Knocking at the Doors of Perception: Relating LSD Effects on Low‐Frequency Fluctuations and Regional Homogeneity to Receptor Densities in fMRI
European Journal of Neuroscience November 1, 2025 Paolo La‐torraca‐vittori, Livio Tarchi, Elisa Arrigo et al. 1 citation
Lysergic acid diethylamide (LSD) reduces local brain activity and connectivity in sensory and association regions, with effects linked to specific neurotransmitter receptors. In 15 healthy adults, fMRI scans under LSD versus placebo showed decreased amplitude of low-frequency fluctuations (ALFF) in somatosensory, visual, default mode, and frontoparietal networks, and decreased regional homogeneity (ReHo) in sensory and subcortical areas. Test-retest reliability was high for ALFF and moderate for ReHo. LSD-induced changes correlated negatively with densities of D2 and 5-HT1A receptors, suggesting the drug engages neurochemical processes beyond its primary 5-HT2A target. These preliminary results indicate complex, dynamic mechanisms underlying LSD's neural effects.