Cannabidiol Inhibits IgE‐Mediated Mast Cell Degranulation and Anaphylaxis in Mice

Scope Cannabidiol (CBD), the most abundant non‐psychoactive constituent of the plant Cannabis sativa , is known to possess immune modulatory properties. This study investigates the effects of CBD on mast cell degranulation in human and mouse primary mast cells and passive cutaneous anaphylaxis in mice. Methods and results Mouse bone marrow‐derived mast cells and human cord‐blood derived mast cells are generated. CBD suppressed antigen‐stimulated mast cell degranulation in a concentration‐dependent manner. Mechanistically, CBD inhibited both the phosphorylation of FcεRI downstream signaling molecules and calcium mobilization in mast cells, while exerting no effect on FcεRI expression and IgE binding to FcεRI. These suppressive effects are preserved in the mast cells that are depleted of type 1 (CB1) and type 2 (CB2) cannabinoid receptors, as well as in the presence of CB1 agonist, CB2 agonist, CB1 inverse agonist, and CB2 inverse agonist. CBD also inhibited the development of mast cells in a long‐term culture. The intraperitoneal administration of CBD suppressed passive cutaneous anaphylaxis in mice as evidenced by a reduction in ear swelling and decrease in the number of degranulated mast cells. Conclusion Based on these results, the administration of CBD is a new therapeutic intervention in mast cell‐associated anaphylactic diseases.