First fMRI study of mescaline in awake rats finds reduced cerebellar activity, increased brain connectivity, and frequency-specific sensory filtering

A study using fMRI in awake rats found that mescaline produces a distinctive pattern of brain changes rather than simply increasing or decreasing sensory processing overall. The drug reduced activity most strongly in the cerebellum while increasing functional connections between the cerebellum and regions involved in memory, sensory organization, bodily perception, alertness, motivation, and reward. Mescaline also weakened the rats' neural response to almond odor, a standardized rewarding smell, and changed prepulse inhibition, improving sound filtering at 4 and 20 kilohertz but worsening it at 12 kilohertz. The researchers describe this as cerebellar-selective hypoactivation combined with global hyperconnectivity. Because the study used one dose in rats and did not measure cardiovascular variables during scanning, the findings may not fully reflect direct neural effects or translate to humans.