Endocannabinoid System

The endocannabinoid system is a widespread cell-signaling system built around endogenous lipid messengers, cannabinoid receptors, and the enzymes that make and break down those messengers. Two well-studied endocannabinoids are anandamide and 2-arachidonoylglycerol, or 2-AG, and the best-characterized receptors are CB1 and CB2 .^1,2

A distinctive feature of the system is that endocannabinoids are often synthesized on demand rather than stored in vesicles like many classical neurotransmitters. In the nervous system they can travel backward across a synapse from a postsynaptic cell and reduce transmitter release from the presynaptic terminal. Through this and other mechanisms, endocannabinoid signaling helps regulate processes that include synaptic activity, pain, appetite, stress responses, immune function, and energy balance .^1,2

The endocannabinoid system is not the same thing as cannabis. Plant cannabinoids such as delta-9-tetrahydrocannabinol can interact with components of this system, but the system exists independently and uses molecules made by the body. It is also broader than cannabinoid receptors alone because ligand synthesis and degradation, receptor distribution, and local tissue context all shape the signal. Its effects therefore vary substantially across organs and cell types .¹