Seegehalli M Anil  - ARO, Volcani Center
Nurit Shalev - ARO, Volcani Center
Ajjampura C Vinayaka - ARO, Volcani Center
Stalin Nadarajan - ARO, Volcani Center
Dvory Namdar  - ARO, Volcani Center
Eduard Belausov  - ARO, Volcani Center
Irit Shoval  - Bar Ilan University
Karthik Ananth Mani  - ARO, Volcani Center
Guy Mechrez  - ARO, Volcani Center
Hinanit Koltai - ARO, Volcani Center

Cannabis sativa is widely used for medical purposes and has anti-inammatory activity. The purpose of this study was to examine the anti-inammatory activity of cannabis on markers of immune responses associated with Coronavirus disease 2019 (COVID-19) inammation. An extract fraction from C. sativa Arbel strain (FCBD ) substantially reduced dose dependently interleukin (IL) 6 and 8 levels in an alveolar epithelial (A549) cell line. FCBD contained cannabidiol (CBD), cannabigerol (CBG) and tetrahydrocannabivarin (THCV), and multiple terpenes. Treatments with FCBD and phytocannabinoid standards that compose FCBD (FCBD:std ) reduced IL-6, IL-8, C-C Motif Chemokine Ligands (CCLs) 2 and 7, and angiotensin I converting enzyme 2 (ACE2) expression in the A549 cell line. Treatment with FCBD induced macrophages (differentiated KG1 cell line) polarization and phagocytosis in vitro, and increased CD36 and type II receptor for the Fc region of IgG (FcγRII) expression. FCBD treatment also substantially increased IL-6 and IL-8 expression in macrophages. FCBD:std , while maintaining the anti-inammatory activity in alveolar epithelial cells, led to reduced phagocytosis and pro-inammatory IL secretion in macrophages in comparison to FCBD . The phytocannabinoid mixture may show superior activity versus cannabis fraction for reduction of lung inammation, yet there is a need of caution in proposing cannabis as treatment for COVID-19.