Category: receptor_pharmacology
On-demand lipid neurotransmitter system. Endogenous ligands synthesized from membrane phospholipids in postsynaptic neurons + immune cells: anandamide (N-arachidonoylethanolamine, AEA) via NAPE-PLD; 2-AG (2-arachidonoylglycerol) via DAGL. Retrograde signaling: endocannabinoids cross synapse to act on presynaptic CB1 (CNS) or peripheral CB2 (immune) — Gi/o-coupled → reduces neurotransmitter release. Degradation: AEA → FAAH (fatty acid amide hydrolase) → arachidonic acid + ethanolamine; 2-AG → MAGL (monoacylglycerol lipase) → AA + glycerol. Pharmacology: THC = partial CB1/CB2 agonist; CBD = weak CB receptor activity + multi-target (TRPV1, 5-HT1A, PPAR); rimonabant (withdrawn — psychiatric side effects) was a CB1 antagonist for obesity. FAAH inhibitors (BIA 10-2474 — fatal trial; others in development) raise endogenous AEA.