Our findings that the peripherally restricted CB1R antagonist JD5037 is as effective as its globally acting, brain-penetrant parent compound, SLV319 (ibipinabant), in ameliorating metabolic abnormalities in hyperphagic, obese Magel2-null mice clearly suggest that blocking CB1R in the periphery, rather than centrally, has potential efficacy for treating obesity in PWS. The gene discussed is CNR1; the disease is Prader-Willi syndrome.