This double-blind, randomized, placebo-controlled, crossover study (n=22) investigates the dose-dependent effects and pharmacokinetics of continuous intravenous DMT infusions over 120 minutes. It finds dose-proportional pharmacokinetics, a rapid onset of subjective effects that plateaus at 30 minutes, and a ceiling effect for positive effects at 1.8 mg/min. Higher doses (2.4 mg/min) induce anxiety and ego dissolution. Moderate acute tolerance and successful self-titration for desired effects were observed.

Abstract of Acute dose-dependent effects and self-guided titration of continuous DMT infusions

“N,N-dimethyltryptamine (DMT) is a serotonergic psychedelic that is known for its short-lasting effects when administered intravenously. Several studies have investigated the administration of intravenous boluses or combinations of a bolus and a subsequent continuous infusion. However, data on dose-dependent acute effects and pharmacokinetics of continuous DMT infusions are lacking. We used a double-blind, randomized, placebo-controlled, crossover design in 22 healthy participants (11 women, 11 men) who received placebo and DMT (0.6, 1.2, 1.8, and 2.4 mg/min) over an infusion duration of 120 min. We also tested a self-guided titration scheme that allowed participants to adjust the DMT dose rate at prespecified time points to achieve their desired level of subjective effects. Outcome measures included subjective effects, autonomic effects, adverse effects, plasma hormone concentrations, and pharmacokinetics up to 3 h after starting the infusion. DMT infusions exhibited dose-proportional pharmacokinetics and rapidly induced dose-dependent subjective effects that reached a plateau after 30 min. A ceiling effect was observed for “good drug effect” at 1.8 mg/min. The 2.4 mg/min dose of DMT induced greater anxious ego dissolution than the 1.8 mg/min dose and induced significant anxiety compared with placebo. We observed moderate acute tolerance to acute effects of DMT. In the self-guided titration session, the participants opted for moderate to strong psychedelic effects, comparable in intensity to the 1.8 mg/min DMT dose rate in the randomized dosing sessions. These results may assist with dose finding for future DMT research and demonstrate that acute subjective effects of DMT can be rapidly adjusted through dose titration.”

Authors: Livio Erne, Severin B. Vogt, Lorenz Müller, Albiona Nuraj, Anna Becker, Aaron Klaiber, Melani Zuparic, Nimmy Varghese, Anne Eckert, Deborah Rudin, Dino Luethi & Matthias E. Liechti

Summary of Acute dose-dependent effects and self-guided titration of continuous DMT infusions

This study investigates the acute dose-dependent effects of intravenous DMT administered via continuous infusion in healthy participants. DMT is a serotonergic psychedelic known for its intense psychoactive effects, which are primarily mediated by serotonin 5-HT2A receptor activation. Unlike oral administration, where DMT is rapidly metabolised by monoamine oxidase (MAO) enzymes, intravenous administration bypasses this metabolic breakdown, enabling systemic absorption and rapid onset of effects.

Previous studies explored combinations of intravenous boluses and continuous infusions, revealing that boluses often induced rapid and overwhelming effects, whereas continuous infusions produced more gradual, sustained experiences. This approach showed improved tolerability but left gaps in understanding dose-response relationships, pharmacokinetics, and subjective effects over extended infusion periods.

The authors aimed to address these gaps by examining different DMT infusion rates (0.6, 1.2, 1.8, and 2.4 mg/min) and incorporating a self-guided titration scheme to allow participants to adjust doses to desired subjective intensities. Key outcomes included subjective effects, autonomic responses, endocrine changes, adverse effects, and pharmacokinetics.

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Find this paper

Acute dose-dependent effects and self-guided titration of continuous N,N-dimethyltryptamine infusions in a double-blind placebo-controlled study in healthy participants

https://doi.org/10.1038/s41386-024-02041-8

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Cite this paper (APA)

Erne, L., Vogt, S. B., Müller, L., Nuraj, A., Becker, A., Klaiber, A., ... & Liechti, M. E. (2024). Acute dose-dependent effects and self-guided titration of continuous N, N-dimethyltryptamine infusions in a double-blind placebo-controlled study in healthy participants. Neuropsychopharmacology, 1-9.

Study details

Compounds studied
DMT

Topics studied
Healthy Subjects

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

Participants
22 Humans

Institutes

Institutes associated with this publication

University of Basel
The University of Basel Department of Biomedicine hosts the Liechti Lab research group, headed by Matthias Liechti.

Compound Details

The psychedelics given at which dose and how many times

DMT 72 - 288
mg | 1x

Linked Clinical Trial

Acute Dose-dependent Effects of DMT in Healthy Subjects: A Placebo-controlled Cross-over Study (DMT DR)
The present study is a modern randomized cross-over trial, investigating different continuous intravenous DMT dose rates over a broad dose range.

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