Clinical and Translational Science
September 11, 2022
Emma Eckernäs, Christopher Timmermann, Daniel Röshammar et al.
22 citations
The psychedelic compound DMT is cleared from the body at a very high rate—26 L/min—indicating its elimination is independent of blood flow. Plasma concentrations follow a two-compartment model, with DMT metabolized to indole 3-acetic acid. The intensity of the psychedelic experience is linked to DMT concentration at an effect site, with half-maximal effect at 95 nM. Simulated median intensity ratings after doses of 1, 4, 7, 14, and 20 mg were zero, 2, 4, 8, and 9 on a 0–10 scale. The model can help predict suitable doses for clinical studies based on desired subjective experience intensity.
CPT Pharmacometrics & Systems Pharmacology
February 10, 2023
Emma Eckernäs, Christopher Timmermann, Robin Carhart-Harris et al.
15 citations
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.
CPT: pharmacometrics & systems pharmacology
October 1, 2023
Emma Eckernäs, Jeroen Koomen, Christopher Timmermann et al.
1 citation
A modeling study designed an infusion protocol for the psychedelic compound DMT, aiming to maintain a specific level of psychedelic intensity. Using computer simulations based on pharmacokinetic/pharmacodynamic models, optimal doses to achieve intensity ratings between 7 and 9 on a 0-10 scale were a bolus of 14-16 mg DMT fumarate followed by an infusion rate of 1.2-1.4 mg/min. However, the proportion of simulated individuals achieving the target intensity was low (below 53%), indicating that individual dose adjustments would be necessary. Differences between the models were observed, particularly at scale boundaries, with bounded integer models predicting more cases exceeding the target than the continuous variable model.