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.
Two synthetic tryptamines, 4-AcO-DET and 4-HO-MET, are abused as recreational hallucinogens and may pose unknown health risks. In laboratory tests, both substances increased the proliferation of rat heart cells in a concentration-dependent manner, prolonged QT intervals in rats, and inhibited potassium channels in hamster cells, indicating potential cardiotoxicity. Expression of the PAK1 protein, involved in cardiovascular function, did not change. The findings suggest these new psychoactive substances could cause adverse cardiovascular effects, supporting evidence for their legal scheduling.