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 severity of the depression. For example, CB1R-immunopositive glial cells in the grey matter were decreased in major depression, whereas no evidence of an altered density of CB1R immunopositive cells in schizophrenia or bipolar disorder was found [113]. The evaluation of the circulating levels of eCBs in body fluids may give an indication as to the role of the ECS in these disorders, although, as mentioned above, the severity of the disease and pre-treatment with other drugs, including antidepressants, may play a role in the final levels quantified. For example, it has been reported that plasma 2-AG levels, as well as CB1 and CB2 mRNA levels, are elevated in the lymphocytes of osteoarthritic patients, with a positive correlation between 2-AG levels, pain and depression [5]. In a recent systematic review of different studies tackling this matter [108], it was reported that differential effects of stress, depression, and anxiety symptoms may modulate endogenous levels of the eCBs. For example, acute psychological stress
