For the first time, Northwestern scientists have identified a set of neurons - cells in the brain - that play a role in generating anxiety after exposure to cannabinoid drugs, especially under stressful conditions. Cannabinoids are a class of substances that includes THC, the main psychoactive ingredient in cannabis.
The study was published today (Oct. 2) in Nature Communications.
In the study, the scientists exposed mice to a threatening odor. Before being exposed to the scent, derived from fox urine, the mice either received a placebo or a synthetic cannabinoid drug.
When they received the drug, the mice froze more often and spent less time investigating the predator odor. These anxious behaviors, the scientists found, were linked to the drug's activation of a small group of cells - known as somatostatin neurons - in the brain's central amygdala, a region that processes fear and stress.
Importantly, when the scientists genetically silenced these somatostatin neurons, the drugged mice did not avoid the predator scent as much anymore.
"The results of this study could explain why a good trip can turn bad pretty quickly if people consume too much cannabis or the situation they are in turns stressful or scary," said study senior author Dr. Sachin Patel, chair of psychiatry and behavioral sciences at Northwestern University Feinberg School of Medicine.
The study will publish on Oct. 2 in Nature Communications.
How the study was conducted
Patel and colleagues tested several doses of the synthetic cannabinoid on mice and tracked how much time they spent near the predator odor, and whether they froze or fled from the scent. To simultaneously record brain activity, the team implanted a small microscope into the mice's brain.
The scientists also conducted brain tissue experiments to analyze how the cannabinoids affected interactions between neurons. They found that the drug weakened the brain's natural "brake" on the somatostatin neurons, allowing them to become more active.
"Higher doses of cannabinoids and environmental stress worked together to synergistically release the 'brake' on the central amygdala, which in turn drove excessive anxiety," Patel explained.
Why the findings matter
Cannabis use in the U.S. has steadily increased in recent years and so have emergency department visits related to adverse effects from the drug. Previous studies have also found an association between cannabis use and increased risk of anxiety in the long term. What's more, anxiety and mood disorders are also on the rise globally.
"Understanding how cannabis affects brain function to generate its psychoactive effects could ultimately reveal new ways to counteract negative consequences should they arise in some people," Patel said.
Patel also noted that the findings could have implications beyond cannabis. "Suppressing the activity of somatostatin neurons in the central amygdala could represent a final pathway for reducing anxiety symptoms, not just in the context of cannabis side effects," he explained.
Other Northwestern co-authors are Farhana Yasmin, Saptarnab Naskar, Danyal Zaidi, Isaac Kandil, Michelle Kwon and Dr. Luis Rosas-Vidal.
The study is titled, "Cannabinoid Modulation of Central Amygdala Population Dynamics During Threat Investigation." It was supported by the National Institutes of Health (grants MH100785 and K08 MH126166) and the Brain & Behavior Research Foundation's Young Investigator Awards.
