**5. Cannabinoids and Lung Inflammatory Conditions**

Cannabis has been known for its recreational use for millennia, so it is not surprising that the effects of cannabinoid inhalation have been thoroughly documented in many studies. Though it is difficult to distinguish from concurrent chronic exposure to tobacco smoke, which is common, cannabis smoke inhalation causes some specific effects in the pulmonary system; it decreases the antimicrobial activity and cytokine production, and increases sputum production, coughing and possibly the risk of lung cancer [93,94]. Furthermore, marijuana smoke induces epithelial hyperplasia, cellular disorganization, cell atypia and fibrosis [95,96]. In vitro studies seem to confirm these findings at a cellular level, as cannabinoids have demonstrated immunosuppressive properties and profibrotic effects [97,98]. However, in vivo studies using the direct administration of pharmaceuticalgrade cannabinoids have revealed benefic effects on several inflammatory conditions, inducing a decrease in the recruitment of inflammatory cells, the suppression of cytokines, and an overall improvement in mortality [99]. These anti-inflammatory and immunomodulatory properties have prompted researchers to investigate the potential of cannabinoids in the management of coronavirus disease (COVID-19) infection [100–102]. However intriguing, the risks of drug interactions and partial inhibition of the immune response seem to outweigh the potential untested benefits in this condition, and the use of these substances is not recommended in this case, according to some authors [103]. Therefore, the main application and use of cannabinoids appear to be inflammatory diseases, and there is a great interest in this topic, which has encouraged numerous studies in the field.

No cannabinoid receptors have been isolated in vivo in the epithelial cells of the lungs; however, CB1 receptors have been identified in the nerve endings of the airways [104]. Both CB1 and CB2 receptors are expressed by eosinophils, monocytes and monocyte-derived macrophages [99,105]. CB1, CB2 and TRPV1 have been identified in situ and in vitro at the protein level in airway epithelial cells; however, the impact of these findings on the biology of respiratory inflammations remains unclear [106].
