Cannabis compounds have both anti-inflammatory and pro-inflammatory activities in lung epithelial and macrophages while substantially increasing phagocytosis in vitro
Seegehalli M Anil1+, Nurit Shalev1+, Ajjampura C Vinayaka1+, Stalin Nadarajan1+, Dvory Namdar1, Eduard Belausov1, Irit Shoval2, Karthik Ananth Mani3, Guy Mechrez3, Hinanit Koltai1*
1 Institute of Plant Science, Agriculture Research Organization, Volcani Center, Rishon LeZion 7528809, Israel
2 The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 5290002, Israel.
3 Institute for Postharvest and Food Science, Agriculture Research Organization, Volcani Center, Rishon LeZion 7528809, Israel
+ These authors contributed equally to this work
Cannabis sativa is used worldwide for medical purposes and is known to have anti-inflammatory activity, yet the potential for use of C. sativa compounds against Coronavirus disease 2019 (COVID-19)-like inflammation is unexplored. The purpose of this study was to examine the anti-inflammatory activity of cannabis on markers of immune responses associated with COVID-19 inflammation. An extract fraction from high cannabidiol (CBD) cannabis strain (FCBD) substantially reduced dose dependently interleukin 6 (IL-6) and interleukin-8 (IL-8) levels in an alveolar epithelial (A549) cell line. FCBD contained CBD, cannabigerol (CBG) and tetrahydrocannabivarin (THCV), and multiple terpenes. Treatments with FCBD and phytocannabinoid standards that compose FCBD (FCBD:std) reduced in a dose dependent way IL-6, IL-8, C-C Motif Chemokine Ligands (CCLs) 2 and 7 in the A549 cell line. It also reduced expression of angiotensin I converting enzyme 2 (ACE2), a receptor for SARS-CoV-2. Treatment with FCBD induced macrophage (differentiated KG1 cell line) polarization and phagocytosis in vitro, and increased expression of scavenger receptor CD36 and that of type II receptor for the Fc region of IgG (FcγRII). FCBD treatment also substantially increased IL-6 and IL-8 expression in macrophages. FCBD:std, while maintaining the anti-inflammatory activity in alveolar epithelial cells, led to reduced pro-inflammatory IL secretion in macrophages in comparison to FCBD and reduced level of phagocytosis. The phytocannabinoid mixture may show superior activity for reduction of lung inflammation over that of the cannabis fraction. Yet, as for now, users and healthcare personnel should avoid the use of cannabis for COVID-19 prevention or treatment.