Overall, we are the first to show that application of C. sativa extracts profoundly decreases the level of pro-inflammatory cytokines in human 3D tissues. Still, our study has several pitfalls. Here, we used human 3D full-thickness skin model to analyze the effects of cannabis extracts on inflammation and fibrosis. While it would be important to replicate the data in an airway epithelial and alveolar tissue models, our data can be used as a roadmap for the future analysis. Moreover, key fundamental mechanisms of inflammation and fibrosis are similar in various tissues, and key roles of TNFα, IL-6 and other interleukins, chemokines, and MMPS have been well-established in an array of fibroproliferative diseases15. Pending further validation in lung tissue models, our novel extracts need to be studied in a clinical trial aimed to prevent or mitigate COVID-19 pneumonia and ARDS. To do so, the extracts have to be administered early upon positive diagnosis has been made to allow sufficient time for modulation of cytokine levels.
Most importantly, out of 7 selected extracts, only 3 performed best, one had no effects at all, and one exerted effects that may in turn be deleterious, signifying that cannabis is not generic and cultivar selection must be based on thorough pre-clinical studies. Furthermore, the current study was developed to analyze the effects of medical cannabis applications rather than smoking.
In the future, anti-TNFα and anti-IL-6 extracts need to be analyzed for their potential to mitigate inflammation in rheumatoid arthritis, ankylosing spondylitis, and other rheumatologic conditions, especially given the fact that extracts profoundly downregulate the RA pathway and target TNFα and IL-6. Also, the effects of novel extracts also need to be analyzed for their potential to combat ‘inflammaging’ – the inflammatory underpinning of aging and frailty.
Anna Kovalchuk, Rocio Rodriguez-Juarez, Slava Ilnytskyy, Dongping Li, Bo Wang, Igor Kovalchuk, Olga Kovalchuk Published 2020 May 22.
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