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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 25 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 suggests LSD may reduce depressive symptoms, but the evidence is mixed and mostly indirect. In controlled trials, a single moderate-to-high dose of LSD with therapy reduced anxiety and comorbid depression with large effects that persisted for months, and a meta-analysis of psychedelic therapy (including LSD) found large short-term reductions in depression, though results at 6-8 weeks were less conclusive. However, the only randomized trial of LSD microdosing for major depression found it was no better than an active placebo (caffeine), and most LSD-specific evidence comes from small samples, animal models, or trials where depression was a secondary outcome.

Evidence by study

Direction is which way each study's own result points, not our rating of the study.

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 LSD-assisted therapy produced significant reductions in comorbid depression symptoms on the Hamilton Depression Rating Scale and Beck Depression Inventory 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 Sustained reductions in depression symptoms (Beck Depression Inventory) were observed at 1-year follow-up after LSD-assisted therapy.
230. LSD microdosing for depression: hype or hope? A randomised controlled trial in major depressive disorder 2026 RCT No effect Microdosed LSD was not superior to active placebo (caffeine) for reducing depressive symptoms, with moderate evidence favoring the null.
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 Classical psychedelics produced large positive effect sizes for 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 Serotonergic hallucinogens including LSD reduced anxiety and depression in patients with life-threatening diseases, with low side effects when safety guidelines were followed.
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.
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 psychedelic-assisted psychotherapy with LSD or psilocybin was associated with significant reductions in depressive symptoms in a real-world clinical cohort.
Reward-related neural activity after low doses of LSD in participants with depressed mood. 2026 RCT 39 Supports Low-dose LSD increased late positive potential amplitude to loss feedback 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 improvements in mood followed microdosed LSD 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 Mixed Participants reported improved mood, increased energy, and greater emotional openness, alongside some negative experiences like anxiety.
Qualitative content analysis of expectations in participants with depression about to begin LSD microdosing treatment: Identifying the need for psychedelic expectancy measures. 2025 qualitative 23 Unclear Participants' expectations before microdosing LSD were shaped by media and prior treatment failure, with hope acting as both a motivator and a disappointment buffer.
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 psilocybin or LSD produced persistent antidepressant-like effects in a rat model, unlike ketamine which produced only transient effects.
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 reversed behavioral deficits and normalized hippocampal 5-HT2 signaling 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.
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 effects 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 show strong potential as therapeutics for psychological distress, depression, and addiction.
Registered clinical studies investigating psychedelic drugs for psychiatric disorders. 2021 review 70 Unclear As of December 2020, 70 registered clinical trials investigate psychedelics for psychiatric disorders, with LSD investigated for MDD, anxiety, and severe somatic disorders, but only 21 studies had published results.
Top Ten Tips Palliative Care Clinicians Should Know About Psychedelic-Assisted Therapy in the Context of Serious Illness. 2022 review Supports Psychedelic-assisted therapy can safely and effectively reduce anxiety, depression, and demoralization in seriously ill and end-of-life patients.
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 receptor agonism, receptor downregulation, effects on brain-derived neurotrophic factor and immune responses, and disruption of the default mode network.
Role of psilocybin in the treatment of depression 2016 review Supports Psilocybin does not lead to serious physical or mental health problems or dependent use and is being explored for therapeutic utility in mood and anxiety disorders.
Psilocybin in Treatment-Resistant Depression 2022 review Supports Existing antidepressants are modestly more effective than placebo and have many side effects, prompting renewed interest in psilocybin and LSD as potential treatments for depression.
Psychedelics in the treatment of unipolar and bipolar depression 2022 narrative review Mixed Classic psychedelics show promise for unipolar depression but may induce mania, while atypical psychedelics like ketamine have evidence for bipolar depression.
[LSD revisited: Mechanisms of action and therapeutic potential in mental health]. 2026 review Supports LSD's modulation of the 5-HT2A serotonin receptor and glutamatergic system, linked to neuroplasticity, is hypothesized to underlie rapid and sustained antidepressant responses observed in early clinical studies for treatment-resistant depression.
Psychedelic Therapies for Comorbid Major Depressive Disorder and Chronic Pain: A Review of Putative Mechanisms of Action. 2026 narrative review Supports Psychedelics may target symptoms of both MDD and chronic pain through shared mechanisms including serotonergic modulation, anti-inflammatory effects, neuroplastic changes, and altered brain network dynamics.

