Moreover, our study demonstrates that (i) chronic blockade of CB1R in the periphery is as effective as globally acting CB1R antagonism in reversing obesity and its metabolic abnormalities in an established mouse model for PWS, and (ii) the disrupted body composition and energy balance in Magel2-null mice is associated with increased eCB ‘tone’ in the hypothalamus. The gene discussed is CNR1; the disease is Prader-Willi syndrome.