Phase I safety and dose finding study of a standardized Ayahuasca analog (SM-001) in healthy adult volunteers

The Investigational New Drug SM-001 is formulated as a hot water decoction of two clonal cultivars of the Peruvian plants, Banisteriopsis caapi (BC) and Psychotria viridis (PV). It represents a modern formulation of an ancient Amazonian botanical medicine, "ayahuasca" ("vine of the soul") that is used by many native South American indigenous and mestizo groups for both religious and medicinal purposes.

This initial Phase 1 study is to be conducted as an open label, dose-ranging safety assessment of a single dose of SM-001 taken orally by healthy adult volunteers. Twelve adult men and women, ages 25-65 years, will be consecutively assigned to one of three dose levels, 4 subjects per group (2 M; 2 F). In the presence of the Clinical Investigator(s), each subject will receive a single dose of SM-001, administered at the Clinical Study Site as a liquid at one of three dose levels: 0.25, 0.5, or1.5 ml SM-001 per kg body weight. To assess systemic exposure to SM-001, plasma levels of the four biomarkers, dimethyltryptamine, harmine, tetrahydroharmine, and harmaline will be measured. Blood samples will be drawn at baseline, HR 0 (pre-Study Drug dose), and then at HR 1, 2, 4, 8, and 24 post dose. Subjects will return to the Clinical Study Site at Study Day 28 for a final in-person assessment.

Inclusion Criteria:

• Healthy adults: men and women ages 25-65 years of age
• Previous experience with a psychedelic drug
• Vital Signs within normal limits for temperature (oral), respiratory rate, heart rate
• Normal blood pressure (for age) in the absence of antihypertensive drugs
• Normal complete blood count and differential, platelets, coagulation ((PT/PTT)
• Liver function tests ≤ 1.5X upper limits of normal
• Renal function (BUN, serum Creatinine) - within normal limits
• Able to understand and willing to comply with Study Protocol requirements.
• Willing to abstain from alcohol for at least 72 hours prior to and following Study Day 0
• No use of recreational drugs for at least 14 days prior to Study Day 0.
• Women who are not pregnant or lactating.

Exclusion Criteria (None can apply):

• Body Mass Index > 30 or < 20
• Systemic condition that includes, but is not limited to: hematological, immunological, hepatic, renal, cardiac, neurological conditions that is under current treatment or causes abnormal physical or laboratory parameters.
• History of seizures
• History of drug or alcohol abuse
• History of psychiatric disorder or history of significant trauma, as defined by DSM- V.
• Use of SSRIs, MAO inhibitors, or other psychoactive compounds either pharmaceutical drugs or botanical in origin (i.e., 5-HTP, St John's Wort)
• Any condition which, in the opinion of the Investigators, would preclude the use of the test article or the successful completion of the study.