Scientists discover powerful molecule, called 2-AG, that explains why people with anxiety use cannabinoid and cannabis

Why people with anxiety and stress use cannabis and cannabinoids (Photo by Shutterstock)

Stress and anxiety are major factors that affect mental health. Across the globe, there are about 284 million people living with an anxiety disorder. When you’re anxious or stressed, you tend to turn to things that make you feel better, and in some people – cannabis and cannabinoid are the choice.

It is known that people smoke cannabis because they’re stressed or anxious, but the reasons behind this mechanism are not yet understood. Now, a team of researchers may have unlocked the key to explain the exact mechanism of how cannabis reduces feelings of stress and anxiety.

In a study published in the journal Neuron, the researchers from the Vanderbilt University Medical Center has found the answer to explain why some people use cannabis or marijuana when they’re feeling anxious or they’re under stress. A molecule, called 2-AG, which is found in the brain could regulate anxiety and depressive symptoms in people.

Stress-anxiety superhighway in the brain

The researchers were already familiar with the stress-anxiety superhighway in the brain, hence, they want to test whether cannabis can alter these connections.

The superhighway links two parts of the brain – the prefrontal cortex, which controls decision-making, and the amygdala, which is responsible for our emotions. During a stressful event, the two brain parts fuse together, producing excitatory neurochemicals, which boosts anxiety levels.

In people with anxiety disorders, the link or circuit between the amygdala and the frontal cortex is stronger than in other people. The brain has an innate network that responds to cannabis, dubbed as the endocannabinoid system. This system is a widespread neuromodulatory system that plays a pivotal role in the development of the central nervous system (CNS), response to endogenous and environmental insults, and synaptic plasticity.

Understanding the 2-AG function

Specifically, 2-AG is a molecule that helps control the interaction between the two brain regions, the amygdala, and the frontal cortex. To test this, they studied laboratory mice and found that when they’re under stress, the two brain regions fuse together. However, when the scientists increased the level of 2-AG, they were able to break short the link and in turn, reduced the anxiety levels of the mice.

The scientists exposed mice to an acute stress for 24 hours and then let them go through a maze. During the process, the researchers measured the mice’ anxiety levels and studied how their brains responded to high-stress levels.

They also found that stress of trauma makes the molecule 2-AG and the endocannabinoid system break down, heightening the feelings and behaviors related to anxiety.

“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,” Dr. Sachin Patel, study author and the director of the Division of General Psychiatry at Vanderbilt University Medical Center, said.

With the new knowledge on hand, the researchers hope their findings can lead to the development of new treatments and therapies aimed to help people with anxiety disorders. Also, further research is still needed to determine how the system reacts to more chronic types of stress and identifying factors that can compromise or enhance the system for behavior regulation.

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Our World in Data. (2017). Mental Health.

Journal reference:

Marcus, D., Bedse, G., Gaulden, A., Ryan, J., Kondev, V., Winters, N., Rosas-Vidal, L., Altemus, M., Mackie, K., Lee, F., Delpire, E., and Patel, S. (2019). Endocannabinoid Signaling Collapse Mediates Stress-Induced Amygdalo-Cortical Strengthening. Neuron.

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