Whereas activation of CB1R by eCBs promotes appetite via a leptin-regulated hypothalamic neural appetitive circuitry [3], its chronic blockade by globally acting CB1R antagonists inhibits food intake both in rodents [4], [5], [6], [7] and individuals with obesity [8], [9], [10], [11]. Here, LEP is linked to obesity due to melanocortin 4 receptor deficiency.