Investigating molecular and hemodynamic effects of LSD in the human brain.

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

• Why it matters: Understanding LSD's target engagement and neurophysiological effects is crucial for advancing its therapeutic potential and differentiating it from other psychedelics like psilocybin.
• What they did: Using simultaneous PET-MRI in seven healthy volunteers, the study measured LSD's brain actions, including receptor occupancy, blood flow, and connectivity, and compared these with psilocybin effects in 25 participants.
• The result: Findings reveal LSD's high receptor affinity, increased cerebral blood flow, decreased global connectivity, and an atypical pharmacodynamic profile, providing key insights for clinical development of psychedelic therapies.