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LSD for depression

Studies whose primary subject is both LSD and Depression, with an evidence synthesis read across the most-cited and most recent of them.

State of the evidence

Synthesized

Synthesized from 24 studies in the library · AI-generated, grounded in the abstracts below

Found by searching the library for LSD, lysergic acid diethylamide, lysergide, Depression, major depressive disorder, MDD, then ranked by relevance.

The research on LSD for depression is promising but preliminary. A placebo-controlled trial in patients with anxiety (with or without life-threatening illness) found that a single 200 µg LSD-assisted therapy session produced large reductions in comorbid depression that persisted for up to a year, and a meta-analysis pooling LSD with psilocybin and ayahuasca found large effects on depressive symptoms, though the 6-8 week follow-up was less conclusive. However, a rigorous triple-masked RCT found that microdosed LSD was no better than an active placebo (caffeine) for major depressive disorder, and most LSD-specific clinical evidence comes from small samples, with several studies still unpublished or ongoing.

Evidence by study

Direction is which way each study's own result points, not our rating of the study. All 25 matching studies were reviewed; the 24 that directly address the question are shown here.

What the directions mean
Supports:
the study found the intervention worked, or its hypothesis held.
Opposes:
it found the opposite, no benefit or a harm.
No effect:
no significant difference either way.
Mixed:
effects in both directions within the same study.
Unclear:
the abstract does not report a direction.
Study Design Sample size Direction Finding
Lysergic Acid Diethylamide-Assisted Therapy in Patients With Anxiety With and Without a Life-Threatening Illness: A Randomized, Double-Blind, Placebo-Controlled Phase II Study. 2023 RCT 42 Supports A single 200 µg LSD-assisted therapy session significantly reduced comorbid depression scores on the Hamilton Depression Rating Scale (d = -1.1) and Beck Depression Inventory (d = -0.72) up to 16 weeks after treatment.
LSD-assisted therapy in patients with anxiety: open-label prospective 12-month follow-up. 2024 RCT (long-term follow-up) 39 Supports One year after the end-of-study visit, LSD-assisted therapy was associated with sustained reductions in Beck Depression Inventory scores (d = 0.71 and 1.21 in the two groups).
Psychedelic therapy for depressive symptoms: A systematic review and meta-analysis. 2023 systematic review and meta-analysis 14 Supports Psychedelic therapy with psilocybin, ayahuasca, or LSD was associated with significant reduction of depressive symptoms at 1 day, 1 week, and 3-5 weeks, but results at 6-8 weeks were less conclusive.
Assessing the effects of methodological differences on outcomes in the use of psychedelics in the treatment of anxiety and depressive disorders: A systematic review and meta-analysis 2021 systematic review and meta-analysis Supports Across nine clinical trials, psychedelics including LSD produced large significant improvements in depression (Cohen's d = 1.38), with no significant differences between agents and greater efficacy with multiple dosing sessions.
Serotonergic hallucinogens in the treatment of anxiety and depression in patients suffering from a life-threatening disease: A systematic review. 2018 systematic review 445 Supports Evidence from 11 clinical trials, including 7 LSD trials (N=323), supports anxiolytic and antidepressant properties of serotonergic hallucinogens in patients with life-threatening disease.
230. LSD microdosing for depression: hype or hope? A randomised controlled trial in major depressive disorder 2026 RCT No effect Microdosed LSD (8 µg titrated to 4-20 µg) was not superior to active placebo (caffeine) for reducing depressive symptoms, with MADRS scores falling 29.9% versus 36.4%.
LSD treatment affects working memory-related brain function in patients with major depressive disorder 2026 RCT 43 Mixed High-dose LSD increased working memory-related brain responses compared with low-dose LSD, but these responses did not correlate with treatment response.
Neuroplastic white matter changes in patients with major depression following lysergic acid diethylamide treatment 2026 RCT 35 Supports LSD-induced increases in white matter fractional anisotropy correlated with improvements in depressive symptoms at 2, 6, and 12 weeks in patients receiving moderate-to-high-dose LSD.
