A molecule produced by the brain known to activate the same receptors as cannabis appears to protect against stress by reducing anxiety-causing connections between two brain regions,
Researchers from Vanderbilt University Medical Center suggest that drug treatments that increase levels of this molecule – known as 2-AG – “could regulate anxiety and depressive symptoms in people with stress-related anxiety disorders, potentially avoiding a reliance on medical marijuana or similar treatments”.
They also suggest their finding “could help explain why some people use marijuana when they’re anxious or under stress”.
What’s behind all this?
The molecule 2-AG is an active part of what’s known as the endocannabinoid system (ECS), a complex cell-signalling system that scientists are still working to fully understand.
It was discovered about 30 years ago by researchers who were investigating tetrahydrocannabinol (THC), the main psychoactive ingredient in cannabis.
The ECS has a functional role in your body whether or not you use cannabis.
It’s understood to play a role in regulating sleep, mood, appetite, memory and reproduction – but other roles and associations continue to be established.
A key part of this system are two endocannabinoids – also known as endogenous cannabinoids.
These are molecules made by your body that help keep internal functions running smoothly. One of these is 2-AG.
What did the scientists discover?
They investigated the circuit or connection between the amygdala (the part of the brain that regulates emotions) and the frontal cortex (the part of the brain in planning complex cognitive behaviour, personality expression, decision making and moderating social behaviour).
Dr Sachin Patel, the paper’s corresponding author and director of the Division of General Psychiatry at Vanderbilt, in a prepared statement explained: “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.”
In experiments that exposed mice to acute stress, they found that the anxiety-producing connection between the amygdala and the frontal cortex is ordinarily prevented by the 2-AG molecule.
When this break temporarily disappears, anxiety-related behaviours are caused to emerge.
“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,” Dr Patel said.
“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 signalling between the amygdala and the frontal cortex can be strengthened through genetic manipulations that compromise endogenous cannabinoid signalling in this pathway – “causing mice to become anxious even without exposure to stress in some cases”.
The researchers say that this finding demonstrates “the cannabinoid signalling system that suppresses information flow between these two brain regions is critical for setting the level of anxiety in animals”.
What causes the connection to break down?
Dr Patel said the researchers don’t know how or why this cannabinoid signalling system “disappears or disintegrates in response to stress”.
“Understanding what’s causing that compromise, what causes the signalling 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 Dr Patel.
This research builds on a 2014 study from Dr Patel’s lab that found that chronic stress or acute, severe emotional trauma can cause a reduction in both the production of endocannabinoids and the responsiveness of the receptors.
Without their “buffering” effect, anxiety goes up, that study concluded.
A 2017 study from the University of Illinois confirmed that low levels of THC does reduce stress, but in a highly dose-dependent manner: Very low doses lessened the jitters of a public-speaking task, while slightly higher doses (enough to produce a mild “high”) actually increased anxiety.
A 2018 study from Washington State University examined how people’s self-reported levels of stress, anxiety and depression were affected by smoking different strains and quantities of cannabis at home.
Their findings suggest smoking cannabis can significantly reduce short-term levels of depression, anxiety, and stress but may contribute to worse overall feelings of depression over time.