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Lysergic Acid Diethylamide (LSD) in Palliative Care

Phase 2
Recruiting
Conditions
Palliative Care
Pain
Anxiety
Depression
Demoralization
Psychological Distress
Quality of Life
Caregiver Burden
Fear of Death
Existential Distress
Interventions
Registration Number
NCT05883540
Lead Sponsor
University Hospital, Basel, Switzerland
Brief Summary

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 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.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
60
Inclusion Criteria
  • Age ≥ 22 years.
  • 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"
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 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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
treatment armLysergic Acid Diethylamide TartrateSubjects in the treatment arm will receive 100 μg LSD (first session) and 100 or 200 μg LSD (second session) per os.
control armLysergic Acid Diethylamide TartrateSubjects in the control arm will receive 25 μg LSD (first session) and 25 μg LSD (second session) per os.
Primary Outcome Measures
NameTimeMethod
Changes in state anxiety assessed by questionnaire (state anxiety inventory, STAI-S) compared with active placebobaseline, 2 weeks after second intervention

State anxiety inventory (STAI-S) scores, 20 items

Secondary Outcome Measures
NameTimeMethod
Changes in pain levels assessed by questionnaire compared with active placebobaseline, 2 days after each intervention and 2 weeks after second intervention; 4 weeks, 6 weeks, and 9 weeks after second intervention

numeric rating scale (NRS) scores ranging from 0 (no pain) to 10 (maximum imaginable pain)

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 placebobaseline, 2 days after each intervention and 2 weeks after second intervention; 4 weeks, 6 weeks, and 9 weeks after second intervention

Functional Assessment of Chronic Illness Therapy - Spiritual Well-Being; The 12-item Spiritual Well-Being Scale (FACIT-Sp-12) scores

Changes in state anxiety assessed by questionnaire (state anxiety inventory, STAI-S) compared with active placebobaseline, 2 days after each intervention, 4 weeks, 6 weeks, and 9 weeks after second intervention

State anxiety inventory (STAI-S) scores, 20 items

Changes in opioid use (dosages of opioids unified according to equivalent dosages of oral morphine) compared with active placeboconcomitant medication will be assessed several times over whole study duration up to 9 weeks after second intervention
Changes in demoralization assessed by questionnaires (Demoralization Scale II (DS-II)) compared with active placebobaseline, 2 days after each intervention and 2 weeks after second intervention; 4 weeks, 6 weeks, and 9 weeks after second intervention

Demoralization Scale II (DS-II) scores

Changes in anxiety, pain levels, quality of life, demoralization, and spiritual well-being shortly after first intervention compared with scores shortly after second interventionpost drug visit 1-3 compared with post drug visit 4-6

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

Expectancy as a mediator for treatment effects assessed with questionnairebaseline

modified version of the Credibility / Expectancy Questionnaire (CEQ)

Changes in patient's behaviour and attitudes rated by community observers compared with active placebobaseline, before second intervention and 2 weeks and 9 weeks after second intervention

community observer rating: rating of the participant's behaviour and attitudes on 11 items by a contact person

Changes in caregiver burden assessed by questionnaire compared with active placebobaseline, before second intervention and 2 weeks and 9 weeks after second intervention

Zarit Burden Inventory (ZBI) scores completed by caregiver, total score

Changes in quality of life assessed with a single-item question compared with active placebobaseline, 2 days after each intervention and 2 weeks after second intervention; 4 weeks, 6 weeks, and 9 weeks after second intervention

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)

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 placebobaseline, one day before second intervention and 2 and 9 weeks after second intervention

Emotional Condition Rating Scale (ECRS) scores, Hamilton depression (GRID-HAM-D17) and Hamilton anxiety rating scale (HAM-A) scores

Changes in burden of suffering assessed with the Pictorial Representation of Illness and Self-Measure (PRISM) compared with active placebobaseline, 2 days after each intervention, 2 weeks and 9 weeks after the second intervention
Qualitative description of subjective changes after intervention assessed with semistructured interviewsbaseline, 2 days after each intervention, 2 weeks and 9 weeks after second intervention
Assessment of adverse events (AE)during the whole study duration up to 9 weeks after second intervention

grading according to Common Terminology Criteria for Adverse Events CTCAE Version 5.0, safety measures

Physical and general discomfort during drug sessions using standardized questions (adapted list of complaints)before and 12 hours after drug administration

adapted list of complaints (LC), safety measures

Changes in vital signs during drug sessionsbefore and up to 12 hours after drug administration

monitoring body temperature using an ear thermometer, safety measure

Associations between acute LSD effects assessed with questionnaires and long-lasting therapeutic effects assessed with questionnaires2,4,6, and 9 weeks after second intervention

acute effects will be assessed using the Mystical experience Questionnaire (MEQ30) and visual analogue scales (VASs)

Trial Locations

Locations (3)

Spital Uster AG

🇨🇭

Uster, Zurich, Switzerland

University Hospital Basel

🇨🇭

Basel, Switzerland

University Hospital Zurich, Clinic for Radio-Oncology, Competence Centre Palliative Care

🇨🇭

Zürich, Switzerland

Spital Uster AG
🇨🇭Uster, Zurich, Switzerland
Sivan Schipper, MD
Contact
+41449111291
sivan.schipper@spitaluster.ch

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