SPL026 (DMT Fumarate) in Healthy Subjects and MDD Patients

Inclusion Criteria: Normotensive male or female, deemed healthy on the basis of a clinical history, physicalexamination, ECG, vital signs, laboratory tests of blood and urine, Mini-InternationalNeuropsychiatric Interview (MINI) and Beck Scale for Suicidal Ideation (BSS); willing tofollow the contraception requirements of the trial; willing to refrain from psychedelicdrug use (excluding the study drug) during the trial and ≥ 3 months afterwards; willing tobe contacted by email and video call, and have online access; able to give fully informedwritten consent. Part A only: psychedelic-naïve, ie have never taken a serotonergicpsychedelic drug, in any form. Must be 25 years or older. Part B only: MDD diagnosis (asper DSM-V); not on antidepressant medication or willing to discontinue antidepressantmedication (eg selective serotonin reuptake inhibitor [SSRI] treatment) for a sufficienttime before and during the study; no psychedelic drug use in the 6 months before dosing.

Exclusion Criteria: Pre-menopausal females who are pregnant or lactating, or who are sexually active and notusing a reliable method of contraception; clinically relevant abnormal findings at thescreening assessment; acute or chronic illness (other than MDD [Part B only]) or infection;clinically relevant abnormal medical history or concurrent medical condition (other thanMDD [Part B only]); positive tests for hepatitis B & C, or HIV; severe adverse reaction toany drug; use of over-the-counter or prescribed medication (excluding oral contraceptives)within previous 28 days (paracetamol [acetaminophen] permitted up to 7 days, andantidepressant medication must have ceased for at least 14 days; 28 days for MOAIs) beforefirst dose of trial medication; drug or alcohol abuse; use of cannabis in the 24 h beforeeach study visit; heavy smokers (> 10 [Part A] or > 20 cigarettes [Part B] daily); supineblood pressure, heart rate, or QTcF outside the acceptable ranges; participation in otherclinical trials of unlicensed medicines, or loss of more than 400 mL blood, within theprevious 3 months; phobia of needles or blood; possibility that volunteer will notcooperate with the study.