Study Identifies Neurons Linked to Cannabis-Induced Anxiety

To explore the impact of cannabinoids on fear and anxiety, scientists exposed mice to a threatening odor derived from fox urine. Prior to the introduction of the scent, some mice were administered either a placebo or a synthetic cannabinoid.

The findings revealed that mice receiving the cannabinoid exhibited increased freezing behavior and decreased exploration of the predator smell. These anxiety-related behaviors were connected to heightened activity in a small group of brain cells known as somatostatin neurons, located in the central amygdala, a region critical for processing fear and stress.

When researchers genetically silenced these somatostatin neurons, cannabinoid-treated mice became less averse to the predator odor, suggesting these neurons play a crucial role in the anxious response. Dr. Sachin Patel, a senior author of the study and chair of psychiatry and behavioral sciences at Northwestern University Feinberg School of Medicine, noted that this could explain why some individuals experience anxiety during heightened cannabis use or in stressful environments.

Published on October 2 in Nature Communications, the study involved mice that received various doses of synthetic cannabinoids to measure their reactions to the threatening odor, including whether they froze or fled. Concurrently, researchers monitored brain activity with a small implanted microscope.

The study also examined how cannabinoids altered neuron communication in brain tissue, discovering that the drug reduced a natural mechanism that inhibits somatostatin neurons. This decrease in inhibitory control led to increased neuron activity.

Dr. Patel explained that higher cannabinoid doses and environmental stress work together to release the 'brake' on the central amygdala, resulting in heightened anxiety.

As cannabis use has increased in the U.S. in recent years, so have emergency room visits related to its adverse effects. Previous studies have also linked cannabis use to a higher long-term risk of anxiety, alongside a global rise in anxiety and mood disorders.

Patel emphasized that understanding how cannabis impacts brain function could offer insights into mitigating negative effects for some users. He noted that the findings might inform broader approaches to anxiety treatment, suggesting that targeting somatostatin neurons in the central amygdala could provide a pathway for alleviating anxiety symptoms beyond cannabis-related effects.

Co-authors from Northwestern include Farhana Yasmin, Saptarnab Naskar, Danyal Zaidi, Isaac Kandil, Michelle Kwon, and Dr. Luis Rosas-Vidal. The research received support from the National Institutes of Health and the Brain & Behavior Research Foundation.