This study will investigate the effects of salvinorin A on human brain activity and connectivity using functional magnetic resonance imaging (fMRI) methods. An inhalation route of administration will be used as it is the most common route for contemporary use of Salvia divinorum, a plant containing salvinorin A.

Volunteers will undergo two experimental sessions that include the inhalation of salvinorin A. The first session will be completed in a comfortable space furnished as a living room, and the second session will be conducted within a magnetic resonance imaging (MRI) scanner.

Inclusion Criteria:

• Have given written informed consent
• Have a high school level of education
• Have a history of hallucinogen use and experience with an inhaled psychoactive drug.
• Recent experience (within the past year) with an inhaled psychoactive drug.
• 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 volunteer 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 and any tobacco product such as cigarettes or any other nicotine product such as e-cigarettes, within 24 hours of each drug administration. Exceptions include daily use of caffeine.
• Be healthy and psychologically stable as determined by screening for medical problems via a personal interview, a medical questionnaire, a physical examination, and routine medical blood and urinalysis laboratory tests
• Agree that for one week before each session, he/she will refrain from taking any nonprescription medication, nutritional supplement, or herbal supplement except if 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
• Agree not to take any Pro-re-nata (PRN) prescription medications on the mornings of the sessions

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, or Transient Ischemic Attack (TIA) in the past year
• Seizure disorder or 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
• More than 25% outside the upper or lower range of ideal body weight
• Current or past history of meeting Diagnostic and Statistical Manual (DSM)-V criteria for schizophrenia, psychotic disorder (unless substance-induced or due to a medical condition), dissociative disorder, bipolar I or II disorder, an eating disorder
• Current or past history of substance-induced psychosis.
• Current or past history within the last 2 years of meeting DSM-5 criteria for moderate or severe alcohol or substance use disorder (excluding caffeine)
• Daily or more frequent tobacco or nicotine use
• Current severe obsessive-compulsive disorder, dysthymic disorder, or panic disorder.
• Current, severe, major depression
• Have a first or second degree relative with schizophrenia, psychotic disorder (unless substance induced or due to a medical condition), or bipolar I or II disorder
• Has a psychiatric condition judged to be incompatible with establishment of rapport or safe exposure to salvinorin A
• Head trauma, traumatic brain injury, or concussion with loss of consciousness for >2 minutes
• Claustrophobia incompatible with MRI scanning
• Medical device incompatible with MRI scanning (e.g. cardiac pacemaker, implanted cardiac defibrillator, aneurysm brain clip, inner ear implant)
• Prior history as a metal worker and/or certain metallic objects in the body -- must complete MRI screening form and be approved by MRI technologist before each scan
• Left-handedness (assessed by the Edinburgh Handedness Inventory)

1 month

Participants will not be aware of exact doses salvinorin A (i.e. they will be told they may receive placebo or up to a moderately high dose of of salvinorin A).