Real-world effectiveness and safety of psychedelic-assisted psychotherapy: Outcomes from a large-scale compassionate use cohort in Switzerland. 2026 retrospective observational cohort 115 Supports A single fully-active dose session of LSD or psilocybin-assisted psychotherapy was associated with significant reductions in depressive symptoms, with no main effect of substance.
Reward-related neural activity after low doses of LSD in participants with depressed mood. 2026 RCT 39 Supports A low dose of LSD (26 µg) increased a reward-related brain potential in participants with higher baseline depressed mood, and this effect was associated with lower depressed mood 48 hours later.
LSD microdosing for major depressive disorder: Mood and pharmacokinetic outcomes from a Phase 2a trial 2026 clinical trial Supports Short-term mood improvements followed microdosed LSD (8 µg) in people with depression, with no tolerance or sensitisation observed.
What is it like to microdose LSD for depression? a thematic analysis of participant interviews from an open-label trial. 2025 qualitative (open-label pilot) 17 Mixed Participants described interlinked benefits including reduced depressive symptoms, but some reported negative effects or no significant improvement, and the absence of a placebo control prevents attributing changes to LSD.
Psychedelics, but Not Ketamine, Produce Persistent Antidepressant-like Effects in a Rodent Experimental System for the Study of Depression 2020 preclinical study Supports A single administration of LSD or psilocybin produced persistent antidepressant-like effects in a rat model, unlike the transient effect of ketamine.
Repeated lysergic acid diethylamide in an animal model of depression: Normalisation of learning behaviour and hippocampal serotonin 5-HT2 signalling 2014 animal model study Supports Repeated LSD treatment largely reversed learning deficits and normalised hippocampal 5-HT2 signalling in bulbectomised rats, suggesting antidepressant-like effects.
401. Prophylactic effects of LSD on inflammatory rodent model of depression 2026 preclinical animal study Supports LSD pretreatment produced long-lasting antidepressant-like effects in rodent models of inflammation-associated depression, apparently independent of 5-HT2B receptor activation.
A non-hallucinogenic LSD analog with therapeutic potential for mood disorders. 2023 preclinical study Supports The non-hallucinogenic LSD analog 2-Br-LSD promoted neuroplasticity and antidepressant-like behavioural effects in mice without inducing tolerance or 5-HT2B-mediated cardiac risk.
Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function. 2019 integrative review Supports Classic psychedelics including LSD show strong potential as therapeutics for psychological distress, depression, and addiction.
Serotonergic psychedelics for depression: What do we know about neurobiological mechanisms of action? 2023 narrative review Supports Serotonergic psychedelics may exert rapid antidepressant effects through 5HT2A agonism, receptor downregulation, effects on BDNF and immune responses, and disruption of the default mode network.
Psychedelics in the treatment of unipolar and bipolar depression 2022 narrative review Mixed Classic psychedelics show promise for unipolar depression but may induce mania, an important consideration for research and clinical protocols.
[LSD revisited: Mechanisms of action and therapeutic potential in mental health]. 2026 review Supports LSD's modulation of 5-HT2A and glutamatergic systems linked to neuroplasticity is hypothesized to underlie rapid and sustained antidepressant responses observed in early clinical studies.
Psychedelic Therapies for Comorbid Major Depressive Disorder and Chronic Pain: A Review of Putative Mechanisms of Action. 2026 narrative review Supports Psychedelics including LSD may target symptoms of both MDD and chronic pain through shared mechanisms, though research on this comorbidity remains largely unexplored.
Top Ten Tips Palliative Care Clinicians Should Know About Psychedelic-Assisted Therapy in the Context of Serious Illness. 2022 review Supports Psychedelic-assisted therapy may lead to sustained reductions in anxiety, depression, and demoralization in seriously ill and end-of-life patients.
Psilocybin in Treatment-Resistant Depression 2022 review Supports Because existing antidepressants are only modestly more effective than placebo, psilocybin and LSD are being revisited as potential treatments for depression.
Registered clinical studies investigating psychedelic drugs for psychiatric disorders. 2021 review 70 Unclear As of December 2020, 70 registered trials investigated psychedelics for psychiatric disorders, with LSD studied for MDD, anxiety, and severe somatic disorders, but only 21 had published results.

