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LSD Therapy for Persons Suffering From Major Depression (LAD)

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ClinicalTrials.gov Identifier: NCT03866252
Recruitment Status : Recruiting
First Posted : March 7, 2019
Last Update Posted : January 16, 2020
Sponsor:
Collaborator:
Department of Psychiatry Basel (UPK Basel; Prof. Dr. med. Stefan Borgwardt)
Information provided by (Responsible Party):
University Hospital, Basel, Switzerland

Brief Summary:

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-SR, BDI), anxiety (STAI), and general psychopathology (SCL-90) compared with active-placebo-assisted psychotherapy.


Condition or disease Intervention/treatment Phase
Major Depressive Disorder Drug: LSD Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: LSD Therapy for Persons Suffering From Major Depression: A Randomised, Double-blind, Active-placebo Controlled Phase II Study
Actual Study Start Date : January 1, 2020
Estimated Primary Completion Date : July 31, 2023
Estimated Study Completion Date : July 31, 2023

Resource links provided by the National Library of Medicine


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: LSD
LSD administration per os
Other Name: Lysergic Acid Diethylamide

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: LSD
LSD administration per os
Other Name: Lysergic Acid Diethylamide




Primary Outcome Measures :
  1. Change in depressive symptomatology 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, IDS-C, self-rated and 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.


Other Outcome Measures:
  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



Information from the National Library of Medicine

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Ages Eligible for Study:   25 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03866252


Contacts
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Contact: Prof. Dr. med. Stefan Borgwardt, MD 061 325 51 11 ext +41 stefan.borgwardt@upkbs.ch
Contact: Prof. Dr. med. Matthias Liechti, MD 061 328 68 68 ext +41 matthias.liechti@usb.ch

Locations
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Switzerland
Universitäre Psychiatrische Kliniken Recruiting
Basel, Basel-Stadt, Switzerland, 4002
Contact: Felix Müller, Dr. med.    +41 61 325 53 94 ext +41    felix.mueller@upkbs.ch   
Sponsors and Collaborators
University Hospital, Basel, Switzerland
Department of Psychiatry Basel (UPK Basel; Prof. Dr. med. Stefan Borgwardt)
Investigators
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Study Chair: Dr. med. Felix Müller, MD Department of Psychiatry

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Responsible Party: University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier: NCT03866252    
Other Study ID Numbers: BASEC 2018-02370
First Posted: March 7, 2019    Key Record Dates
Last Update Posted: January 16, 2020
Last Verified: January 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Depression
Depressive Disorder
Depressive Disorder, Major
Behavioral Symptoms
Mood Disorders
Mental Disorders
Lysergic Acid Diethylamide
Hallucinogens
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Serotonin Receptor Agonists