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Completed

NCT Number: NCT03866252

LSD Therapy for Persons Suffering From Major Depression

Background: Major Depressive Disorder is one of the most prevalent mental illnesses, leading to substantial personal distress and economical consequences. Pharmacological Treatment is limited and relapse is frequent.

Lysergic acid diethylamide (LSD) was extensively investigated in humans in the 1950s and 1960s and was shown to attenuate depressive symptoms. Clinical research with LSD ended in the 1970s due to regulatory restrictions but its use for personal and recreational purposes continued. In recent years, there has been a renewed interest in the use of hallucinogens in psychiatric research and practices, reconsidering LSD's antidepressant potential. Larger, well-designed and placebo-controlled studies are warranted. This study will evaluate the potential benefits of LSD-assisted psychotherapy in patients suffering from Major Depressive Disorder.

Objective: To test the efficacy of LSD in patients with Major Depressive Disorder.

Design: Randomised, double-blind, active-placebo-controlled trial using 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.

Participants: 60 patients aged > 25 years with Major Depressive Disorder (according to DSM-V).

Main outcome measures: Change in depressive symptomatology (IDS, BDI), anxiety (STAI), and general psychopathology (SCL-90) compared with active-placebo-assisted psychotherapy.

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Key information

Conditions

Major Depressive Disorder Depressive Disorder Depressive Disorder, Major Mental Disorders Mood Disorders

Age range

25 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Universitäre Psychiatrische Kliniken

Basel, Canton of Basel-City, 4002, Switzerland

Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

  • Major Depressive Disorder according to Diagnostic and Statistical Manual of Mental Disorders (DSM-V)
  • > 25 years
  • Sufficient understanding of the German language

Exclusion criteria

  • < 25 years
  • Concomitant diagnosis of past or present psychotic disorder
  • Concomitant diagnosis of past or present bipolar disorder
  • First degree relative with a psychotic disorder
  • Unable or unwilling to discontinue antidepressant medication
  • Pregnancy or breastfeeding
  • Known hypersensitivity to LSD
  • Somatic disorders including central nervous system (CNS) involvement
  • Known or suspected non-compliance, drug or alcohol abuse
  • Metal implants
  • Weight < 42 kg
  • Suicide risk or very likely to require psychiatric hospitalisation

Treatment and study plan

LSD

Drug

LSD administration per os

Other names: Lysergic Acid Diethylamide

Primary outcomes

  1. Change in depressive symptoms assessed by questionnaire compared with active placebo

    Time frame: Baseline; 1 week before first intervention; 2 weeks after first intervention; 2, 6, and 12 weeks after LSD

    Inventory of Depressive Symptomatology (IDS-C, clinician-rated). Scores are obtained by summing responses to the items, with a total score ranging from 0 to 84 and higher scores indicating more and/or stronger depressive symptoms.

  2. Change in depressive symptoms assessed by questionnaire compared with active placebo

    Time frame: Baseline; 1 week before first intervention; 2 weeks after first intervention; 2, 6, and 12 weeks after LSD

    Inventory of Depressive Symptomatology (IDS-SR, self-rated). Scores are obtained by summing responses to the items, with a total score ranging from 0 to 84 and higher scores indicating more and/or stronger depressive symptoms.

Other outcomes

  1. Change in depressive symptoms assessed by questionnaire compared with active placebo

    Time frame: Baseline; 1 week before first intervention; 2 weeks after first intervention; 2, 6, and 12 weeks after LSD

    Beck Depression Inventory (BDI). Scores are obtained by summing responses to the items, with a total score ranging from 0 to 63 and higher scores indicating more and/or stronger depressive symptoms.

  2. Changes in state and trait anxiety assessed by questionnaire compared with active placebo

    Time frame: Baseline; 2 weeks post-intervention

    State-Trait Anxiety Inventory (STAI). State and trait anxiety are being assessed separately. Each type of anxiety is being represented by 20 different items. Scores range from 20 to 80, with higher scores indicating greater anxiety.

  3. Changes in general psychopathology assessed by questionnaire compared with active placebo

    Time frame: Baseline; 1 week before first intervention; 2 weeks after first intervention; 2, 6, and 12 weeks after LSD

    Symptom Check List (SCL-90, 90-item version). Consists of 9 subscales investigating psychopathological symptoms (somatization, obsessive-compulsivity, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation, psychoticism), offering five answers (i.e. not at all, a little, fairly, a lot, extremely). SCL-90 total score = 360; subscale total score = 40. Higher scores indicate greater psychological impairment.

  4. Changes in existential anxiety assessed by questionnaire compared with active placebo

    Time frame: Baseline; 2 weeks after first treatment; 2 weeks after second treatment

    Existential Concerns Questionnaire (EAQ). Item scores are assessed in a yes/no format.

  5. Changes in mindfulness assessed by questionnaire compared with active placebo

    Time frame: Baseline; 2 weeks after first treatment; 2 weeks after second treatment

    Five Facet Mindfulness Questionnaire (FFMQ). Item scores are assessed on a scale from 1 (never) to 5 (very often or always). Higher scores indicate higher greater levels of mindfulness.

  6. Changes in humility assessed by questionnaire compared with active placebo

    Time frame: Baseline; 6 weeks post-treatment

    Elliot Humility Scale (EHS). Item scores are assessed on a scale from 1 (strongly disagree) to 5 (strongly agree). Higher scores indicate higher greater levels of humility.

  7. Changes in humility assessed by questionnaire

    Time frame: Baseline; 6 weeks post-treatment compared with active placebo

    Jankowski Humility Scale (JHS). Item scores are assessed on a scale from 1 (not at all) to 5 (absolutely). Higher scores indicate higher greater levels of humility.

