Abstract/Summary

Cardiovascular disease (CVD) is the leading cause of death worldwide each year. Antiplatelet therapies have been found to reduce the risk of mortality for CVD patients and prevent subsequent occurrences. Platelets are small circulating blood cells that perform critical roles in blood clotting and the maintenance of haemostasis. In pathological settings, inappropriate activation of platelets causes thrombosis in the arterial circulation, obstructing blood flow to key organs such as the heart and brain, resulting in myocardial infarction and stroke, respectively. Anti-platelet medications are currently in use, and while they do help save lives, they are accompanied by several undesirable side effects, including gastrointestinal toxicity, gastrointestinal ulcers, nausea, and bleeding. These adverse reactions are caused by the therapeutic agents themselves. Therefore, the development of improved therapeutic strategies to treat/prevent thrombotic disorders is a pressing concern. Non-psychoactive phytocannabinoids derived from the Cannabis Sativa plant, such as cannabigerol (CBG) and cannabidiol (CBD), have been shown to possess several therapeutic benefits in a variety of pathological disorders. As a result, the purpose of this study was to demonstrate the effects of CBD and CBG on agonists-induced platelet activation, thrombus formation under arterial flow conditions, and haemostasis in mice. CBD and CBG were found at the used concentrations (1.56, 3.125, 6.25, 12.5 and 25 μM) to reduce platelet aggregation when stimulated by a variety of agonists, showing their broad impact on platelet signalling pathways. Moreover, each of CBD and CBG at the mentioned concentrations was found to block granule release and intracellular calcium mobilisation in platelets, as well as inside-out signalling of the integrin αIIb- β3 and outside-in signalling that was activated by the same integrin. CBD and CBG also decreased thrombus formation on a collagen-coated surface under arterial flow conditions. In addition, CBD and CBG had modest effects on the haemostasis of mice. Even at high concentrations such as 100 μM, CBD and CBG did not have any cytotoxic effects on platelets. Their anti-inflammatory properties decrease inflammatory cytokines released by induced platelets and reduce platelet-leukocyte aggregates. It has been found that CBD and CBG impair platelet activity by interacting with a variety of molecules, including AKT, Src, and cAMP. In light of these findings, the study shows that CBD and CBG have the potential to operate as treatments to regulate inappropriate platelet reactivity under a variety of pathophysiological condition.