What Goes on in the Brain When a Good Buzz Gets Harshed

In 1974, Pfizer developed a synthetic cannabinoid that mimicked the effects of tetrahydrocannabinol (THC), but was around 40 times stronger. Unfortunately, this synthetic super weed was never marketed. Instead, it’s used to test the effects of THC on lab animals, like the mice in a new Nature study.

Using cannabis (as you may know from firsthand experience), can be very relaxing, but it can also produce anxiety. It turns out mice experience the same thing. Now scientists might know what’s going on in the brain during a bad trip.

Neuroscientists from Northwestern University dosed a group of mice with different levels of the synthetic cannabinoid (called CP55940) and placed them in an enclosure with a petri dish of fox urine. Confronted with the scent of a predator, control mice would approach the dish to investigate, give it a few sniffs, and run away. Mice under the influence of CP55940, on the other hand, resisted the urge to investigate and tended to freeze more often.

Read more: “Is Cannabis Good for Your Heart?” To get a look at what was going on inside the rodents’ brains, the researchers implanted tiny microscopes in their heads targeted at the brain’s central amygdala, where fear and stress are processed. They traced the anxious behavior to a small bundle of neurons that secrete the inhibitory hormone somatostatin. According to the team, the synthetic cannabis released the natural “brake” on these neurons, allowing them to become hyperactive in the presence of an environmental stressor.

When they genetically silenced these neurons, the anxious behaviors stopped. Importantly, the implications of these findings extend beyond knowing the neurological mechanics of buzz-harshing. Anxiety and mood disorders are steadily climbing in the general population, and according to the team, this dynamic might provide a new therapeutic target.

Whether it’s with cannabis or not, we could all stand to mellow out a bit more. Subscribe to our free newsletter.