CNR1 and major depressive disorder: The anandamide level is directly correlated with the activity of the HPA axis; activation of CB1R inhibits the release of corticotropin-releasing hormone and the release of downstream cortisol, decreasing chronic stress levels, but the synaptic levels of anandamide are low with decreased expression of CB1R and correlate with psychopathology, including anxiety, depression, and post-traumatic stress disorder (PTSD) [110].