As for the periodontium itself, Nakajima et al. have reported that LPS-triggered NF-κB activation, the key event in the induction of pro-inflammatory cytokine expression, is blocked in gingival fibroblasts by the endocannabinoid, anandamide (65), while the synthetic anandamide analog, methanandamide, has been shown to suppress local TNF production and reduce alveolar bone loss and in an LPS-injection model of periodontitis (66). This evidence concerns the gene TNF and periodontitis.