Clinical trial NCT03866252: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Major Depressive Disorder
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
Collaborators: name: Department of Psychiatry Basel (UPK Basel; Prof. Dr. med. Stefan Borgwardt)
First posted: 2019-03-07
Enrollment: 60
Sex: ALL
Minimum age (years): 25
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


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

Primary outcomes:
measure: Change in depressive symptoms assessed by questionnaire compared with active placebo
timeFrame: Baseline; 1 week before first intervention; 2 weeks after first intervention; 2, 6, and 12 weeks after LSD
measure: Change in depressive symptoms assessed by questionnaire compared with active placebo
timeFrame: Baseline; 1 week before first intervention; 2 weeks after first intervention; 2, 6, and 12 weeks after LSD
Secondary outcomes:
Other outcomes:
measure: Change in depressive symptoms assessed by questionnaire compared with active placebo
timeFrame: Baseline; 1 week before first intervention; 2 weeks after first intervention; 2, 6, and 12 weeks after LSD
measure: Changes in state and trait anxiety assessed by questionnaire compared with active placebo
timeFrame: Baseline; 2 weeks post-intervention
measure: Changes in general psychopathology assessed by questionnaire compared with active placebo
timeFrame: Baseline; 1 week before first intervention; 2 weeks after first intervention; 2, 6, and 12 weeks after LSD
measure: Changes in existential anxiety assessed by questionnaire compared with active placebo
timeFrame: Baseline; 2 weeks after first treatment; 2 weeks after second treatment
measure: Changes in mindfulness assessed by questionnaire compared with active placebo
timeFrame: Baseline; 2 weeks after first treatment; 2 weeks after second treatment
measure: Changes in humility assessed by questionnaire compared with active placebo
timeFrame: Baseline; 6 weeks post-treatment
measure: Changes in humility assessed by questionnaire
timeFrame: Baseline; 6 weeks post-treatment compared with active placebo
measure: Changes in the personality trait "absorption" assessed by questionnaire compared with active placebo
timeFrame: Baseline
measure: Acute subjective effects assessed via questionnaire compared with active placebo
timeFrame: At weeks 3 and 7
measure: Characteristics of altered states of consciousness assessed by questionnaire
timeFrame: At weeks 3 and 7
measure: Characteristics of altered states of consciousness assessed by questionnaire compared with active placebo
timeFrame: At weeks 3 and 7
measure: Changes in mystical-type experiences assessed by questionnaire
timeFrame: Baseline; 6 weeks post-treatment compared with active placebo
measure: Acquisition of physical conditions / complaints assessed by questionnaire
timeFrame: Baseline; at weeks 2, 3, 5, 7, 9, 13
measure: Perception of therapeutic alliance assessed by questionnaire
timeFrame: 1 week pre-treatment
measure: Subjective evaluation of mood assessed by questionnaire
timeFrame: Baseline; at weeks 2, 3, 5, 7, 9, 13
measure: Assessment of personality by questionnaire
timeFrame: Baseline
measure: Assessment of religiosity by questionnaire
timeFrame: Baseline
measure: Persisting effects of treatment assessed by questionnaire
timeFrame: 12 weeks post-treatment
measure: Changes in brain-derived neurotrophic factor (BDNF)
timeFrame: One day and 12 weeks post-treatment
measure: Changes in hypothalamic-pituitary-adrenal (HPA) axis function
timeFrame: 2 weeks post-treatment
measure: Changes in immunoregulation and Inflammation compared with active placebo
timeFrame: One day and 12 weeks post-treatment
measure: Brain activation during fearful face processing and working memory processing compared with placebo
timeFrame: One week pre-treatment and one day post-treatment
measure: Brain Perfusion in treatment condition compared with active placebo
timeFrame: One week pre-treatment and one day post-treatment
measure: Brain Perfusion compared with active placebo
timeFrame: One week pre-treatment and one day post-treatment
measure: Changes in sleep patterns
timeFrame: From one week pre-treatment to two weeks post-treatment
Locations:
city: Basel
country: Switzerland
facility: Universitäre Psychiatrische Kliniken
state: Basel-Stadt
Study officials:
affiliation: Department of Psychiatry
name: Dr. med. Felix Müller, MD
role: STUDY_CHAIR
References: