Randomised, two-period crossover fMRI study (n=24) in healthy volunteers comparing single oral LSD (100 µg) with placebo to assess neuronal correlates of altered consciousness.
This study uses a random-order two-period crossover design in healthy volunteers to compare normal and pharmacologically induced altered states of consciousness using fMRI.
Altered states are induced with a single oral dose of LSD (100 µg) versus an identical-appearing mannitol placebo; subjective alterations will be correlated with objective imaging measures to identify neuronal correlates of psychotic-like perception changes.
Outcomes inform the relationship between subjective phenomenology and brain activation patterns, with implications for understanding early schizophrenia and consciousness research.
Two-period crossover (LSD vs placebo) within-subject design for fMRI assessment.
Single oral 100 µg dose
Mannitol capsule visually identical to LSD
In a double-blind, placebo-controlled crossover study in 18 healthy volunteers, 100 µg LSD impaired response inhibition and reduced activation in right middle temporal, bilateral frontal, anterior cingulate, left postcentral and cerebellar regions, with altered parahippocampal–prefrontal relationships. These results indicate that 5‑HT2A receptor activation disrupts hippocampal–prefrontal inhibitory control, which may facilitate the emergence of LSD-induced visual imagery and hallucinations.