CNR1 and major depressive disorder: Accumulating evidence supports the role of CB1 receptors (CB1Rs) in regulating the response to stress, anxiety, and depression.133 For example, mutant mice lacking CB1Rs (CB1R knockout, CB1KO mice) displayed anhedonia before control (wild type) mice when exposed to chronic mild stress,134 suggesting genetic deletion of CB1R results in an increased susceptibility to the development of an anhedonic state in these animals.