Scientists have identified a molecule in the brain that may help to protect the body from anxiety, and could help explain people's use of marijuana in times of stress.
In a study conducted in mice and published in Neuron, researchers looked at the molecule 2-arachidonoylglycerol (2-AG). This molecule is involved in a connection between the amygdala and frontal cortex. These parts of the brain are responsible for regulating emotions, memory and empathy, among other things.
Normally, 2-AG maintains a break in a connection between the two regions. However, the break appears to disappear in moments of stress, allowing the two parts of the brain to "glue" together, say researchers. In the mouse subjects, this was linked to a spike in anxiety-related behaviors.
2-AG and Tetrahydrocannabinol (THC), the main psychoactive component of cannabis, both target the same receptor. While the paper did not directly look at the effect of marijuana on the brain, the findings may help explain why people turn to the drug when stressed.
"These findings may help clarify—at a mechanistic level—why many people report using cannabis to cope with stress and anxiety, specifically if they have a deficiency in their own production of these molecules," study co-author Sachin Patel, from Vanderbilt University Medical Center, Tennessee, told Newsweek. "But this is just a theory at this point," he added.
For the study, Patel and colleagues issued a series of electrical shocks to the feet of mice. They observed that in moments of stress, the break between the amygdala and frontal cortex temporarily disappeared—fortifying the connection and triggering a spike in anxiety-related symptoms.
In a second experiment, the researchers inserted a virus into the mice that compromised the signalling of 2-AG. This strengthened the connection between the amygdala and frontal cortex, exacerbating anxiety-related behavior—even in animals that had not been exposed to stress.
The researchers hypothesize the break disappears when the endocannabinoid system—a cell-signalling system responsible for directing and removing cannabinoids like 2-AG—collapses.
"One of the implications of the study is that when this 'endogenous' cannabinoid system breaks down within specific neural pathways in the brain, mice become anxious. When we restore levels of these endogenous molecules, they become less anxious after stress," said Patel.
There are, however, limitations to studying mice rather than humans, which is "a large issue" in mental health research in general, said Patel. "While there are some things that can be modeled well in laboratory rodents, the translatability of mouse studies to patients is always a question," he explained.
"In this particular study, we focused on a brain pathway that is also present in humans and known to regulate anxiety and stress-related affect, making it more likely that the finding would be relevant to humans. But studying this directly in patients with anxiety disorders and PTSD needs to happen before any firm conclusions can be made," he said.
Next, the researchers intend to find how stress alters levels of 2-AG in the brain. It is hoped this will result in the development of new drugs that boost levels of 2-AG produced in the human brain.
"Some of these drugs are already in early phase clinical trials, so we may hopefully have the answers to these questions within the next few years," said Patel.
Eventually, this could lead to an alternative to medical marijuana, which comes with its own set of problems, Patel said. "There are a number of issues with medical cannabis including side effects, dependence liability, and others, and in many states this is still inaccessible and/or illegal...Although people often cite stress-coping motives for cannabis use, there is also little evidence that cannabis itself effectively treats anxiety disorders like PTSD, although more high-quality clinical trials are definitely needed in this area."
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