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LSD research: what the evidence shows

(Lysergic acid diethylamide) A classic serotonergic psychedelic used in early and contemporary research on anxiety, cluster headache, and models of consciousness.

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, then ranked by relevance.

Research on LSD spans mechanistic, clinical, and observational work. Modern neuroimaging consistently shows LSD occupies 5-HT2A receptors and alters brain connectivity and blood flow, correlating with subjective effects like ego dissolution and hallucinations. Small randomized trials and a meta-analysis suggest LSD-assisted psychotherapy may reduce anxiety and alcohol misuse, with some benefits sustained to 12 months, but samples are small and blinding is difficult. Adverse psychological reactions are documented in case reports, and long-term safety in large populations remains poorly characterized.

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
Neural correlates of the LSD experience revealed by multimodal neuroimaging. 2016 experimental neuroimaging study Supports LSD increased visual cortex blood flow, decreased visual cortex alpha power, and expanded primary visual cortex connectivity, correlating with visual hallucinations, while reduced parahippocampus-retrosplenial connectivity correlated with ego-dissolution and altered meaning.
Increased Global Functional Connectivity Correlates with LSD-Induced Ego Dissolution. 2016 observational cohort (fMRI) Supports LSD increased global functional connectivity in association cortices and thalamus, overlapping with 5-HT2A receptor density maps, and this increase correlated with subjective ego dissolution.
Safety and Efficacy of Lysergic Acid Diethylamide-Assisted Psychotherapy for Anxiety Associated With Life-threatening Diseases 2014 RCT (pilot, active placebo) 12 Supports LSD-assisted psychotherapy reduced state and trait anxiety at 2 months with large effect sizes, and reductions were sustained for 12 months with no serious adverse events.
LSD-assisted psychotherapy for anxiety associated with a life-threatening disease: A qualitative study of acute and sustained subjective effects 2014 prospective follow-up with qualitative analysis 10 Supports Twelve months after LSD psychotherapy, anxiety benefits were sustained, most participants reported reduced anxiety and improved quality of life, and none reported lasting adverse reactions.
Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized controlled trials 2012 meta-analysis of RCTs 536 Supports A single dose of LSD within alcoholism treatment programs was associated with reduced alcohol misuse (OR 1.96), with negligible between-trial heterogeneity.
Acute Effects of Lysergic Acid Diethylamide in Healthy Subjects 2014 double-blind randomized placebo-controlled crossover 16 Mixed LSD produced pronounced alterations of consciousness, increased well-being and closeness to others, decreased prepulse inhibition, and raised blood pressure, heart rate, temperature, pupil size, and several hormones, with adverse effects subsiding within 72 hours.
LSD treatment affects working memory-related brain function in patients with major depressive disorder 2026 randomized double-blind parallel-group trial 43 Supports High-dose LSD treatment significantly increased working-memory-related brain responses in task-activated regions compared with low-dose treatment, and these responses correlated with task performance and subjective perceptual changes but not treatment response.
722. Predictors of therapeutic response to LSD in anxiety: short- and long-term outcomes 2026 randomized controlled trial (crossover) Supports Positive acute subjective effects and mystical-type experiences predicted short-term and one-year anxiety reductions, while negative acute effects did not correlate with outcomes.
720. Unraveling anxiolytic and anti-addictive properties of lysergic acid diethylamide in a model of alcohol use disorder 2026 phase 2b randomized double-blind placebo-controlled trial 198 Supports A single dose of MM120 produced dose-dependent anxiety reduction at week 4, with 100 μg and 200 μg significantly reducing HAM-A scores versus placebo while 25 μg and 50 μg did not.
Investigating molecular and hemodynamic effects of LSD in the human brain. 2026 PET-MRI experimental study 7 Supports LSD occupied 5-HT2A receptors with high affinity, increased global cerebral blood flow and carotid flow, decreased global connectivity, and showed hysteresis between plasma levels and subjective effects.
