Psychological and physiological effects of extended DMT
This single-blind, placebo-controlled crossover study (n=11) investigated a novel administration method for DMT involving a bolus injection followed by a constant-rate infusion to extend the experience over 30 minutes. Results demonstrate that the method was safe and maintained stable subjective effects, although the plateauing of psychological effects despite rising plasma concentrations suggests the development of acute tolerance.
Authors
- Fernando Rosas
- Robin Carhart-Harris
- David Nutt
Published
Abstract
Background
N,N-Dimethyltryptamine (DMT) is a serotonergic psychedelic that when injected as a bolus intravenous injection induces a rapid and transient altered state of consciousness. Its marked and novel subjective effects make DMT a powerful tool for the neuroscientific study of consciousness and preliminary results show its potential role in treating mental health conditions.
Aims
In a within-subjects, placebo-controlled study, we investigated a novel method of DMT administration involving a bolus injection paired with a constant-rate infusion, with the goal of extending the DMT experience.
Methods
Pharmacokinetic parameters of DMT estimated from plasma data of a previous study of bolus intravenous DMT were used to derive dose regimens necessary to keep subjects in steady levels of immersion into the DMT experience over an extended period of 30 minutes, and four dose regimens were tested.
Results
The present method is effective for extending the DMT experience in a stable and tolerable fashion. While subjective effects were maintained over the period of active infusion, anxiety ratings remained low and heart rate habituated within 15 minutes, indicating psychological and physiological safety of extended DMT. Plasma DMT concentrations increased consistently starting ten minutes into DMT administration, whereas psychological effects plateaued into the desired steady state, suggesting the development of acute psychological tolerance to DMT.
Conclusion
Taken together, these findings demonstrate the safety and effectiveness of continuous IV DMT administration, laying the groundwork for the further development of this method of administration for basic and clinical research.
Research Summary of 'Psychological and physiological effects of extended DMT'
Introduction
Luan and colleagues frame N,N-dimethyltryptamine (DMT) as a fast-acting serotonergic psychedelic that produces a brief but intense altered state of consciousness, often described as immersion into an alternate world and sometimes involving encounters with apparent 'entities'. Earlier work has used bolus intravenous (IV) administration, inhalation or the oral preparation ayahuasca; IV bolus dosing offers precise control but produces effects that peak within two to three minutes and largely subside within about 30 minutes. The brief time-course limits opportunities to study sustained phenomenology and neurobiology, and no pharmacokinetically informed continuous IV DMT protocols had been systematically tested in humans prior to this study. This study set out to develop and test a bolus-plus-constant-rate IV infusion method intended to prolong and stabilise the DMT experience for 30 minutes. The investigators aimed to derive infusion regimens from prior pharmacokinetic data to maintain moderate-to-high levels of subjective immersion while monitoring psychological safety and physiological responses, thereby creating a platform for extended experimental and potentially therapeutic applications of DMT.
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Study Details
- Study Typeindividual
- Journal
- Compounds
- Topics
- Authors
- APA Citation
Luan, L. X., Eckernäs, E., Ashton, M., Rosas, F. E., Uthaug, M. V., Bartha, A., Jagger, S., Gascon-Perai, K., Gomes, L., Nutt, D. J., Erritzøe, D., Carhart-Harris, R. L., & Timmermann, C. (2024). Psychological and physiological effects of extended DMT. Journal of Psychopharmacology, 38(1), 56-67. https://doi.org/10.1177/02698811231196877
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Zuiker, R. G. J. A., Otto, M. E., Bryan, C. S. et al. · Clinical and Translational Science (2025)
Egger, K., Redondo, J. J., Müller, J. et al. · Biomedicine & Pharmacotherapy (2025)
Erne, L., Vogt, S. B., Müller, L. et al. · Neuropsychopharmacology (2024)
Shinozuka, K., Jerotic, K., Mediano, P. A. M. et al. · Translational Psychiatry (2024)
Juliani, A., Chelu, V., Graesser, L. et al. · Biorxiv (2024)
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Aicher, H. D., Mueller, M. J., Dornbierer, D. A. et al. · Frontiers in Psychiatry (2024)
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Eckernäs, E., Koomen, J., Timmermann, |. C. et al. · Pharmacometrics and Systems Pharmacology (2023)
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