Study: CBD May Protect Against Heart Failure by Improving Mitochondrial Function and Reducing Inflammation

In an animal model of heart failure (HF), researchers administered subcutaneous doses of CBD every three days for four weeks. The study found that CBD effectively reduced cardiac fibrosis, hypertrophy, and inflammation while improving contractile function and ejection fraction. These improvements were linked to CBD’s role in maintaining redox balance and mitochondrial integrity in cardiomyocytes, the muscle cells of the heart. In the study, mice receiving CBD displayed preserved heart function across several key parameters, including stroke volume and cardiac output. Importantly, CBD treatment prevented the decline in mitochondrial membrane potential and respiratory efficiency seen in untreated HF mice. It also reduced markers of oxidative stress, such as protein carbonylation, and normalized the GSH/GSSG ratio, a key indicator of antioxidant capacity.

CBD also altered intracellular calcium (Ca²⁺) dynamics, mitigating the delayed relaxation and impaired calcium reuptake common in heart failure. It reduced the frequency of abnormal Ca²⁺ sparks, suggesting improved stability of calcium-handling proteins such as ryanodine receptors.

Mechanistically, the cardioprotective effects appear to be partially mediated by activation of the PPAR-γ pathway, a nuclear receptor involved in regulating inflammation and metabolism. The study confirmed CBD’s interaction with PPAR-γ through molecular docking simulations and showed that blocking PPAR-γ with an antagonist eliminated CBD’s protective effects. CBD also reduced expression of the mitochondrial calcium uniporter (MCU), helping to prevent mitochondrial calcium overload and subsequent oxidative damage.

Collectively, the results suggest that CBD could serve as a therapeutic agent for heart failure by targeting multiple pathophysiological pathways.

The study concludes by stating:

This study demonstrated that cannabidiol offers cardioprotection in a HF mouse model induced by L-NAME and ANGII administration. The results showed improved cardiac function and reduced cardiac hypertrophy, remodeling, inflammation, and cell death. In cardiomyocytes from the HF model, cannabidiol restored cell shortening, which was linked to improved calcium Ca2+ handling.

Additionally, it helped preserve cellular oxidative status, mitochondrial bioenergetics, and notably, modulated mCa2+ overload by affecting MCU expression. This suggests that the cardioprotective effects of cannabidiol are caused by the preservation of excitation-contraction-energetic coupling. The identified cellular mechanisms through which cannabidiol exerts its cardioprotective effects include reducing oxidative stress and the activation of PPAR-γ, which helps prevent mitochondrial dysfunction by decreasing MCU hyperactivity.