Lysergic Acid Diethylamide (LSD) in Palliative Care (LPC)

Lysergic Acid Diethylamide (LSD) in Palliative Care: a Randomised, Double-blind, Active-placebo Controlled Phase II Study (LPC-Study)

Background: 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 hallucinogens 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 hallucinogens may produce antinociceptive effects.

Objective and Design: The study aims to evaluate effects of LSD on psychosocial distress in 60 patients suffering from an advanced or end-stage fatal disease with a life expectancy ≥12wks and ≤2yrs in an active placebo-controlled double-blind parallel study. Patients will be allocated in a 2:1 ratio to one of the two intervention arms receiving either two moderate to high doses of LSD (100 µg and 100 µg or 100 µg and 200 µg) as intervention and two low doses of LSD (25 µg and 25 µg) as active-placebo control.

Study Overview

• Status: Recruiting
• Conditions: Depression; Quality of Life; Pain; Anxiety; Caregiver Burden; Psychological Distress; Palliative Care; Demoralization; Fear of Death; Existential Distress
• Intervention / Treatment: Drug: Lysergic Acid Diethylamide Tartrate; Drug: Lysergic Acid Diethylamide Tartrate

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yasmin Schmid, PD Dr. med.; Phone Number: : +41 61 328 68 47; Email: yasmin.schmid@usb.ch

Study Locations

• Switzerland
  • Basel, Switzerland, 4031
    • Recruiting
    • University Hospital Basel, Division of Clinical Pharmacology and Toxicology
    • Sub-Investigator: Matthias Liechti, Prof. Dr. med.
    • Contact: Yasmin Schmid, PD Dr. med.; Phone Number: +41 61 328 68 47; Email: yasmin.schmid@usb.ch
    • Contact: Melani Zupari, MSc; Phone Number: +41 61 328 77 42; Email: melani.zuparic@usb.ch
    • Principal Investigator: Yasmin Schmid, PD Dr. med.
  • Collonge-Bellerive, Switzerland, 1245
    • Recruiting
    • University Hospital Geneva, Palliative medicine department
    • Contact: Michael Ljuslin, Dr. med.; Phone Number: +41 79 553 87 92; Email: michael.ljuslin@hug.ch
  • Uster, Switzerland, 8610
    • Recruiting
    • Spital Uster AG, Division of Internal Medicine
    • Contact: Sivan Schipper, MD; Phone Number: +41 44 911 12 91; Email: sivan.schipper@spitaluster.ch
  • Zurich, Switzerland
    • Recruiting
    • University Hospital Zurich, Clinic for Radio-Oncology, Competence Centre Palliative Care
    • Contact: David Blum, Prof Dr med; Phone Number: +41 44 255 37 42; Email: david.blum@usz.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: treatment arm; Subjects in the treatment arm will receive 100 μg LSD (first session) and 100 or 200 μg LSD (second session) per os.	Drug: Lysergic Acid Diethylamide Tartrate; 25 μg p.o.; Other Names: LSD; Drug: Lysergic Acid Diethylamide Tartrate; 100 or 200 μg p.o.; Other Names: LSD
Active Comparator: control arm; Subjects in the control arm will receive 25 μg LSD (first session) and 25 μg LSD (second session) per os.	Drug: Lysergic Acid Diethylamide Tartrate; 25 μg p.o.; Other Names: LSD; Drug: Lysergic Acid Diethylamide Tartrate; 100 or 200 μg p.o.; Other Names: LSD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in state anxiety assessed by questionnaire (state anxiety inventory, STAI-S) compared with active placebo	State anxiety inventory (STAI-S) scores, 20 items	baseline, 2 weeks after second intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in state anxiety assessed by questionnaire (state anxiety inventory, STAI-S) compared with active placebo	State anxiety inventory (STAI-S) scores, 20 items	baseline, 2 days after each intervention, 4 weeks, 6 weeks, and 9 weeks after second intervention
Changes in pain levels assessed by questionnaire compared with active placebo	numeric rating scale (NRS) scores ranging from 0 (no pain) to 10 (maximum imaginable pain)	baseline, 2 days after each intervention and 2 weeks after second intervention; 4 weeks, 6 weeks, and 9 weeks after second intervention
Changes in opioid use (dosages of opioids unified according to equivalent dosages of oral morphine) compared with active placebo		concomitant medication will be assessed several times over whole study duration up to 9 weeks after second intervention
Changes in spiritual well-being assessed by questionnaires (Functional Assessment of Chronic Illness Therapy - Spiritual Well-Being; The 12-item Spiritual Well-Being Scale (FACIT-Sp-12)) compared with active placebo	Functional Assessment of Chronic Illness Therapy - Spiritual Well-Being; The 12-item Spiritual Well-Being Scale (FACIT-Sp-12) scores	baseline, 2 days after each intervention and 2 weeks after second intervention; 4 weeks, 6 weeks, and 9 weeks after second intervention
Changes in demoralization assessed by questionnaires (Demoralization Scale II (DS-II)) compared with active placebo	Demoralization Scale II (DS-II) scores	baseline, 2 days after each intervention and 2 weeks after second intervention; 4 weeks, 6 weeks, and 9 weeks after second intervention
Changes in quality of life assessed with a single-item question compared with active placebo	single-item question "how satisfied are you currently with your physical and emotional well-being" rated on a 7-point scale (1 dissatisfied, 7 satisfied)	baseline, 2 days after each intervention and 2 weeks after second intervention; 4 weeks, 6 weeks, and 9 weeks after second intervention
Changes in anxiety, pain levels, quality of life, demoralization, and spiritual well-being shortly after first intervention compared with scores shortly after second intervention	State anxiety inventory (STAI-S), NRS, QoL single-item, Functional Assessment of Chronic Illness Therapy - Spiritual Well-Being; The 12-item Spiritual Well-Being Scale (FACIT-Sp-12), and Demoralization Scale II (DS-II) scores	post drug visit 1-3 compared with post drug visit 4-6
Changes in patient's depression, isolation, anxiety, fear and denial of imminence of death, and pre-occupation with pain using investigator-ratings compared with active placebo	Emotional Condition Rating Scale (ECRS) scores, Hamilton depression (GRID-HAM-D17) and Hamilton anxiety rating scale (HAM-A) scores	baseline, one day before second intervention and 2 and 9 weeks after second intervention
Changes in patient's behaviour and attitudes rated by community observers compared with active placebo	community observer rating: rating of the participant's behaviour and attitudes on 11 items by a contact person	baseline, before second intervention and 2 weeks and 9 weeks after second intervention
Changes in caregiver burden assessed by questionnaire compared with active placebo	Zarit Burden Inventory (ZBI) scores completed by caregiver, total score	baseline, before second intervention and 2 weeks and 9 weeks after second intervention
Associations between acute LSD effects assessed with questionnaires and long-lasting therapeutic effects assessed with questionnaires	acute effects will be assessed using the Mystical experience Questionnaire (MEQ30) and visual analogue scales (VASs)	2,4,6, and 9 weeks after second intervention
Changes in burden of suffering assessed with the Pictorial Representation of Illness and Self-Measure (PRISM) compared with active placebo		baseline, 2 days after each intervention, 2 weeks and 9 weeks after the second intervention
Qualitative description of subjective changes after intervention assessed with semistructured interviews		baseline, 2 days after each intervention, 2 weeks and 9 weeks after second intervention
Expectancy as a mediator for treatment effects assessed with questionnaire	modified version of the Credibility / Expectancy Questionnaire (CEQ)	baseline
Assessment of adverse events (AE)	grading according to Common Terminology Criteria for Adverse Events CTCAE Version 5.0, safety measures	during the whole study duration up to 9 weeks after second intervention
Physical and general discomfort during drug sessions using standardized questions (adapted list of complaints)	adapted list of complaints (LC), safety measures	before and 12 hours after drug administration
Changes in vital signs during drug sessions	monitoring blood pressure and heart rate with an automatic oscillometric device, safety measure	before and up to 12 hours after drug administration
Changes in vital signs during drug sessions	monitoring body temperature using an ear thermometer, safety measure	before and up to 12 hours after drug administration

