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NCT Number: NCT05883540

Lysergic Acid Diethylamide (LSD) in Palliative Care

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.

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Key information

Age range

22 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

University Hospital Basel, Division of Clinical Pharmacology and Toxicology, Basel, Switzerland

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Lysergic Acid Diethylamide Tartrate

Drug

25 μg p.o.

Other names: LSD

Primary outcomes

  1. Changes in state anxiety assessed by questionnaire (state anxiety inventory, STAI-S) compared with active placebo

    Time frame: baseline, 2 weeks after second intervention

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

Secondary outcomes

  1. Changes in state anxiety assessed by questionnaire (state anxiety inventory, STAI-S) compared with active placebo

    Time frame: baseline, 2 days after each intervention, 4 weeks, 6 weeks, and 9 weeks after second intervention

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

  2. Changes in pain levels assessed by questionnaire compared with active placebo

    Time frame: baseline, 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)

  3. Changes in opioid use (dosages of opioids unified according to equivalent dosages of oral morphine) compared with active placebo

    Time frame: concomitant medication will be assessed several times over whole study duration up to 9 weeks after second intervention

  4. 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

    Time frame: baseline, 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

  5. Changes in demoralization assessed by questionnaires (Demoralization Scale II (DS-II)) compared with active placebo

    Time frame: baseline, 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

  6. Changes in quality of life assessed with a single-item question compared with active placebo

    Time frame: baseline, 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)

  7. Changes in anxiety, pain levels, quality of life, demoralization, and spiritual well-being shortly after first intervention compared with scores shortly after second intervention

    Time frame: post 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

  8. 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

    Time frame: baseline, 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

  9. Changes in patient's behaviour and attitudes rated by community observers compared with active placebo

    Time frame: baseline, 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

  10. Changes in caregiver burden assessed by questionnaire compared with active placebo

    Time frame: baseline, before second intervention and 2 weeks and 9 weeks after second intervention

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

  11. Associations between acute LSD effects assessed with questionnaires and long-lasting therapeutic effects assessed with questionnaires

    Time frame: 2,4,6, and 9 weeks after second intervention

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

  12. Changes in burden of suffering assessed with the Pictorial Representation of Illness and Self-Measure (PRISM) compared with active placebo

    Time frame: baseline, 2 days after each intervention, 2 weeks and 9 weeks after the second intervention

  13. Qualitative description of subjective changes after intervention assessed with semistructured interviews

    Time frame: baseline, 2 days after each intervention, 2 weeks and 9 weeks after second intervention

  14. Expectancy as a mediator for treatment effects assessed with questionnaire

    Time frame: baseline

    modified version of the Credibility / Expectancy Questionnaire (CEQ)

  15. Assessment of adverse events (AE)

    Time frame: 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

  16. Physical and general discomfort during drug sessions using standardized questions (adapted list of complaints)

    Time frame: before and 12 hours after drug administration

    adapted list of complaints (LC), safety measures

  17. Changes in vital signs during drug sessions

    Time frame: before and up to 12 hours after drug administration

    monitoring blood pressure and heart rate with an automatic oscillometric device, safety measure

  18. Changes in vital signs during drug sessions

    Time frame: before and up to 12 hours after drug administration

    monitoring body temperature using an ear thermometer, safety measure

Study contacts

Contact information is provided by the study sponsor or research team.

Yasmin Schmid, PD Dr. med.

CONTACT

[email protected]

: +41 61 328 68 47

Sponsors and collaborators

Lead sponsor

University Hospital, Basel, Switzerland

Other

Collaborators

  • Spital Uster AG, Uster, Switzerland
  • University Hospital, Geneva
  • University Hospital, Zürich

Registry information

Official study title

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

Acronym: LPC

Important dates

Study start
2024
Primary completion
2027
Study completion
2028
First posted
Jun 1, 2023
Registry last updated
Apr 29, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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