Evaluation of the Effects Of Phytocannabinoids on Human Gingival Fibroblast Proliferation, Migration, Growth And Inflammatory Cytokine Production

Overview

Periodontitis is one of the most prevalent inflammatory conditions affecting more than 46% of the US adult population representing 64.7 million people, according to the latest NHANES survey and contributing significantly to the global burden of oral diseases. Polymicrobial biofilm (etiological factor) induces specific inflammatory responses which initiate a complex prolonged biological immune response from the host resulting in elevated levels of several pro-inflammatory cytokines and chemokines like IL-1ß, TNF-a, IL-1a, IL-6, IL-17, and matrix metalloproteinase (MMPs) resulting in collagen destruction and subsequent periodontal attachment loss. One reported factor that may affect the incidence and progression of periodontal disease is the use of marijuana and/or hemp-based product (CBD oils) for medical and recreational purposes. Considering, the recent cultural shift in the perception of marijuana and hemp-based product (CBD oils), the dental consequence of which, especially on gingival tissues and implant are broadly unknown. Cannabinoids refer to a heterogeneous group of molecules acting on cannabinoid receptors (CBR) are of three types; endocannabinoids, that is produced endogenously, phytocannabinoids derived from the marijuana/hemp plants (~120 known), and synthetics (chemically synthesized). Some cannabinoids are known to induce psychotropic effects such as tetrahydrocannabinol (THC), while others namely cannabidiol are non-psychoactive. Studies have shown that non-psychoactive components like cannabidiol decrease MMP production and activity while promoting gingival proliferation and TGF-ß production. 4 A novel approach to treat the chronic inflammation in periodontal disease is to utilize non-psychoactive cannabinoid-based drugs due to their potent immunomodulatory and anti-inflammatory activity. The cannabinoid type 2 receptor (CB2R) is emerging as a promising target for inflammatory diseases as it is readily expressed on immune cells and is involved with immune-modulatory and anti-inflammatory activity, while the CB1 receptor is associated with the psychotropic effects. Little is known about the oral immunomodulatory effects of various non-psychoactive cannabinoids like cannabidiol, cannabidivarin, and cannabigerol. Therefore, in this study, we aim to examine cell viability and proliferation in primary human gingival fibroblasts (HGFs) with cannabidiol, cannabidivarin, and cannabigerol. These cannabinoids will also be tested for cytokines and chemokines production INF, IL-6, IL-8, MCP-1, TNF-a in IL-1ß stimulated and non-stimulated HGFs. The results of these studies will yield data that will provide insight into emerging concepts of hemp-based/marijuana products in periodontal inflammation.