Points of agreement

  • Controlled and observational clinical studies of fully-active LSD doses report large reductions in depressive symptoms, sustained for weeks to a year.
  • Meta-analyses pooling LSD with psilocybin and ayahuasca find large effects on depression, with no clear difference between agents.
  • Rodent studies consistently show antidepressant-like effects of LSD, including after single or repeated dosing.
  • Reviews converge on 5-HT2A agonism, neuroplasticity, and default mode network disruption as plausible mechanisms.
  • Multiple dosing sessions appear to yield greater efficacy than single sessions.

Conflicts

  • A triple-masked RCT found microdosed LSD no better than active placebo (caffeine), contradicting open-label reports of microdosing benefit.
  • Open-label qualitative data report benefits but acknowledge no placebo control, conflicting with the null controlled microdosing result.
  • One review warns classic psychedelics may induce mania, a risk not emphasized in efficacy-focused reviews.
  • Brain-response changes after LSD did not correlate with treatment response in one trial, while white matter changes did in another.

Gaps

  • Most LSD-specific clinical trials are small (roughly 35-43 patients) and few are fully published.
  • Long-term durability beyond one year is largely unstudied, and crossover designs complicate long-term analysis.
  • Blinding is difficult given LSD's subjective effects; meaningful placebo control remains a methodological hurdle.
  • Optimal dose is unresolved, ranging from microdoses (8-26 µg) to full doses (100-200 µg).
  • Populations studied are mostly anxiety with or without life-threatening illness or treatment-resistant depression; bipolar depression and comorbid chronic pain are largely unexplored.
  • Risk of mania induction and safety in vulnerable populations are under-studied.
Browse these studies in the library

Common questions

What does the research agree on about LSD for depression?
  • Controlled and observational clinical studies of fully-active LSD doses report large reductions in depressive symptoms, sustained for weeks to a year.
  • Meta-analyses pooling LSD with psilocybin and ayahuasca find large effects on depression, with no clear difference between agents.
  • Rodent studies consistently show antidepressant-like effects of LSD, including after single or repeated dosing.
  • Reviews converge on 5-HT2A agonism, neuroplasticity, and default mode network disruption as plausible mechanisms.
  • Multiple dosing sessions appear to yield greater efficacy than single sessions.
Where do studies on LSD for depression conflict?
  • A triple-masked RCT found microdosed LSD no better than active placebo (caffeine), contradicting open-label reports of microdosing benefit.
  • Open-label qualitative data report benefits but acknowledge no placebo control, conflicting with the null controlled microdosing result.
  • One review warns classic psychedelics may induce mania, a risk not emphasized in efficacy-focused reviews.
  • Brain-response changes after LSD did not correlate with treatment response in one trial, while white matter changes did in another.
What is still unknown about LSD for depression?
  • Most LSD-specific clinical trials are small (roughly 35-43 patients) and few are fully published.
  • Long-term durability beyond one year is largely unstudied, and crossover designs complicate long-term analysis.
  • Blinding is difficult given LSD's subjective effects; meaningful placebo control remains a methodological hurdle.
  • Optimal dose is unresolved, ranging from microdoses (8-26 µg) to full doses (100-200 µg).
  • Populations studied are mostly anxiety with or without life-threatening illness or treatment-resistant depression; bipolar depression and comorbid chronic pain are largely unexplored.
  • Risk of mania induction and safety in vulnerable populations are under-studied.
How we analyze this

This synthesis reads the 15 most-cited and 10 most recent studies whose primary subject is LSD for depression, up to 25 in all. The most-cited set anchors the established evidence, and the recent set surfaces work that is too new to have gathered citations yet.

A study qualifies only when LSD for depression or a known alias appears in its title or keywords, so broad reviews that mention it only in passing are left out. Each study is read from its abstract, strongest evidence first, and the summary reports the direction of the results along with any conflicts and gaps.

