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Acting through cannabinoid receptors, endogenous endocannabinoids (eCBs), such as anandamide, modulate pain and anxiety, among other things; substances that inhibit enzymes that break down eCBs may have antianxiety properties. Because cyclooxygenase-2 (COX-2), which catalyzes synthesis of prostaglandins from arachidonic acid, also inactivates anandamide, researchers explored the antianxiety qualities of a substrate-selective COX-2 inhibitor that selectively augments eCBs without the other effects of nonselective COX-2 inhibitors, such as nonsteroidal anti-inflammatory drugs (NSAIDs). The researchers hold patent interests in the molecule, LM-4131, a derivative of the COX inhibitor indomethacin.
In mice, LM-4131 increased brain anandamide leve…