Journal of psychopharmacology (Oxford, England)
January 1, 2024
Lisa X Luan, Emma Eckernäs, Michael Ashton et al.
41 citations
A novel method of administering the psychedelic DMT via a bolus injection followed by a constant-rate infusion safely extends the experience to 30 minutes in a stable and tolerable fashion. In eleven healthy volunteers, subjective effects plateaued into a steady state while plasma DMT concentrations continued to rise, indicating acute psychological tolerance. Anxiety ratings remained low and heart rate habituated within 15 minutes, demonstrating psychological and physiological safety. This continuous intravenous administration method lays groundwork for further basic and clinical research into DMT's potential for treating mental health conditions and studying consciousness.
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.
bioRxiv (Cold Spring Harbor Laboratory)
May 12, 2023
Christopher Timmermann, Emma Eckernäs, Leor Roseman et al.
17 citations
preprint
The serotonergic psychedelic DMT rapidly induces a profoundly immersive altered state lasting less than 20 minutes, allowing the entire drug experience to be captured during a single fMRI scan. Using network control theory, which quantifies the input needed to drive transitions between brain states, brain structure and function were integrated to map energy trajectories of 14 individuals undergoing fMRI during DMT and placebo. Global control energy was reduced following DMT compared to placebo. Longitudinal trajectories of global control energy correlated with EEG signal diversity and subjective drug intensity ratings. Regional effects correlated with serotonin 2a receptor density. Receptor distribution and pharmacokinetic information successfully recapitulated DMT's effects on global control energy trajectories.
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.
Communications biology
April 18, 2025
S Parker Singleton, Christopher Timmermann, Andrea I Luppi et al.
7 citations
After DMT injection, the brain requires less control energy to transition between states compared to placebo, indicating a more flexible and less constrained brain dynamic. These energy changes track with EEG signal diversity and subjective intensity of the drug experience. The regional pattern of DMT's effects aligns with serotonin 2a receptor density, and a model using receptor distribution and pharmacokinetics can predict the drug's impact on brain energy trajectories.
Xenobiotica; the fate of foreign compounds in biological systems
December 1, 2023
Emma Eckernäs, Alicia Macan-Schönleben, Moa Andresen-Bergström et al.
6 citations
The psychedelic compound DMT is metabolized primarily by monoamine oxidase A, but other pathways are poorly understood. This work investigated cytochrome P450 (CYP) enzymes in DMT metabolism by incubating DMT with recombinant human CYP enzymes and human liver microsomes, then analyzing metabolites with high-resolution mass spectrometry. DMT was rapidly metabolized by CYP2D6, while stable with all other tested CYP enzymes. Metabolism in human liver microsomes was reduced by harmine and SKF-525A but not quinidine, likely due to residual MAO-A activity. CYP2D6 incubations produced mono-, di-, and tri-oxygenated metabolites, probably from hydroxylation on the indole core. The findings may affect safety for ayahuasca use in slow CYP2D6 metabolizers or with CYP2D6 inhibitors.
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.