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 DOI: 10.1007/s12264-026-01632-3 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Pharmacological and resting-state fMRI in awake rats Peer reviewed |
|---|---|
| Population | Awake rats |
| Intervention | Mescaline |
| Topics | Mescaline |
| Keywords | Cerebellum Fear Hippocampus Pharmacological MRI Reward |
| Key points | Mescaline produces cerebellar-selective BOLD suppression and global resting-state hyperconnectivity, abolishes reward-related BOLD responses, and shows frequency-dependent effects on acoustic startle, distinguishing it from LSD and psilocybin. |
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.