Intervention: Salvinorin A
Trial phase: Phase 1 | Phase 2
SMILES: COC(=O)[C@@H]1C[C@H](OC(C)=O)C(=O)[C@H]2[C@@]1(C)CC[C@H]1C(=O)O[C@H](c3ccoc3)C[C@]21C
Sex: All
Age groups: Adult
Healthy volunteers: Accepts Healthy Volunteers
Participants at risk: 13
Group description: All volunteers will be assigned to the salvinorin A administration arm.

Salvinorin A: Salvinorin A, blinded doses
Eligibility criteria:
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)