Effect of ketanserin, olanzapine, and lorazepam after LSD administration on the acute response to LSD in healthy subjects (LBL-Study)

Acute LSD administration may induce schizophrenia-like symptoms, including pseudohallucinations, visionary restructuralization, and ego-dissolution, but also prepulse inhibition disruption, which seems primarily associated with the activity at the 5-HT_2A receptor. However, the exact mechanisms underlying psychosis-like symptoms of LSD remain to be investigated. The primary goal of the study is to investigate whether ketanserin, olanzapine, and lorazepam administration after LSD administration might attenuate and shorten the LSD response compared to the administration of LSD alone. Additionally, the present study examines changes in the quality of the LSD experience after administration of ketanserin, olanzapine, or lorazepam and its effects on sensorimotor gating and sleep. The study provides insight into the receptor mechanisms involved in alterations of consciousness and, specifically, the relevance of ongoing 5-HT_2A receptor stimulation in the mediation of the psychedelic response to LSD and psychotic symptoms.