Study Summary

Twenty-five participants were included in this double-blind, randomized, cross-over study investigating the effective connectivity between selected cortico–striato–thalamo-cortical (CTSC) regions after acute administration of lysergic acid diethylamide (LSD), as well as the underlying receptor pharmacology. Participants were administered three different combination treatment protocols (placebo plus placebo, placebo plus LSD, Ketanserin plus LSD) across three sessions with a washout period of two weeks between sessions. Resting-state scans were obtained using fMRI and analyzed using spectral dynamic causal modeling and subjective drug effects were assessed using the Altered States of Consciousness (5D-ASC) questionnaire. All LSD-induced subjective drug effects were shown to be blocked by Ketanserin. Results also indicate that LSD increased effective connectivity from the thalamus to the posterior cingulate cortex in a way that depended on serotonin 2A receptor activation, and decreased effective connectivity from the ventral striatum to the thalamus independently of serotonin 2A receptor activation.