Therapeutic Applications of Cannabinoids in Cardiomyopathy and Heart Failure

Abstract

A large number of cannabinoids have been discovered that could play a role in mitigating cardiac affections. However, none of them has been as widely studied as cannabidiol (CBD), most likely because, individually, the others offer only partial effects or can activate potential harmful pathways. In this regard, CBD has proven to be of great value as a cardioprotective agent since it is a potent antioxidant and anti-inflammatory molecule. Thus, we conducted a review to condensate the currently available knowledge on CBD as a therapy for different experimental models of cardiomyopathies and heart failure to detect the molecular pathways involved in cardiac protection. CBD therapy can greatly limit the production of oxygen/nitrogen reactive species, thereby limiting cellular damage, protecting mitochondria, avoiding caspase activation, and regulating ionic homeostasis. Hence, it can affect myocardial contraction by restricting the activation of inflammatory pathways and cytokine secretion, lowering tissular infiltration by immune cells, and reducing the area of infarct and fibrosis formation. These effects are mediated by the activation or inhibition of different receptors and target molecules of the endocannabinoid system. In the final part of this review, we explore the current state of CBD in clinical trials as a treatment for cardiovascular diseases and provide evidence of its potential benefits in humans.

Cannabidiol Alleviates Perfluorooctanesulfonic Acid-Induced Cardiomyocyte Apoptosis by Maintaining Mitochondrial Dynamic Balance and Energy Metabolic Homeostasis

“…27 CBD can limit cardiac injury by improving the antioxidant capacity of cells and alleviating apoptosis caused by the mitochondrial death pathway. 33 CBD restores ATP levels and mitochondrial function, reduces oxidative damage, and prevents cardiomyocytes from entering the apoptosis phase in rats poisoned with aluminum phosphide (AlP). 61 This study also found that CBD treatment can protect cardiomyocytes from PFOS-induced oxidative stress, thereby alleviating PFOSinduced mitochondrial dynamic imbalance and energy metabolism disorder, suggesting that CBD can ameliorate PFOS-induced heart injury by controlling myocardial apoptosis mediated by the mitochondrial death pathway.…”

“…Meanwhile, energy metabolism disorders caused by mitochondrial dysfunction further aggravate PFOS-induced apoptosis . CBD can limit cardiac injury by improving the antioxidant capacity of cells and alleviating apoptosis caused by the mitochondrial death pathway . CBD restores ATP levels and mitochondrial function, reduces oxidative damage, and prevents cardiomyocytes from entering the apoptosis phase in rats poisoned with aluminum phosphide (AlP) .…”

“…32 The protective effect of CBD on the heart is also reflected in its ability to restore function of damaged mitochondria in cardiomyocytes and avoid apoptosis caused by the activation of the caspase cascade. 33 As one of the upstream mechanisms of apoptosis, mitochondrial structure and dysfunction can be activated by oxidative stress. Many studies have shown that PFOS is harmful to multitissue and multiorgan of animals.…”

Experimental Studies and First Retrospective Clinical Data Suggest a Possible Benefit of CBD in COVID-19

“…Intriguingly, brain hypoxemia, often silent, occurs also with COVID-19, potentially inducing long lasting sequelae even after remission. Furthermore, CBD mitigates in vivo widely differing forms of cardiomyopathies as has been shown in various animal models including ischemia/reperfusion arrhythmias, myocardial infarction, autoimmune myocarditis or diabetic cardiomyopathy (reviewed recently by [34,35]). This includes also a mouse model of doxorubicin-induced cardiotoxicity [36].…”

Ndufs1 Deficiency Aggravates the Mitochondrial Membrane Potential Dysfunction in Pressure Overload‐Induced Myocardial Hypertrophy

“…Under pathological conditions of CH, the activities of ATP synthase and mitochondrial oxidative phosphorylation complex are attenuated, which results in reduced production of ATP [12,13]. Moreover, attenuated mitochondrial dynamics, reduced mitochondrial volume, and abnormal mitochondrial morphology were detected in cardiomyocytes in CH [14,15]. Mitochondrial dysfunction was shown to increase the production of reactive oxygen species (ROS) via impaired electron transport chains, which can lead to increased oxidative stress and decreased energy production in cardiomyocytes [9,16,17].…”