To circumvent untoward behavioral effects observed after treatment with brain-penetrant CB1 antagonists, peripherally restricted CB1-targeting drugs have been developed, with positive results on cardiometabolic parameters in obese mice,48–50 as well as liver steatosis.51 Clinical trials have already started,52,53 with drugs deemed ready to move to phase 2 studies,54 thus opening the way to a promising new treatment paradigm for obesity-related disorders such as liver steatosis. The gene discussed is CNR1; the disease is fatty liver disease.