710. The neuropsychopharmacology of LSD 2026 observational PET-MRI imaging study 7 Supports LSD occupied up to 97.4% of cerebral 5-HT2A receptors, increased global cerebral blood flow by 19.3% and carotid flow by 28%, and decreased global connectivity, with blood-flow increases opposite to those reported for psilocybin.
Increased spontaneous MEG signal diversity for psychoactive doses of ketamine, LSD and psilocybin 2017 observational MEG study Supports LSD, psilocybin, and ketamine all reliably increased spontaneous neural signal diversity above normal waking consciousness, with changes correlating with phenomenological intensity.
Crystal structure of an LSD-bound human serotonin receptor 2017 structural biology and molecular dynamics Supports The crystal structure of LSD bound to human 5-HT2B revealed slow dissociation kinetics, and simulations suggested an extracellular loop 2 'lid' explains this slow binding, with a mutation accelerating kinetics and dampening β-arrestin2 recruitment.
The Pharmacology of Lysergic Acid Diethylamide: A Review 2008 review Mixed LSD's pharmacology is complex and incompletely understood; it is physiologically well tolerated and psychological reactions can be controlled in supervised settings, but complications may result from uncontrolled use.
Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function. 2019 integrative review Supports Classic psychedelics including LSD show promise as therapeutics for psychological distress, depression, and addiction, and as tools for studying mystical experience and brain function, with epidemiological studies suggesting associations between nonmedical use and positive mental health outcomes.
Serotonin research: contributions to understanding psychoses 2008 review Supports Sixty years of research support a relationship between serotonin, serotonergic hallucinogens, and both drug-induced and disorder-based psychotic states.
Study of a New Schizophrenomimetic Drug—Sernyl 1959 review Unclear Presents opposing views on whether drug-induced model psychoses are useful for studying schizophrenia, without reaching a conclusion.
Structural Features for Functional Selectivity at Serotonin Receptors 2013 structural biology study Supports Crystal structures of serotonin receptors bound to antimigraine drugs or an LSD precursor show that subtle ligand binding differences cause substantial differences in receptor signaling.
Amphetamine, 3,4-Methylenedioxymethamphetamine, Lysergic Acid Diethylamide, and Metabolites of the Catecholamine Neurotransmitters Are Agonists of a Rat Trace Amine Receptor 2001 pharmacological characterization Supports LSD and other compounds act as agonists at a rat trace amine receptor, suggesting a potential additional signaling mechanism beyond previously characterized targets.
Psychedelic Hormesis: LSD Activates Adaptive Stress Transcriptional Programs in the Prefrontal Cortex 2026 preclinical gene-expression study in mice Supports A single LSD administration induced a temporally organized transcriptional program in mouse prefrontal cortex with early stress/metabolic and later circadian/neuroendocrine responses, which the authors argue reflects adaptive hormetic stress.
Deconstruction of lysergic acid diethylamide. 2026 laboratory study Mixed Argues that simplified ergoline analogues can retain LSD-like 5-HT2A agonism while offering improved safety profiles, identifying a 5-HT2C-preferring analogue with antipsychotic-like properties in mice.
Le LSD comme traitement de la dépendance à ­­l’alcool en France (1960-1967) 2026 historical analysis Unclear Argues that France was distinctive in the first wave of Western LSD research by conducting clinical trials of LSD for alcoholism using a specific 'shock' model, contrasting with North American psychedelic and European psycholytic models.
Prolonged Psychological Distress Following Recreational LSD Use in a Young Adult with Multiple Vulnerability Factors: A Case Report 2026 case report 1 Opposes Describes a young man whose LSD use was followed by recurrent suicidal thoughts, panic, and pervasive doubt requiring multiple emergency visits and psychiatric admissions, with authors suggesting possible underlying obsessive functioning and highlighting set, setting, and harm reduction.
Adverse Health Outcomes of Psilocybin, LSD, MDMA, Ibogaine, and 5-MeO-DMT 2026 cross-sectional survey Unclear Describes self-reported health outcomes attributed to recent use of LSD and other substances in a US survey, without reporting specific outcomes or effect sizes in the available text.

