The nebulous connection between cannabis and anxiety is clearer than ever before, according to a new study.

Researchers have found that 2-arachidonoylglycerol (2-AG), a molecule produced by the brain which can activate the body’s cannabinoid receptors, is able to protect the brain against stress by reducing connections between two brain regions which heighten anxiety.

The new findings, published in the neuroscience research journal Neuron, may help scientists to better understand why many people turn to cannabis when they feel anxious or stressed, and why many find it an effective treatment.





2-AG, cannabis, and acute stress

The endocannabinoid system is hugely important in maintaining the normal function of the body and plays an important role in the development of the central nervous system.

The active compounds in cannabis, such as tetrahydrocannabinol (THC) and cannabidiol (CBD), are exogenous cannabinoids, a type of compound that can modulate the body’s endocannabinoid system by interacting with one or more of its receptors. In the case of THC, it’s a partial agonist at the CB1 receptor, and its action with this receptor gives the user the feeling of a cannabis high.

As an endocannabinoid, 2-AG is produced naturally inside the body. And like THC, it’s also a CB1 receptor agonist, and can exert powerful effects on the body through its interaction with the endocannabinoid system.

In this latest research, scientists from Vanderbilt University Medical Center observed that when mice were subject to acute stress, a connection appeared between two brain regions, the amygdala and the frontal cortex. This connection in brain circuitry was determined to be tied to the mice exhibiting anxiety-related behaviors. Ordinarily, the researchers say, 2-AG would be responsible for maintaining the disconnect between these two regions.

“The circuit between the amygdala and the frontal cortex has been shown to be stronger in individuals with certain types of anxiety disorders,” said Dr Sachin Patel, and one of the authors on the new paper, in a statement. “As people or animals are exposed to stress and get more anxious, these two brain areas glue together, and their activity grows stronger together.”

“We might predict there’s a collapse in the endocannabinoid system, which includes 2-AG, in the patients that go on to develop [an anxiety] disorder. But not everyone develops a psychiatric disorder after trauma exposure, so maybe the people who don’t develop a disorder are able to maintain that system in some way,” Patel continued.

“Those are the things we’re interested in testing next.”





The cannabinoid system might be the key to controlling stress levels

Also observed during the course of the study, the scientists found that genetic manipulations that compromised the mice’s endogenous cannabinoid signaling pathways were able to strengthen the signaling between the amygdala and the frontal cortex. This caused the mice in question to exhibit anxious behaviors, even without the initial application of acute stress.

From this, the researchers concluded that the cannabinoid signalling system is able to effectively suppress the information flow between these two brain regions, making the system a crucial part of setting anxiety levels in animals.

“We don't know how or why this cannabinoid signaling system disappears or disintegrates in response to stress, but it results in the strengthening of the connection between these two regions and heightened anxiety behaviors in mice,” added Patel.

“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.”

The study’s authors are now interested in how the endocannabinoid system might react to more chronic forms of stress. From there, the researchers wish to determine whether there are other environmental exposures that might compromise or enhance the system to regulate behavior.

With improved insight into the molecular mechanisms behind feelings of stress and the endocannabinoid system, the researchers believe that it may be possible to develop more effective pharmacological treatments for stress and anxiety in the future, which could provide current medical cannabis users with an alternative treatment route.