Asthma is characterized by chronic lung inflammation and airway hyperresponsiveness. Asthma remains a major public health problem and, at present, there are no effective interventions capable of reversing airway remodelling. Cannabidiol (CBD) is known to exert immunomodulatory effects through the activation of cannabinoid-1 and − 2 (CB₁ and CB₂) receptors located in the central nervous system and immune cells, respectively. However, as the role of CBD on airway remodelling and the mechanisms of CB₁ and CB₂ aren’t fully elucidated, this study was designed to evaluate the effects of cannabidiol in this scenario. Allergic asthma was induced in Balb/c mice exposed to ovalbumin, and respiratory mechanics, collagen fibre content in airway and alveolar septa, cytokine levels, and CB₁ and CB₂ expression were determined. Moreover, expressions of CB₁ and CB₂ in induced sputum of asthmatic individuals and their correlation with airway inflammation and lung function were also evaluated. CBD treatment, regardless of dosage, decreased airway hyperresponsiveness, whereas static lung elastance only reduced with high dose. These outcomes were accompanied by decreases in collagen fibre content in both airway and alveolar septa and the expression of markers associated with inflammation in the bronchoalveolar lavage fluid and lung homogenate. There was a significant and inverse correlation between CB¹ levels and lung function in asthmatic patients. CBD treatment decreased the inflammatory and remodelling processes in the model of allergic asthma. The mechanisms of action appear to be mediated by CB₁/CB₂ signalling, but these receptors may act differently on lung inflammation and remodelling.

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