In the present study, obvious dose-dependent effects were not observed for CB1 agonists, and seemed to be due to the mechanisms related to multiple neurotransmitter systems including both ECB and stress-related neurotransmitter systems involved in anti-anxiety and/or anti-depression (e.g. GABAergic, glutamatergic and serotonergic systems) [129, 130, 136, 137]. The gene discussed is CNR1; the disease is major depressive disorder.