Effects of cannabidiol on activated immune-inflammatory pathways in major depressive patients and healthy controls

Abstract Background Major depressive disorder and a major depressive episode (MDD/MDE) are characterized by activation of the immune-inflammatory response system (IRS) and the compensatory immune-regulatory system (CIRS). Cannabidiol (CBD) is a phytocannabinoid isolated from the cannabis plant which was reported to have antidepressant-like and anti- inflammatory effects. The aim of the present study is to examine the effects of CBD on IRS, CIRS, M1, T helper (Th)-1, Th-2, Th-17, T regulatory (Treg) profiles, and growth factors in depression and healthy controls. Methods Culture supernatant of stimulated (5 μg/mL of PHA and 25 μg/mL of LPS) whole blood of 30 depressed patients and 20 controls was assayed for cytokines using the LUMINEX assay. The effects of three CBD concentrations (0.1 µg/ml, 1 µg/mL, and 10 µg/mL) were examined. Results Depression was characterized by significantly increased Th-1, Th-2, Th-17, Treg, IRS, CIRS and neurotoxicity profiles. CBD 0.1 µg/mL did not have any immune effects. CBD 1.0 µg/mL decreased CIRS activities but increased growth factor production, while CBD 10.0 µg/mL suppressed Th-1, Th-17, IRS, CIRS, and a neurotoxicity profile and enhanced T cell growth and growth factor production. CBD 1.0 to 10.0 µg/mL dose-dependently decreased sIL- 1RA, IL-8, IL-9, IL-10, IL-13, CCL11, G-CSF, IFN-γ, CCL2, CCL4, and CCL5, and increased IL-1β, IL-4, IL-15, IL-17, GM-CSF, TNF-α, FGF, and VEGF. Conclusion CBD has very complex immunomodulatory effects which depend on the CBD dose. CBD does not normalize the activated immune profiles observed in depression while higher concentrations can worsen inflammatory processes.