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LSD microdosing in major depressive disorder: results from an open-label trial

Dimitri Daldegan-Bueno, C Donegan, Rachael Sumner, Anna Forsyth, William Evans, Malak Alshakhouri, Lisa Reynolds, Rhys Ponton, Thomas A. Smith, Partha Roop, Nicholas Hoeh, Nathan Allen, Frederick Sundram, David B Menkes, Suresh Muthukumaraswamy

Neuropharmacology November 5, 2025 DOI: 10.1016/j.neuropharm.2025.110762 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Open-label phase 2A trial Randomized Peer reviewed
Sample size 19
Population Participants with major depressive disorder, most taking antidepressant medication
Intervention LSD
Dose 8 μg initially, then 6-20 μg twice weekly
Duration 8-week intervention, 6-month follow-up
Topics Anxiety Depression LSD Microdosing
Keywords Tolerability Adverse effect Clinical trial Depression economics Rating scale Antidepressant Randomized controlled trial Regimen Mental health Major depressive episode Visual analogue scale
Citations 4
Key findings Microdosed LSD was safe and feasible, and was associated with a 59.5% reduction in depression scores sustained for up to six months.

Abstract

Major depressive disorder (MDD) affects approximately 5 % of the global population. Classic psychedelics have shown promise in treating various mental health disorders. This study evaluated the feasibility and tolerability of an 8-week regimen of microdosed lysergic acid diethylamide (LSD) as a treatment for major depressive disorder in an open-label phase 2A trial (LSDDEP1). Nineteen participants (15 male), most of whom were taking an antidepressant medication (n = 15), took 16 doses of LSD (8 μg initially, then 6-20 μg twice weekly at home), with the first dose administered in the clinic. We assessed tolerability through withdrawal rates due to adverse events and feasibility by clinic visit attendance. Safety measures included adverse events, blood laboratory tests, electrocardiography (ECG), and echocardiography. Depression was measured using the Montgomery-Åsberg Depression Rating Scale (MADRS). No serious or severe adverse events and clinical alterations in safety measures were observed, being this the first study to evaluate valvulopathy after repeated psychedelic administration in humans. One participant withdrew due to experiencing anxiety when dosing; all scheduled clinic visits were attended. MADRS scores were reduced by 59.5 % at the end of the intervention and were sustained for up to six months. Improvements were also noted in anxiety, rumination, stress, and quality of life. While limited by an open-label design and small sample size, this study provides preliminary evidence supporting the safety and feasibility of treating moderate depression with microdosed LSD and underscores a need for further randomised controlled trials. Trial registration: ANZCTR, ACTRN12623000486628 (12 May 2023).

Comparable studies

Other non-randomized and open-label trials on LSD and microdosing, most cited first.

Study Year Design Participants
An open-label pilot trial assessing tolerability and feasibility of LSD microdosing in patients with major depressive disorder (LSDDEP1). Patients with major depressive disorder meeting DSM-5 criteria 2023 Open-label pilot trial n = 20
Evaluating the Potential of Microdosing 1cp-LSD for the Treatment of Canine Anxiety: A One-Month Case Study. A 13-year-old female dog with severe separation anxiety 2025 Pilot study, single-case study n = 1
LSD microdosing for major depressive disorder: Mood and pharmacokinetic outcomes from a Phase 2a trial People with depression 2026 Clinical trial
What is it like to microdose LSD for depression? a thematic analysis of participant interviews from an open-label trial. Adults with major depressive disorder 2025 Open-label pilot trial (phase IIa) with post-intervention qualitative interviews n = 17
155. EXPLORING LSD MICRODOSING IN AN OPEN-LABEL PILOT FOR MAJOR DEPRESSIVE DISORDER: THE INTERPLAY OF BEHAVIORAL ACTIVATION, MOOD IMPROVEMENT, AND CONNECTEDNESS Individuals with major depressive disorder 2025 Open label trial n = 17

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