Scientists identify brain cells that could explain why cannabis triggers anxiety: ScienceAlert

Cannabis is known to relax, amuse and even exhilarate people, but it can sometimes have almost the opposite effect.

In some cases, cannabis use can trigger feelings of anxiety, panic, and paranoia, and evidence suggests that continued use could lead to mood and anxiety disorders.

Now, a new study published in Natural communications may have identified why the drug fuels such negative and intense reactions.

“The results of this study could explain why a good trip can turn into a bad trip quite quickly if people consume too much cannabis,” says Sachin Patel, a psychiatric neuroscientist and lead author from Northwestern University, “or the situation they find themselves in is alternately stressful or frightening.”

Previously, scientists knew that cannabinoids, including tetrahydrocannabinol (THC), strongly affect the central amygdala (CeA), which helps control anxiety, stress responses, and emotional behaviors.

One way cannabinoids might affect the amygdala is by activating neurons in the CeA that produce a neuropeptide called somatostatin (SOM), which helps regulate stress responses.

In the context of rodent experiments, this can be observed in various threat reactivity behaviors, including threat avoidance and freezing in response to threats.

Activation of CeA SOM neurons may also explain why cannabis can trigger feelings of anxiety, but there is still much we don’t know about how cannabinoids interact with CeA SOM neurons.

To further explore the relationship, Patel’s team conducted an experiment with mice, giving them a powerful synthetic cannabinoid called CP 55,940, then exposing them to a synthetic predator odor similar to a compound found in fox droppings.

When exposed to the predator’s scent, the mice displayed defensive behaviors, including slowing down and freezing.

But compared to mice given only a placebo, animals given the cannabinoid froze more and spent less time near the source of the odor, with the effects increasing at higher doses.

Small microscopes implanted into the mice’s brains during the experiment revealed higher activation of CeA SOM neurons in mice given the cannabinoid, and the effect was dose-dependent, with a higher dose of CP 55,940 leading to greater activity of SOM neurons.

In a separate experiment, the researchers blocked the usual behavior of SOM neurons by injecting genetically modified mice with a virus carrying a toxin that inhibits their synaptic production. This prevented the release of neurotransmitters when neurons were activated.

When these modified mice were given the cannabinoid and exposed to the predator’s odor, they no longer avoided the predator’s odor to the same extent, suggesting that their heightened anxiety response to threat had been partially suppressed.

Researchers compare the situation to the brakes of a car. In its natural state, the brain regulates the activity of SOM neurons, but when cannabinoids kick in, the brakes are released and its ability to control anxiety slips away.

“Higher doses of cannabinoids and environmental stress worked together to synergistically release the central amygdala ‘brake,’ which led to excessive anxiety,” says Patel.

It’s worth noting that so far we’ve only seen this brain circuit work this way in mice, but if future research can demonstrate that the same mechanism occurs in the human brain — and we can find a way to dampen activated stress responses — it could point to new ways to manage people’s anxiety, whether it results from drug use or other scenarios.

“Understanding how cannabis affects brain function to generate its psychoactive effects could ultimately reveal new ways to counteract the negative consequences that might occur in some people,” says Patel.

“Suppression of somatostatin neuron activity in the central amygdala may represent a final avenue for reducing anxiety symptoms, not just in the context of cannabis side effects.”

The results are reported in Natural communications.