- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03866252
LSD Therapy for Persons Suffering From Major Depression (LAD)
LSD Therapy for Persons Suffering From Major Depression: A Randomised, Double-blind, Active-placebo Controlled Phase II Study
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.
Study Overview
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Basel-Stadt
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Basel, Basel-Stadt, Switzerland, 4002
- Universitäre Psychiatrische Kliniken
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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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.
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LSD administration per os
Other Names:
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Active Comparator: Control Arm
Subjects in the control arm will receive 25 μg LSD (first session) and 25 μg LSD (second session) per os.
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LSD administration per os
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
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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.
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Baseline; 1 week before first intervention; 2 weeks after first intervention; 2, 6, and 12 weeks after LSD
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
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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.
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Baseline; 1 week before first intervention; 2 weeks after first intervention; 2, 6, and 12 weeks after LSD
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
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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.
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Baseline; 1 week before first intervention; 2 weeks after first intervention; 2, 6, and 12 weeks after LSD
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Changes in state and trait anxiety assessed by questionnaire compared with active placebo
Time Frame: Baseline; 2 weeks post-intervention
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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.
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Baseline; 2 weeks post-intervention
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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
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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.
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Baseline; 1 week before first intervention; 2 weeks after first intervention; 2, 6, and 12 weeks after LSD
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Changes in existential anxiety assessed by questionnaire compared with active placebo
Time Frame: Baseline; 2 weeks after first treatment; 2 weeks after second treatment
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Existential Concerns Questionnaire (EAQ).
Item scores are assessed in a yes/no format.
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Baseline; 2 weeks after first treatment; 2 weeks after second treatment
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Changes in mindfulness assessed by questionnaire compared with active placebo
Time Frame: Baseline; 2 weeks after first treatment; 2 weeks after second treatment
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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.
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Baseline; 2 weeks after first treatment; 2 weeks after second treatment
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Changes in humility assessed by questionnaire compared with active placebo
Time Frame: Baseline; 6 weeks post-treatment
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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.
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Baseline; 6 weeks post-treatment
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Changes in humility assessed by questionnaire
Time Frame: Baseline; 6 weeks post-treatment compared with active placebo
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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.
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Baseline; 6 weeks post-treatment compared with active placebo
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Changes in the personality trait "absorption" assessed by questionnaire compared with active placebo
Time Frame: Baseline
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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.
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Baseline
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Acute subjective effects assessed via questionnaire compared with active placebo
Time Frame: At weeks 3 and 7
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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.
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At weeks 3 and 7
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Characteristics of altered states of consciousness assessed by questionnaire
Time Frame: At weeks 3 and 7
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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.
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At weeks 3 and 7
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Characteristics of altered states of consciousness assessed by questionnaire compared with active placebo
Time Frame: At weeks 3 and 7
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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.
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At weeks 3 and 7
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Changes in mystical-type experiences assessed by questionnaire
Time Frame: Baseline; 6 weeks post-treatment compared with active placebo
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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.
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Baseline; 6 weeks post-treatment compared with active placebo
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Acquisition of physical conditions / complaints assessed by questionnaire
Time Frame: Baseline; at weeks 2, 3, 5, 7, 9, 13
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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.
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Baseline; at weeks 2, 3, 5, 7, 9, 13
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Perception of therapeutic alliance assessed by questionnaire
Time Frame: 1 week pre-treatment
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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.
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1 week pre-treatment
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Subjective evaluation of mood assessed by questionnaire
Time Frame: Baseline; at weeks 2, 3, 5, 7, 9, 13
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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.
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Baseline; at weeks 2, 3, 5, 7, 9, 13
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Assessment of personality by questionnaire
Time Frame: Baseline
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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.
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Baseline
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Assessment of religiosity by questionnaire
Time Frame: Baseline
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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.
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Baseline
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Persisting effects of treatment assessed by questionnaire
Time Frame: 12 weeks post-treatment
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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.
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12 weeks post-treatment
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Changes in brain-derived neurotrophic factor (BDNF)
Time Frame: One day and 12 weeks post-treatment
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Changes in brain-derived neurotrophic factor as measured by blood concentrations compared with active placebo
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One day and 12 weeks post-treatment
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Changes in hypothalamic-pituitary-adrenal (HPA) axis function
Time Frame: 2 weeks post-treatment
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Changes in hypothalamic-pituitary-adrenal (HPA) axis function as measured with salivary cortisol awakening responses compared with active placebo
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2 weeks post-treatment
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Changes in immunoregulation and Inflammation compared with active placebo
Time Frame: One day and 12 weeks post-treatment
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Measured via blood levels of macrophage migration inhibitory factor and interleukin-1 beta
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One day and 12 weeks post-treatment
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Brain activation during fearful face processing and working memory processing compared with placebo
Time Frame: One week pre-treatment and one day post-treatment
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Functional Magnetic Resonance Imaging (fMRI)
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One week pre-treatment and one day post-treatment
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Brain Perfusion in treatment condition compared with active placebo
Time Frame: One week pre-treatment and one day post-treatment
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Diffusion Tensor Imaging (DTI)
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One week pre-treatment and one day post-treatment
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Brain Perfusion compared with active placebo
Time Frame: One week pre-treatment and one day post-treatment
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Arterial Spin Labeling (ASL)
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One week pre-treatment and one day post-treatment
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Changes in sleep patterns
Time Frame: From one week pre-treatment to two weeks post-treatment
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Actigraphy
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From one week pre-treatment to two weeks post-treatment
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Collaborators and Investigators
Investigators
- Study Chair: Dr. med. Felix Müller, MD, Department of Psychiatry
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Mental Disorders
- Mood Disorders
- Depressive Disorder
- Depressive Disorder, Major
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Psychotropic Drugs
- Serotonin Agents
- Serotonin Receptor Agonists
- Serotonin Antagonists
- Hallucinogens
- Lysergic Acid Diethylamide
Other Study ID Numbers
- BASEC 2018-02370
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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