Team discovers potential new way to treat anxiety

Lawrence Marnett, Ph.D., (left) and Sachin Patel, M.D., Ph.D., have discovered that chemically modified inhibitors of the COX-2 enzyme relieve anxiety behaviors in mice by activating natural "endocannabinoids" without gastrointestinal side effects. Credit: Vanderbilt University/Stephen Doster

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 in the brain, the same receptors turned on by the active ingredient in marijuana.

These receptors are also found in the 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 .

"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 .

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."

More information: Substrate-selective COX-2 inhibition decreases anxiety via endocannabinoid activation, DOI: 10.1038/nn.3480

Related Stories

Study puts a new spin on ibuprofen's actions

Sep 25, 2011

Ibuprofen, naproxen, and related non-steroidal anti-inflammatory drugs (NSAIDs) – the subjects of years of study – still have some secrets to reveal about how they work.

Licorice compound offers new cancer prevention strategy

Mar 23, 2009

A chemical component of licorice may offer a new approach to preventing colorectal cancer without the adverse side effects of other preventive therapies, Vanderbilt University Medical Center researchers report.

NSAIDs and cardiovascular risk explained

May 02, 2012

After nearly 13 years of study and intense debate, a pair of new papers from the Perelman School of Medicine, at the University of Pennsylvania have confirmed exactly how a once-popular class of anti-inflammatory drugs leads ...

Recommended for you

Emotional adjustment following traumatic brain injury

Oct 24, 2014

Life after a traumatic brain injury resulting from a car accident, a bad fall or a neurodegenerative disease changes a person forever. But the injury doesn't solely affect the survivor – the lives of their spouse or partner ...

New ALS associated gene identified using innovative strategy

Oct 22, 2014

Using an innovative exome sequencing strategy, a team of international scientists led by John Landers, PhD, at the University of Massachusetts Medical School has shown that TUBA4A, the gene encoding the Tubulin Alpha 4A protein, ...

User comments

Adjust slider to filter visible comments by rank

Display comments: newest first

Tom_Hennessy
not rated yet Aug 04, 2013
The plant fatt acid alpha-linolenic acid inhibits COX-2.
"Dietary alpha-linolenic acid reduces COX-2 expression and induces apoptosis of hepatoma cells"
http://www.ncbi.n...14563831