  8. Changes in the personality trait "absorption" assessed by questionnaire compared with active placebo

    Time frame: Baseline

    Tellegen Absorption Scale (TAS). Item scores are assessed on a scale from 0 (not at all) to 4 (absolutely). Higher scores indicate higher greater levels of trait absorption.

  9. Acute subjective effects assessed via questionnaire compared with active placebo

    Time frame: At weeks 3 and 7

    The Visual Analog Scale (VAS). Items assess acute subjective drug effects (e.g. intensity, liking) Item scores are assessed on a visual scale ranging from 1% to 100%. Higher scores indicate greater subjective effects.

  10. Characteristics of altered states of consciousness assessed by questionnaire

    Time frame: At weeks 3 and 7

    States of Consciousness Questionnaire (SCQ). Items retrospectively assess subjective drug effects. Item scores are assessed on a scale ranging from 0 to 5. Higher scores indicate greater subjective effects associated with a different state of consciousness.

  11. Characteristics of altered states of consciousness assessed by questionnaire compared with active placebo

    Time frame: At weeks 3 and 7

    5-Dimensional Altered States of Consciousness Questionnaire (5D-ASC). Items retrospectively assess subjective drug effects. Item scores are assessed on a visual scale ranging from 1% to 100%. Higher scores indicate greater subjective effects associated with a different state of consciousness.

  12. Changes in mystical-type experiences assessed by questionnaire

    Time frame: Baseline; 6 weeks post-treatment compared with active placebo

    Mysticism Scale (MS). Item scores are assessed on a scale ranging from +4 (extremely accurate) to -4 (extremely inappropriate). Higher scores indicate greater levels of mystical experiences.

  13. Acquisition of physical conditions / complaints assessed by questionnaire

    Time frame: Baseline; at weeks 2, 3, 5, 7, 9, 13

    List of complaints (LC). Assesses acute complaints (e.g. pain, coughing, nausea) in a yes/no frmat. A higher number of "yes" answers indicates more complaints. Total "yes" score ranges from 0 to 65.

  14. Perception of therapeutic alliance assessed by questionnaire

    Time frame: 1 week pre-treatment

    Helping Alliance Questionnaire (therapist version (HAQ-T), patient version (HAQ-P). Item scores are assessed on a scale ranging from 1 (very accurate) to 6 (very inaccurate). Lower scores indicate increased subjective helping alliance.

  15. Subjective evaluation of mood assessed by questionnaire

    Time frame: Baseline; at weeks 2, 3, 5, 7, 9, 13

    Adjective Mood Rating Scale (clinician version (AMRS-C), patient version (AMRS-P). Scale consists of 60 adjectives describing different moods (e.g. "nervous", "concentrated", "drowsy"), offering four response possibilities (i.e. not at all, a little, fairly, strongly). Items are analyzed separately.

  16. Assessment of personality by questionnaire

    Time frame: Baseline

    NEO-Five-Factor-Inventory (NEO-FFI). The NEO-FFI assesses five personality traits (i.e. neuroticism, extraversion, openness, agreeableness and conscientiousness) on a scale from 1 (strongly disagree) to 5 (strongly agree). Higher scores indicate higher manifestation of a particulare personality trait.

  17. Assessment of religiosity by questionnaire

    Time frame: Baseline

    Religiosity Scale (Z-Scale). This 7-item scale assesses the degree of religiosity on ascending scales ranging from "not at all" to "very often". Higher scores indicate higher levels of religiosity.

  18. Persisting effects of treatment assessed by questionnaire

    Time frame: 12 weeks post-treatment

    Persisting Effects Questionnaire (PEQ). Scores are assessed on a scale from 0 (not at all) to 5 (extremely). Higher scores (under consideration of reverse-scored items) indicate stronger persisting treatment effects.

  19. Changes in brain-derived neurotrophic factor (BDNF)

    Time frame: One day and 12 weeks post-treatment

    Changes in brain-derived neurotrophic factor as measured by blood concentrations compared with active placebo

  20. Changes in hypothalamic-pituitary-adrenal (HPA) axis function

    Time frame: 2 weeks post-treatment

    Changes in hypothalamic-pituitary-adrenal (HPA) axis function as measured with salivary cortisol awakening responses compared with active placebo

  21. Changes in immunoregulation and Inflammation compared with active placebo

    Time frame: One day and 12 weeks post-treatment

    Measured via blood levels of macrophage migration inhibitory factor and interleukin-1 beta

  22. Brain activation during fearful face processing and working memory processing compared with placebo

    Time frame: One week pre-treatment and one day post-treatment

    Functional Magnetic Resonance Imaging (fMRI)

  23. Brain Perfusion in treatment condition compared with active placebo

    Time frame: One week pre-treatment and one day post-treatment

    Diffusion Tensor Imaging (DTI)

  24. Brain Perfusion compared with active placebo

    Time frame: One week pre-treatment and one day post-treatment

    Arterial Spin Labeling (ASL)

  25. Changes in sleep patterns

    Time frame: From one week pre-treatment to two weeks post-treatment

    Actigraphy

Sponsors and collaborators

Lead sponsor

University Hospital, Basel, Switzerland

Other

Collaborators

  • Department of Psychiatry Basel (UPK Basel; Prof. Dr. med. Stefan Borgwardt)

Registry information

Official study title

LSD Therapy for Persons Suffering From Major Depression: A Randomised, Double-blind, Active-placebo Controlled Phase II Study

Acronym: LAD

Important dates

Study start
2019
Primary completion
2022
Study completion
2022
First posted
Mar 7, 2019
Registry last updated
Apr 23, 2025

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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