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

This re-analysis (n=13) of EEG (brain activity over time) data whilst under the influence of DMT (7-20mg iv) is the first to show a concentration-dependent suppression of alpha power (brain waves), which was partially true for beta power too. The (Lempel-Ziv) complexity of brain signals increased whilst under the influence of DMT.

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 (EC50,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 EC50,e values, respectively. Alpha power appeared to be the most robust response, with a 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.”

Authors: Emma Eckernäs, Christopher Timmermann, Robin L. Carhart-Harris, Daniel Röshammar & Michael Ashton

Authors

Authors associated with this publication with profiles on Blossom

Chris Timmermann
Chris Timmerman is a postdoc at Imperial College London. His research is mostly focussed on DMT.

Robin Carhart-Harris
Dr. Robin Carhart-Harris is the Founding Director of the Neuroscape Psychedelics Division at UCSF. Previously he led the Psychedelic group at Imperial College London.

Linked Research Papers

Notable research papers that build on or are influenced by this paper

Population pharmacokinetic/pharmacodynamic modelling of the psychedelic experience induced by N,N-dimethyltryptamine – implications for dose considerations
This follow-up analysis (n=13) of data from a DMT study (7-20mg iv) describes in detail how it's metabolised in the brain (clearance of 26 L/min). A simulation (100 people at doses from 1-10mg) was then employed to delineate further DMT's effects (both the chemistry and the subjective effects). This is the first study to explore DMT's pharmacokinetics and -dynamics.

Neural correlates of the DMT experience assessed via multivariate EEG
This placebo-controlled EEG study (n=13) found that DMT reduces (oscillatory power) activity in the alpha and beta bands and increases them (especially at the peak) in the delta and theta bands.

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