Safety, Pharmacokinetics, and Pharmacodynamics of a 6-h N,N-Dimethyltryptamine (DMT) Infusion in Healthy Volunteers: A Randomized, Double-Blind, Placebo-Controlled Trial

This randomised, double-blind, placebo-controlled single ascending dose study (n=29) tested prolonged intravenous DMT administration (30-s bolus (1.5-7.5mg) + 6-h infusion (4.4-33.3nl/ml)) in healthy volunteers. It found the treatment to be safe, with only mild, self-limiting adverse events, and observed mild psychedelic effects, reduced attention and stability, and decreased occipital alpha EEG power at higher doses, supporting further investigation in stroke recovery contexts.

Abstract of Safety, Pharmacokinetics, and Pharmacodynamics of a 6-h DMT Infusion in Healthy Volunteer

“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.”

Authors: 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 M. A. van Gerven & Gabriel E. Jacobs

Summary of Safety, Pharmacokinetics, and Pharmacodynamics of a 6-h DMT Infusion in Healthy Volunteer

Stroke remains the second leading cause of death worldwide and one of the main drivers of long‑term disability; roughly four in five survivors experience upper‑limb weakness that limits everyday activities. Current rehabilitation relies on stimulating neuroplasticity—the brain’s ability to re‑wire and form new connections—within a “critical period” that peaks during the first three months after the event. Pre‑clinical and human data indicate that serotonergic psychedelics can amplify this plastic window by activating the 5‑HT2A receptor and the sigma‑1 receptor, thereby promoting dendrite growth and synaptogenesis. Yet full psychedelic doses of agents such as LSD or DMT also trigger perceptual and cognitive disturbances that would interfere with stroke therapy. Consequently, van der Heijden and colleagues set out to test whether a sub‑psychedelic intravenous regimen of DMT can be delivered safely for six hours, while maintaining steady plasma levels under the putative 35–45 ng ml-1 “psychedelic threshold”. The primary objectives were to characterise safety, pharmacokinetics (how the body handles the drug), and pharmacodynamics (how the drug affects the body) in healthy volunteers, laying the groundwork for future stroke studies.

Methods

Study design

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Study details

Compounds studied
DMT

Topics studied
Neurocognitive Disorders Healthy Subjects

Study characteristics
Original Placebo-Controlled Double-Blind Within-Subject Randomized

Participants
29 Humans

Institutes

Institutes associated with this publication

Algernon Pharmaceuticals
Algernon is a clinical stage pharmaceutical company that is developing novel psychedelic molecules (based on DMT) for the treatment of stroke-related dysfunction.

Compound Details

The psychedelics given at which dose and how many times

DMT 1.5 - 7.5
mg | 3x

Linked Clinical Trial

Single and Repeat Doses of DMT in Healthy Subjects
This double-blind trial (n=60) by Algernon Pharmaceuticals will give participants several 6-hour (you read that right) infusions of DMT. The first part will start with a 1.5mg bolus followed by 6.3mg (0.105mg p/m) each hour. If read correctly, the second part of the study will do six doses over six hours but doesn't specify if a continuous infusion will also be given.

PDF of Safety, Pharmacokinetics, and Pharmacodynamics of a 6-h N,N-Dimethyltryptamine (DMT) Infusion in Healthy Volunteers: A Randomized, Double-Blind, Placebo-Controlled Trial