Abstract
Cannabis use is associated with known cardiovascular side effects such as cardiac arrhythmias or even sudden cardiac death. The mechanisms behind these adverse effects are unknown. The aim of the present work was to study the cellular cardiac electrophysiological effects of cannabidiol (CBD) on action potentials and several transmembrane potassium currents, such as the rapid (IKr) and slow (IKs) delayed rectifier, the transient outward (Ito) and inward rectifier (IK1) potassium currents in rabbit and dog cardiac preparations. CBD increased action potential duration (APD) significantly in both rabbit (from 211.7 ± 11.2. to 224.6 ± 11.4 ms, n = 8) and dog (from 215.2 ± 9.0 to 231.7 ± 4.7 ms, n = 6) ventricular papillary muscle at 5 µM concentration. CBD decreased IKr, IKs and Ito (only in dog) significantly with corresponding estimated EC50 values of 4.9, 3.1 and 5 µM, respectively, without changing IK1. Although the EC50 value of CBD was found to be higher than literary Cmax values after CBD smoking and oral intake, our results raise the possibility that potassium channel inhibition by lengthening cardiac repolarization might have a role in the possible proarrhythmic side effects of cannabinoids in situations where CBD metabolism and/or the repolarization reserve is impaired.
Highlights
Cannabis has been one of the most abused hallucinogenic drugs since ancient times with an estimated 150 million consumers worldwide (Kalla et al 2018)
Whole-cell patch-clamp experiments in rabbit cardiac ventricular myocytes revealed significant inhibition of the rapid delayed rectifier potassium current ( IKr) (Figs. 2A and 3) with an estimated EC50 value of 4.9 μM. IKr was activated by 1000 ms long depolarizing voltage pulses with pulse frequency of 0.05 Hz to the potentials ranging from − 30 mV to 50 mV and the cell was repolarized to − 40 mV
In similar experiments in rabbit myocytes CBD depressed the slow delayed rectifier potassium current (IKs, Fig. 2B) with an estimated EC50 value of 3.1 μM (Fig. 4), after 20 mV 5 s long test pulse measured at − 40 mV. IKs was recorded to IKr
Summary
Cannabis has been one of the most abused hallucinogenic drugs since ancient times with an estimated 150 million consumers worldwide (Kalla et al 2018). The enhanced general interest for the use of cannabis and cannabis-derived products was facilitated following the discovery of the cannabinoid system in humans (Sierra et al 2018). There are cannabis-based drugs on the market with well-defined indications, including treatment of nausea and vomiting following chemotherapy, anorexia, pain related to cancer, spasticity and pain associated with multiple sclerosis, and Dravet and Lennox-Gastaut syndromes (FraguasSánchez and Torres-Suárez 2018). These drugs contain known amounts of CBD and/or THC in pure form or as
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
