Researchers have identified a neural pathway that explains how cannabinoids may heighten anxiety under stressful conditions. In a study published on October 2 in Nature Communications, scientists from Northwestern University observed that mice administered a synthetic cannabinoid, similar to THC, exhibited heightened anxiety responses when exposed to a scent derived from fox urine. These mice froze more frequently and spent less time investigating the scent compared to those given a placebo.
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The study traced the anxiety response to a specific group of neurons, known as somatostatin neurons, located in the central amygdala, a brain region involved in processing fear and stress. By tracking the behaviors of the mice while monitoring neural activity through implanted microscopes, the researchers connected the drug's effects to alterations in brain cell communication.
Dr. Sachin Patel, senior author and chair of psychiatry and behavioral sciences at Northwestern University Feinberg School of Medicine, explained that cannabinoids appear to disrupt inhibition on the somatostatin neurons. This results in a release of the ‘brake’ on anxiety responses, particularly in stressful situations. Testing revealed that genetically silencing these neurons reduced the anxiety-driven avoidance of the predator scent in drug-treated mice.
Patel indicated that the findings could shed light on why some individuals experience rapid shifts from pleasant to unpleasant effects when using cannabis, especially under stress. As cannabis use has surged in the United States, so have emergency department visits related to its adverse effects. Previous research has also indicated a long-term risk of anxiety associated with cannabis use.
The implications of these findings extend beyond cannabinoids themselves, as silencing somatostatin neurons in the central amygdala could emerge as a potential target for treating anxiety symptoms generally. However, further research is necessary to determine if the same mechanisms affect anxiety in humans. The paper was co-authored by Farhana Yasmin, Saptarnab Naskar, and other colleagues, funded in part by the National Institutes of Health and the Brain & Behavior Research Foundation.