Extensive research focused on the central and peripheral role of the eECS in the energy balance [73], and it is convincingly shown that the controlled downregulation of the CB1 receptors and upregulation of PPAR-α and PPAR-γ are involved in the therapeutic effects exhibited by eCB-s and eCB-like NAEs in the role of the regulation of lipid metabolism and obesity [74,75]. This evidence concerns the gene PPARA and obesity due to melanocortin 4 receptor deficiency.