Points of agreement

  • Multiple controlled trials and meta-analyses report that moderate-to-high doses of LSD or other classic psychedelics, given with psychological support, reduce depressive symptoms with large effect sizes.
  • Antidepressant effects of single high-dose sessions appear to persist for weeks to months in several studies.
  • Preclinical rodent studies consistently show LSD produces antidepressant-like behavioral and neuroplastic effects.
  • Several reviews converge on 5-HT2A receptor modulation and neuroplasticity as plausible mechanisms.

Conflicts

  • A randomized controlled trial of LSD microdosing found no benefit over active placebo for major depressive disorder, contrasting with positive findings for higher-dose LSD-assisted therapy and with open-label microdosing reports.
  • One narrative review notes classic psychedelics may induce mania, a risk not emphasized in the positive efficacy reports.
  • Meta-analytic evidence is less conclusive at 6-8 weeks follow-up than at earlier timepoints.

Gaps

  • Most LSD-specific clinical evidence comes from small samples and trials where depression was a secondary outcome rather than the primary endpoint.
  • Long-term durability beyond one year is largely unstudied, and crossover designs limit long-term follow-up.
  • Blinding is difficult due to LSD's subjective effects, and expectancy effects are poorly measured.
  • Optimal dose, number of sessions, and whether microdosing has any antidepressant effect remain unresolved.
  • Populations studied are narrow (often treatment-resistant or life-threatening illness), limiting generalizability.
Browse these studies in the library

Common questions

What does the research agree on about LSD for depression?
  • Multiple controlled trials and meta-analyses report that moderate-to-high doses of LSD or other classic psychedelics, given with psychological support, reduce depressive symptoms with large effect sizes.
  • Antidepressant effects of single high-dose sessions appear to persist for weeks to months in several studies.
  • Preclinical rodent studies consistently show LSD produces antidepressant-like behavioral and neuroplastic effects.
  • Several reviews converge on 5-HT2A receptor modulation and neuroplasticity as plausible mechanisms.
Where do studies on LSD for depression conflict?
  • A randomized controlled trial of LSD microdosing found no benefit over active placebo for major depressive disorder, contrasting with positive findings for higher-dose LSD-assisted therapy and with open-label microdosing reports.
  • One narrative review notes classic psychedelics may induce mania, a risk not emphasized in the positive efficacy reports.
  • Meta-analytic evidence is less conclusive at 6-8 weeks follow-up than at earlier timepoints.
What is still unknown about LSD for depression?
  • Most LSD-specific clinical evidence comes from small samples and trials where depression was a secondary outcome rather than the primary endpoint.
  • Long-term durability beyond one year is largely unstudied, and crossover designs limit long-term follow-up.
  • Blinding is difficult due to LSD's subjective effects, and expectancy effects are poorly measured.
  • Optimal dose, number of sessions, and whether microdosing has any antidepressant effect remain unresolved.
  • Populations studied are narrow (often treatment-resistant or life-threatening illness), limiting generalizability.
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

56 articles · 21 from the last two years · 723,088 participants across 23 studies reporting sample size

Common study designs

review 11 narrative review 5 systematic review 6 randomized controlled trial 7 systematic review and meta-analysis 2

Research volume by year

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55 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 1
2015 0
2016 1
2017 1
2018 1
2019 2
2020 1
2021 6
2022 5
2023 9
2024 10
2025 10
2026 8

Research

Synthesize the evidence →

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

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 (Oxford, England) 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

Qualitative content analysis of expectations in participants with depression about to begin LSD microdosing treatment: Identifying the need for psychedelic expectancy measures.

Neuropharmacology December 1, 2025 Carina Joy Donegan, Dimitri Daldegan-Bueno, Tehseen Noorani et al. 4 citations

Expectations can impact antidepressant treatment and psychedelic therapy, often enhancing placebo effects and influencing outcomes. However, research in this context is lacking. Our study explored the expectations of participants with major depressive disorder (MDD) before microdosing lysergic acid diethylamide (LSD) in an open-label trial. Twenty-three individuals with MDD completed a...

DOI: 10.1016/j.neuropharm.2025.110670 (opens in new tab) Full text (opens in new tab) Depression LSD Microdosing Expectancy +4

Clinical trials

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