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Collaborators: University Hospital, Geneva; University Hospital, Zürich; Spital Uster AG, Uster, Switzerland
• Investigators: Principal Investigator: Yasmin Schmid, PD Dr. med., University Hospital, Basel, Switzerland

Publications and helpful links

General Publications

• Schipper S, Nigam K, Schmid Y, Piechotta V, Ljuslin M, Beaussant Y, Schwarzer G, Boehlke C. Psychedelic-assisted therapy for treating anxiety, depression, and existential distress in people with life-threatening diseases. Cochrane Database Syst Rev. 2024 Sep 12;9(9):CD015383. doi: 10.1002/14651858.CD015383.pub2.

Study record dates

Study Major Dates

• Study Start (Actual): June 9, 2024
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): May 1, 2028

Study Registration Dates

• First Submitted: May 8, 2023
• First Submitted That Met QC Criteria: May 22, 2023
• First Posted (Actual): June 1, 2023

Study Record Updates

• Last Update Posted (Actual): April 29, 2026
• Last Update Submitted That Met QC Criteria: April 23, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Mental Disorders; Behavioral Symptoms; Stress, Psychological; Pathological Conditions, Signs and Symptoms; Behavior; Signs and Symptoms; Caregiver Burden; Pain; Anxiety Disorders; Depression; Necrophobia; Heterocyclic Compounds; Heterocyclic Compounds, Fused-Ring; Alkaloids; Heterocyclic Compounds, 4 or More Rings; Ergot Alkaloids; Ergolines; Lysergic Acid; Lysergic Acid Diethylamide
• Other Study ID Numbers: BASEC 2022-01818

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No