Scientists discover potential new way to treat anxiety and stress


2013-08-09 16:52

Scientists at Vanderbilt University have discovered a potential new treatment for anxiety and stress.

While studying chemically modified inhibitors of the COX-2 enzyme, the researchers found that they relieved anxiety in mice by activating “endocannabinoids”, which are natural signaling 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, as well as other parts of the human body, and evidence supports that they play a role in a variety of physiological and pathological processes, which includes controlling stress and anxiety.

Accordingly, the researchers are studying the “substrate-selective” COX-2 inhibitors developed at Vanderbilt to see if they also work in humans without side effects, like they did with mice. If they do work in humans, they could open the door to a new approach for the treatment of anxiety and mood disorders, report the researchers in an article to be published online in the journal Nature Neuroscience this Sunday.

Indeed, clinical trials for some of these potential drugs could begin in the next several years, according to Lawrence Marnett, Ph.D., director of the Vanderbilt Institute of Chemical Biology and the paper's co-senior author with Sachin Patel, M.D., Ph.D.

The Vanderbilt scientists are also pursuing other possible applications for activating endocannabinoids by substrate-selective COX-2 inhibition, including applications for pain relief, movement disorder treatments, and the prevention of colon cancer.

"The door is really wide open," said Patel, assistant professor of Psychiatry and of Molecular Physiology & Biophysics. "We've just scratched the surface."

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.

Meanwhile, it has been known for years that COX-2 inhibition also activates endocannabinoids.

Because the "substrate selective" inhibitors developed at Vanderbilt 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, University Professor and Mary Geddes Stahlman Professor of Cancer Research.

"We thought we knew everything there was to know about (COX-2 inhibitors) until about five years ago when we discovered the substrate selective inhibition," he added. The approach used by the Vanderbilt team "is a really powerful way to help design the next generation of drugs."

SOURCE: "Substrate-selective COX-2 inhibition decreases anxiety via endocannabinoid activation" Nature Neuroscience (2013) doi:10.1038/nn.3480