Modulation of Respiratory Diseases by the Endocannabinoid System: A Therapeutic Perspective

Respiratory system diseases represent a major global health burden, characterized by high prevalence and significant morbidity and mortality. The respiratory tract's direct and continuous exposure to the external environment makes it particularly vulnerable to pathogens, pollutants and other injurious agents. This exposure often triggers excessive inflammatory responses and compromises the integrity of the air-blood barrier, leading to impaired gas exchange, hypoxia and respiratory failure. Therefore, modulating pulmonary inflammation and enhancing barrier function are critical therapeutic objectives. The endocannabinoid system, a ubiquitous signalling network comprising cannabinoid receptors, endogenous ligands and metabolic enzymes, has emerged as a crucial modulator of these processes. This review summarizes the role of the ECS in major respiratory diseases, including asthma, pulmonary fibrosis, respiratory syncytial virus infection and acute lung injury. The evidence highlights the therapeutic potential of targeting the ECS through strategies such as receptor-specific ligands and inhibitors of endocannabinoid-degrading enzymes. However, the context-dependent nature of ECS modulation necessitates precise intervention. Future efforts should focus on developing selective therapeutics and validating their efficacy in clinical settings, positioning the ECS as a sophisticated target for innovative respiratory disease management.