Impact of CSE and THC on the Respiratory System Mucosa: Insights on Novel Experimental Models

The significant role of tobacco smoking as a primary risk factor for respiratory diseases has been extensively substantiated. In addition, cannabis use has been linked to persistent respiratory symptoms and numerous lung disorders in several case studies. Tetrahydrocannabinol (THC), the major active principle in all cannabis products, exerts its effects by binding to cannabinoid type 1 (CB1) receptors and, to a lesser extent, cannabinoid type 2 (CB2) receptors, which are differentially expressed in both the central and peripheral nervous systems, as well as other anatomical systems, including the respiratory one. Research conducted to date has enabled a comprehensive understanding of the mechanisms involved in cigarette smoking and its role in the development of chronic respiratory conditions. Recent investigations have also postulated that smoking cannabis may increase the risk of airway obstruction. This review focuses on fully understanding the impact of cigarette smoke extract (CSE) and THC on the human respiratory mucosa by using a methodological approach to assess the administration techniques and experimental models used in this field. Traditional single-layer cell cultures are a cost-effective research solution. However, they fail to replicate the complex structure and function of human organs' microenvironments in vivo. Therefore, after analysing various experimental models proposed in the literature, we concluded that the three-dimensional ex vivo culture model could be considered the most suitable one for studying the effects of CSE and THC on the respiratory mucosa.