Refilling the supply of cannabinoid receptors in the brain could help relieve mood and anxiety disorders and can enable some people to quit using marijuana, demonstrates a new study.
The study conducted by Vanderbilt University showed that chronic use of marijuana down-regulates cannabinoid receptors, and thus paradoxically increases anxiety and this can lead to a "vicious cycle" of increasing marijuana use that in some cases leads to addiction.
Cannabinoid receptors are normally activated by compounds in the brain called endocannabinoids, the most abundant of which is 2-AG. They 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.
Research confirmed that some people who were anxious and depressed had low levels of 2-AG, this method of normalizing 2-AG deficiency could represent a viable and therapeutic strategy for the treatment of mood and anxiety disorders.
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.
The study is published in online edition of the journal Cell Reports.