[FG] Schmid Yasmin

Terminally ill patients often experience significant psychosocial distress having depressed mood, death anxiety, pain, and an overall poor quality of life. Recent evidence from pilot studies suggests that serotonergic psychedelics, including lysergic acid diethylamide (LSD) and psilocybin, produce significant and sustained reductions of depressive symptoms and anxiety, along with increases in quality of life and life meaning in patients suffering from life-threatening diseases. Additionally, serotonergic psychedelics may produce antinociceptive effects.

Cluster headache (CH) is often rated as the most painful of all primary headaches, which not only causes significant disability, but is also associated with enormous personal, economic, and psychiatric burden. At the moment, there is no specific treatment available for CH, but serotonergic compounds represent an important drug class, especially in the abortive management of cluster attacks. However, there is a need for new treatment approaches, as CH is also often insufficiently managed with available medication. This study will evaluate the potential benefit and safety of a treatment with LSD (pulse regimen) for patients with CH.

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.