Compelling evidence indicates an important role for the endocannabinoid system (ECS) in the regulation of mood disorders, including anxiety and depression. The involvement of the ECS in mood disorders is linked to its wide presence throughout different brain structures involved in the regulation of mood, emotion, and reward. In addition, there are strong scientific indications showing a wide range of interactions between the ECS and many other endogenous transmitter systems, with its capacity to modulate GABAergic and glutamatergic tones, as well as the release of dopamine, serotonin, opioids, norepinephrine, among many other effects, including regulating astrocyte and glial functions. Changes affecting ECS signaling produce a plethora of physiological and behavioral effects consistent with symptoms of depression and anxiety, in line with the hypothesis that a deficit in endocannabinoid signaling may yield a susceptibility to, or directly participate in, the development of a depressive episode [169]. Perturbations affecting the levels of eCBs seem to affect depression and anxiety symptomatology in humans and associated behaviors in animal models. In severe mood disorders, such as MDD and BD, decreases in eCBs and/or cannabinoid
