Naunyn-Schmiedeberg's archives of pharmacology
January 1, 2024
Ulrich Gergs, Hannes Jacob, Pauline Braekow et al.
16 citations
Lysergic acid diethylamide (LSD) increases the force and rate of heart contractions by activating two types of receptors: 5-HT4 serotonin receptors and H2 histamine receptors. In transgenic mouse hearts overexpressing human 5-HT4 or H2 receptors, LSD (up to 10 µM) increased contraction force and beating rate, effects blocked by specific antagonists (tropisetron for 5-HT4, cimetidine and GR 125487 for H2). In human atrial muscle strips from bypass surgery patients, LSD (10 µM) also increased contraction force after cilostamide pre-stimulation. These findings indicate LSD directly stimulates cardiac function through both receptor pathways.
Naunyn-Schmiedeberg's archives of pharmacology
July 1, 2023
Joachim Neumann, Nils Schulz, Charlotte Fehse et al.
13 citations
Bufotenin, a hallucinogenic drug, can stimulate human cardiac serotonin 5-HT4 receptors, increasing the force of contraction and beating rate. In transgenic mice expressing only the human 5-HT4 receptor in heart cells, bufotenin enhanced left atrial contraction and right atrial beating rate, with effects potentiated by a monoamine oxidase inhibitor. In isolated human atrial muscle strips, bufotenin concentration-dependently increased contraction force, reversed by the 5-HT4 antagonist tropisetron. Bufotenin also increased phosphorylation of phospholamban, a protein regulating heart muscle relaxation, in transgenic mouse and human atrial tissue. These findings indicate bufotenin acts as a positive inotropic and chronotropic agent through human 5-HT4 receptors.
Frontiers in Pharmacology
February 2, 2024
Joachim Neumann, Stefan Dhein, Uwe Kirchhefer et al.
12 citations
Hallucinogenic drugs like LSD, psilocybin, and DMT affect the brain by stimulating serotonin receptors, particularly 5-HT2A receptors, which likely causes their hallucinogenic effects. However, these drugs also act on the heart, potentially increasing the force of contraction and heart rate, and may lead to arrhythmias. This review examines the inotropic and chronotropic actions of bufotenin, psilocin, psilocybin, LSD, ergotamine, ergometrine, N,N-dimethyltryptamine, and 5-methoxy-N,N-dimethyltryptamine in the human heart.
Naunyn-Schmiedeberg s Archives of Pharmacology
November 1, 2022
Joachim Neumann, Karyna Azatsian, Christian Höhm et al.
7 citations
Ephedrine, norephedrine, and MDMA, but not mescaline, increased the force of contraction and beating rate in isolated mouse and human heart tissue preparations, starting at concentrations of 1–3 µM. These effects were less potent than those of isoprenaline and were accompanied by increased phosphorylation of troponin’s inhibitory subunit. Cocaine or propranolol greatly attenuated the effects, suggesting these drugs act indirectly by releasing noradrenaline in the human atrium. Mescaline showed no inotropic effect even with phosphodiesterase inhibitors. The findings indicate that ephedrine, norephedrine, and MDMA can be classified as indirect sympathomimetics in human atrial muscle, which may contribute to cardiac arrhythmias and fatal intoxication.
Toxicology Letters
June 12, 2024
Joachim Neumann, Kiril Dimov, Karyna Azatsian et al.
5 citations
Psilocybin and psilocin, the hallucinogenic compounds in magic mushrooms, activate cardiac serotonin (5-HT4) receptors, increasing the force and rate of heart contractions. In isolated left and right atrial preparations from transgenic mice overexpressing the human 5-HT4 receptor, both drugs enhanced contraction force and beating rate, though their effects at 10 µM were weaker than those of 1 µM serotonin. No effects were seen in wild-type mice. In human atrial tissue, the positive inotropic effects required inhibition of phosphodiesterase III to become apparent. The effects were blocked by the 5-HT4 receptor antagonists tropisetron and GR125487, confirming that psilocybin and psilocin act as agonists on cardiac 5-HT4 receptors.
Scientific reports
February 25, 2025
Joachim Neumann, Tobias Dietrich, Karyna Azatsian et al.
2 citations
Hallucinogenic 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.
Research Square
Ulrich Gergs, Hannes Jacob, Pauline Braekow et al.
1 citation
LSD increases the force and rate of heart muscle contraction by activating H2-histamine receptors in humans, and also acts as a partial agonist at 5-HT4 serotonin receptors in mice. In human atrial tissue from heart surgery patients, LSD's contractile effects were blocked by cimetidine, an H2-receptor antagonist. These findings clarify the cardiac effects of LSD, which is being studied again for psychiatric uses.
Pharmaceuticals
July 6, 2025
Pauline Braekow, Joachim Neumann, Uwe Kirchhefer et al.
Psilocybin and psilocin enhance the force of contraction and increase phospholamban phosphorylation in isolated mouse hearts that overexpress human 5-HT4 receptors, but have little effect in hearts overexpressing human H2 receptors. LSD increases both force and phosphorylation in hearts with either receptor. Ergometrine and ergotamine only increase force in H2-receptor-overexpressing hearts, with ergometrine also increasing phosphorylation. None of these substances affect force or phosphorylation in wild-type mouse hearts. The findings suggest that phospholamban phosphorylation partly explains the positive inotropic and relaxant effects of these hallucinogenic compounds in these animal models.