CNR1 and major depressive disorder: For example, various polymorphisms of CB1 and CB2 receptors have been identified in patients with major depression and bipolar disorder (Monteleone et al., 2010; Minocci et al., 2011; Mitjans et al., 2012; Mitjans et al., 2013) with a single nucleotide polymorphism in the CB1 receptor reported to enhance the risk of treatment resistance in depression (Domschke et al., 2008) and the development of anhedonic depression following early life trauma (Agrawal et al., 2012).