Mescaline Alters Cerebellar Function, Global Connectivity, and Frequency-Selective Acoustic Gating: A BOLD fMRI Study...

Area of Science:

• Neuroscience
• Pharmacology

Background:

• Mescaline, a 5-HT2A agonist psychedelic, has limited neuroimaging data due to regulatory status.
• Ancient ceremonial use contrasts with a lack of modern neurobiological characterization.

Purpose of the Study:

• To provide the first comprehensive neurobiological profile of mescaline using neuroimaging.
• To investigate mescaline's effects on brain activity and connectivity in a preclinical model.

Main Methods:

• Utilized pharmacological and resting-state functional magnetic resonance imaging (fMRI) in awake rats.
• Assessed brain-wide Blood-Oxygen-Level-Dependent (BOLD) signals and pre-pulse inhibition (PPI).

Main Results:

• Acute mescaline administration caused cerebellar-selective BOLD suppression and abolished responses to olfactory stimuli.
• Resting-state fMRI revealed global hyperconnectivity, with enhanced cerebellar connections to the hippocampus, thalamus, somatosensory cortex, and midbrain.
• Mescaline demonstrated frequency-dependent effects on acoustic gating via pre-pulse inhibition.

Conclusions:

• Mescaline's neurobiological profile differs from LSD and psilocybin.
• The cerebellum may act as a dysregulated sensory filter, impacting forebrain processing and psychedelic perception.
• Findings suggest a novel mechanism for psychedelic-induced alterations in sensory processing.