Institute for Pharmacology and Toxicology, Medical Faculty, Martin Luther University Halle-Wittenberg, Magdeburger Straße 4, 06097, Halle (Saale), Germany.
3 papers in the library · 17 citations · publishing 2024-2025
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.
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.
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.