LSD microdosing in major depressive disorder: results from an open-label trial
Dimitri Daldegan‐bueno, C Donegan, Rachael L. Sumner, Anna Forsyth, William J. Evans, Malak Alshakhouri, Lisa Reynolds, Rhys Ponton, Thomas A. Smith, Partha S. Roop, Nicholas Hoeh, Nathan Allen, Frederick Sundram, David B Menkes, Suresh Muthukumaraswamy
Neuropharmacology November 5, 2025 DOI: 10.1016/j.neuropharm.2025.110762 via OpenAlex
Summary
AI-generated from the abstractIn an open-label phase 2A trial, 19 participants with major depressive disorder, most of whom were taking antidepressants, took microdoses of LSD twice weekly for eight weeks. No serious adverse events occurred, and one participant withdrew due to anxiety. Depression scores on the Montgomery-Åsberg Depression Rating Scale dropped by 59.5% at the end of the intervention, with improvements sustained for up to six months. Anxiety, rumination, stress, and quality of life also improved. The results provide preliminary evidence that microdosed LSD is safe and feasible for treating moderate depression, but randomized controlled trials are needed.
Study at a glance
| 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 |
| Keywords | Tolerability Adverse effect Clinical trial Depression economics |
| Citations | 4 |
| Key finding | 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).