Nature neuroscienceOct 12, 2026

LSD's effects on brain molecules and blood flow in humans

Psychedelic Science Weekly Brief ↗PubMed ↗DOI ↗

Updated Oct 14, 2026

Abstract

LSD occupies 5-HT2AR with high affinity and increases both global cerebral blood flow and internal carotid artery flow.

LSD administration leads to increased global cerebral blood flow and internal carotid artery flow.
Decreases in global connectivity are observed, which are negatively associated with changes in cerebral blood flow.
An anticlockwise hysteresis loop between plasma drug levels and subjective effects suggests unusual pharmacodynamic mechanisms.
Comparative analysis with psilocybin shows both similarities and differences in cerebral blood flow and connectivity effects.

Simplified

Lysergic acid diethylamide (LSD) is a potent psychedelic with increasing therapeutic interest, yet qualification of target engagement using in vivo neuroimaging has not yet been performed. Using simultaneous positron emission tomography-magnetic resonance imaging technology, we describe multiple brain actions of LSD in seven healthy volunteers blinded to LSD dose received. Here we show that LSD occupies 5-HT2AR with a high affinity and increases both global cerebral blood flow (CBF) and internal carotid artery flow. LSD also decreases global connectivity, which was negatively associated with changes in CBF. We observe an anticlockwise hysteresis loop between plasma drug levels and subjective effects, suggesting atypical pharmacodynamic mechanisms. We contrast our CBF and global connectivity findings and their relation in a separate cohort of 25 participants administered psilocybin, highlighting key consistencies and differences. By establishing the dose-occupancy relation of LSD in humans, our findings provide insights for the clinical development of psychedelic compounds and demonstrate unique neurophysiological effects that distinguish LSD from psilocybin.