Inhibition of cyclooxygenase 2 (COX2) activity is thought to activate endocannabinoid signalling. This study identified a substrate-selective COX2 inhibitor that did not modulate non-endocannabinoid lipids or prostaglandin synthesis. In mice, the inhibitor reduced anxiety-like behaviours by increasing endocannabinoid signalling without inducing detrimental cannabimimetic effects. The results confirm that COX2 regulates endocannabinoid signalling and suggest that substrate-selective COX2 inhibitors have therapeutic potential, possibly without gastrointestinal or cardiac side effects.
References
Hermanson, D. J. et al. Substrate selective COX-2 inhibition decreases anxiety via endocannabinoid activation. Nature Neurosci. 16, 1291–1298 (2013)
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Harrison, C. Selectively targeting COX2 decreases anxiety. Nat Rev Drug Discov 12, 742 (2013). https://doi.org/10.1038/nrd4144
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DOI: https://doi.org/10.1038/nrd4144
