Cardiac effects of two hallucinogenic natural products, N,N-dimethyl-tryptamine and 5-methoxy-N,N-dimethyl-tryptamine.
Joachim Neumann, Tobias Dietrich, Karyna Azatsian, Britt Hofmann, Ulrich Gergs
Scientific Reports February 25, 2025 DOI: 10.1038/s41598-025-91400-6 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Isolated atrial preparations from transgenic mice overexpressing human 5-HT4 receptors and from adult human patients undergoing open heart surgery for coronary heart disease |
| Interventions | DMT 5-MeO-DMT cilostamide |
| Dose | 10 µM DMT, 10 µM 5-MeO-DMT, 1 µM 5-HT, 1 µM cilostamide |
| Topics | DMT Serotonin 5-MeO-DMT |
| Keywords | Serotonin sign N,N-Dimethyl-Tryptamine DMT 5-ht4 receptor 5-Methoxy-N,N-Dimethyl-Tryptamine 5-MEO-DMT Chronotropy Human atrium Inotropy Phospholamban Transgenic mice Psychedelics hallucinogens Entheogens Cardiac muscle |
| Citations | 2 |
| Key findings | DMT and 5-MeO-DMT act as partial agonists at human 5-HT4 receptors, producing positive inotropic and chronotropic effects that are weaker than those of serotonin. |
Abstract
It is unclear whether hallucinogenic tryptamine derivatives namely N,N-dimethyl-tryptamine (DMT) and 5-methoxy-N,N-dimethyl-tryptamine (5-MeO-DMT) exert positive inotropic effects in the human heart. Therefore, we measured the inotropic effects of these drugs in isolated left and right atrial preparations of mice that overexpress human 5-HT4 receptors (5-HT4-TG) and preparations from wild type mice (WT). Moreover, we measured force of contraction in isolated right atrial preparations from adult patients, obtained in the process of open heart surgery due to severe coronary heart disease. DMT and 5-MeO-DMT augmented the force of contraction in isolated paced (1 Hz) left atrial preparations from 5-HT4-TG and raised the spontaneous beating rate of right atrial preparations from 5-HT4-TG. The drugs elevated force of contraction in paced (1 Hz) human right atrial muscle preparations. The maximum inotropic effects of DMT and 5-MeO-DMT were smaller at 10 µM (about 65%) than that of 1 µM 5-HT on the left atria from 5-HT4-TG. The maximum increase in the beating rate due to DMT and 5-MeO-DMT amounted 40 ± 5% of the effect of 5-HT on right atrial preparations from 5-HT4-TG (n = 5-6). DMT and 5-MeO-DMT were inactive in WT. The potency of 5-MeO-DMT to increase force of contraction could be increased by pre-treatment of human atrial preparations by the phosphodiesterase inhibitor cilostamide (1 µM). 5-MeO-DMT increased the phosphorylation state of phospholamban at serine 16 in isolated left atrial muscle strips of 5-HT4-TG. In summary, DMT and 5-MeO-DMT acted as partial agonists on human 5-HT4 receptors.
Comparable studies
Other preclinical and animal studies on 5-MeO-DMT, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelic N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine modulate innate and adaptive inflammatory responses through the sigma-1 receptor of human monocyte-derived dendritic cells. Human primary monocyte-derived dendritic cells | 2014 | In vitro study | |
| Effects of N,N-Dimethyltryptamine on Rat Behaviors Relevant to Anxiety and Depression Adult male Sprague-Dawley rats | 2018 | Experimental study | |
| Hallucinogen-like actions of 5-methoxy-N,N-diisopropyltryptamine in mice and rats. Mice and rats | 2006 | Preclinical study | |
| Agonist Properties of N,N-Dimethyltryptamine at Serotonin 5-HT2A and 5-HT2C Receptors Rats and transfected fibroblasts | 1998 | Experimental study | |
| Subtypes of the 5-HT receptor mediating the behavioural responses to 5-methoxy-N,N-dimethyltryptamine in the rat Intact rats and rats depleted of monoamines with reserpine | 1985 | Experimental study |
Citations in the library
Cited by 2
- Preclinical Comparison of DMT and 5-MeO-DMT Reveals Behavioral Dissociation, Distinct TrkB Activation and Differential Plasticity Profiles bioRxiv (Cold Spring Harbor Laboratory) August 12, 2026
- In-silico toxicity study of tryptamine, psilocin, psilocybin, N,N-dimethyltryptamine, 5'-methoxy-N,N-dimethyltryptamine and O-acetylpsilocin. Archives of Toxicology March 31, 2026
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and 12 more in the library