This Phase I, randomised, placebo-controlled, triple-masked, crossover design trial (n=60) will investigate the safety, tolerability, electrophysiological effects, and efficacy of dimethyltryptamine (DMT) in individuals with major depressive disorder (MDD) and healthy controls.
Phase I randomised, triple-masked crossover in 60 participants (MDD and healthy controls) with two dosing sessions separated by 4 weeks to compare low and medium IV DMT, low and medium IV THC, and placebo.
Primary aims are safety, tolerability and electrophysiological/neuroplastic effects measured with EEG and task-based measures; clinical measures include depressive symptom scales (HAMD) and other psychometrics.
Dosing involves IV bolus over 5 minutes followed by ~55-minute infusion (DMT: 10 mg + 0.01 mg/kg/min or 14 mg + 0.015 mg/kg/min). Subjects receive preparation and debriefing around each session.
10 mg IV bolus over 5 min then infusion 0.01 mg/kg/min for 55 min (low DMT).
10 mg bolus over 5 min then 0.01 mg/kg/min infusion for 55 min.
14 mg IV bolus over 5 min then infusion 0.015 mg/kg/min for 55 min (medium DMT).
14 mg bolus over 5 min then 0.015 mg/kg/min infusion for 55 min.
THC infusion: 0.5 mg over 5 min then 2 mg over 55 min (medium THC).
0.5 mg over 5 min then 2 mg over 55 min (THC), treated as non-listed active comparator; name/dose in notes.
Placebo infusion matching active infusions.
Saline/matching placebo infusion.
THC infusion: 0.1 mg bolus over 5 min then 1 mg over 55 min (low THC).
0.1 mg bolus over 5 min then 1 mg over 55 min (THC), treated as non-listed active comparator; name/dose in notes.