Why Too Much Cannabis Can Flip an Anxiety Switch in the Brain

For the first time, researchers have identified brain cells that help drive anxiety in mice exposed to cannabinoids.

Confronted with a scent derived from fox urine, mice given a synthetic cannabinoid froze more often and spent less time investigating the odor than mice given a placebo. The drug belongs to the same class of substances as THC, the main psychoactive ingredient in cannabis. Following the animals’ reactions gave Northwestern University researchers a way to investigate how cannabinoids can heighten anxiety when the surroundings turn threatening.

The researchers traced the response to a small group of brain cells called somatostatin neurons in the central amygdala, a region that processes fear and stress. Their study, published October 2 in Nature Communications, identified these cells as contributors to the anxious behavior, opening a path to understanding how the drug and a stressful encounter work together.

Cannabinoids weaken the brain’s anxiety brake

To connect the animals’ behavior with activity inside their brains, the team tested several doses of the synthetic cannabinoid while tracking how long the mice stayed near the predator odor and whether they froze or fled. A small microscope implanted in the animals’ brains recorded neural activity during those encounters, allowing the researchers to watch the cells as the mice responded.

Experiments on brain tissue let the scientists examine how the drug altered communication between neurons. Somatostatin cells normally receive signals that restrain their activity, effectively putting a brake on them. Senior author Dr. Sachin Patel, chair of psychiatry and behavioral sciences at Northwestern University Feinberg School of Medicine, explained what happened when that restraint weakened: “Higher doses of cannabinoids and environmental stress worked together to synergistically release the ‘brake’ on the central amygdala, which in turn drove excessive anxiety.”

Genetically silencing the somatostatin neurons reduced the drug-treated mice’s avoidance of the predator scent, providing evidence that these cells helped drive the response. “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.

A possible anxiety target beyond cannabis

Cannabis use in the United States has increased in recent years, along with emergency department visits related to its adverse effects. Earlier research has also linked cannabis use with a greater long-term risk of anxiety, while anxiety and mood disorders have been rising 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. The current experiments used a synthetic cannabinoid in mice, leaving researchers to establish whether the same cellular mechanism explains anxiety in people who use 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,” Patel explained. Quieting those cells made mice less avoidant of the fox-derived scent. Whether that change in their response to a predator’s odor can point toward relief for human anxiety remains to be tested.

Reference: “Cannabinoid modulation of central amygdala population dynamics during threat investigation” by Farhana Yasmin, Saptarnab Naskar, Danyal Zaidi, Isaac Kandil, Michelle Kwon, Luis E. Rosas-Vidal and Sachin Patel, 2 October 2026, Nature Communications.
DOI: 10.1038/s41467-026-77957-4

Supported by the National Institutes of Health (grants MH100785 and K08 MH126166) and the Brain & Behavior Research Foundation’s Young Investigator Awards.

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