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N,N‐dimethyltryptamine affects electroencephalography response in a concentration‐dependent manner—A pharmacokinetic/pharmacodynamic analysis

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

CPT: Pharmacometrics & Systems Pharmacology February 10, 2023 DOI: 10.1002/psp4.12933 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Population pharmacokinetic/pharmacodynamic analysis Peer reviewed
Sample size 13
Population Healthy subjects
Intervention DMT
Dose intravenous bolus dose
Topics DMT 5-MeO-DMT
Keywords Psychedelics Brain waves Consciousness research
Citations 15
Key points DMT fully suppresses alpha power, partially suppresses beta power, and increases Lempel-Ziv complexity, with alpha suppression being the most consistent response across individuals.

Abstract

Abstract N,N‐dimethyltryptamine (DMT) is a psychedelic substance and is being used as a research tool in investigations of the neurobiology behind the human consciousness using different brain imaging techniques. The effects of psychedelics have commonly been studied using electroencephalography (EEG) and have been shown to produce suppression of alpha power and increase in signal diversity. However, the relationship between DMT exposure and its EEG effects has never been quantified. In this work, a population pharmacokinetic/pharmacodynamic analysis was performed investigating the relationship between DMT plasma concentrations and its EEG effects. Data were obtained from a clinical study where DMT was administered by intravenous bolus dose to 13 healthy subjects. The effects on alpha power, beta power, and Lempel‐Ziv complexity were evaluated. DMT was shown to fully suppress alpha power. Beta power was only partially suppressed, whereas an increase in Lempel‐Ziv complexity was observed. The relationship between plasma concentrations and effects were described using effect compartment models with sigmoidal maximum inhibitory response or maximum stimulatory response models. Values of the concentration needed to reach half of the maximum response (EC 50,e ) were estimated at 71, 137, and 54 nM for alpha, beta, and Lempel‐Ziv complexity, respectively. A large amount of between‐subject variability was associated with both beta power and Lempel‐Ziv complexity with coefficients of variability of 75% and 77% for the corresponding EC 50,e values, respectively. Alpha power appeared to be the most robust response, with a between‐subject variability in EC 50,e of 29%. Having a deeper understanding of these processes might prove beneficial in choosing appropriate doses and response biomarkers in the future clinical development of DMT.

Comparable studies

Other experimental studies on DMT, most cited first.

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
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
Metabolism and disposition of N,N‐dimethyltryptamine and harmala alkaloids after oral administration of ayahuasca Healthy male volunteers 2012 Observational pharmacokinetic study n = 10
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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DMT 5-MeO-DMT Addiction Philosophy of mind