The Effect of Cannabidiol on Ischemia/Reperfusion-Induced Ventricular Arrhythmias

Abstract

Cannabidiol (CBD) is a nonpsychoactive phytocannabinoid with anti-inflammatory activity mediated by enhancing adenosine signaling. As the adenosine A1 receptor activation confers protection against ischemia/reperfusion (I/R)-induced ventricular arrhythmias, we hypothesized that CBD may have antiarrhythmic effect through the activation of adenosine A1 receptor. Cannabidiol has recently been shown to suppress ischemia-induced ventricular arrhythmias. We aimed to research the effect of CBD on the incidence and the duration of I/R-induced ventricular arrhythmias and to investigate the role of adenosine A1 receptor activation in the possible antiarrhythmic effect of CBD. Myocardial ischemia and reperfusion was induced in anesthetized male rats by ligating the left anterior descending coronary artery for 6 minutes and by loosening the bond at the coronary artery, respectively. Cannabidiol alone was given in a dose of 50 µg/kg, 10 minutes prior to coronary artery occlusion and coadministrated with adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) in a dose of 100 µg/kg, 15 minutes prior to coronary artery occlusion to investigate whether the antiarrhythmic effect of CBD is modified by the activation of adenosine A1 receptors. The experimental groups were as follows: (1) vehicle control (n = 10), (2) CBD (n = 9), (3) DPCPX (n = 7), and (4) CBD + DPCPX group (n = 7). Cannabidiol treatment significantly decreased the incidence and the duration of ventricular tachycardia, total length of arrhythmias, and the arrhythmia scores compared to control during the reperfusion period. The DPCPX treatment alone did not affect the incidence and the duration of any type of arrhythmias. However, DPCPX aborted the antiarrhythmic effect of CBD when it was combined with it. The present results demonstrated that CBD has an antiarrhythmic effect against I/R-induced arrhythmias, and the antiarrhythmic effect of CBD may be mediated through the activation of adenosine A1 receptor.

Molecular Targets of Cannabidiol in Neurological Disorders

“…CBD (50 μg/kg) inhibits the subsequent ventricular tachycardia following coronary artery occlusion in rats-an effect abolished by 8-cyclopentyl-1,3-dipropylxanthine, an adenosine A 1 receptor antagonist (Table 1). These results demonstrate that CBD can exert an antiarrhythmic effect, possibly mediated by the adenosine A 1 receptor [36]. In addition to effects on the A 1 receptor, A 2 receptor-mediated effects of CBD have also been reported and claimed to mediate antiinflammatory effects of CBD [10,31,37,38].…”

Molecular Targets of the Phytocannabinoids: A Complex Picture

“…Different studies revealed that this phytocannabinoid acts as a full 5HT 1A agonist, a 5HT 2A weak partial agonist and a non-competitive antagonist of 5HT 3A [48–50]. The ability of CBD to activate the A 1A adenosine receptors has also been proposed [51]. Its activity at these receptors could mediate the anti-inflammatory and immunosuppressive effects of CBD.…”

Network construction of aberrantly expressed miRNAs and their target mRNAs in ventricular myocardium with ischemia–reperfusion arrhythmias

“…Previous research has reported that miRNAs and Cx43 take part in the formation of RA [20], while the correlation mechanism between the two is rarely investigated in detail. Apart from ventricular arrhythmia, upward shift of the S-T segment, and QT prolongation, the ECG also exhibited prolonged QRS interval after ischemia reperfusion, all of which are associated with a slower intermyocardial conduction velocity after ischemia reperfusion [21]. GJ, as the basic structure of cardiac electrophysiology, maintains the normal coupling in EGC signals and mechanical coupling by mediating intercellular electrochemical 10 communications.…”