Dose-dependent pharmacokinetics and acute effects of intravenous bolus N,N-dimethyltryptamine: double-blind, randomized versus open-label dose-escalation administration study in healthy participants
Livio Erne, Lorenz Mueller, Isabelle Straumann, Bislim Ademaj, Anne Eckert, Ina Vukalović, Jan Valenta, Dino Luethi, Matthias E. Liechti, Severin B Vogt
Translational Psychiatry March 27, 2026 DOI: 10.1038/s41398-026-03987-7 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Placebo-controlled Double-blind Open-label Peer reviewed |
|---|---|
| Sample size | 20 |
| Population | Healthy participants |
| Interventions | N N-dimethyltryptamine (DMT) |
| Dose | 5, 10, 15, and 20 mg; up to 25 mg in dose-escalation |
| Duration | Up to 55 min after each bolus administration |
| Topics | 5-MeO-DMT DMT |
| Keywords | Tolerability Pharmacokinetics Crossover study Placebo Bolus digestion Adverse effect Randomized controlled trial Blinding Anesthesia Randomization Ceiling effect |
| Key findings | A ceiling effect for peak subjective effects was reached at the 15 mg dose, and open-label dose-escalation improved tolerability compared with double-blind, randomized administration. |
Abstract
N,N-dimethyltryptamine (DMT) is a serotonergic psychedelic that produces short-lived peak effects when administered intravenously as a bolus dose. Initial trials suggested therapeutic effects of DMT in depressive disorders. However, systematic data on dose-dependent pharmacokinetics and acute effects of intravenous bolus DMT administration are currently lacking. We used a double-blind, randomized, placebo-controlled, crossover design in 20 healthy participants who received placebo and DMT (5, 10, 15, and 20 mg) within a single test session. In a separate study arm, we used an open-label, DMT dose-escalation administration design where 16 participants received stepwise increases of 5 mg DMT until reaching a maximally tolerated dose (max. 25 mg). Outcome measures included subjective effects, autonomic effects, adverse effects, and pharmacokinetics that were assessed up to 55 min after each bolus administration. Bolus DMT doses induced very strong subjective effects with a very rapid onset and peak within the first 2 min after administration. Subjective effects declined quickly and subsided completely within 12-30 min, consistent with the short elimination half-life of approximately 6-7 min. A ceiling effect for peak subjective effects was reached at the 15 mg dose. No tolerance was observed to acute effects of DMT. The tolerability markedly improved with open-label dose-escalation compared with double-blinded, randomized administration, and at equivalent dose levels, subjective effects were rated as less intense. These findings highlight the impact of blinding and expectancy on the subjective experience and suggest that individual dose-escalation may improve tolerability and help with dose selection for future DMT studies.
Comparable studies
Other randomized controlled trials on 5-MeO-DMT, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Dose-Response Study of N,N-Dimethyltryptamine in Humans Experienced hallucinogen users | 1994 | Double-blind, saline placebo-controlled, randomized study | n = 12 |
| Psychological Effects of (S)-Ketamine and N,N-Dimethyltryptamine (DMT): A Double-Blind, Cross-Over Study in Healthy Volunteers Healthy volunteers | 2005 | Double-blind crossover study | n = 9 |
| Differential tolerance to biological and subjective effects of four closely spaced doses of N,N-dimethyltryptamine in humans Experienced hallucinogen users | 1996 | Randomized controlled trial | n = 13 |
| Pharmacokinetics of N,N-dimethyltryptamine in Humans. Healthy adults | 2023 | Phase I component of a phase I/IIa randomised, double-blind, placebo-controlled, parallel-group, dose-escalation trial | n = 24 |
| Prepulse inhibition of the startle reflex and its attentional modulation in the human S-ketamine and N,N-dimethyltryptamine (DMT) models of psychosis Healthy volunteers | 2007 | Double-blind crossover study | n = 15 |
Citations in the library
Cites 33
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- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
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- Psychometric Evaluation of the Altered States of Consciousness Rating Scale (OAV) PLoS One August 31, 2010
- Psychedelics and the essential importance of context. Journal of Psychopharmacology February 15, 2018
and 28 more in the library