Emerging evidence indicates that the endogenous neurotransmitter DMT exerts neuroprotective effects during acute ischemic stroke[1,2]. Additionally, DMT has demonstrated neuroplasticity stimulating effects in in vitro and in vivo rat studies[3,4]. Since neuroplasticity has been implicated in the mechanism of action of the physical therapy used in stroke recovery[5], a pharmacological augmentation strategy that facilitates neuroplasticity could be beneficial. Consequently, this study investigated the safety, pharmacokinetics and pharmacodynamics of a 6-hour intravenous DMT infusion.

DMT fumarate was administered intravenously in a randomized, double-blind, placebo-controlled, single ascending dose (30-second bolus + 6-hour infusion of 1.5mg + 0.105mg/min, 7.5mg + 0.525mg/min and 5.0mg + 0.7875mg/min) study to healthy subjects.

12 female and 17 male volunteers, aged 19-57 years, being both psychedelic experienced and inexperienced, were included. No SAEs or drop-outs occurred. All AEs were mild in intensity and self-limiting. No significant abnormalities in vital signs, 12-lead electrocardiography and physical examination were observed. No suicidality or significant psychiatric phenomena occurred.  PK demonstrated dose proportionality and high interindividual variability. Decreases in sustained attention, postural stability and (predominantly) occipital alpha EEG power were observed. Additionally, subjects reported moderate psychedelic effects on validated self-report instruments. Pharmacodynamic effects increased dose-dependently and mainly occurred at the highest dose, peaking rapidly after bolus administration and remaining at a relatively steady level.

Administration of a 6-hour intravenous DMT infusion to healthy volunteers was considered safe. Pharmacokinetics demonstrated dose proportionality, while pharmacodynamic effects increased dose dependently. Taken together, these results pave the way for future proof-of-concept studies with DMT in stroke patients.