Pharmacokinetics, pharmacodynamics and safety of N,N -dimethyltryptamine administered intravenously in healthy smoking and non-smoking volunteers
Katelijne V. van der Heijden, Soma Makai‐bölöni, Amir Inamdar, Marije E. Otto, Andrew P. Hegle, Liam Van der Aa, Rob G J A Zuiker, Román Bohoslavsky, Marieke L De Kam, Ellen James, Joop van Gerven, Gabriël E. Jacobs
Journal of Psychopharmacology August 31, 2026 DOI: 10.1177/02698811261473451 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial (single-ascending dose part) and open-label single-sequence two-period escalating dose study Placebo-controlled Double-blind Peer reviewed |
|---|---|
| Population | Healthy smokers (Part 1) and healthy non-smokers (Part 2) |
| Dose | 0.10, 0.20, 0.40, 0.81 mg/min (Part 1); 3.64 mg/min loading dose plus 0.81 or 1.29 mg/min infusion (Part 2) |
| Duration | 90-minute infusion (Part 1); 5-minute loading dose plus 55-minute infusion (Part 2) |
| Topics | 5-MeO-DMT DMT |
| Key findings | DMT produced mild to moderate psychedelic effects at plasma concentrations around 35 ng/mL, with no differences between smokers and non-smokers despite higher plasma levels in smokers. Pharmacokinetic variability was moderate, and adverse effects were mild to moderate and self-limiting. |
Abstract
Background: -dimethyltryptamine (DMT) might have therapeutic effects in various psychiatric disorders.
Aims: Prior to exploring this clinical potential, it is essential to determine an optimal administration regimen for DMT, explore the relationship between its pharmacokinetics (PK) and pharmacodynamics and identify potential sources of pharmacokinetic variability.
Methods: Therefore, DMT was administered as a 90-minute intravenous infusion (0.10, 0.20, 0.40 and 0.81 mg/min DMT) in a randomised, double-blind, placebo-controlled, single-ascending dose part in healthy smokers . Subsequently, DMT was administered as a 5-minute loading dose followed by a 55-minute infusion (3.64 mg/min + 0.81 mg/min and 3.64 mg/min + 1.29 mg/min) in an open-label, single-sequence two-period escalating dose study in healthy non-smokers. Outcome measures included PK of DMT and subjective, autonomic, neurophysiological and adverse effects.
Results: All adverse events were mild to moderate in intensity and self-limiting. Two subjects requested their infusion to be discontinued following the loading dose in Part 2 due to anxiety and intense effects. Moderate inter- and intra-individual pharmacokinetic variability was observed, while DMT plasma concentrations at similar infusion rates in smokers were roughly double that of non-smokers, probably due to mono-amine oxidase A-inhibiting compounds in cigarette smoke. Mild to moderate subjective psychedelic effects emerged at plasma concentrations of ~35 ng/mL in both parts, while only limited undesired effects such as sedation or impaired sustained attention occurred for DMT 0.81 ng/mL. Interestingly, no differences were noted in psychoactive effects between smokers and non-smokers.
Conclusion: These findings provide a basis for future studies exploring the (inter)relationships between DMT PK, different infusion regimens and subjective, neurophysiological and neuroendocrine effects resulting from 5-HT2A agonism.