“The cannabinoid type 2 receptor (CB2) has recently emerged as an important therapeutic target for cancer as well as cardiovascular diseases. The CB2 receptor downregulation has been reported in solid tumors and cardiovascular diseases, therefore the CB2receptor activation has been considered as a viable strategy for chemotherapy as well as cardioprotection.
In chemotherapy, doxorubicin (DOX) is an important drug that continues to be the mainstay of chemotherapy in solid tumors, leukemia, and lymphoma. However, the use of DOX is often limited due to its lethal cardiotoxicity. Considering the role of CB2 receptors in cardiovascular diseases and cancer, the activation of CB2 receptors may protect against DOX-induced chronic cardiotoxicity in rats.
In the present study, we investigated the cardioprotective effect of a selective CB2 receptor agonist; β-Caryophyllene (BCP), a natural bicyclic sesquiterpene, against DOX-induced chronic cardiotoxicity in rats. AM630, a CB2 receptor antagonist was administered as a pharmacological challenge prior to BCP treatment to demonstrate CB2 receptor mediated cardioprotective mechanism of BCP. DOX (2.5 mg/kg) was injected intraperitoneally once a week for five weeks to induce chronic cardiotoxicity in rats.
BCP was also injected into rats six days a week for a total duration of five weeks. DOX induced a significant decline in cardiac function and oxidative stress evidenced by the depletion of antioxidant enzymes, glutathione, and increased lipid peroxidation. DOX also triggered activation of nuclear factor kappa B (NF-κB) and increased the levels of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) and expression of the inflammatory mediators (iNOS and COX-2) in the heart.
Furthermore, DOX also upregulated the expression of pro-apoptotic markers such as Bax, p53, cleaved PARP, active caspase-3 and downregulated anti-apoptotic marker Bcl-2 in the myocardium. BCP treatment exerted significant cardioprotective effect by salvaging the heart tissues, improving cardiac function, mitigating oxidative stress, inflammation, and apoptosis. The histological and ultrastructural studies also appear in line with our findings of biochemical and molecular parameters.
The CB2 receptor-mediated cardioprotective mechanism was further confirmed by the abrogation of the beneficial effects of BCP with prior administration of the CB2 receptor antagonist; AM630.
Our study revealed the novel mechanism of BCP in cardioprotection against DOX-induced chronic cardiotoxicity by the activation of CB2 receptors.”
https://www.ncbi.nlm.nih.gov/pubmed/30836069
https://www.sciencedirect.com/science/article/pii/S0009279718316284?via%3Dihub
“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.” http://www.ncbi.nlm.nih.gov/pubmed/23138934
“This study tested longitudinal associations between 
“The administration of cannabinoid receptor 2 (CB2R) agonist has been reported to produce a cardioprotective effect against the pathogenesis and progression of myocardial infarction (MI).
Here in this study, we investigated the specific mechanism related to inflammatory suppression. JWH-133 was used for the activation of CB2R.
Taken together, we demonstrated for the first time the cardioprotective effect of CB2R agonist and its NLRP3 inflammasome-related mechanism in MI.”
“The endocannabinoids anandamide (AEA) and 2-arachidonoylglyerol (2-AG) are endogenous lipid mediators that exert protective roles in pathophysiological conditions, including cardiovascular diseases. In this brief review, we provide a conceptual framework linking endocannabinoid signaling to the control of the cellular and molecular hallmarks, and categorize the key components of endocannabinoid signaling that may serve as targets for novel therapeutics. The emerging picture not only reinforces endocannabinoids as potent regulators of cellular metabolism but also reveals that endocannabinoid signaling is mechanistically more complex and diverse than originally thought.”
“Cannabinoids have been increasingly gaining attention for their therapeutic potential in treating various cardiovascular disorders. These disorders include myocardial infarction, hypertension, atherosclerosis, arrhythmias, and metabolic disorders.
The aim of this review is to cover the main actions of cannabinoids on the cardiovascular system by examining the most recent advances in this field and major literature reviews.
It is well recognized that the actions of cannabinoids are mediated by either cannabinoid 1 or cannabinoid 2 receptors (CB2Rs). Endocannabinoids produce a triphasic response on blood pressure, while synthetic cannabinoids show a tissue-specific and species-specific response.
Blocking cannabinoid 1 receptors have been shown to be effective against cardiometabolic disorders, although this should be done peripherally. Blocking CB2Rs may be a useful way to treat atherosclerosis by affecting immune cells. The activation of CB2Rs was reported to be useful in animal studies of myocardial infarction and cardiac arrhythmia.
Although cannabinoids show promising effects in animal models, this does not always translate into human studies, and therefore, extensive clinical studies are needed to truly establish their utility in treating cardiovascular disease.”
“Cannabinoid receptor 2 (CB2) has been reported to produce a cardio-protective effect in cardiovascular diseases such as myocardial infarction. Here in this study, we investigated the role of CB2 in diabetic cardiomyopathy (DCM) and its underlying mechanisms.
In conclusion, we initially demonstrated that activating CB2 produced a cardio-protective effect in DCM as well as cardiomyocytes under HG challenge through inducing the AMPK-mTOR-p70S6K signaling-mediated autophagy.”
“The transient global cerebral hypoperfusion/reperfusion achieved by induction of Bilateral Common Carotid Artery Occlusion followed by Reperfusion (BCCAO/R) has been shown to stimulate early molecular changes that can be easily traced in brain tissue and plasma, and that are indicative of the tissue physiological response to the reperfusion-induced oxidative stress and inflammation.
The aim of the present study is to probe the possibility to prevent the molecular changes induced by the BCCAO/R with dietary natural compounds known to possess anti-inflammatory activity, such as the phytocannabinoid beta-caryophyllene (BCP).