Northwestern study identifies brain neurons linked to cannabis anxiety in mice

Northwestern University scientists have identified a group of brain cells that appear to contribute to anxiety caused by cannabinoid drugs, particularly when the drugs are combined with stressful conditions, according to a study reported by ScienceDaily. Cannabinoids are a category of substances that includes THC, the main psychoactive ingredient in cannabis. The experiments were carried out in mice.

The researchers exposed mice to a threatening smell derived from fox urine after giving them either a placebo or a synthetic cannabinoid drug. Mice that received the cannabinoid froze more frequently and spent less time exploring the predator scent, according to the report. The team traced these behaviors to increased activity in somatostatin neurons located in the central amygdala, an area of the brain involved in processing fear and stress.

When the researchers genetically silenced the somatostatin neurons, the mice that received the cannabinoid became less likely to avoid the predator odor. The report said the result suggested the cells play an important role in producing the anxious response. The team gave the mice several doses of the drug, recorded their reactions, monitored brain activity with a small implanted microscope, and studied brain tissue.

The experiments showed the drug weakened a natural brain mechanism that normally acts as a "brake" on the somatostatin neurons; with that restraint reduced, the neurons became more active, according to the report. "Higher doses of cannabinoids and environmental stress worked together to synergistically release the 'brake' on the central amygdala, which in turn drove excessive anxiety," said study senior author Dr. Sachin Patel, chair of psychiatry and behavioral sciences at Northwestern University Feinberg School of Medicine.

"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," Patel said. ScienceDaily reported that cannabis use in the U.S. has steadily increased in recent years and that emergency department visits involving adverse effects from the drug have also risen. Previous studies have found an association between cannabis use and a higher long-term risk of anxiety, and anxiety and mood disorders are on the rise globally, according to the report.

"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. "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 said. Other Northwestern co-authors listed by ScienceDaily are Farhana Yasmin, Saptarnab Naskar, Danyal Zaidi, Isaac Kandil, Michelle Kwon and Dr. Luis Rosas-Vidal.