17 Cannabidiol as an anti-arrhythmic, the role of the CB1 receptors

Abstract

Cannabidiol (CBD) has been shown to be anti-arrhythmic (Walsh et al, 2010) and tissue sparing (Durst et al, 2007) in an in vivo rat model of coronary artery occlusion (CAO), although the receptors through which this occurs have yet to be identified. This study was designed to investigate whether the antiarrhythmic effects of CBD are modified by co-administration with a CB1 receptor antagonist (AM251). Experimental CAO was induced by ligation of the LAD coronary artery for 30 min; in sodium pentobarbitone anaesthetised male SD rats. Experimental groups included; (i) vehicle, (ii) CBD (50 μg/kg) alone, (iii) AM251 (1 mg/kg) alone, (iv) CBD followed by AM251, and (v) AM251 followed by CBD. CBD or AM251 alone each reduced the incidence of VT and the total number of VEBs compared with the control group, as did AM251 when administered 5 min after CBD. However, in animals treated with AM251 followed by CBD, the antiarrhythmic effect was significantly more pronounced 1274±303 (VT, P<0.01) and 1727±416 (total VEBs, P<0.001) when compared with all other treatment groups. The ability of AM251 to suppress arrhythmias suggests that endocannabinoids may exert pro-arrhythmic effects via the CB1 receptor. The preservation of anti-arrhythmic effects of both AM251 and CBD when co-administered, implies that a simple agonist/antagonist relationship at the CB1 receptor, may not be responsible for the antiarrhythmic effects of either alone. The observed synergism which persists when CB1 receptors are blocked prior to CBD administration, suggests cross-talk between CB1 and other CB receptors in the heart during ischaemia.

The Endocannabinoid System of Animals

“…CB 1 antagonists were able to lower blood pressure better in the hypertensive rats than the normotensive rats. This may be due to the upregulation of CB 1 receptors in heart and aortic endothelium in hypertensive rats, but not the normotensive cohort [73].…”

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

“…11 In their following studies, the same researchers reveal that the antiarrhythmic effect of CBD may not be mediated through the CBD 1 receptor activation during the ischemia. 39 In the present study, although CBD alone suppressed I/Rinduced ventricular arrhythmias, it was not found to be effective against I/R-induced arrhythmias in the presence of adenosine A 1 receptor blockage with DPCPX. These results reveal that the antiarrhythmic effect of CBD may be mediated through the adenosine A 1 receptor activation.…”

“…11 In their following studies, the same researchers reveal that the antiarrhythmic effect of CBD may not be mediated through the CBD 1 receptor activation during the ischemia. 39…”

The Effects of Cannabinoid Receptor Antagonists Am251 and Am630 on Ischemia/Reperfusion-Induced Arrhythmias in Anesthetized Rats

“…Hepburn ve ark. (14) anestezi altındaki sıçanlarda bir seçici KB 1 reseptör antagonisti AM251'in miyokardiyal iskemi ile uyarılan ventriküler aritmileri azalttığını göstermiştir. Andrag ve Curtis (15) ise izole sıçan kalbinde AM251'in ventriküler fibrilasyon sıklığını akut iskeminin geç döneminde artırdığı göstermiştir.…”

“…Çalışmamızda AM251 ve AM630'un, I/R ile uyarılan ventriküler aritmiler üzerine etkisi ilk kez araştırılmıştır. (17,18), uygulanan dozları ve veriliş zamanı için benzer çalışmalar temel alındı (14,16). AM251 ve AM630 (Sigma Chemical Co.; St. Louis, MO, ABD)1mg/kg/ml dozda intravenöz yolla ligasyondan 10 dakika önce bolus olarak verildi.…”