Endocannabinoid system (ECS)

The endocannabinoid system was identified when researchers traced how THC acts on the body and found receptors built for molecules the body already makes. Lu and Mackie's 2016 review describes its 3 parts: receptors, endogenous ligands and metabolic enzymes (Lu and Mackie 2016).

CB1 receptors are the most abundant cannabinoid receptor in the central nervous system, sitting mostly on nerve terminals. CB2 receptors appear at much lower levels in the nervous system and are concentrated in immune cells (Lu and Mackie 2016).

The body's own cannabinoids are anandamide, a low-efficacy partial agonist, and 2-arachidonoylglycerol or 2-AG, a high-efficacy agonist at both receptors. They are made on demand from membrane lipids and act as retrograde messengers, traveling backward across synapses to adjust how much neurotransmitter is released. FAAH breaks down anandamide and MAGL breaks down 2-AG (Lu and Mackie 2016).

THC mimics these ligands at CB1. CBD works differently, with weak direct receptor binding and effects on enzymes and other targets. NIH describes cannabinoids as a group of substances found in the plant, with THC and CBD the main two (NCCIH).