The Brain Produces Its Own Version of THC

It’s no great secret that many people smoke pot to combat anxiety and stress. Researchers have long examined just how that effect works; weed’s components can affect a varied collection of receptors spread throughout the body. Now a new mouse study builds on that work, finding that a signaling molecule called 2-arachidonoylglycerol (2-AG)—a naturally occurring chemical affecting some of those receptors—plays a critical role in how the brain responds to stress. Understanding the biological mechanisms for coping with stress might reveal why some people seem to be better at it, and help treat those who don’t do so well. The findings could lead to better treatment and prevention for mood disorders, including post-traumatic stress disorder (PTSD) and major depression.

The study, conducted by researchers at Vanderbilt University Medical Center, looks at the body’s endocannabinoid system, a collection of molecules and receptors found in the brain, organs, connective tissue—basically everywhere. Scientists in the 1960s discovered the system by studying how marijuana affects the body. Thus the name: “endo” indicates it’s inside the body, and “cannabinoid” relates to the many different compounds found in marijuana.

By studying how weed affects us, researchers got a much better sense of how the body functions when not under the influence of tetrahydrocannabinol (THC), the main active ingredient in cannabis. Because, it turned out, the endocannabinoid system wasn’t just lying dormant waiting for THC to enter the body. It’s working all the time. And, as one paper put it, “the endocannabinoids are literally a bridge between body and mind.”

You can see why scientists would want to study this complex system. In the present study, the researchers tinkered with the amount 2-AG, which is the most abundant endocannabinoid, in mice’s amygdalas—a part of the brain associated with emotions, including anxiety. Increasing the amount of 2-AG produced mice that were stress-resilient; depleting the 2-AG produced mice more likely to develop “anxiety-like behaviors” after facing stress. (Please, a tear for the poor, harried mice.)

Previous research has found that THC promoted stress resilience in mice, and obviously stressed out humans find some value in smoking weed to relax. But marijuana contains a lot of compounds and can have side effects that are hard to manage. By looking at naturally occurring endocannabinoids like 2-AG, researchers get a more nuanced picture of how biology mitigates stress—or doesn’t. That could lead to better treatments for depression and PTSD, or another way to screen for who might be susceptible to it. And, if you’ll excuse the pun, it might replace a very blunt method of treatment with one that’s much more refined.

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