A delicate balance of signaling in the endocannabinoid system could be responsible for anxiety symptoms as a result of stress. At least for mice. A new study indicates that 2-AG produced in the brain activates the same receptors that marijuana does, and 2-AG signaling is a vital component in determining mental health.
2-AG is a cannabinoid produced inside the body (endocannabinoid). 2-AG and another endocannabinoid, anandamide, are the two most studied cannabinoids of their kind. Endocannabinoids as well as phytocannabinoids, which are produced by plants like cannabis, play a functional role in the endocannabinoid system by activating cannabinoid receptors in the body.
The basis of the new study is a connection built by 2-AG between the amygdala and the frontal cortex of the brain. This connection produces anxiety symptoms, and it is known to be stronger in people with anxiety, says corresponding author Sachin Patel, MD, PhD.
When the connection is broken, it cannot produce anxiety symptoms. But in the new study, researchers observed the broken connection mending itself temporarily after mice were exposed to acute stress. With the connection in tact, anxiety symptoms occurred.
“As people or animals are exposed to stress and get more anxious, these two brain areas glue together, and their activity grows stronger together," Patel explained.
The 2-AG-directed amygdala-frontal cortex connection grows stronger with genetic manipulations and disrupted endocannabinoid signaling, resulting in unprovoked anxiety symptoms. This relationship strengthens the idea that cannabinoid signaling balance is crucial.
“Understanding what's causing that compromise, what causes the signaling system to return after a few days, and many other questions about the molecular mechanisms by which this is happening are things we're interested in following up on," Patel explained.
This new understanding of the mental health implications of endocannabinoid signaling could help explain why marijuana use is perceived as a remedy for stress and anxiety. Additionally, it is plausible that scientists could harness the effect of 2-AG and develop new pharmaceutical therapeutics for mental health conditions like anxiety and depression.
Sources: Vanderbilt University Medical Center, Neuron, Journal of Biological Chemistry
