Non-opioid Analgesics and the Endocannabinoid System

• Published in: Balkan Medical Journal
• Main Authors: Ruhan Deniz Topuz, Özgür Gündüz, Çetin Hakan Karadağ, Ahmet Ulugöl
• Format: Article
• Language: English
• Published: Trakya University 2020-11-01
• Subjects: dipyrone; endocannabinoids; nsaids; paracetamol
• Online Access: http://www.balkanmedicaljournal.org/text.php?lang=en&id=2226

Non-steroidal anti-inflammatory drugs produce antinociceptive effects mainly through peripheral cyclooxygenase inhibition. In opposition to the classical non-steroidal anti-inflammatory drugs, paracetamol and dipyrone exert weak anti-inflammatory activity, their antinociceptive effects appearing to be mostly due to mechanisms other than peripheral cyclooxygenase inhibition. In this review, we classify classical non-steroidal anti-inflammatory drugs, paracetamol and dipyrone as "non-opioid analgesics" and discuss the mechanisms mediating participation of the endocannabinoid system in their antinociceptive effects. Non-opioid analgesics and their metabolites may activate cannabinoid receptors, as well as elevate endocannabinoid levels through different mechanisms: reduction of endocannabinoid degradation via fatty acid amide hydrolase and/or cyclooxygenase-2 inhibition, mobilization of arachidonic acid for the biosynthesis of endocannabinoids due to cyclooxygenase inhibition, inhibition of endocannabinoid cellular uptake directly or through the inhibition of nitric oxide synthase production, and induction of endocannabinoid release.