Lysergic Acid Diethylamide (LSD) in Palliative Care

Inclusion criteria

• Age ≥ 22 years.
• Advanced or End-stage fatal disease of any cause with a life expectancy ≥ 12 weeks and ≤ 2 years
• Sufficient understanding of the study procedures and risks associated with the study.
• Participants must be willing to adhere to the study procedures and sign the consent form.
• Participants must be willing not to drive a traffic vehicle or to operate machines within 24 h after LSD administration.
• Participants must complete an actual "Emergency Medical Directive"
• Participants with central nervous system (CNS) involvement of cancer are eligible if the following apply:
• treated and stable CNS lesion(s) OR untreated but asymptomatic/stable lesions, defined as clinically and/or radiologically stable for ≥ 4 weeks before screening
• no seizures within ≥ 4 weeks; if on antiepileptic medication: stable dose ≥ 4 weeks and no relevant drug-drug interactions expected
• no requirement for high-dose corticosteroids, defined as ≤10 mg prednisone equivalent per day on a stable or decreasing dose
• no leptomeningeal metastases
• no concomitant therapeutic anticoagulation

Exclusion criteria

• Life expectancy \< 12 weeks
• Known hypersensitivity to LSD
• Requiring ongoing concomitant therapy with a psychoactive prescription drug which might interfere with the study drug, and unable or unwilling to comply with the washout period.
• Current use of a potent drug CYP2D6 inhibitor
• Women who are pregnant or nursing or intend to become pregnant during the course of the study.
• Somatic disorders including CNS involvement of cancer, untreated epilepsy with a history of generalized grand-mal seizures, history of delirium, end-stage heart failure (NYHA IV), untreated hypertension or insufficiently treated hypertension, angina pectoris, severe liver disease or severely impaired renal function, or other that in the judgement of the investigators pose too great potential for side effects.
• Inability to follow the procedures of the study, e.g., due to language problems, psychological disorders, dementia, etc. of the participant.
• Participation in another study with an investigational drug within the 30 days preceding and during the present study
• concomitant diagnosis of past or present psychotic disorder, first-degree relative with psychotic disorders
• concomitant diagnosis of past or present bipolar disorder
• current delirium
• substance use disorder (within the last 2 months, except nicotine, opioids used for analgesia, and benzodiazepine treatment for anxiety).
• Weight \< 45 kg
• Suicidal ideation with active intent or plan to act on suicidal thoughts as assessed by the treating investigator.
• CNS involvement of cancer if
• CNS disease is unstable or high-risk, including clinically and/or radiologically progressive lesions, signs of raised intracranial pressure, radiologically uncontrolled edema, need for escalating corticosteroid doses, or any neurological condition judged to pose too excessive risk.
• CNS-directed therapy (surgery and/or radiation) within ≤ 4 weeks