, stroke, angina, uncontrolled hypertension, a clinically significant ECG abnormality (e.g., atrial fibrillation), or transient ischemic attack-that in the clinical opinion of the screening physician or mid-level provider would put the participant at an especially high risk for adverse effects from the study.
• 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 pharmacological effect on serotonin neurons or medications that are Monoamine oxidase (MAO) inhibitors. For individuals who have intermittent or as needed (PRN) use of such medications, sessions will not be conducted until at least 5 half-lives of the agent have elapsed after the last dose.
• Use of nonprescription medications, nutritional supplements, or herbal supplements 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
• History of meeting Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria for moderate or severe substance use disorder (including alcohol use disorder, but excluding tobacco), requiring that at least one of the endorsed criteria relates to prior loss of control of substance use (e.g. consuming the substance in larger amounts and for a longer amount of time than intended; persistent desire to cut down or regulate use; unsuccessful attempts to stop use; spending a great deal of time obtaining, using, or recovering from the effects of substance use).
• Active suicidal ideation and/or behavior at time of screening.
• Psychiatric disorder that in the clinical opinion of the study team would put the participant at an especially high risk for adverse effects from the study.
• First-degree relative who meets DSM-5 criteria for a Schizophrenia Spectrum or Other Psychotic Disorder (unless disorder is Substance/Medication-Induced Psychotic Disorder or Psychotic Disorder Due to Another Medical Condition), Bipolar I Disorder, or Bipolar II disorder.
• Enrolled in another clinical trial or have received any drug as part of a research study within 30 days prior to dosing.
• Known allergy or prior adverse reaction to any of the study drugs judged by the investigator and/or medical staff to put the study volunteer at greater risk.
• Known allergy or intolerance to nitroglycerin.
• Concomitant use of any CYP2C9 and CYP3A4 inhibitors.