Development of a medication to replenish the supply of a molecule that normally activates cannabinoid receptors in the brain may be an answer to relieve mood and anxiety disorders.
Vanderbilt researchers believe this effect would enable some people to quit using marijuana.
In the brain, cannabinoid receptors are normally activated by natural compounds called endocannabinoids, the most abundant of which is 2-AG. The cannabinoid receptors can also are “turned on” by the active ingredient in marijuana.
Sachin Patel, M.D., Ph.D., and his colleagues developed a genetically modified mouse with impaired ability to produce 2-AG in the brain. The mice exhibited anxiety-like behaviors, and female mice also displayed behaviors suggestive of depression.
When an enzyme that normally breaks down 2-AG was blocked, and the supply of the endocannabinoid was restored to normal levels, these behaviors were reversed.
The study has been published in the online edition of the journal Cell Reports.
If further research confirms that some people who are anxious and depressed have low levels of 2-AG, this method of “normalizing 2-AG deficiency could represent a viable … therapeutic strategy for the treatment of mood and anxiety disorders,” say the researchers.
However, this approach has not been tested in humans, they cautioned.
Relief of tension and anxiety is the most common reason cited for chronic marijuana use. Thus, restoring depleted levels of 2-AG also “could be a way to help people using marijuana,” added Patel, the paper’s senior author and professor of Psychiatry and of Molecular Physiology and Biophysics.
Chronic use of marijuana down-regulates cannabinoid receptors, and thus paradoxically increases anxiety. This can lead to a “vicious cycle” of increasing marijuana use that in some cases leads to addiction.
Patel and his colleagues previously have found cannabinoid receptors in the central nucleus of the amygdala of the mouse. The amygdala is a key emotional hub in the brain involved in regulating anxiety and the flight-or-fight response.
They also have found that chemically modified inhibitors of the COX-2 enzyme they developed relieve anxiety behaviors in mice by activating natural “endocannabinoids” without gastrointestinal side effects.
Clinical trials of some of these potential drugs could begin in the next several years.
Source: Vanderbilt University/EurekAlert