Molecular, haemodynamic and functional effects of LSD in the human brain
medRxiv June 18, 2025 Drummond E-Wen Mcculloch, K. M. Larsen, Annette Johansen et al. preprint
Lysergic acid diethylamide (LSD) increases global cerebral blood flow and internal carotid artery flow without affecting artery diameter, effects opposite to those of psilocybin. Functional connectivity analyses show decreases in global connectivity (GCOR), which is negatively correlated with the increase in cerebral blood flow. An anticlockwise hysteresis loop between plasma drug levels and subjective effects suggests atypical pharmacodynamic mechanisms. These findings, derived from simultaneous PET-MRI in seven healthy volunteers, establish the dose-occupancy relation of LSD at cerebral serotonin 2A receptors and highlight neurophysiological differences from related psychedelics, providing insights for clinical development.