Cannabidiol exerts multitarget immunomodulatory effects on PBMCs from individuals with psoriasis vulgaris

Abstract

IntroductionThe involvement of endocannabinoid system (ECS) in the inflammatory cascade, and the ability of phytocannabinoids, endocannabinoids and their synthetic analogues to modulate it has become an interesting research area for new therapeutic approaches in inflammatory skin diseases. Cannabidiol (CBD) appears to be the most promising among phytocannabinoids, due to the lack of psychotropic effects and low toxicity profile. Its anti-inflammatory action has been highlighted in different preclinical models, ranging from experimental colitis to arthritis and neuroinflammation. Our aim was to evaluate CBD immune-modulatory effects in peripheral blood mononuclear cells (PBMC) of psoriasis individuals with particular attention to both innate and adaptative immune arms.MethodsWe performed in vitro immune functional experiments to analyze CBD action on various immune cells active in psoriatic lesions.ResultsThe results showed that CBD produced a shift from Th1 to Th2 response, while boosting cytotoxic activity of Natural Killer (NK) cells. Furthermore, it also exerted a potent action on monocyte differentiation as, after CBD treatment, monocytes from psoriatic individuals were unable to migrate in response to inflammatory stimuli and to fully differentiate into mature dendritic cells. Finally, a M2 skewing of monocyte-derived macrophages by CBD also contributed to the fine tuning of the magnitude of immune responses.ConclusionsThese data uncover new potential immunomodulatory properties of this cannabinoid suggesting a possible therapeutic action in the treatment of multiple inflammatory skin diseases.

The Perspective of Cannabidiol in Psoriasis Therapy

“…Specifically, it has been observed that CBD reduces the secretion of inflammatory cytokines such as IFNγ and TNFα in peripheral blood mononuclear cells (PBMCs) from individuals with psoriasis, which are key factors in the disease’s pathophysiology. 20 …”

“…Specifically, it has been observed that CBD reduces the secretion of inflammatory cytokines such as IFNγ and TNFα in peripheral blood mononuclear cells (PBMCs) from individuals with psoriasis, which are key factors in the disease's pathophysiology. 20 Additionally, CBD has demonstrated potential in minimizing oxidative stress in keratinocytes from psoriatic skin, which could help avert the metabolic effects related to peroxidation. This beneficial action may stem from CBD's capability to influence the activity of enzymes that promote pro-oxidative conditions and to bolster the antioxidant defenses in these cells.…”