Anti-inflammatory properties of cannabidiol, a non-psychotropic cannabinoid, in experimental allergic contact dermatitis.
J Pharmacol Exp Ther. 2018 Apr 9. Epub 2018 Apr 9. PMID: 29632236
Phytocannabinoids modulate inflammatory responses by regulating the production of cytokines in several experimental models of inflammation. Cannabinoid type-2 (CB2) receptor activation was shown to reduce the production of the monocyte chemotactic protein-2 (MCP-2) chemokine in polyinosinic-polycytidylic acid [poly-(I:C)]-stimulated human keratinocyte (HaCaT) cells, an in vitro model of allergic contact dermatitis (ACD). We investigated if non-psychotropic cannabinoids like cannabidiol (CBD) produced similar effects in this experimental model of ACD. HaCaT cells were stimulated with poly-(I:C) and the release of chemokines and cytokines was measured in the presence of CBD or other phytocannabinoids (such as CBDA, CBDV, CBDVA, CBC, CBG, CBGA, CBGV, THCV, THCVA) and antagonists of cannabinoid type-1 (CB1), CB2 or transient receptor potential vanilloid type 1 (TRPV1) receptors. HaCaT cell viability following phytocannabinoid treatment was also measured. The cellular levels of endocannabinoids [anandamide (AEA), 2-arachidonoylglycerol (2-AG)] and related molecules [palmitoylethanolamide (PEA), oleoylethanolamide (OEA)] were quantified in poly-(I:C)-stimulated HaCaT cells treated with CBD. We showed that in poly-(I:C)-stimulated HaCaT cells, CBD elevated the levels of AEA and dose-dependently inhibited poly-(I:C)-induced release of MCP-2, IL-6, IL-8 and TNF-α in a manner reversed by CB2 and TRPV1 antagonists, AM630 and I-RTX, respectively, with no cytotoxic effect. This is the first demonstration of the anti-inflammatory properties of CBD in an experimental model of ACD.