Cannabis use is associated with cardiovascular adverse effects ranging from arrhythmias to sudden cardiac death. The exact mechanism of action behind these activities is unknown. The aim of our work was to study the effect of cannabidiol (CBD), tetrahydrocannabinol and 11-nor-9-carboxy-tetrahydrocannabinol on cellular cardiac electrophysiological properties including ECG parameters, action potentials, hERG and I_Kr ion channels in HEK cell line and in rabbit and guinea pig cardiac preparations. CBD increased action potential duration in rabbit and guinea pig right ventricular papillary muscle at lower concentrations (1 µM, 2.5 µM and 5 µM) but did not significantly change it at 10 µM. CBD at high concentration (10 µM) decreased inward late sodium and L-type calcium currents as well. CBD inhibited hERG potassium channels with an IC₅₀ value of 2.07 µM at room temperature and delayed rectifier potassium current with 6.5 µM at 37 °C, respectively. The frequency corrected QT interval (QT_c) was significantly lengthened in anaesthetized guinea pig without significantly changing other ECG parameters. Although the IC₅₀ value of CBD was higher than literary C_max values after CBD smoking and oral intake, our results raise the possibility that hERG and potassium channel inhibition might have a role in the possible proarrhythmic adverse effects of cannabinoids in situations where metabolism of CBD impaired and/or the repolarization reserve is weakened.

大麻的使用与心血管不良反应有关，范围从心律失常到心源性猝死。这些活动背后的确切作用机制尚不清楚。我们工作的目的是研究大麻二酚 (CBD)、四氢大麻酚和 11-nor-9-羧基四氢大麻酚对细胞心脏电生理特性的影响，包括心电图参数、动作电位、hERG 和 I _KrHEK 细胞系和兔和豚鼠心脏制剂中的离子通道。CBD 在较低浓度（1 µM、2.5 µM 和 5 µM）下增加了兔和豚鼠右心室乳头肌的动作电位持续时间，但在 10 µM 时没有显着改变。高浓度 (10 µM) 的 CBD 也会降低内向晚期钠电流和 L 型钙电流。CBD 抑制 hERG 钾通道，室温下IC ₅₀值为 2.07 µM，延迟整流钾电流在 37 °C 时分别为 6.5 µM。麻醉豚鼠的频率校正 QT 间期 (QT _c ) 显着延长，而其他心电图参数没有显着改变。虽然CBD的IC ₅₀值高于文学C _max CBD 吸烟和口服摄入后的值，我们的结果提出了一种可能性，即在 CBD 代谢受损和/或复极储备减弱的情况下，hERG 和钾通道抑制可能在大麻素可能的促心律失常不良反应中起作用。