A CBD-rich cannabis extract reduced IL-6 and IL-8 in lung epithelial cells relevant to COVID-19 inflammation, but paradoxically increased these same inflammatory markers in macrophages.
Immunology researchers, clinicians evaluating cannabis for inflammatory conditions, and scientists studying cannabinoid effects on different cell types.
Anti-inflammatory in lung cells, pro-inflammatory in macrophages
What the researchers found
The cannabis fraction (FCBD, containing CBD, CBG, and THCV) dose-dependently reduced IL-6, IL-8, CCL2, CCL7, and ACE2 expression in A549 lung epithelial cells. However, FCBD increased IL-6 and IL-8 in macrophages while inducing polarization and phagocytosis. A synthetic phytocannabinoid formulation (FCBD:std) maintained anti-inflammatory activity in lung cells while reducing pro-inflammatory effects in macrophages.
Why it matters
COVID-19 can cause severe lung inflammation. While cannabis compounds showed anti-inflammatory effects in lung cells, the opposite effect in immune cells highlights the complexity of using cannabinoids for inflammatory conditions and argues against simplistic claims about cannabis for COVID.
The numbers in context
FCBD reduced IL-6 and IL-8 dose-dependently in A549 cells. FCBD reduced ACE2 expression. FCBD increased IL-6 and IL-8 in macrophages. FCBD:std reduced macrophage pro-inflammatory effects compared to FCBD. FCBD contained CBD, CBG, and THCV plus terpenes.
How the study worked
In vitro study using A549 alveolar epithelial cells and differentiated KG1 macrophages. Cannabis extract fraction (FCBD) and a phytocannabinoid standard formulation (FCBD:std) tested for effects on COVID-19-relevant inflammatory markers, ACE2 expression, macrophage polarization, and phagocytosis.
What this study cannot tell us
In vitro cell line study, not clinical research. A549 and KG1 cell lines may not represent actual human lung and immune cells during COVID-19 infection. No virus was used; only inflammatory markers were measured. The extract composition may vary between batches.
How to read the evidence
In vitro study in cell lines, not clinical research. Interesting mechanistic finding but far from clinical application.
When this study was published
2021 in vitro study. The authors caution against proposing cannabis as a COVID-19 treatment based on these results.
The bigger picture
The divergent effects in different cell types serve as a reminder that anti-inflammatory claims about cannabis are oversimplified. What reduces inflammation in one tissue may worsen it in another.
Questions still open
- Would these effects be seen in actual COVID-19 patients? Could the phytocannabinoid formulation be optimized to maintain lung anti-inflammatory effects without macrophage activation? Is ACE2 reduction beneficial or harmful in the context of COVID-19?
Common questions
Can cannabis treat COVID-19?
Why did the effects differ between cell types?
Read the original research
Cannabis compounds exhibit anti-inflammatory activity in vitro in COVID-19-related inflammation in lung epithelial cells and pro-inflammatory activity in macrophages.
Scientific reports, 11(1), 1462
Citation
Anil, Seegehalli M; Shalev, Nurit; Vinayaka, Ajjampura C; Nadarajan, Stalin; Namdar, Dvora; Belausov, Eduard; Shoval, Irit; Mani, Karthik Ananth; Mechrez, Guy; Koltai, Hinanit. (2021). Cannabis compounds exhibit anti-inflammatory activity in vitro in COVID-19-related inflammation in lung epithelial cells and pro-inflammatory activity in macrophages.. Scientific reports, 11(1), 1462. https://doi.org/10.1038/s41598-021-81049-2
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