Mescaline Alters Cerebellar Function, Global Connectivity, and Frequency-Selective Acoustic Gating: A BOLD fMRI Study in Awake Rats.
Noah Cavallaro, Priya Rai, David Akins, Sima Soltanpour, Md Taufiq Nasseef, Richard J Ortiz, Rachel Utama, Caitlyn R Cody, Anoushka Mistry, Heather C Brenhouse, Praveen P Kulkarni, Craig F Ferris
Neuroscience bulletin May 21, 2026 Peer reviewed DOI: 10.1007/s12264-026-01632-3 via PubMed
Summary
Mescaline, a psychedelic, was found to cause specific changes in brain connectivity in awake rats. It led to reduced activity in the cerebellum but increased overall connectivity with areas like the hippocampus and thalamus. Additionally, mescaline disrupted normal responses to rewarding smells and affected sound processing differently at various frequencies. These results suggest that mescaline alters sensory processing, highlighting its unique effects compared to other psychedelics like LSD and psilocybin.
Study at a glance
| Design | pharmacological MRI |
|---|---|
| Population | awake rats |
| Key finding | Mescaline caused cerebellar-selective BOLD suppression while simultaneously increasing global hyperconnectivity with other brain regions. |
Abstract
Mescaline, a 5-HT2A agonist psychedelic used ceremonially for millennia, lacks neuroimaging characterization due to its Schedule 1 status. Using pharmacological and resting-state fMRI in awake rats, we report mescaline's first comprehensive neurobiological profile. Acutely, mescaline produced cerebellar-selective BOLD suppression, suggesting functional disconnection from forebrain structures. Paradoxically, resting-state analysis revealed global hyperconnectivity, with the cerebellum forming enhanced connections to the hippocampus, thalamus, somatosensory cortex, and midbrain. Mescaline abolished normal BOLD responses to rewarding olfactory stimuli, indicating disrupted sensory processing. Pre-pulse inhibition showed frequency-dependent acoustic gating effects: enhancement at 4 kHz (+ 27.6%) and 20 kHz (+ 27.3%), but impairment at 12 kHz (- 16.4%). These findings distinguish mescaline from LSD and psilocybin, implicating the cerebellum as a dysregulated sensory filter that floods forebrain circuits with unprocessed sensorimotor information-a potential mechanism underlying psychedelic-induced perceptual alterations.