GPR18

N-arachidonyl glycine receptor also known as G-protein coupled receptor 18 (GPR18) is a protein that in humans is encoded by the GPR18 gene. Along with the other previously "orphan" receptors GPR55 and GPR119, GPR18 has been found to be a receptor for endogenous lipid neurotransmitters, several of which also bind to cannabinoid receptors.

Research supports the hypothesis that GPR18 is the abnormal cannabidiol receptor and N-arachidonoyl glycine, the endogenous lipid metabolite of anandamide, initiates directed microglial migration in the CNS through activation of GPR18, though recent evidence demonstrates that NAGly was not shown to be a GPR18 agonist in rat sympathetic neurons.

Ligands

Agonists

Ligands found to bind to GPR18 as agonists include:

• N-Arachidonoylglycine (NAGly)
• Abnormal cannabidiol (Abn-CBD)
• AM-251 - partial agonist
• Cannabidiol - partial agonist
• O-1602
• Δ⁹-Tetrahydrocannabinol (Δ⁹-THC) - THC is actually a more potent agonist at GPR18 than at CB₁ or CB₂, with Ki of 0.96nM at GPR18, 8.1nM at GPR55, 25.1nM at CB₁ and 35.2nM at CB₂.
• Anandamide (N-arachidonoyl ethanolamine, AEA)
• Arachidonylcyclopropylamide (ACPA)
• Resolvin D2 (RvD2)

Antagonists

• O-1918
• CID-85469571