CB1 receptors may be upregulated in an attempt to compensate for reduced endocannabinoid signaling. In line with this, mutations in CB1 (the major cannabinoid receptor) and FAAH (the major endocannabinoid degrading enzyme) were found to be associated with anorexia and Bulimia (Monteleone et al., 2009).
GPR119 is involved in food intake and glucose homeostasis (keeping blood glucose levels within acceptable limits). GPR119 is mainly expressed in the pancreas and tissues of the gastrointestinal tract. GPR119 binds to endocannabinoids Anandamide, 2OG, PEA and OEA. OEA is actually the strongest endogenous activator of GPR119 and was shown to reduce food intake and weight gain in rodents via PPARα and TRPV1 (Overton et al., 2006). GPR119 and OEA may work synergistically with other cannabinoids and receptors in reducing food intake but more research is required.
Monteleone, P., Bifulco, M., Di Filippo, C., Gazzerro, P., Canestrelli, B., Monteleone, F., Proto, M.C., Di Genio, M., Grimaldi, C., and Maj, M. (2009). Association of CNR1 and FAAH endocannabinoid gene polymorphisms with anorexia nervosa and Bulimia nervosa: evidence for synergistic effects. Genes Brain Behav. 8, 728–732.
Overton, H.A., Babbs, A.J., Doel, S.M., Fyfe, M.C.T., Gardner, L.S., Griffin, G., Jackson, H.C., Procter, M.J., Rasamison, C.M., Tang-Christensen, M., et al. (2006). Deorphanization of a G protein-coupled receptor for oleoylethanolamide and its use in the discovery of small-molecule hypophagic agents. Cell Metab. 3, 167–175.