Replenishing the supply of a molecule that normally activates cannabinoid receptors in the brain could relieve mood and anxiety disorders and enable some people to quit using marijuana, a Vanderbilt University study suggests.
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.
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 researchers reported on Nov. 26 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," they concluded.
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.
Cyclooxygenase (COX) enzymes produce pro-inflammatory prostaglandins and are the target of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs), used to relieve pain and inflammation. It has been known for several years that COX-2 inhibition also activates endocannabinoids.
The current study was led by first authors Brian Shonesy, Ph.D., research fellow in the lab of Roger Colbran, Ph.D., professor of Molecular Physiology and Biophysics, and Rebecca Bluett, a graduate student in Patel's lab.
The research was supported in part by National Institutes of Health grants MH065215, NS078291, MH0903412, MH100096, GM015431 and DA031572.
Craig Boerner | Vanderbilt University Medical Center
On track to heal leukaemia
18.01.2017 | Universitätsspital Bern
Penn vet research identifies new target for taming Ebola
12.01.2017 | University of Pennsylvania
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).
Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...
10.01.2017 | Event News
09.01.2017 | Event News
05.01.2017 | Event News
18.01.2017 | Materials Sciences
18.01.2017 | Information Technology
18.01.2017 | Ecology, The Environment and Conservation