Brain Cells Behind Cannabinoid-Driven Anxiety Identified in Mice
In mice exposed to a predator odor, a synthetic cannabinoid increased freezing and reduced investigation compared with placebo. The response was linked to somatostatin neurons in the central amygdala, a brain region involved in fear and stress. Silencing those neurons reduced the drug-treated animals' avoidance, pointing to a pathway that may explain cannabis-related anxiety.
The study, published October 2 in Nature Communications, used a synthetic cannabinoid from the same class as THC, cannabis's main psychoactive compound. Mice encountering fox-urine scent received several drug doses while implanted microscopes recorded central amygdala activity, and researchers noted how long animals stayed near the odor and whether they froze or fled.
Tissue experiments showed the drug weakened signals that normally restrain somatostatin neurons. Senior author Sachin Patel, chair of psychiatry and behavioral sciences at Northwestern, said high cannabinoid doses plus environmental stress jointly released this brake, driving excessive anxiety. Silencing the cells reduced avoidance.
If the mechanism holds in humans, it could inform why some cannabis users experience intense anxiety, particularly at high doses or in frightening settings. Clinicians and emergency departments, which have seen rising cannabis-related visits, might eventually gain a target for calming such reactions. Still, the experiments involved mice and a synthetic compound, so implications for people remain uncertain and would require human studies.