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 via PubMed
Summary
AI-generated from the abstractHallucinogenic tryptamines DMT and 5-MeO-DMT increase the force of contraction and beating rate in heart muscle tissue from mice engineered to overexpress human 5-HT4 receptors, and also increase force of contraction in human atrial tissue from cardiac surgery patients. These effects are smaller than those of serotonin, reaching about 65% of serotonin's maximum inotropic effect at 10 µM in mouse left atria, and 40 ± 5% of serotonin's chronotropic effect in mouse right atria. The drugs are inactive in wild-type mice. The potency of 5-MeO-DMT is enhanced by a phosphodiesterase inhibitor, and it increases phosphorylation of phospholamban at serine 16. DMT and 5-MeO-DMT act as partial agonists at human 5-HT4 receptors.
Study at a glance
| 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 |
| Keywords | Serotonin sign N,N-Dimethyl-Tryptamine DMT 5-ht4 receptor 5-Methoxy-N,N-Dimethyl-Tryptamine 5-MEO-DMT Chronotropy |
| Citations | 2 |
| Key finding | 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.