Can LSD Help Treat Depression? A Closer Look at the Role of Dosage
Article Title: “Efficacy and Safety of Low- versus High-Dose LSD-Assisted Therapy in Patients with Major Depression: A Randomized Trial”
Author: Felix Müller, Hannes Zaczek, Anna M. Becker, Laura Ley, Stefan Borgwardt, Joyce Santos de Jesus, Nico Loh, Jan Kohut, Mathias Auernig, Christopher Boehlke, Matthias E. Liechti
Publication Date: 2025
Background
Lysergic acid diethylamide (LSD) was first studied as a psychiatric aid in the 1950s, but modern research into its antidepressant effects has only recently regained momentum. This study addresses a significant gap: no randomised trial had directly tested LSD for major depressive disorder (MDD) until now. Given the limitations of conventional antidepressants—including delayed onset and side effects—psychedelic-assisted therapy offers a new avenue worth exploring.
Study Overview
This double-blind, randomised phase 2 clinical trial was conducted in Switzerland to compare the antidepressant effects of high-dose vs. low-dose LSD in individuals with moderate-to-severe MDD.
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Participants: 61 adults aged 25 and over
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Design: Two therapy sessions with either 25μg + 25μg (low-dose group) or 100μg + 200μg (high-dose group) of LSD, alongside psychotherapy
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Assessments: Depression severity was tracked using clinician-rated (IDS-C) and self-rated (IDS-SR) symptom scales up to 12 weeks after treatment
Key Findings
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Greater reduction in depressive symptoms was observed in the high-dose group at nearly all checkpoints
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IDS-C scores improved by −12.9 vs. −3.6 in the low-dose group at the main endpoint (week 9)
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This result was statistically significant even after correction for multiple comparisons
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Effects were durable, with improvements sustained at 13 and 19 weeks post-treatment
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Response and remission rates were higher in the high-dose group (up to 36% remission vs. 20% in the low-dose group)
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Adverse events were comparable across groups and mostly mild—e.g., headache, fatigue, or nausea
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No evidence of increased suicidal ideation in the high-dose group, despite isolated distress events
Discussion
While high-dose LSD led to greater improvements in depressive symptoms, not all statistical measures reached significance when adjusting for initial differences in depression severity. Some patients had strong reactions, and a few found the experience distressing. Still, the therapeutic outcomes aligned with those of earlier psilocybin trials, and no serious safety concerns emerged. Importantly, the use of a low-dose control helped improve the trial’s blinding—an issue that has plagued many previous psychedelic studies.
Implications
This study reinforces the potential of psychedelic-assisted therapy to offer fast and sustained relief for depression. The high-dose LSD group experienced improvements with only two sessions—an appealing prospect compared to daily antidepressants. These findings open the door to larger phase 3 trials and highlight the importance of proper preparation, support, and follow-up in psychedelic treatment models.
Potential Application
For retreats and clinics exploring psychedelic-assisted therapy these findings support structured, high-dose sessions guided by trained therapists. Given the observed durability and depth of therapeutic effects, LSD may eventually complement or even replace conventional antidepressants for select individuals—particularly those who haven’t responded to other treatments.
Conclusions
High-dose LSD-assisted therapy showed promising antidepressant effects with manageable risks. While more research is needed, this trial supports LSD’s potential as a novel and effective treatment for depression.
Reference:
Muller et al., Efficacy and safety of low- versus high-dose-LSD-assisted therapy in patients with major depression: A randomized trial, Med (2025), https://doi.org/10.1016/j.medj.2025.100725
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