Old drugs, new mechanisms
A recent review by Vandevoorde in Current Topics in Medicinal Chemistry states that non-steroidal anti-inflammatory drugs (NSAIDs) are inhibitors of endocannabinoid metabolism. This drug class includes ibuprofen (sold as Nurofen and Advil in Australia) and indomethacin (sold as Indocid), both used for inflammatory pain and arthritic conditions. It is well established that NSAIDs inhibit a form of an enzyme called cyclo-oxygenase (COX) in order to block the production of inflammatory molecules called prostaglandins. It has also been demonstrated that endogenous cannabinoids such as anandamide, which are produced in brain, liver, lung, spleen and kidney, play a role in mediating pain in multiple sclerosis, head injury and many other inflammatory and autoimmune conditions. Recent evidence suggests that in addition to inhibiting COX, NSAIDs also stop the action of an enzyme called FAAH, which breaks down anandamide. Thus NSAIDs contribute towards pain relief in part by elevating the level of circulating anandamide.
Since other compounds that inhibit FAAH activity and thus elevate anandamide levels are proposed to have anxiolytic and antidepressant potential, I wonder therefore if there are any effects of NSAIDs on behaviour?
Such effects are not widely reported for NSAIDs. One clinical report suggests that in post-operative situations indomethacin produces dizziness and anxiety, but in another study, healthy elderly volunteers experienced improved cognitive performance, sensorimotor coordination and short term memory following the same drug.
I think it is worth investigating, in comparison with other known modulators of endocannabinoid metabolism, to see how these drugs affect various models of working and reference memory as well as anxiety.
Since other compounds that inhibit FAAH activity and thus elevate anandamide levels are proposed to have anxiolytic and antidepressant potential, I wonder therefore if there are any effects of NSAIDs on behaviour?
Such effects are not widely reported for NSAIDs. One clinical report suggests that in post-operative situations indomethacin produces dizziness and anxiety, but in another study, healthy elderly volunteers experienced improved cognitive performance, sensorimotor coordination and short term memory following the same drug.
I think it is worth investigating, in comparison with other known modulators of endocannabinoid metabolism, to see how these drugs affect various models of working and reference memory as well as anxiety.