DMT for Medicinal Chemistry & Drug Development

27 papers and 2 clinical trials exploring dmt as a treatment for medicinal chemistry & drug development.

CompoundTryptamine

DMT

A powerful, short-acting tryptamine psychedelic found in many botanical sources, known for rapid onset and intense subjective experiences.

Full DMT profile

IndicationOver 300 million people worldwide experience depression, with many also suffering from related anxiety disorders.

Medicinal Chemistry & Drug Development

Medicinal chemistry plays a crucial role in the development of novel psychedelic compounds, focusing on their molecular structures and interactions. Researchers utilise innovative methods to enhance safety and efficacy in psychedelic substances.

Full Medicinal Chemistry & Drug Development profile

Academic Research

27 papers

Open Accessindividual

Serotonergic Polypharmacology of 2-Halogenated Tryptamines

This mouse study found that 2-halogenated tryptamine derivatives of DMT and psilocybin had reduced activity at receptors linked to psychedelic effects and heart-related risks, while keeping strong activity at 5-HT6 receptors. In mice, 2-Br-psilacetin did not trigger the usual head-twitch response and showed some improvements in stress-related behaviour and cued learning.

Published: April 21, 2026
Journal: Biorxiv
Authors: Yacoub, J., Bray, E., Bayyat, J., Glatfelter, G. C., Leake, A., Buitrago, E. M., Maitland, A. D., Partilla, J., Cavalco, N. G., Schalk, S. S., Lammers, J. C., Baumann, M. H., McCorvy, J., Leahy, J. W., Gulick, D., Witowski, C. G., von Salm, J. L.

Open Accessindividual

A novel psychedelic 5-HT2A receptor agonist GM-2505: The pharmacokinetic, safety, and pharmacodynamic profile from a randomized trial healthy volunteer

In a randomized, placebo‑controlled ascending‑dose study in 48 healthy volunteers, single IV doses of GM‑2505 up to 20 mg were well tolerated and showed dose‑proportional pharmacokinetics (t1/2 40–50 min) with dose‑dependent neuroendocrine, neurophysiological and subjective psychedelic effects, including decreased theta/alpha and increased gamma EEG power. The duration of cardiovascular and subjective effects was intermediate between psilocybin and DMT, indicating a practical 10–15 mg IV dose range for supervised clinical use.

Published: October 16, 2025
Journal: Journal of Psychopharmacology
Authors: Marek, G. J., Makai-Bölöni, S., Umbricht, D., Christian, E. P., Winters, J., Dvorak, D., Raines, S., Hughes, Z. A., Austin, E. W., Klein, A. K., Leong, W., Krol, F. J., Van Der Graaf, A. J., Juachon, M. J., Otto, M. E., Borghans, L. G. J. M., Jacobs, G., Kruegel, A. C., Sporn, J.

Paywallindividual

Zalsupindole is a Nondissociative, Nonhallucinogenic Neuroplastogen with Therapeutic Effects Comparable to Ketamine and Psychedelics

This rat study found that zalsupindole (third-generation psychedelic) produced robust effects on structural and functional neuroplasticity in the prefrontal cortex as well as sustained antidepressant-like responses comparable to or greater than those of ketamine, psilocybin, and DMT, despite lacking any of the acute cellular and behavioural characteristics of hallucinogenic or dissociative compounds.

Published: October 13, 2025
Journal: ACS Chemical Neuroscience
Authors: Agrawal, R., Gillie, D., Mungenast, A., Chytil, M., Engel, S., Wu, M. C., Rasmussen, K., Salinas, E., Olson, D. E.

Open Accessindividual

DMT and harmala alkaloids: an exploratory study of oral Acacia based formulations in healthy volunteers

In this open-label exploratory crossover study of nine experienced ayahuasca users, three Acacia‑derived oral formulations delivering DMT plus harmala alkaloids were well tolerated, produced no clinically significant physiological changes, and elicited psychedelic effects rated comparable to (and for ACL‑010 sometimes more beneficial than) traditional ayahuasca. These findings suggest Acacia‑based DMT/harmala formulations are a feasible alternative for future clinical trials, although generalisability is limited by the small sample size and open‑label design.

Published: August 15, 2025
Journal: Frontiers in Psychiatry
Authors: Bonomo, Y. A., Norman, A. F., Collins, L., Ross, M., Dwyer, J., Perkins, D., Sarris, J.

Open Accessindividual

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

This secondary of a single-blind, randomised study (n=16) using DMT (0-120mg) with harmine (0-180mg) in an ayahuasca-inspired (‘pharmahuasca’) formulation found that harmine significantly enhanced DMT bioavailability and prolonged absorption, resulting in higher sustained plasma concentrations and increased subjective psychedelic effects, with population pharmacokinetic/pharmacodynamic modeling revealing substantial interindividual variability in clearance, bioavailability, and sensitivity to psychedelic effects.

