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2-Arachidonoylglycerol, the most abundant endocannabinoid that activates both CB1 and CB2 receptors in the body.
2-Arachidonoylglycerol, commonly known as 2-AG, is the most abundant endocannabinoid in the human body. It activates both CB1 and CB2 receptors, giving it a broader signaling role than anandamide, which primarily targets CB1. Discovered in 1995 by Raphael Mechoulam and Shimon Ben-Shabat, 2-AG is found at concentrations roughly 170 times higher than anandamide in the brain.
2-AG serves as a key regulator of synaptic transmission in the brain. It works through retrograde signaling: when a postsynaptic neuron is overstimulated, it produces 2-AG, which travels backward to the presynaptic neuron and tells it to reduce neurotransmitter release. This feedback mechanism helps prevent excessive neural activity and plays a role in pain modulation, immune function, appetite regulation, and emotional processing. The enzyme monoacylglycerol lipase (MAGL) breaks down 2-AG after it completes its signaling task.
Because 2-AG activates the same receptors as THC and CBD, understanding this endocannabinoid helps explain why cannabis has such wide-ranging effects on the body. THC essentially amplifies what 2-AG does naturally, while CBD may modulate 2-AG signaling indirectly. Researchers are exploring MAGL inhibitors as potential pharmaceutical targets, which would increase 2-AG levels without requiring cannabis consumption. This line of research could lead to new treatments for pain, anxiety, and neuroinflammation.
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