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

A single intravenous dose of DMT fully suppresses alpha brain wave power, partially suppresses beta power, and increases signal diversity (Lempel-Ziv complexity) in the EEG of 13 healthy volunteers. The concentration needed to reach half of the maximum effect (EC50) was 71 nM for alpha suppression, 137 nM for beta suppression, and 54 nM for increased complexity. Alpha suppression showed the least variability between individuals (29%), while beta suppression and complexity varied widely (75% and 77%). These quantified relationships between DMT blood levels and brain activity may help select appropriate doses and response markers in future clinical research.

Study at a glance

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.