As highlighted throughout this review, modulation of endogenous cannabinoid tone provides an alternative to direct CB1 receptor agonism and although still in the early stages of clinical investigation, FAAH inhibitors such as PF-04457845 have demonstrated safety and tolerability in patients, although no effect on pain associated with osteoarthritis was reported (Huggins et al., 2012). This evidence concerns the gene FAAH and osteoarthritis.