Written by Renata Filiaci, MSHW

Cardiovascular disease (CVD) is a global epidemic representing the leading cause of death in some Western countries. According to the American Heart Association, a total of 92.1 million US citizens currently have ≥1 forms of CVD, with numbers expected to grow reaching up to 43.9% of the US population by 2030. In 2013, 17.3 million people (≈31% of all deaths) died due to CVD, and the number is expected to rise to at least 23.6 million in the next 15 years and cause an estimated economic burden of 1.0 trillion US dollars by 2030.

Given its pathological and economic burden, there is a striking need for both mechanistic insights into CVD and the development of avenues for therapy. This review highlights the potential of cannabinoids and their receptors as targets for intervention. Many 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.

High Blood Pressure/Hypertension

Preclinical studies show CBD has numerous cardiovascular benefits, including a reduced blood pressure (BP) response to stress. Nine healthy male volunteers were given 600 mg of CBD or placebo in a randomized, placebo-controlled, double-blind, crossover study. Cardiovascular parameters were monitored. CBD reduced resting systolic BP and stroke volume, with increased heart rate (HR) and maintained cardiac output. Subjects who had taken CBD had lower BP (especially before and after stress), increased HR, and decreased stroke volume. This data shows that acute administration of CBD reduces resting BP and the BP increase to stress in humans, associated with increased HR. These hemodynamic changes should be considered for people taking CBD.

Researchers conducted a prospective study of patients aged 60 years or more with hypertension and a new prescription of cannabis. They performed multiple assessments: 24-hours ambulatory blood pressure monitoring, ECG, blood tests, and anthropometric measurements prior to the initiation of cannabis therapy and 3 months afterward. A total of 38 participants were recruited to the study and 26 of them continued cannabis treatment and completed follow-up of 3 months since treatment initiation. In this prospective cohort study of older adults with hypertension, we have shown that cannabis treatment for 3 months was associated with a reduction in both systolic and diastolic blood pressure values. Fasting plasma glucose was also significantly decreased (this means after not having anything to eat or drink (except water) for at least 8 hours before the test).

Myocarditis

Many cases of myocarditis are associated with autoimmune processes in which cardiac myosin is a major autoantigen. Conventional immunosuppressive therapies often provide unsatisfactory results and are associated with adverse toxicities during the treatment of autoimmune myocarditis. Herein, using a well-established mouse model of experimental autoimmune myocarditis (EAM) induced by immunization with cardiac myosin emulsified in adjuvant resulting in T cell–mediated inflammation, cardiomyocyte cell death, fibrosis, and myocardial dysfunction, we studied the potential beneficial effects of CBD. EAM was characterized by marked myocardial T-cell infiltration, profound inflammatory response, and fibrosis (measured by quantitative real-time polymerase chain reaction, histology, and immunohistochemistry analyses) accompanied by marked attenuation of both systolic and diastolic cardiac functions measured with a pressure-volume conductance catheter technique. Chronic treatment with CBD largely attenuated the CD3+ and CD4+ T cell–mediated inflammatory response and injury, myocardial fibrosis, and cardiac dysfunction in mice. In conclusion, CBD may represent a promising novel treatment for managing autoimmune myocarditis and possibly other autoimmune disorders and organ transplantation.

Atherosclerosis

In recent decades, epidemiological, clinical, and experimental studies have demonstrated that a diet with antioxidant or anti-inflammatory function plays a central role in the prevention of atherosclerosis (AS). The purpose of this study was to explore the effects of Cannabis seed oil (CO) administration on in vitro antioxidant capacity as well as blood lipid profiles, lipid peroxidation, inflammatory response, and endothelial cell integrity. Female ApoE–/– mice were fed a high-cholesterol diet and administrated with CO or phosphate-buffered saline (PBS) and seal oil by gavage for 8 weeks. The results show that CO administration reduced the levels of serum triglycerides and low-density lipoprotein cholesterol at week 6. Additionally, a decrease in serum tumor necrosis factor α and nitric oxide was also observed. Moreover, results from CD31 staining and scanning electron microscopy revealed that CO treatment alleviated the endothelial cell damage and lipid deposition induced by a high-cholesterol diet. The ratio of lesion area to the total aorta area was 19.57% for the CO group, which was lower than the PBS control group (24.67%). Collectively, CO exerted anti-atherosclerotic effects by modulating serum lipid profiles and inflammatory responses and improving endothelial cell integrity and arterial lipid deposition. The results provide a promising preventive strategy for the early progression of AS.

Cardiomyopathy

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.