Safety, Pharmacokinetics, and Pharmacodynamics of a 6-h N,N-Dimethyltryptamine (DMT) Infusion in Healthy Volunteers: A Randomized, Double-Blind, Placebo-Controlled Trial.
Katelijne V. van der Heijden, Rob G J A Zuiker, Marije E. Otto, Christopher S Bryan, Nancy Stewart, Christopher Stillwell, Marieke L De Kam, Marloes B van Leuken, Joop van Gerven, Gabriël E. Jacobs
Clinical and Translational Science May 1, 2025 DOI: 10.1111/cts.70234 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized, double-blind, placebo-controlled, single ascending dose study Peer reviewed |
|---|---|
| Sample size | 29 |
| Population | Healthy volunteers (12 female, 17 male; mean age 27.3 years, range 19-57) |
| Intervention | DMT |
| Dose | 1.5 mg + 0.105 mg/min, 7.5 mg + 0.525 mg/min, and 5.0 mg + 0.7875 mg/min |
| Duration | Single session with 6-hour infusion; no follow-up period stated |
| Topics | 5-MeO-DMT Neuroplasticity DMT |
| Keywords | N,N‐Dimethyltryptamine Healthy volunteers Intravenousinfusion Pharmacodynamics Pharmacokinetics Safety Stroke Psychedelics DMT Hallucinogens Entheogens Human studies Neuroscience neuroplasticity Brain |
| Citations | 7 |
| Registration | NCT05559931 |
| Key points | Intravenous DMT given as a 30-s bolus plus 6-h infusion up to 35 ng/mL was safe, with only mild, self-limiting adverse events and no serious effects, supporting future studies in patient populations. |
Abstract
The serotonergic psychedelic N,N-dimethyltryptamine (DMT) presumably stimulates neuroplasticity in vitro and in vivo, by which it may exert neuroprotective effects during acute ischemic stroke. Since neuroplasticity has been implicated in the mechanism of action of rehabilitative therapy in stroke recovery, a pharmacological augmentation strategy facilitating neuroplasticity could be beneficial. To optimize this treatment strategy, a detailed understanding of the safety, pharmacokinetics, and pharmacodynamics of prolonged DMT administration is required. This randomized, double-blind, placebo-controlled, single ascending dose study administered three intravenous doses of DMT as a 30-s bolus followed by a 6-h infusion: 1.5 mg + 0.105 mg/min, 7.5 mg + 0.525 mg/min, and 5.0 mg + 0.7875 mg/min. Twelve female and seventeen male psychedelic-experienced and naïve healthy participants, with a mean age of 27.3 (SD 10.2, range 19-57) years, were included. No serious adverse events occurred, and all adverse events were mild in intensity and self-limiting. No significant abnormalities in vital signs or 12-lead electrocardiography, and no suicidality or treatment-emergent psychopathology occurred. Moderate interindividual pharmacokinetic variability was observed. Mild psychedelic effects were accompanied by decreases in sustained attention, postural stability, and occipital alpha electroencephalographic power at the highest dose, which peaked rapidly after bolus administration and remained relatively stable or decreased over time. Together, DMT administered intravenously as a 30-s bolus followed by a 6-h infusion and reaching maximal exposures of approximately 35 ng/mL in healthy volunteers was safe and demonstrated rapidly occurring but mild psychedelic effects, providing the basis for future proof-of-mechanism studies in patient populations. Trial Registration: ClinicalTrial.gov identifier: NCT05559931.
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
Cited by 5
- Predicting drug–drug interactions between ayahuasca alkaloids and SSRIs using physiologically based pharmacokinetic modeling Frontiers in Molecular Biosciences February 18, 2026
- Direct anti-inflammatory actions of N,N -dimethyltryptamine on microglia are revealed by proteomic profiling and receptor pharmacology bioRxiv (Cold Spring Harbor Laboratory) August 11, 2026
- Overcoming Pharmacokinetic and Peripheral Safety Challenges in Psychedelic Therapies: The Promise of Advanced Drug Delivery Systems. ACS Pharmacology & Translational Science June 12, 2026
- A systematic review of the pharmacokinetics of classical serotonergic psychedelic compounds in healthy adult subjects. Journal of Psychopharmacology May 29, 2026
- 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 Translational Psychiatry March 27, 2026
Cites 18
- Human hallucinogen research: guidelines for safety. Journal of Psychopharmacology July 1, 2008
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors Science February 16, 2023
- Psychedelics promote plasticity by directly binding to BDNF receptor TrkB Nature Neuroscience June 1, 2023
- The neural basis of psychedelic action. Nature Neuroscience October 24, 2022
and 13 more in the library