LSD Therapy for Persons Suffering From Major Depression

Major Depressive Disorder Clinical Trial

— LAD  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03866252
• Other study ID #: BASEC 2018-02370
• Status: Completed
• Phase: Phase 2
• Start date: November 1, 2019
• Est. completion date: December 1, 2022

Study information

• Verified date: March 2023
• Source: University Hospital, Basel, Switzerland
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: December 1, 2022
• Est. primary completion date: September 29, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 25 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

Intervention

Drug:
• LSD
LSD administration per os

Locations

Country	Name	City	State
Switzerland	Universitäre Psychiatrische Kliniken	Basel	Basel-Stadt

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Basel, Switzerland	Department of Psychiatry Basel (UPK Basel; Prof. Dr. med. Stefan Borgwardt)

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in depressive symptoms assessed by questionnaire compared with active placebo	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.	Baseline; 1 week before first intervention; 2 weeks after first intervention; 2, 6, and 12 weeks after LSD
Other	Changes in state and trait anxiety assessed by questionnaire compared with active placebo	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.	Baseline; 2 weeks post-intervention
Other	Changes in general psychopathology assessed by questionnaire compared with active placebo	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.	Baseline; 1 week before first intervention; 2 weeks after first intervention; 2, 6, and 12 weeks after LSD
Other	Changes in existential anxiety assessed by questionnaire compared with active placebo	Existential Concerns Questionnaire (EAQ). Item scores are assessed in a yes/no format.	Baseline; 2 weeks after first treatment; 2 weeks after second treatment
Other	Changes in mindfulness assessed by questionnaire compared with active placebo	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.	Baseline; 2 weeks after first treatment; 2 weeks after second treatment
Other	Changes in humility assessed by questionnaire compared with active placebo	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.	Baseline; 6 weeks post-treatment
Other	Changes in humility assessed by questionnaire	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.	Baseline; 6 weeks post-treatment compared with active placebo
Other	Changes in the personality trait "absorption" assessed by questionnaire compared with active placebo	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.	Baseline
Other	Acute subjective effects assessed via questionnaire compared with active placebo	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.	At weeks 3 and 7
Other	Characteristics of altered states of consciousness assessed by questionnaire	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.	At weeks 3 and 7
Other	Characteristics of altered states of consciousness assessed by questionnaire compared with active placebo	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.	At weeks 3 and 7
Other	Changes in mystical-type experiences assessed by questionnaire	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.	Baseline; 6 weeks post-treatment compared with active placebo
Other	Acquisition of physical conditions / complaints assessed by questionnaire	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.	Baseline; at weeks 2, 3, 5, 7, 9, 13
Other	Perception of therapeutic alliance assessed by questionnaire	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.	1 week pre-treatment
Other	Subjective evaluation of mood assessed by questionnaire	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.	Baseline; at weeks 2, 3, 5, 7, 9, 13
Other	Assessment of personality by questionnaire	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.	Baseline
Other	Assessment of religiosity by questionnaire	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.	Baseline
Other	Persisting effects of treatment assessed by questionnaire	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.	12 weeks post-treatment
Other	Changes in brain-derived neurotrophic factor (BDNF)	Changes in brain-derived neurotrophic factor as measured by blood concentrations compared with active placebo	One day and 12 weeks post-treatment
Other	Changes in hypothalamic-pituitary-adrenal (HPA) axis function	Changes in hypothalamic-pituitary-adrenal (HPA) axis function as measured with salivary cortisol awakening responses compared with active placebo	2 weeks post-treatment
Other	Changes in immunoregulation and Inflammation compared with active placebo	Measured via blood levels of macrophage migration inhibitory factor and interleukin-1 beta	One day and 12 weeks post-treatment
Other	Brain activation during fearful face processing and working memory processing compared with placebo	Functional Magnetic Resonance Imaging (fMRI)	One week pre-treatment and one day post-treatment
Other	Brain Perfusion in treatment condition compared with active placebo	Diffusion Tensor Imaging (DTI)	One week pre-treatment and one day post-treatment
Other	Brain Perfusion compared with active placebo	Arterial Spin Labeling (ASL)	One week pre-treatment and one day post-treatment
Other	Changes in sleep patterns	Actigraphy	From one week pre-treatment to two weeks post-treatment
Primary	Change in depressive symptoms assessed by questionnaire compared with active placebo	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.	Baseline; 1 week before first intervention; 2 weeks after first intervention; 2, 6, and 12 weeks after LSD
Secondary	Change in depressive symptoms assessed by questionnaire compared with active placebo	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.	Baseline; 1 week before first intervention; 2 weeks after first intervention; 2, 6, and 12 weeks after LSD