Conference Paper

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

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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.

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... 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]. ...
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... 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]. ...
Preprint
Full-text available
The endocannabinoid system has been found to be pervasive in mammalian species. It has also been described in invertebrate species primitive as the Hydra. Insects apparently are devoid of this otherwise ubiquitous system that provides homeostatic balance to the nervous and immune systems, as well as many other organ systems. The endocannabinoid system (ECS) has been defined to consist of three parts: 1. Endogenous ligands, 2. G-protein coupled receptors (GPCRs), and 3. Enzymes to degrade and recycle the ligands. Two endogenous molecules have been identified as ligands in the ECS to date. These are the endocannabinoids: Anandamide (arachidonoyl ethanolamide) and 2-AG (2-arachidonoyl glycerol). Two G-coupled protein receptors have been described as part of this system, with other putative GPC being considered. Coincidentally, the phytochemicals produced in large quantities by the Cannabis sativa L plant, and in lesser amounts by other plants, can interact with this system as ligands. These plant-based cannabinoids are termed, phytocannabinoids. The precise determination of the distribution of cannabinoid receptors in animal species is an ongoing project, with the canine cannabinoid receptor distribution currently receiving the most interest in non-human animals.
... CBD has been found to have anti-arrhythmic effects in an in vivo rat model of coronary artery occlusion which may not be mediated through the CB 1 receptors found on myocardial cell membranes, but may have other non-receptor-mediated pathways that allow its control over cardiac rhythm (Hepburn et al. 2011). ...
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... The evidence of a potential role for cannabinoid in various cardiovascular pathologies, together with the safety data gleaned from various human intervention studies, indicate that now is the time to show efficacy across species and continue toward human trials." In Cannabidiol as an anti-arrhythmic, the role of the CB1 receptors (Hepburn et al. 2011), we read: "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. . . . 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 evidence of a potential role for cannabinoid in various cardiovascular pathologies, together with the safety data gleaned from various human intervention studies, indicate that now is the time to show efficacy across species and continue toward human trials." In Cannabidiol as an anti-arrhythmic, the role of the CB1 receptors (Hepburn et al. 2011), we read: "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. . . . 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." ...
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