Since previous data have consistently shown that genetic or pharmacological blockade of intracerebral CB1 receptors leads to sustained conditioned fear in rodents (for reviews see Riebe et al., 2012; Micale et al., 2013), a CB1 antagonist with confined actions in the periphery is expected to preserve its beneficial functions on several aspects of the metabolic syndrome, without exerting its psychopathological side effects. This evidence concerns the gene CNR1 and metabolic syndrome.