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

Intravenous DMT administered as a 30-second bolus followed by a 6-hour infusion, reaching peak blood concentrations around 35 ng/mL, is safe in healthy volunteers. No serious adverse events occurred; all side effects were mild and self-limiting. Vital signs, electrocardiography, and measures of suicidality or psychopathology showed no significant abnormalities. Mild psychedelic effects were accompanied by temporary decreases in sustained attention, postural stability, and occipital alpha brain wave power at the highest dose. Moderate variability in drug levels between individuals was observed. These findings support further testing of prolonged DMT infusion as a potential treatment to promote neuroplasticity in stroke recovery.

Study at a glance

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.