Vanderbilt scientists discover potential new way to treat anxiety

Chemically modified inhibitors of the COX-2 enzyme relieve anxiety behaviors in mice by activating natural "endocannabinoids" without gastrointestinal side effects, Vanderbilt University scientists will report next week.

Endocannabinoids 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 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 developed at Vanderbilt also work in humans without side effects, they could represent a new approach to treating mood and anxiety disorders, the researchers conclude in a paper to be posted online Sunday in the journal Nature Neuroscience.

Clinical trials of some of these potential drugs could begin in the next several years, said 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 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," 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.

It has been known for several years that COX-2 inhibition also activates endocannabinoids.

Generalized anxiety disorder facts

Generalized anxiety disorder (GAD) is a mood disorder that is characterized by multiple and/or nonspecific worries that interfere with the person's life in some way.

The most common anxiety disorders are specific phobias. Other anxiety disorders include social anxiety disorder, panic disorder, generalized anxiety disorder, obsessive compulsive disorder, and posttraumatic stress disorder.

GAD is quite common, affecting millions of people.

While there is no single cause of GAD, there are many factors that increase the risk of developing this disorder.

Signs and symptoms of anxiety can include those that are emotional or behavioral and ways of thinking that are responses to feeling as if one is in danger.