The full method, including what a person does and does not review, is on the methods page.

Ask your own question in the Research Synthesis Tool

58 articles · 21 from the last two years · 723,528 participants across 25 studies reporting sample size

Common study designs

review 12 narrative review 5 systematic review 6 randomized controlled trial 7 systematic review and meta-analysis 2

Research volume by year

Compare topics →

58 studies whose primary subject is LSD for depression since 2014

Studies about LSD for depression per year, 2014 to 2026, peaking at 10 in 2024 Bar chart: one bar per year, taller where more studies were published that year. 0 5 10 2015 2020 2025
2026 is partial
Show the numbers
Studies about LSD for depression per year, 2014 to 2026, peaking at 10 in 2024
Year Studies
2014 2
2015 0
2016 1
2017 1
2018 2
2019 2
2020 1
2021 6
2022 5
2023 9
2024 10
2025 10
2026 9

Research

Synthesize the evidence →

LSD treatment affects working memory-related brain function in patients with major depressive disorder

Translational Psychiatry October 8, 2026 Friederike Holze, Kristian Larsen, Brice Ozenne et al.

Abstract Classic psychedelics, including lysergic acid diethylamide (LSD), are currently under investigation for the treatment of major depressive disorder (MDD). Cognitive dysfunction is common in MDD, but effects of psychedelic treatment on cognitive brain function, measured by magnetic resonance imaging, are sparsely reported. The present study investigated effects of LSD treatment on...

DOI: 10.1038/s41398-026-04522-4 (opens in new tab) Full text (opens in new tab)

401. Prophylactic effects of LSD on inflammatory rodent model of depression

The International Journal of Neuropsychopharmacology September 1, 2026 Amel Bouloufa, Sarah Delcourte, Renaud Rovera et al.

Abstract Background Recent clinical findings have highlighted the therapeutic potential of serotonergic psychedelics, including lysergic acid diethylamide (LSD), in the treatment of affective disorders. Despite these advances, the mechanisms driving their beneficial effects remain partially understood. Aims & Objectives This study sought to assess the prophylactic effects of LSD in rodent...

DOI: 10.1093/ijnp/pyag040.286 (opens in new tab) Full text (opens in new tab)

230. LSD microdosing for depression: hype or hope? A randomised controlled trial in major depressive disorder

The International Journal of Neuropsychopharmacology September 1, 2026

Abstract Background Depressive disorders affect approximately 280 million people worldwide, with many patients finding existing treatments ineffective or limited by adverse effects. Growing evidence from community microdosing reports suggests that psychedelic therapies may help alleviate depressive symptoms. Among these, lysergic acid diethylamide (LSD) microdosing has shown particular promise...

DOI: 10.1093/ijnp/pyag040.021 (opens in new tab) Full text (opens in new tab)

Neuroplastic white matter changes in patients with major depression following lysergic acid diethylamide treatment

Cell Reports Medicine May 7, 2026 Mihai Avram, Aurore Menegaux, Felix Müller et al. 1 citation

The clinical trial NCT03866252 investigates the antidepressant effects of lysergic acid diethylamide (LSD) in 61 patients with major depressive disorder (MDD) randomized to low-dose LSD (LD-LSD; 2 × 25 μg) or moderate-to-high-dose LSD (HD-LSD; 100 μg followed by 200 μg) 4 weeks apart. Although the trial reports positive clinical outcomes, underlying mechanisms remain unclear. Here, we test...

DOI: 10.1016/j.xcrm.2026.102791 (opens in new tab) Full text (opens in new tab) Neuroplasticity Lysergic acid diethylamide Depression economics White matter +2

[LSD revisited: Mechanisms of action and therapeutic potential in mental health].

L'Encephale April 9, 2026 Amel Bouloufa, Sarah Delcourte, Thomas Delannay et al.

Major depressive disorder (MDD) represents a colossal worldwide burden of health, affecting more than 350 million individuals. While traditional antidepressants with mechanisms of action at the serotonin, dopamine, or norepinephrine pathways are routinely prescribed, approximately one-third of patients fail to achieve adequate remission and develop treatment-resistant depression (TRD). This...

