Acute effects of intravenous DMT in a randomized placebo-controlled study in healthy participants.
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
Translational Psychiatry May 23, 2023 DOI: 10.1038/s41398-023-02477-4 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Placebo-controlled Double-blind Peer reviewed |
|---|---|
| Sample size | 27 |
| Population | Healthy participants with lifetime psychedelic use ≤20 times |
| Intervention | Intravenous DMT |
| Dose | 0.6 mg/min, 1 mg/min, 15 mg + 0.6 mg/min, 25 mg + 1 mg/min |
| Duration | 5-hour sessions, separated by at least 1 week |
| Topics | DMT |
| Keywords | Psychedelic medicine DMT Research Clinical trials Intravenous drug administration Psychopharmacology |
| Citations | 85 |
| Registration | NCT04353024 |
| Key findings | Intravenous DMT infusions produce a controllable, short-lasting psychedelic state with acute tolerance, making them suitable for tailored therapeutic sessions. |
Abstract
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 neurotropic 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 (t1/2α) of 5.0-5.8 min, followed by longer late elimination (t1/2β = 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.Trial registration: ClinicalTrials.gov identifier: NCT04353024.
Comparable studies
Other randomized controlled trials on 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 |
| DMT Models the Near-Death Experience Healthy participants | 2018 | Within-subjects placebo-controlled study | n = 13 |
| Human brain effects of DMT assessed via EEG-fMRI. Healthy volunteers | 2023 | Within-subjects, placebo-controlled design | n = 20 |
| 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 |
Citations in the library
Cited by 83
- Efficacy and safety of psychedelics for the treatment of mental disorders: A systematic review and meta-analysis. Psychiatry Research May 1, 2024
- Cardiovascular safety of psychedelic medicine: current status and future directions Pharmacological Reports October 24, 2023
- In vitro and in vivo metabolism of psilocybin’s active metabolite psilocin Frontiers in Pharmacology April 29, 2024
- Serotonergic Psychedelics: A Comparative Review of Efficacy, Safety, Pharmacokinetics, and Binding Profile Biological Psychiatry: Cognitive Neuroscience and Neuroimaging February 1, 2024
- Exploring DMT: Endogenous role and therapeutic potential. Neuropharmacology May 1, 2025
and 78 more in the library
Cites 29
- Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance Psychopharmacology July 7, 2006
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- Psychometric Evaluation of the Altered States of Consciousness Rating Scale (OAV) PLoS One August 31, 2010
- Validation of the revised Mystical Experience Questionnaire in experimental sessions with psilocybin Journal of Psychopharmacology October 6, 2015
- The Standardized Psychometric Assessment of Altered States of Consciousness (ASCs) in Humans Pharmacopsychiatry July 1, 1998
and 24 more in the library