Study Links Cannabis Use to Activation of Brain Cells Associated with Anxiety

Sachin Patel, a psychiatric neuroscientist at Northwestern University and senior author of the study, noted that the research could explain why some individuals experience negative reactions after consuming cannabis. He stated, "The results of this study could explain why a good trip can turn bad pretty quickly if people consume too much cannabis or if the situation they are in turns stressful or scary."

Previously, scientists recognized that cannabinoids, such as tetrahydrocannabinol (THC), influence the central amygdala (CeA), a brain region involved in controlling anxiety and stress responses. This study further investigates how cannabinoids may activate CeA neurons that produce a neuropeptide called somatostatin (SOM), relevant to stress regulation.

To explore this relationship, Patel's team conducted experiments on mice, administering a potent synthetic cannabinoid, CP 55,940, while exposing them to a synthetic predator odor resembling a compound found in fox feces. The results showed that mice under the influence of the cannabinoid exhibited intensified defensive behaviors, including increased freezing and reduced proximity to the threatening scent, with effects correlating to the dosage received.

Analysis of the mice's brains revealed that cannabinoid administration led to heightened activation of CeA SOM neurons, a response that was dose-dependent. In a separate experiment, genetically engineered mice had their SOM neuron function inhibited through a viral toxin. These mice, when exposed to the predator odor after receiving the cannabinoid, did not display the same level of avoidance, suggesting that the cannabinoid-induced anxiety response was diminished.

The researchers compared the influence of cannabinoids on SOM neurons to loosening a brake in a car, allowing for uncontrolled anxiety. Patel commented on how high doses of cannabinoids combined with stress can amplify anxiety levels: "Higher doses of cannabinoids and environmental stress worked together to synergistically release the 'brake' on the central amygdala, which in turn drove excessive anxiety."

Although these findings have been observed in mice, researchers hope to investigate whether similar mechanisms function in humans. Understanding how cannabis impacts brain function could lead to new strategies for managing anxiety, regardless of its source. Patel concluded, "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."