LSD Therapy for Persons Suffering From Major Depression

NCT03866252 | Completed Phase 2

• 1 other identifier: BASEC 2018-02370
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Major Depressive Disorder

Outcome Measures

Primary Outcomes (2)

• 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

• 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

Other Outcomes (25)

• Change in depressive symptoms assessed by questionnaire compared with active placebo

  Baseline; 1 week before first intervention; 2 weeks after first intervention; 2, 6, and 12 weeks after LSD

• Changes in state and trait anxiety assessed by questionnaire compared with active placebo

  Baseline; 2 weeks post-intervention

• Changes in general psychopathology assessed by questionnaire compared with active placebo

  Baseline; 1 week before first intervention; 2 weeks after first intervention; 2, 6, and 12 weeks after LSD

Study Arms (2)

Treatment Arm

EXPERIMENTAL

Subjects in the treatment arm will receive 100 μg LSD (first session) and 100 or 200 μg LSD (second session) per os.

Drug: LSD

Control Arm

ACTIVE COMPARATOR

Subjects in the control arm will receive 25 μg LSD (first session) and 25 μg LSD (second session) per os.

Drug: LSD

Interventions

LSD DRUG

LSD administration per os

Also known as: Lysergic Acid Diethylamide

Control Arm; Treatment Arm

Eligibility Criteria

• Age: 25 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Major Depressive Disorder according to Diagnostic and Statistical Manual of Mental Disorders (DSM-V)
• \> 25 years
• Sufficient understanding of the German language

You may not qualify if:

• \< 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

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead
• Department of Psychiatry Basel (UPK Basel; Prof. Dr. med. Stefan Borgwardt): collaborator

Study Sites (1)

Universitäre Psychiatrische Kliniken

Basel, Canton of Basel-City, 4002, Switzerland

Location

Related Publications (1)

• Muller F, Zaczek H, Becker AM, Ley L, Borgwardt S, Santos de Jesus J, Loh N, Kohut J, Auernig M, Boehlke C, Liechti ME. Efficacy and safety of low- versus high-dose-LSD-assisted therapy in patients with major depression: A randomized trial. Med. 2025 Sep 12;6(9):100725. doi: 10.1016/j.medj.2025.100725. Epub 2025 Jun 6.

  PMID: 40482648 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Lysergic Acid Diethylamide

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Lysergic Acid; Ergolines; Ergot Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring

Study Officials

• Dr. med. Felix Müller, MD

  Department of Psychiatry

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2019
• First Posted: March 7, 2019
• Study Start: November 1, 2019
• Primary Completion: September 29, 2022
• Study Completion: December 1, 2022
• Last Updated: April 23, 2025

Record last verified: 2025-04

Locations

CH (1)