Exploring the Role of Cannabidiol (CBD) in Hypertension and Cardiac Protection

Cannabidiol (CBD), a non-psychoactive cannabis plant constituent, has a wide range of applications. Many clinicians are familiar with CBD’s analgesic and mood-boosting properties but may not have considered its role in cardiovascular (CV) health. Preclinical trials have confirmed CBD's antioxidant, anti-inflammatory, and cardioprotective properties, and newer evidence suggests that CBD may play a role in hypertension.

What is CBD’s Mechanism in Cardiovascular Health?

The body’s endocannabinoid system (ECS) is composed of cannabinoid receptors CB1 and CB2 and endogenous ligands. Plant cannabinoids, such as CBD, interact with these receptors and exert effects throughout the body, including the cardiovascular system.¹ For example, CBD enhances endothelial function by stimulating nitric oxide production, leading to vasorelaxation of human arteries through CB1 receptor activation.²

The ECS is not a significant regulator of CV function under normal physiologic conditions; however, it becomes activated under pathological conditions, which may be protective. CBD not only affects cannabinoid receptors, but also a variety of other receptors located in the nervous system, blood vessels, and heart.¹

Numerous preclinical studies have investigated the effect of CBD on cardiovascular function using human cells, tissues, and animal models. Researchers have identified five main mechanisms responsible for CBD's beneficial effects:^1,3

• Antioxidant and anti-nitrosative
• Anti-inflammatory
• Vasorelaxant and vasodilatory
• Regulates cardiac contractility
• Antiproliferative and antiapoptotic properties

CBD also has anxiolytic properties and can mitigate the negative effects of stress. Epidemiological studies show a positive relationship between chronic stress and cardiovascular disease (CVD) development.⁴ CBD interacts with serotonin 5-HT1A receptors, affecting stress-related changes in the CV system.¹

Animal studies have revealed CBD’s cardioprotective properties. CBD administration prior to inducing myocardial ischemia/infarction reduced the infarct size, number of ventricular arrhythmias, cardiac troponin I levels, myocellular apoptosis, and collagen-induced platelet aggregation. CBD mitigates doxorubicin cardiotoxicity by decreasing histopathological heart changes and reducing serum markers of myocardial damage, including creatine kinase, lactate dehydrogenase, and troponin T.¹ There is also evidence for CBD in cerebrovascular disease and stroke.⁵ Human studies are needed to confirm these findings.

CBD may also help CVD by supporting a healthy weight and other metabolic parameters.^6,7

Clinical Trials: CBD and Hemodynamic Effects

CBD in Hypertension

A 5-week, randomized, triple-blind, placebo-controlled, crossover study examined the influence of CBD administration on blood pressure and arterial stiffness in 70 patients with hypertension. Patients had stage 1 or stage 2 hypertension and were either treated or untreated with standard hypertensive therapy. Participants received CBD in divided doses of 225 or 300 mg/day for 2.5 weeks, then doses were increased to 375 or 450 mg/day for the remainder of the study. Patients were equipped with a 24-hour ambulatory BP monitoring system at the start of each treatment period, at 2.5 weeks, and after 5 weeks. The crossover study design then had the group go through a 2-week washout period and complete another 5 weeks on placebo.

There was a statistically significant reduction in 24-hour average mean arterial pressure (MAP), systolic blood pressure (SBP), and diastolic blood pressure (DBP) in those taking CBD but not placebo. Notably, these reductions were seen after 2.5 weeks and did not change significantly following dose increases. Office blood pressure showed significantly reduced MAP and SBP, but not DBP, after 5 weeks of CBD. No difference was found between CBD and placebo for pulse wave velocity (arterial stiffness).⁸

These researchers assessed additional data in subsequent studies on this same population to learn more about the mechanisms. Reductions were observed in serum concentrations of cytokines IL-8, IL-18, IL-10, the neuroendocrine peptide catestatin, and the vasoconstricting peptide urotensin-II after 5 weeks of CBD, but not placebo. The anti-hypertensive effect of CBD may be in part due to inflammation-, neuroendocrine-, and endothelial-modulating properties.^9–11

CBD in Healthy Humans

In two randomized controlled trials, researchers investigated the effect of 600 mg of CBD or placebo on BP and other hemodynamic parameters in healthy males. In one study on nine males, acute CBD administration reduced resting SBP and stroke volume and prevented increases due to stressful situations. Heart rate was higher in those taking CBD.⁴

In the other study on 26 males, various cardiovascular parameters were assessed at rest and after isometric exercise. At rest, acute CBD dosing reduced MAP but did not affect other CV parameters. In response to exercise, SBP was significantly lower in the CBD-treated group compared to placebo after acute and repeated CBD dosing for 7 days. Repeated CBD dosing significantly reduced arterial stiffness, increased internal carotid artery diameter, and improved endothelial function compared to acute dosing, but not when compared to placebo.²

Larger trials and more research are needed to understand the effects of dosing, delivery method, and long-term CBD administration on cardiovascular parameters, especially under pathological conditions.^1,4 Clinical trials testing the efficacy of CBD in myocarditis and pericarditis are in progress.¹²

CBD Safety and Cardiovascular Medications

In general, CBD is well-tolerated with minor side effects and no known adverse cardiovascular effects.^1,8 CBD is a substrate for cytochrome P450 enzymes and influences their activity; therefore, caution should be exercised when using other medications. For example, studies on FDA-approved CBD medicine Epidiolex® showed interaction with warfarin, intensifying the antithrombotic effect by increasing the international normalized ratio (INR).¹ However, in the hypertension study, researchers did not observe any drug interactions between CBD and anti-hypertensive medications.⁸

CBD’s Therapeutic Potential for Cardiovascular Health

Chronic inflammation and oxidative stress are key contributors to CVD pathogenesis. Emerging research suggests that CBD, with its well-documented anti-inflammatory, antioxidant, and anxiolytic properties, may offer complementary support in addressing these underlying mechanisms. While more clinical studies are needed to confirm its long-term benefits and optimal use in cardiovascular care, CBD shows promising potential for hypertension and as part of a holistic approach to heart health.

References

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4. Jadoon KA, Tan GD, O'Sullivan SE. A single dose of cannabidiol reduces blood pressure in healthy volunteers in a randomized crossover study. JCI Insight. 2017;2(12).
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9. Urlic H, Kumric M, Dujic G, et al. Antihypertensive effects of CBD are mediated by altered inflammatory response: A sub-study of the HYPER-H21-4 trial. J Funct Foods. 2023;110:105873.
10. Kumric M, Dujic G, Vrdoljak J, et al. CBD supplementation reduces arterial blood pressure via modulation of the sympatho-chromaffin system: A substudy from the HYPER-H21-4 trial. Biomed Pharmacother. 2023;160:114387.
11. Kumric M, Dujic G, Vrdoljak J, et al. Effects of CBD supplementation on ambulatory blood pressure and serum urotensin-II concentrations in Caucasian patients with essential hypertension: A sub-analysis of the HYPER-H21-4 trial. Biomed Pharmacother. 2023;164:115016.
12. Naya NM, Kelly J, Hogwood A, Abbate A, Toldo S. Therapeutic potential of cannabidiol (CBD) in the treatment of cardiovascular diseases. Expert Opin Investig Drugs. 2024;33(7):699-712.