CB1 KO mice showed increased sensitivity toward developing learned helplessness, an animal model of depression, as well as anhedonia upon exposure to chronic mild stress (Gorzalka et al., 2008), and CB1 receptor mediated endocannabinoid transmission was found to play a role in influencing affective processing under stress exposure in both rodents (McLaughlin et al., 2012; Wang et al., 2012; Morena et al., 2016) and humans (Wirz et al., 2018). This evidence concerns the gene CNR1 and major depressive disorder.