Cannabidiol, unlike synthetic cannabinoids, triggers activation of RBL-2H3 mast cells.

Cannabidiol (CBD), a prominent psychoinactive component of cannabis with negligible affinity for known cannabinoid receptors, exerts numerous pharmacological actions, including anti-inflammatory and immunosuppressive effects, the underlying mechanisms of which remain unclear. In the current study, we questioned whether CBD modulates activation of mast cells, key players in inflammation. By using the rat basophilic leukemia mast cell line (RBL-2H3), we demonstrate that CBD (3-10 muM) augments beta-hexosaminidase release, a marker of cell activation, from antigen-stimulated and unstimulated cells via a mechanism, which is not mediated by G(i)/G(o) protein-coupled receptors but rather is associated with a robust rise in intracellular calcium ([Ca(2+)](i)) levels sensitive to clotrimazole and nitrendipine (10-30 muM).