The classic model for the function of the endocannabinoid system is the retrograde feedback loop first characterized on pre- and postsynaptic cells of the central nervous system. Endocannabinoids are produced in the postsynaptic cell in response to presynaptic cell neurotransmitter release. 2AG is synthesized by the enzyme DAG-L and AEA by NAPE-PLD. These endocannabinoids then diffuse back across the synaptic cleft to the presynaptic neuron aided by fatty acid binding proteins and membrane transport proteins. They then bind to and activate the cell membrane-bound, G protein-coupled cannabinoid receptors, CB1 and CB2. They are then immediately broken down by the enzymes MAGL and FAAH. Regulation of the endocannabinoid system is dynamic and can occur not only with regulation of its receptors but also regulation of its synthesis and degradation enzymes. Palmitoylethanolamide (PEA) and oleoylethanolamide (OEA) are not endocannabinoids but are capable of interacting with cannabinoid receptors, as is the pepcan hemopressin. Endocannabinoids in addition to activating cannabinoid receptors also interact with a variety of other receptors such as PPAR gamma, TRPV1, GPR18, GPR55, and GPR119.