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.
The similarities and differences in symptoms of anxiety in adults compared to children and adolescents depend on the diagnosis.
There seem to be gender differences in the expression of anxiety.
If a medical or mental health professional suspects that you have GAD, you will likely undergo an extensive medical interview and physical examination.
Treatment of GAD usually involves some combination of lifestyle changes, psychotherapy, and/or medication.
As anything that is ingested carries risk of side effects, it is important for the anxiety disorder sufferer to work closely with the prescribing doctor to decide whether treatment with medications is an appropriate intervention, and if so, which medication should be administered.
There are many possible complications associated with anxiety.
Various lifestyle choices and family interventions can help prevent anxiety.
GAD usually requires treatment for it to resolve.
There are many support groups for people who suffer from generalized anxiety disorder.
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.”
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Daniel Hermanson, a graduate student in Chemistry, was first author of the paper. Other co-authors were Nolan Harley, Joyonna Gamble-George, Naoko Brown, Brian Shonesy, Ph.D., Phillip Kingsley, Roger Colbran, Ph.D., and Jeffrey Reese, M.D.
How to treat anxiety
COGNITIVE BEHAVIOUR TECHNIQUES:
Positive thinking: This is simply having a positive outlook on your anxiety. It involves taking one day at a time and avoiding the things or situations that make you anxious and trying not to let worries dominate your day.
Structuring the day: This involves finding ways of motivating yourself, such as setting small and achievable goals.
Relaxation: This involves learning to relax by thinking about things that make you feel calm such as listening to music or reading.
Exercise: Sufferers are advised to do some form of exercise on a regular basis. Physical exercise can trigger brain chemicals that will improve your mood.
Diet: Eating a low fat, high fibre diet, with lots of fresh vegetables and fruit will increase body energy. Sufferers should try to avoid drinking too much tea and coffee as caffeine can increase anxiety levels.
Breathing: Incorrect breathing causes many symptoms. Most anxious people are very tense and consequently tend to breath from their upper chest which upsets the mixture of carbon dioxide and oxygen causing sight problems, exhaustion, dizziness and chest pains. The remedy is to learn to breathe from the abdomen.
The three-year-long study was supported by National Institutes of Health grants CA089450, GM015431, NS064278, DA031572, HL096967, HL109199, MH063232, NS078291 and MH065215.
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Bill Snyder
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615-322-4747
Vanderbilt University Medical Center