Researchers at Northwestern University have identified a specific group of neurons involved in anxiety responses triggered by exposure to cannabinoid drugs, particularly in stressful situations. Cannabinoids, including THC, are the main psychoactive compounds found in cannabis.
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In a study published in Nature Communications, scientists exposed mice to a threatening odor derived from fox urine. Prior to this exposure, some mice received a placebo while others were administered a synthetic cannabinoid. The results showed that mice receiving the cannabinoid displayed increased freezing behavior and spent less time exploring the predator scent. These anxiety-related behaviors were found to correlate with the activation of somatostatin neurons in the brain's central amygdala, a region associated with fear and stress processing.
Notably, genetically silencing these somatostatin neurons resulted in a decrease in the avoidance behavior of drugged mice towards the predator scent.
Sachin Patel, MD, PhD, senior author of the study, highlighted that the findings could help explain why cannabis experiences can turn negative in stressful situations or with excessive consumption.
The research team tested various doses of the synthetic cannabinoid, monitoring how long the mice remained near the predator odor and their behavioral responses. Additionally, they utilized a small implanted microscope to record brain activity during the experiments.
Further analysis indicated that cannabinoids weakened the brain’s natural regulatory mechanisms on somatostatin neurons, leading to heightened activity. Patel elaborated that increased cannabinoid dosage and environmental stress together diminished the brain's control to drive excessive anxiety.
The implications of these findings are significant, especially given the rising use of cannabis in the U.S. and its associated adverse effects reflected in emergency department visits. Prior studies have suggested a link between cannabis use and long-term anxiety risk, amidst a global increase in anxiety and mood disorders.
Patel expressed the potential for these insights to inform new strategies for mitigating negative effects of cannabis and noted that manipulating somatostatin neuron activity could be a pathway for reducing anxiety symptoms more broadly.
Co-authors of the study include Farhana Yasmin, PhD, and several others from the Department of Psychiatry and Behavioral Sciences, with support from the National Institutes of Health and the Brain & Behavior Research Foundation.