As the link between c-Fos expression in micturition centers and the activation of CB1 receptors by ACEA may be indirect, it has been shown that in depression, the hallmark of which is hypothalamic-pituitary-adrenal (HPA) axis hyperactivation, stimulation of endocannabinoid system through CB1 receptors suppresses the HPA axis [28]. The gene discussed is FOS; the disease is major depressive disorder.