What is the effect of cannabinoids?

Currently, no treatment can completely cure pulmonary hypertension (PH), which can lead to right ventricular failure and thus death. Cannabinoids, a group of lipophilic compounds that interact with cannabinoid receptors, have potential beneficial effects on pulmonary circulation and pH.

Pulmonary hypertension (PH) refers to a group of clinical symptoms caused by elevated blood pressure (BP) in the pulmonary circulation. According to the latest classification, PH is diagnosed when the mean pulmonary arterial pressure (mPAP) at rest exceeds 25 mmHg, as confirmed by right-sided cardiac catheterization . The World Health Organization (WHO) classifies PH into 5 groups: pulmonary arterial hypertension (PAH), PH due to left-sided heart disease, PH due to chronic lung disease, chronic thromboembolic PH, and PH of unknown and/or multifactorial pathology . PH often leads to heart failure due to excessive overloading of the right ventricle (RV), resulting in death of the patient. The development of PH is complex and its pathogenesis includes vascular endothelial cell dysfunction, excessive pulmonary artery constriction, vascular and RV remodeling (myocyte proliferation and hypertrophy), inflammation, oxidative stress, and thrombosis.

As in the systemic circulation, cannabinoids have also been shown to have vasodilatory effects in isolated pulmonary vessels. Cannabinoids exhibit concentration-dependent vasorelaxation in human pulmonary arteries (hPA). Notably, the most commonly used pulmonary vasoconstrictors mirror those involved in the pathophysiology of PH. LPI showed the strongest vasodilatory effect, but this effect may be due to the use of phenylephrine to constrict blood vessels. Furthermore, CBD and LPI cause time-dependent relaxation of human pulmonary vessels. A single concentration of CBD and LPI produced an initial relaxation of the vessels of about 20% after 15 minutes, increasing to about 70% after 120 minutes.

Cannabinoids play a role in modulating pulmonary vascular tone through endothelium-dependent or receptor-based mechanisms (above), which may help reduce pulmonary resistance. Furthermore, an endocannabinoid negative feedback mechanism in the pulmonary artery was found to be responsible for attenuating agonist-induced vasoconstriction, which may also play an important role in the treatment of PH. CBD is approved by the U.S. Food and Drug Administration and the European Medicines Agency for the treatment of drug resistance in adult patients with multiple sclerosisSeizures and spasms, also have a protective effect on the vascular endothelium, reduce RVSP and/or cardiac remodeling and increase the saturation of experimental PH, and its vasodilatory effect on the pulmonary artery. Therefore, (endo)cannabinoids represent a potential new therapeutic strategy as an add-on therapy for PH. Nonetheless, it should be emphasized that no clinical trials of cannabinoids for the treatment of PH have been conducted; therefore, their therapeutic potential has not yet been translated into clinical practice. In addition, a single experimental study showed that AEA and 2-AG can constrict blood vessels and/or increase PAP. Further experimental and clinical studies are needed to explain these inaccuracies.