“Currently, no treatment can completely cure pulmonary hypertension (PH), which can lead to right ventricular failure and, consequently, death. Therefore, searching for new therapies remains important. Increased resistance in pulmonary circulation is mainly caused by the excessive contraction and proliferation of small pulmonary arteries.

Cannabinoids, a group of lipophilic compounds that all interact with cannabinoid receptors, exert a pulmonary vasodilatory effect through several different mechanisms, including mechanisms that depend on vascular endothelium and/or receptor-based mechanisms, and may also have anti-proliferative and anti-inflammatory properties.

The vasodilatory effect is important in regulating pulmonary resistance, which can improve patients’ quality of life. Moreover, experimental studies on the effects of cannabidiol (plant-derived, non-psychoactive cannabinoid) in animal PH models have shown that cannabidiol reduces right ventricular systolic pressure and excessive remodelling and decreases pulmonary vascular hypertrophy and pulmonary vascular resistance.

Due to the potentially beneficial effects of cannabinoids on pulmonary circulation and PH, in this work, we review whether cannabinoids can be used as an adjunctive therapy for PH. However, clinical trials are still needed to recommend the use of cannabinoids in the treatment of PH.”

https://pubmed.ncbi.nlm.nih.gov/34576212/

“CBD, which was approved by the U.S. Food and Drug Administration and the European Medicines Agency for the treatment of drug-resistant seizures and spasticity in adult patients with multiple sclerosis, also exerts a protective effect on the vascular endothelium, decreases RVSP and/or heart remodelling and increases saturation in experimental PH, in addition to its vasorelaxant effects on pulmonary arteries.”

https://www.mdpi.com/1422-0067/22/18/10048

“Cannabidiol (CBD) is a plant-derived compound with antioxidant and anti-inflammatory properties. Pulmonary hypertension (PH) is still an incurable disease. CBD has been suggested to ameliorate monocrotaline (MCT)-induced PH, including reduction in right ventricular systolic pressure (RVSP), a vasorelaxant effect on pulmonary arteries and a decrease in the white blood cell count.

The aim of our study was to investigate the effect of chronic administration of CBD (10 mg/kg daily for 21 days) on the parameters of oxidative stress and inflammation in the lungs of rats with MCT-induced PH.

In MCT-induced PH, we found a decrease in total antioxidant capacity (TAC) and glutathione level (GSH), an increase in inflammatory parameters, e.g., tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), nuclear factor kappa B (NF-κB), monocyte chemoattractant protein-1 (MCP-1), and cluster of differentiation 68 (CD68), and the overexpression of cannabinoid receptors type 1 and 2 (CB₁-Rs, CB₂-Rs). Administration of CBD increased TAC and GSH concentrations, glutathione reductase (GSR) activity, and decreased CB₁-Rs expression and levels of inflammatory mediators such as TNF-α, IL -1β, NF-κB, MCP-1 and CD68.

In conclusion, CBD has antioxidant and anti-inflammatory effects in MCT-induced PH. CBD may act as an adjuvant therapy for PH, but further detailed preclinical and clinical studies are recommended to confirm our promising results.”

https://pubmed.ncbi.nlm.nih.gov/35630804/

“The evidence presented the antioxidant and anti-inflammatory effects of CBD in the lung tissue of rats with MCT-induced PH; as well, we reported on its relaxing effect on pulmonary vessels and the properties of reducing RVSP, suggesting that CBD could be a successful adjunctive therapy in the treatment of PH. The NF-κB pathway and downregulation of CB₁-Rs, the activation of which has pro-oxidative and proinflammatory effects, may play a special role in the antioxidant and anti-inflammatory CBD-mediated effect. The available therapies for PH treatment are focused only on vascular effects; CBD has multipotent beneficial effects, which is in line with the current trend of seeking multidirectional therapies. The promising results of our research may form the basis for a more detailed study of the effects of CBD or its derivatives on PH, especially in humans.”

https://www.mdpi.com/1420-3049/27/10/3327

“Cannabidiol Found to Ease Oxidative Stress, Inflammation in Rat Model”

“Background: Pulmonary hypertension (PH) can cause right ventricular (RV) failure and subsequent cardiohepatic syndrome referred to as congestive hepatopathy (CH). Passive blood stasis in the liver can affect inflammation, fibrosis, and ultimately cirrhosis. Cannabidiol (CBD) has many beneficial properties including anti-inflammatory and reduces RV systolic pressure and RV hypertrophy in monocrotaline (MCT)-induced PH in rats. Thus, it suggests that CBD may have the potential to limit CH development secondary to RV failure. The present study aimed to determine whether chronic administration of CBD can inhibit the CH secondary to RV hypertrophy associated with MCT-induced PH.

Methods: The experiments involved rats with and without MCT-induced PH. CBD (10 mg/kg) or its vehicle was administered once daily for 3 weeks after MCT injection (60 mg/kg).

Results: Monocrotaline administration increased the liver/body weight ratio. In histology examinations, we observed necrosis and vacuolar degeneration of hepatocytes as well as sinusoidal congestion. In biochemical studies, we observed increased levels of nuclear factor-κappa B (NF-κB), tumour necrosis factor-alpha (TNA-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6). CBD administration to PH rats reduced the liver/body weight ratio, improved the architecture of the liver, and inhibited the formation of necrosis. Cannabidiol also decreased the level of NF-κB, TNF-α, IL-1β and IL-6.

Conclusions: The studies show that CBD can protect the liver from CH probably through attenuating PH, protective effects on the RV, and possibly direct anti-inflammatory effects on liver tissue through regulation of the NF-κB pathway.”

https://pubmed.ncbi.nlm.nih.gov/38519732/

“In conclusion, we confirmed that the NF-κB pathway may be involved in the development of CH, especially at an early stage. Furthermore, the studies presented show that CBD can protect the liver from CH probably through attenuating PH [9], protective effects on the RV [10], and possibly direct anti-inflammatory effects on liver tissue through regulation of the NF-κB pathway (Fig. 5). In addition, like other authors, we confirm that CBD did not cause any adverse changes in the liver of healthy rats, demonstrating its high safety potential.”

https://link.springer.com/article/10.1007/s43440-024-00579-4