An Introduction to the Endogenous Cannabinoid System

Summary & key facts

The endocannabinoid system (ECS) is a widespread brain signaling system made of cannabinoid receptors, naturally made lipid messengers, and the enzymes that make and break those messengers. The two best-studied messengers are 2-AG and anandamide, and they are produced and degraded by different enzyme pathways. CB1 receptors are common in cortex, hippocampus, basal ganglia, and cerebellum and sit mainly on axon terminals. CB2 receptors are much less common in a healthy brain, are often found on microglia and blood-vessel elements, and can rise a lot after injury. The ECS helps control synaptic plasticity and brain development, and it is linked to psychiatric conditions such as schizophrenia,

Key facts:

• The ECS is made of three parts: cannabinoid receptors, endogenous cannabinoids (endocannabinoids), and the enzymes that synthesize and degrade those endocannabinoids.
• The two best-studied endocannabinoids are 2-arachidonoyl glycerol (2-AG) and anandamide (arachidonoyl ethanolamide).
• 2-AG is a high-efficacy agonist at CB1 and CB2 receptors, while anandamide is a low-efficacy agonist at CB1 and a very low-efficacy agonist at CB2.
• 2-AG and anandamide are synthesized and degraded by largely distinct enzyme pathways, which gives them different physiological roles.
• Endocannabinoids are released on demand from membrane lipids rather than being stored in synaptic vesicles.
• CB1 receptors are abundant in the central nervous system, especially in cortex, basal ganglia, hippocampus, and cerebellum, and are mainly located on axon terminals and pre-terminal axon segments.
• CB2 receptors are expressed at much lower levels in the healthy brain, are primarily found in microglia and vascular elements, and can increase up to about 100-fold after tissue injury or inflammation.
• It is unclear whether observed increases in CNS CB2 come from increased expression on cells already in the brain or from migration of peripheral immune cells that express CB2.
• 2-AG serves not only as a cannabinoid receptor ligand but also as a major source of arachidonic acid for prostaglandin synthesis in brain, liver, and lung (but not in gut, heart, kidney, or spleen).
• Measurements of total tissue 2-AG do not necessarily reflect the synaptically active 2-AG that signals at receptors; techniques like microdialysis may be more accurate for that purpose.

Topics

Cannabis and Cannabinoid Research Neuroscience and Neuropharmacology Research Neurotransmitter Receptor Influence on Behavior

Categories

Health Sciences Medicine Pharmacology

Tags

Agonist Anandamide Biochemistry Biology Cannabinoid Cannabinoid receptor Chemistry Depolarization-induced suppression of inhibition Endocannabinoid system GPR18 Neuroscience Pharmacology Receptor Synaptic plasticity