DOI: 10.1016/j.encep.2026.02.008 (opens in new tab) Full text (opens in new tab) LSD Treatment-resistant depression Fast-acting antidepressants Psychedelics +1

Psychedelic Therapies for Comorbid Major Depressive Disorder and Chronic Pain: A Review of Putative Mechanisms of Action.

Pharmacology Research & Perspectives April 1, 2026 Jordana Kazdan, Karim S Ladha, Muhammad Ishrat Husain

Major Depressive Disorder (MDD) and chronic pain are independently debilitating conditions that frequently co-occur. This comorbidity poses a significant clinical challenge, resulting in greater symptom severity, higher disability, and worse prognosis than either condition alone. Current therapies often address each disorder in isolation, leaving individuals with comorbid MDD and chronic pain...

DOI: 10.1002/prp2.70238 (opens in new tab) Full text (opens in new tab) LSD Mdd Depression Psilocybin +3

LSD microdosing for major depressive disorder: Mood and pharmacokinetic outcomes from a Phase 2a trial

Progress in Neuro-Psychopharmacology and Biological Psychiatry February 18, 2026 Dimitri Henriques Daldegan-Bueno, C Donegan, Rachael Sumner et al. 1 citation

Results suggest short-term improvements in mood following microdosed LSD in people with depression, warranting confirmation in controlled trials. It provides the pharmacokinetic parameters of 8 μg of LSD in a sample of people with depression and indicates no tolerance or sensitisation to repeated microdoses of LSD, despite incremental dose titration.

DOI: 10.1016/j.pnpbp.2026.111645 (opens in new tab) Major depressive disorder Pharmacokinetics Depression economics Depressive symptoms +6

Real-world effectiveness and safety of psychedelic-assisted psychotherapy: Outcomes from a large-scale compassionate use cohort in Switzerland.

Psychiatry Research February 2, 2026 Tatiana Aboulafia Brakha, Albert Buchard, Cédric Mabilais et al. 1 citation

Classic serotonergic psychedelics such as LSD and psilocybin show promising antidepressant effects in controlled trials, but real-world data from routine clinical care remain limited. This study retrospectively analysed routine data from adults with treatment-resistant depressive and/or anxiety disorders who received a first standardized Psychedelic-assisted Psychotherapy (PAP) cycle with 100...

DOI: 10.1016/j.psychres.2026.116992 (opens in new tab) Full text (opens in new tab) Anxiety Depression LSD Mystical experience +2

Reward-related neural activity after low doses of LSD in participants with depressed mood.

Journal of Psychopharmacology January 13, 2026 James Glazer, Hanna Molla, Royce Lee et al.

Lysergic acid diethylamide (LSD) has been considered as a potential treatment for depression for over 75 years, but its therapeutic potential has only recently been considered in mainstream psychiatry. Repeated ingestion of low doses of LSD ("microdoses") is thought to reduce depression, but the neurobiology underlying this effect is unknown. We previously reported that low doses of LSD...

DOI: 10.1177/02698811251405686 (opens in new tab) Full text (opens in new tab) LSD Depression EEG Erp +2

What is it like to microdose LSD for depression? a thematic analysis of participant interviews from an open-label trial.

Therapeutic Advances in Psychopharmacology December 4, 2025 Carina Joy Donegan, Dimitri Daldegan-Bueno, Rachael Sumner et al.

Background: Depressive disorders affect approximately 280 million globally, with many finding treatments ineffective or limited by side effects. Growing evidence suggests that psychedelic therapies may help alleviate depressive symptoms. Among these, lysergic acid diethylamide (LSD) microdosing shows promise for major depressive disorder (MDD). However, research on LSD microdosing in clinical...

DOI: 10.1177/20451253251396253 (opens in new tab) Full text (opens in new tab) Lysergic acid diethylamide Major depressive disorder Microdosing Qualitative research +2

Clinical trials

All lsd for depression trials →