Information pertaining to the role of ECS in human depression, anxiety and stress is relatively scarce, and not completely validated, as reviewed in [67,108,109]. From post-mortem studies, an upregulation of CB1R and its G-protein signaling has been observed in the dorsolateral prefrontal cortex of depressed suicide victims [110]. Elevated levels of the eCBs AEA and 2-AG, and CB1R-mediated G-protein signaling in the prefrontal cortex of alcoholic suicide victims were also observed [111]. The up-regulation of CB1R coupling to G-proteins, specifically to Gαo, and not Gαi or Gαz protein subunits, has also been observed in the prefrontal cortex of depressed suicide victims [112]. It has been revealed, however, that this up-regulated CB1R/Gαo functionality might be due in part to the administration of antidepressants [67,112]. An interesting point is that the fluctuations of the eCBs seem to be linked to the gravity of depression [67]. Increases in serum levels of 2-AG and/or AEA has been observed in patients with minor depression, whereas patients with major depression showed reduced serum levels of 2-AG and/or AEA. Similarly, CB1R levels seem to depend on the
