endocannabinoidsthat

Endocannabinoids are endogenous lipid mediators that activate the cannabinoid receptors of the endocannabinoid system. The two best characterized endocannabinoids are anandamide (AEA) and 2-arachidonoylglycerol (2-AG). They are synthesized on demand in response to neuronal activity and are released from postsynaptic neurons to act retrogradely on presynaptic cannabinoid receptors, thereby modulating neurotransmitter release.

Most cannabinoid signaling in the brain is mediated by CB1 receptors, which are highly expressed in regions involved in pain, mood, and memory, while CB2 receptors are primarily in immune cells and peripheral tissues. Endocannabinoids can also interact with other targets, such as the TRPV1 receptor and peroxisome proliferator-activated receptors, contributing to diverse effects. AEA is mainly degraded by fatty acid amide hydrolase (FAAH), while 2-AG is primarily broken down by monoacylglycerol lipase (MAGL). The synthesis of AEA involves N-acyl phosphatidylethanolamines and the enzyme NAPE-PLD, whereas 2-AG is produced through the action of diacylglycerol lipase on diacylglycerol.

Endocannabinoids regulate numerous physiological processes, including pain sensation, appetite and energy balance, mood, memory, and immune function. Because exogenous cannabinoids like delta-9-tetrahydrocannabinol (THC) can activate these receptors, the endocannabinoid system is a major focus of research into analgesics, antiemetics, and treatments for neuropsychiatric and inflammatory conditions. Studying the balance between synthesis and degradation of AEA and 2-AG helps explain how endocannabinoids contribute to homeostasis in health and disease.