This randomised, placebo-controlled, quadruple-masked trial (n=112) will investigate whether the antidepressant effects of DMT (2 mg/min over 20 minutes; total ~40 mg) in patients with MDD depend on the subjective psychedelic experience by comparing DMT vs placebo under propofol sedation or no sedation.
This 2x2 factorial randomized trial compares DMT infusion to placebo, each administered with or without propofol sedation, to determine whether antidepressant effects require the subjective psychedelic experience.
Outcomes include depressive symptom change (MADRS), measures of neuroplasticity and inflammation, safety and adverse events; participants receive a single 20-minute infusion (2 mg/min) with follow-up assessments.
DMT infusion without propofol sedation
2 mg/min infusion over 20 min (total 40 mg)
no sedation
DMT infusion with propofol sedation
2 mg/min infusion over 20 min (total 40 mg)
Propofol sedation ~30 min
Placebo infusion without propofol
Placebo perfusion over 20 min
no sedation
Placebo infusion with propofol sedation
Placebo perfusion over 20 min
Propofol sedation ~30 min