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Michael Ashton

10 papers in the library · 444 citations · publishing 2019-2025

Papers

Neural correlates of the DMT experience assessed with multivariate EEG.

Sci Rep November 19, 2019 Christopher Timmermann, Leor Roseman, Michael Schartner et al. 325 citations

Intravenous DMT, a fast-acting psychedelic, markedly reduces alpha and beta brain wave power and increases spontaneous signal diversity in the human brain, as measured by EEG. The emergence of delta and theta oscillatory activity correlates with the peak of the subjective experience, especially its eyes-closed visual component. Relationships between changes in subjective experience and brain activity were observed across time, linking specific brain changes to specific aspects of the experience.

Psychological and physiological effects of extended DMT.

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.

Population pharmacokinetic/pharmacodynamic modeling of the psychedelic experience induced by N,N‐dimethyltryptamine – Implications for dose considerations

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.

Development and application of a highly sensitive LC-MS/MS method for simultaneous quantification of N,N-dimethyltryptamine and two of its metabolites in human plasma.

J Pharm Biomed Anal February 3, 2022 Emma Eckernäs, Adam Bendrioua, Chiara Cancellerini et al. 18 citations

A highly sensitive LC-MS/MS method was developed and applied to simultaneously quantify N,N-dimethyltryptamine (DMT) and two of its metabolites in human plasma. This new method accurately and precisely measures DMT and its breakdown products, providing a robust tool for studying how DMT behaves in the body, its metabolism, and its effects.

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

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.

Psychological and physiological effects of extended DMT

PsyArXiv April 13, 2023 Lisa Xiaolu Luan, Emma Eckernäs, Michael Ashton et al. 9 citations preprint

A within-subjects, placebo-controlled study tested a novel method of administering N,N-Dimethyltryptamine (DMT) by combining a bolus injection with a constant-rate infusion to extend the experience to 30 minutes. The method effectively maintained stable and tolerable subjective effects over the infusion period. Anxiety ratings remained low, and heart rate habituated within 15 minutes, indicating psychological and physiological safety. Plasma DMT concentrations increased consistently starting ten minutes into administration, while psychological effects plateaued, suggesting acute psychological tolerance to DMT. These findings demonstrate the safety and effectiveness of continuous intravenous DMT administration for basic and clinical research.

N, N-dimethyltryptamine forms oxygenated metabolites via CYP2D6 - an in vitro investigation.

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.

Neural correlates of the DMT experience as assessed via multivariate EEG

bioRxiv July 18, 2019 Christopher Timmermann, Leor Roseman, Michael Schartner et al. 4 citations preprint

Intravenous DMT, a fast-acting psychedelic, markedly alters human brain activity. Compared with a placebo, DMT reduced oscillatory power in alpha and beta brainwaves and increased spontaneous signal diversity. Time-referenced analyses linked changes in subjective experience to changes in brain activity. Emergence of delta and theta frequency oscillations correlated with the peak of the experience, particularly its eyes-closed visual component. These findings advance understanding of the neurobiological underpinnings of immersive states of consciousness.

Population pharmacokinetic-pharmacodynamic modeling of co-administered N,N-dimethyltryptamine and harmine in healthy subjects.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie July 9, 2025 Angela Äbelö, John W Smallridge, Robin von Rotz et al. 3 citations

The psychedelic compound DMT is often taken with harmine, a monoamine oxidase inhibitor, as in ayahuasca, but how harmine alters DMT's effects was not well understood. In a study of 16 healthy adults, six combinations of buccal DMT (0-120 mg) and harmine (0-180 mg) were given. Harmine increased DMT's bioavailability and prolonged its absorption, leading to higher and more sustained blood levels. The intensity of subjective psychedelic effects rose with dose, and harmine potentiated these effects at higher DMT doses. A mathematical model captured these relationships and individual variability, offering a foundation for more personalized dosing in psychedelic therapy.

Optimized infusion rates for N,N-dimethyltryptamine to achieve a target psychedelic intensity based on a modeling and simulation framework.

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.