- The endocannabinoid system (ECS) is a regulatory body system that consists of cannabinoid molecules synthesized internally and called endocannabinoids, and their target receptors – called cannabinoid receptors (CB) proteins. See Graphic.
- Endocannabinoids – Anandamide and 2-Arachidonoylglycerol (2-AG) are endogenous molecules that were discovered in the 1990’s. Endocannabinoids are produced and released on demand, during heightened levels of stress on the brain or the body. Endocannabinoids are lipid soluble and are not stored in vesicles, like traditional neurotransmitters. When endocannabinoids are released in the brain, they travel in a retrograde way (from post-synaptic to pre-synaptic side) and target cannabinoid receptors.
Synthesis and degradation of AEA and 2-AG
- Cannabinoid receptors are divided into two subtypes: CB1 and CB2.
- Agonist – compounds activate receptors
- CB1 receptors are predominantly expressed in the brain. They can also be found in the heart and the digestive system. 2-AG has higher affinity to CB1 receptors. CB1 receptors ae the most abundant G-protein coupled receptor in the brain.
- CB2 receptors are mostly found in the peripheral body organs and cells that contribute to the normal function of the immune system, such as spleen, and pancreas. Recently CB2 receptors were also found in the brain, but to a lesser extent than CB1.
- Full agonist is more potent than partial
- Affinity – potency of compound binding
- High affinity receptors require lower concentrations of ligands
- Endocannabinoid deficiencies are thought to be disorders that stem from the lack of proper ECS functions. These disorders are usually hyperalgesia: Migraines, fibromyalgia, irritable bowel syndrome, neurotransmitter disorders, and epilepsies (Dr. Ethan Russo).
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