Scientists, including one of Indian-origin, have discovered a potential new way to treat anxiety and mood disorders.
Chemically modified inhibitors of the COX-2 enzyme relieve anxiety behaviours in mice by activating natural "endocannabinoids" without gastrointestinal side effects, researchers said.
Endocannabinoids are natural signalling molecules that activate cannabinoid receptors in the brain, the same receptors turned on by the active ingredient in marijuana.
These receptors are also found in the gastrointestinal system and elsewhere in the body, and there is evidence that they play a role in wide range of physiological and pathological processes, in addition to modulating stress and anxiety.
If the "substrate-selective" COX-2 inhibitors also work in humans without side effects, they could represent a new approach to treating mood and anxiety disorders, the researchers said.
Clinical trials of some of these potential drugs could begin in the next several years, said Lawrence Marnett, director of the Vanderbilt Institute of Chemical Biology and the paper's co-senior author with Sachin Patel from Vanderbilt University.
The scientists are pursuing other potential applications of activating endocannabinoids by substrate-selective COX-2 inhibition, including relieving pain, treating movement disorders, and possibly preventing colon cancer.
"The door is really wide open. We've just scratched the surface," said Patel, assistant professor of Psychiatry and of Molecular Physiology & Biophysics.
Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) relieve pain and inflammation by blocking either or both of the cyclooxygenase (COX) enzymes, which produce pro-inflammatory prostaglandins.
It has been known for several years that COX-2 inhibition also activates endocannabinoids, researchers said.
Because the "substrate selective" inhibitors increase endocannabinoid levels in the mouse without blocking prostaglandin production, "we think (they) will not have the gastrointestinal and possibly cardiovascular side effects that other NSAIDs do," said Marnett.
The approach used by the Vanderbilt team "is a really powerful way to help design the next generation of drugs," researchers said.
The study was published in the journal Nature Neuroscience.
