The effects of oleylethanolamide on feeding behavior involve hypothalamic oxytocin neurons

In December 1992 Devane and his collaborators (Devane et al., 1992) reported the isolation and structure elucidation of a porcine brain lipid component that selectively displaced the binding of a high-affinity cannabinoid receptor ligand to brain membrane preparations. This compound was the ethanolamide of arachidonic acid (20:4, n-6) and was named anandamide (AEA) (Figure 1), after the Sanskrit word for “bliss”, ananda. AEA was shown to be active in the tetrade of mouse behavioral tests suggestive of cannabinoid-like activity, i.e. inhibition of locomotor and rearing activity, hypothermy, catalepsy, and analgesia (Fride and Mechoulam, 1993; Crawley et al., 1993). Another derivative of arachidonic acid that activates cannabinoid receptors, 2-arachidonoylglycerol (2-AG), was discovered in 1995 (Mechoulam et al., 1995; Sugiura et al., 1995). Although structurally different from plant-derived cannabinoids, these compounds, in analogy with the “endorphins” (i.e. the endogenous ligands of opiate receptors), were named “endocannabinoids”.