LSD Therapy for Persons Suffering From Major Depression

Study Overview
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Brief Summary
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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.

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

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: LSD


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 25 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Arm<br>Subjects in the treatment arm will receive 100 μg LSD (first session) and 100 or 200 μg LSD (second session) per os. | Drug: LSD<br>* LSD administration per os<br>* Other names: Lysergic Acid Diethylamide;|
| Active Comparator: Control Arm<br>Subjects in the control arm will receive 25 μg LSD (first session) and 25 μg LSD (second session) per os. | Drug: LSD<br>* LSD administration per os<br>* Other names: Lysergic Acid Diethylamide;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |