Acute effects of intravenous DMT in a randomized placebo-controlled study in healthy participants

This double-blind, placebo-controlled crossover study (n=27) investigated different intravenous DMT administration regimens, including placebo, low and high infusion (0.6-1mg/min), and bolus doses (15-25mg) combined with low and high infusion. The study found that bolus doses rapidly induced intense psychedelic effects, with infusions causing slowly increasing, dose-dependent effects. Despite the plasma concentrations of DMT increasing over time, the subjective effects experienced by individuals remained consistent from 30 to 90 minutes. This suggests that there is acute tolerance to the continuous administration of DMT. Both bolus doses produced more negative subjective effects and anxiety than infusions, and all effects rapidly subsided within 15 minutes after stopping the infusion.

Abstract of Acute effects of IV DMT in an RCT in healthy participants

“N,N-dimethyltryptamine (DMT) is distinct among classic serotonergic psychedelics because of its short-lasting effects when administered intravenously. Despite growing interest in the experimental and therapeutic use of intravenous DMT, data are lacking on its clinical pharmacology. We conducted a double-blind, randomized, placebo-controlled crossover trial in 27 healthy participants to test different intravenous DMT administration regimens: placebo, low infusion (0.6 mg/min), high infusion (1 mg/min), low bolus + low infusion (15 mg + 0.6 mg/min), and high bolus + high infusion (25 mg + 1 mg/min). Study sessions lasted for 5 h and were separated by at least 1 week. Participant’s lifetime use of psychedelics was ≤20 times. Outcome measures included subjective, autonomic, and adverse effects, pharmacokinetics of DMT, and plasma levels of brain-derived nvogteurotropic factor (BDNF) and oxytocin. Low (15 mg) and high (25 mg) DMT bolus doses rapidly induced very intense psychedelic effects that peaked within 2 min. DMT infusions (0.6 or 1 mg/min) without a bolus induced slowly increasing and dose-dependent psychedelic effects that reached plateaus after 30 min. Both bolus doses produced more negative subjective effects and anxiety than infusions. After stopping the infusion, all drug effects rapidly decreased and completely subsided within 15 min, consistent with a short early plasma elimination half-life (t_1/2α) of 5.0–5.8 min, followed by longer late elimination (t_1/2β = 14–16 min) after 15–20 min. Subjective effects of DMT were stable from 30 to 90 min, despite further increasing plasma concentrations, thus indicating acute tolerance to continuous DMT administration. Intravenous DMT, particularly when administered as an infusion, is a promising tool for the controlled induction of a psychedelic state that can be tailored to the specific needs of patients and therapeutic sessions.”

Authors: Severin B. Vogt, Laura Ley, Livio Erne, Isabelle Straumann, Anna M. Becker, Aaron Klaiber, Friederike Holze, Anja Vandersmissen, Lorenz Mueller, Urs Duthaler, Deborah Rudin, Dino Luethi, Nimmy Varghese, Anne Eckert & Matthias E. Liechti

Summary of Acute effects of IV DMT in an RCT in healthy participants