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N,N-dimethyltryptamine affects EEG response in a concentration dependent manner – a pharmacokinetic/pharmacodynamic analysis


Web link: onlinelibrary.wiley.com/doi/abs/1...

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 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 was obtained from a clinical study where DMT was administered by intravenous bolus dose to thirteen 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 Imax or Emax models. EC50,e values 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 EC50,e values, respectively. Alpha power appeared to be the most robust response with between subject variability in EC50,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.