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Optimized infusion rates for N,N-dimethyltryptamine to achieve a target psychedelic intensity based on a modeling and simulation framework.

Emma Eckernäs, Jeroen Koomen, Christopher Timmermann, Robin Carhart-Harris, Daniel Röshammar, Michael Ashton

CPT: Pharmacometrics & Systems Pharmacology October 1, 2023 DOI: 10.1002/psp4.13037 (opens in new tab)

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AI-extracted from the abstract
Characteristics Pharmacokinetic/pharmacodynamic modeling and simulation study Peer reviewed
Dose 16 mg bolus followed by 1.4 mg/min infusion (continuous variable model); 14 mg bolus followed by 1.2 mg/min infusion (bounded integer models)
Topics 5-MeO-DMT DMT
Keywords Psychedelic-therapy DMT-Research Clinical-protocols Pharmacology Drug-dosing
Citations 1
Key points Optimal DMT infusion doses for target psychedelic intensity of 7-9 were a bolus of 14-16 mg followed by 1.2-1.4 mg/min, but the low proportion within target (below 53%) suggests individual dose adjustments are needed.

Abstract

N,N-dimethyltryptamine (DMT) is a psychedelic compound that is being studied as a therapeutic option in various psychiatric disorders. Due to its short half-life, continuous infusion of DMT has been proposed to extend the psychedelic experience and potential therapeutic effects. The primary aim of this work was to design an infusion protocol for DMT based on a desired level of psychedelic intensity using population pharmacokinetic/pharmacodynamic modeling. As a secondary aim, the impact of choosing a continuous variable or a bounded integer pharmacokinetic/pharmacodynamic model to inform such an infusion protocol was investigated. A previously published continuous variable model and two newly developed bounded integer models were used to assess optimal doses for achieving a target response. Simulations were performed to identify an optimal combination of a bolus dose and an infusion rate. Based on the simulations, optimal doses to achieve intensity ratings between 7 and 9 (possible range = 0-10) were a bolus dose of 16 mg DMT fumarate followed by an infusion rate of 1.4 mg/min based on the continuous variable model and 14 mg with 1.2 mg/min for the two bounded integer models. However, the proportion within target was low (<53%) for all models, indicating that individual dose adjustments would be necessary. Furthermore, some differences between the models were observed. The bounded integer models generally predicted lower proportions within a target of 7-9 with higher proportions exceeding target compared with the continuous variable model. However, results varied depending on target response with the major differences observed at the boundaries of the scale.

Comparable studies

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Study Year Design Participants
Short term changes in the proteome of human cerebral organoids induced by 5-MeO-DMT. Human cerebral organoids 2017 Experimental study
Bufo alvarius: a potent hallucinogen of animal origin. Bufo alvarius toad venom 1994 Experimental study
Prospective examination of synthetic 5-methoxy-N,N-dimethyltryptamine inhalation: effects on salivary IL-6, cortisol levels, affect, and non-judgment Volunteers 2019 Within-subjects experimental study n = 11
Unmasking of a neonatal somatovesical reflex in adult cats by the serotonin autoreceptor agonist 5-methoxy-N,N-dimethyltryptamine. Adult cats 1990 Experimental study n = 10
Studies on the Mechanism of Action of Monoamine Oxidase: Metabolism of N,N-Dimethyltryptamine and N,N-Dimethyltryptamine-N-Oxide 1962 Experimental study

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