Recent data indicate that the endocannabinoid system negatively regulates the neuroendocrine response to psychological stress (see Gorzalka et al., 2008 and Steiner and Wotjak, 2008). The endocannabinoid system is composed of two neuroactive signaling lipids, N-arachidonylethanolamine (anandamide; AEA) and 2-arachidonoylglycerol (2-AG), which bind to the cannabinoid type 1 (CB1) receptor localized to axonal processes (Freund et al., 2003). Both endocannabinoid ligands and the CB1 receptor are expressed within the amygdala (Herkenham et al., 1991; Bisogno et al., 1999), and endocannabinoid signaling within the amygdala is known to modulate both excitatory and inhibitory neurotransmission (Katona et al., 2001; Azad et al., 2003, 2004; Zhu and Lovinger, 2005; Domenici et al., 2006). Additionally, tissue contents of AEA and 2-AG within the amygdala is modulated in response to psychological stressors (Patel et al., 2005c; Hill et al., 2008; Rademacher et al., 2008).
