LSD Therapy for Persons Suffering From Major Depression (LAD)

• ClinicalTrials.gov Identifier: NCT03866252
• Recruitment Status: Completed
• First Posted: March 7, 2019
• Last Update Posted: March 8, 2023
• Sponsor: University Hospital, Basel, Switzerland
• Collaborator: Department of Psychiatry Basel (UPK Basel; Prof. Dr. med. Stefan Borgwardt)
• Information provided by (Responsible Party): University Hospital, Basel, Switzerland

Tracking Information

• First Submitted Date: February 8, 2019
• First Posted Date: March 7, 2019
• Last Update Posted Date: March 8, 2023
• Actual Study Start Date: November 1, 2019
• Actual Primary Completion Date: September 29, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 6, 2023)

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.

Original Primary Outcome Measures (submitted: March 4, 2019)

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.

Current Secondary Outcome Measures (submitted: March 6, 2023)

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.

• Original Secondary Outcome Measures: Not Provided

Current Other Pre-specified Outcome Measures (submitted: March 4, 2019)

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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
• 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
• 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
• 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)
• Brain Perfusion in treatment condition compared with active placebo [ Time Frame: One week pre-treatment and one day post-treatment ]
  Diffusion Tensor Imaging (DTI)
• Brain Perfusion compared with active placebo [ Time Frame: One week pre-treatment and one day post-treatment ]
  Arterial Spin Labeling (ASL)
• Changes in sleep patterns [ Time Frame: From one week pre-treatment to two weeks post-treatment ]
  Actigraphy

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

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

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Major Depressive Disorder

Intervention

Drug: LSD

LSD administration per os

Other Name: Lysergic Acid Diethylamide

Study Arms

• 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.
  Intervention: Drug: LSD
• Active Comparator: Control Arm
  Subjects in the control arm will receive 25 μg LSD (first session) and 25 μg LSD (second session) per os.
  Intervention: Drug: LSD

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 4, 2019): 60
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: December 1, 2022
• Actual Primary Completion Date: September 29, 2022 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 25 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Switzerland

Administrative Information

• NCT Number: NCT03866252
• Other Study ID Numbers: BASEC 2018-02370
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• 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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: University Hospital, Basel, Switzerland
• Original Responsible Party: Same as current
• Current Study Sponsor: University Hospital, Basel, Switzerland
• Original Study Sponsor: Same as current
• Collaborators: Department of Psychiatry Basel (UPK Basel; Prof. Dr. med. Stefan Borgwardt)

Investigators

• Study Chair: Dr. med. Felix Müller, MD; Department of Psychiatry

• PRS Account: University Hospital, Basel, Switzerland
• Verification Date: March 2023