Published: August 1, 2025
Journal: Biomedicine & Pharmacotherapy
Authors: Äbelö, A., Smallridge, J. W., Von Rotz, R., Dornbierer, D. A., Egger, K., Ashton, M., Scheidegger, M.

Open Accessindividual

Safety, Pharmacokinetics, and Pharmacodynamics of a 6-h N,N-Dimethyltryptamine (DMT) Infusion in Healthy Volunteers: A Randomized, Double-Blind, Placebo-Controlled Trial

This randomized, double‑blind, placebo‑controlled study found that a 30‑s bolus followed by a 6‑hour intravenous DMT infusion (maximal exposures ≈35 ng/mL) was well tolerated in healthy volunteers with no serious adverse events and only mild, rapidly occurring psychedelic effects. Moderate interindividual pharmacokinetic variability was observed and the highest dose produced transient reductions in sustained attention, postural stability and occipital alpha power, providing a safety and PK/PD basis for future proof‑of‑mechanism studies in patient populations.

Published: May 13, 2025
Journal: Clinical and Translational Science
Authors: Zuiker, R. G. J. A., Otto, M. E., Bryan, C. S., Stewart, N., Stillwell, C., de Kam, M. L., van Leuken, M. B., van Gerven, J. M. A., Jacobs, G. E., van der Heijden, K. V.

Clinical Trials

2 trials

CompletedPhase I

Safety, tolerability, pharmacokinetics, pharmacodynamics and exploratory efficacy of intravenous dosing of SPL026 drug product (N, N-dimethyltryptamine fumarate; DMT Fumarate [A Serotonergic Psychedelic]) alone or in combination with selective serotonin reuptake inhibitors in patients with major depressive disorder

Open-label Phase I study (n=24 planned; 18 enrolled) single 27.5 mg IV SPL026 (DMT fumarate) 10-minute infusion in adults with major depressive disorder, comparing patients on stable SSRI versus those not on pharmacotherapy; primary outcomes: safety, PK/PD and exploratory efficacy.

Started: December 13, 2022
Type: interventional
Blinding: none
Randomized: No
Registry ID: ISRCTN10974027

CompletedPhase I

Safety, blood levels and effects of N,N-dimethyltryptamine [DMT (SPL026)] in healthy participants that have taken psychedelic substances before (Part A) and in healthy participants with little to no psychedelic experience (Part B)

Open-label, crossover Phase I study (target n=30, actual enrolment 14) assessing safety, blood levels and effects of SPL026 (DMT fumarate) given IM and IV in healthy psychedelic-experienced (Part A) and little/no-experience (Part B) participants.

Started: May 22, 2022
Type: interventional
Blinding: none
Randomized: No
Registry ID: ISRCTN63723571

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DMT for Medicinal Chemistry & Drug Development

DMT

Medicinal Chemistry & Drug Development

Academic Research

Serotonergic Polypharmacology of 2-Halogenated Tryptamines

A novel psychedelic 5-HT2A receptor agonist GM-2505: The pharmacokinetic, safety, and pharmacodynamic profile from a randomized trial healthy volunteer

Zalsupindole is a Nondissociative, Nonhallucinogenic Neuroplastogen with Therapeutic Effects Comparable to Ketamine and Psychedelics

DMT and harmala alkaloids: an exploratory study of oral Acacia based formulations in healthy volunteers

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

Safety, Pharmacokinetics, and Pharmacodynamics of a 6-h N,N-Dimethyltryptamine (DMT) Infusion in Healthy Volunteers: A Randomized, Double-Blind, Placebo-Controlled Trial

Clinical Trials

Safety, blood levels and effects of N,N-dimethyltryptamine [DMT (SPL026)] in healthy participants that have taken psychedelic substances before (Part A) and in healthy participants with little to no psychedelic experience (Part B)

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DMT for Medicinal Chemistry & Drug Development

DMT

Medicinal Chemistry & Drug Development

Academic Research

Serotonergic Polypharmacology of 2-Halogenated Tryptamines

A novel psychedelic 5-HT2A receptor agonist GM-2505: The pharmacokinetic, safety, and pharmacodynamic profile from a randomized trial healthy volunteer

Zalsupindole is a Nondissociative, Nonhallucinogenic Neuroplastogen with Therapeutic Effects Comparable to Ketamine and Psychedelics

DMT and harmala alkaloids: an exploratory study of oral Acacia based formulations in healthy volunteers

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

Safety, Pharmacokinetics, and Pharmacodynamics of a 6-h N,N-Dimethyltryptamine (DMT) Infusion in Healthy Volunteers: A Randomized, Double-Blind, Placebo-Controlled Trial

Clinical Trials

Safety, blood levels and effects of N,N-dimethyltryptamine [DMT (SPL026)] in healthy participants that have taken psychedelic substances before (Part A) and in healthy participants with little to no psychedelic experience (Part B)

Explore further