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Study sheds light on link between cannabis, anxiety and stress

A molecule produced by the brain that activates the same receptors as marijuana is protective against stress by reducing anxiety-causing connections between two brain regions, Vanderbilt University Medical Center researchers report.

This finding, published today in Neuron, could help explain why some people use marijuana when they’re anxious or under stress. It could also mean that pharmacologic treatments that increase levels of this molecule, known as “2-AG,” in the brain could regulate anxiety and depressive symptoms in people with stress-related anxiety disorders, potentially avoiding a reliance on medical marijuana or similar treatments.

When mice are exposed to acute stress, a break in an anxiety-producing connection between the amygdala and the frontal cortex caused by 2-AG temporarily disappears, causing the emergence of anxiety-related behaviors.

“The circuit between the amygdala and the frontal cortex has been shown to be stronger in individuals with certain types of anxiety disorders. As people or animals are exposed to stress and get more anxious, these two brain areas glue together, and their activity grows stronger together,” said Sachin Patel, MD, PhD, the paper’s corresponding author and director of the Division of General Psychiatry at Vanderbilt University Medical Center.

“We might predict there’s a collapse in the endocannabinoid system, which includes 2-AG, in the patients that go on to develop a 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. Those are the things we’re interested in testing next.”

The study also found that signaling between the amygdala and the frontal cortex can be strengthened through genetic manipulations that compromise endogenous cannabinoid signaling in this pathway, causing mice to become anxious even without exposure to stress in some cases. This finding demonstrates that the cannabinoid signaling system that suppresses information flow between these two brain regions is critical for setting the level of anxiety 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. 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,” said Patel, also the James G. Blakemore Professor of Psychiatry and Behavioral Sciences, Molecular Physiology and Biophysics and Pharmacology.

David Marcus, Neuroscience graduate student and first author on the paper, and Patel are also interested in how the system reacts to more chronic forms of stress and determining whether there are other environmental exposures that compromise or enhance this system to regulate behavior.

This research was supported by the National Institute of Mental Health (grant MH107435).

A molecule produced by the brain that activates the same receptors as marijuana is protective against stress by reducing anxiety-causing connections between two brain regions, researchers report.

The Link Between Cannabis and Anxiety Has Been Found, According to New Study

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.

Alexander Beadle

Alexander Beadle has been working as a freelance science writer since 2017 and has covered the cannabis industry for Analytical Cannabis since 2018. He has also written for our sister publication, Technology Networks, and the cannabis industry consultant firm Prohibition Partners, among others. Alexander holds an MChem in materials chemistry from the University of St Andrews, where he won a Chemistry Purdie Scholarship and conducted research into zeolite crystal growth mechanisms and the action of single-molecule transistors.

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The Link Between Cannabis and Anxiety Has Been Found, According to New Study The nebulous connection between cannabis and anxiety is clearer than ever before, according to a new study.