Purified Cannabidiol isolate does not inhibit active caspase-1 release in NLRP inflammasome-mediated UVB or ATP-activated keratinocytes or appear to reduce key inflammatory cytokines in UVB-irradiate keratinocytes.

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Cannabidiol is a plant-derived cannabinoid that has been suggested to have several human health benefits including potential anti-inflammatory effects. It is now common to find various forms of Cannabidiol, most often referred to as CBD, in nutritional supplements and topical treatments. The mechanisms by which CBD can influence inflammatory pathways in the body, and more particularly in the skin, are presently still unclear. It is known that CBD will bind to cannabinoid receptors, CB1 and CB2, in the body and recent work has shown that in keratinocytes, CBD can regulate inflammation through transcriptional regulation involving the NFƙβ nuclear pathways. The fact that CBD operates through the NFƙβ pathways suggests that, perhaps, the molecule may influence the expression of active caspase-1 through NLRP inflammasome-mediated pathways. Recently, work has published demonstrating that Normal Human Epidermal Keratinocytes (NHEKs) can be activated by UVB and ATP to express active caspase-1 via NLRP inflammasome-mediated pathways. There was a strong interest to see whether highly purified Cannabidiol Isolate (>99% purity) might function to control release of active caspase-1 by testing of NHEKs using the previously described models. In addition, NHEKs expression of non-NLRP inflammasome-induced inflammation markers including IL-6, IL-8 and PGE2 was examined in UVB-activated NHEKs. It was found that purified Cannabidiol Isolate did not influence active caspase-1 release in either UVB or ATP-activated NHEKs suggesting the molecule does not influence the NLRP inflammasome pathways. In addition, it was surprisingly found that the Cannabidiol Isolate did not impact the expression of additional UVB-activated non-NLRP inflammatory markers. Data presented suggest that if Cannabidiol functions as an anti-inflammatory, it does so through pathways not associated with either the NLRP inflammasome-mediated expression of caspase-1 or through the more commonly known expression of interleukin or prostaglandin inflammatory pathways.