Points of agreement

  • Modern neuroimaging consistently shows LSD occupies 5-HT2A receptors and alters functional connectivity and cerebral blood flow, with changes correlating with subjective effects such as ego dissolution and hallucinations.
  • Small randomized trials and a meta-analysis suggest LSD-assisted psychotherapy may reduce anxiety and alcohol misuse, with some benefits sustained to 12 months.
  • Positive acute subjective and mystical-type experiences appear to predict therapeutic anxiety outcomes.
  • LSD is generally physiologically well tolerated in supervised settings, with acute adverse effects typically resolving within days.
  • Structural and pharmacological work converges on 5-HT2A agonism and unusual binding kinetics as central to LSD's effects.

Conflicts

  • LSD increased global cerebral blood flow in PET-MRI studies, whereas the authors note psilocybin's blood-flow effects are opposite despite shared 5-HT2A agonism.
  • One imaging study reported increased global connectivity under LSD while PET-MRI work reported decreased global connectivity.
  • Clinical trials and reviews emphasize safety in supervised settings, while a case report documents severe prolonged psychological distress after recreational use.

Gaps

  • Most clinical trials are small, and blinding is difficult with psychoactive drugs.
  • Long-term safety and adverse outcomes in large, representative populations are poorly characterized.
  • Dose-response relationships are established only for some indications and settings.
  • Effects in older adults, diverse populations, and non-clinical users are understudied.
  • Mechanisms linking acute receptor occupancy and connectivity changes to durable therapeutic effects remain unclear.
  • Cognitive and functional outcomes beyond single tasks are sparsely reported.
Browse these studies in the library

Common questions

What does the research agree on about LSD?
  • Modern neuroimaging consistently shows LSD occupies 5-HT2A receptors and alters functional connectivity and cerebral blood flow, with changes correlating with subjective effects such as ego dissolution and hallucinations.
  • Small randomized trials and a meta-analysis suggest LSD-assisted psychotherapy may reduce anxiety and alcohol misuse, with some benefits sustained to 12 months.
  • Positive acute subjective and mystical-type experiences appear to predict therapeutic anxiety outcomes.
  • LSD is generally physiologically well tolerated in supervised settings, with acute adverse effects typically resolving within days.
  • Structural and pharmacological work converges on 5-HT2A agonism and unusual binding kinetics as central to LSD's effects.
Where do studies on LSD conflict?
  • LSD increased global cerebral blood flow in PET-MRI studies, whereas the authors note psilocybin's blood-flow effects are opposite despite shared 5-HT2A agonism.
  • One imaging study reported increased global connectivity under LSD while PET-MRI work reported decreased global connectivity.
  • Clinical trials and reviews emphasize safety in supervised settings, while a case report documents severe prolonged psychological distress after recreational use.
What is still unknown about LSD?
  • Most clinical trials are small, and blinding is difficult with psychoactive drugs.
  • Long-term safety and adverse outcomes in large, representative populations are poorly characterized.
  • Dose-response relationships are established only for some indications and settings.
  • Effects in older adults, diverse populations, and non-clinical users are understudied.
  • Mechanisms linking acute receptor occupancy and connectivity changes to durable therapeutic effects remain unclear.
  • Cognitive and functional outcomes beyond single tasks are sparsely reported.
How we analyze this

This synthesis reads the 15 most-cited and 10 most recent studies whose primary subject is LSD, 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 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

Latest monthly recap: September 2026 →

2,815 articles · 620 from the last two years · 11,587,215 participants across 795 studies reporting sample size

Common study designs

review 561 systematic review 133 experimental study 222 historical analysis 143 theoretical or philosophical paper 184

LSD research by condition and practice

Data updated

Studies whose primary subject is both LSD and the condition or practice, with reviews counted by the study design extracted from each abstract. Registered trials are from ClinicalTrials.gov. This maps how much research exists, not how well anything works.

LSD research by condition and practice: studies, meta-analyses and systematic reviews, registered clinical trials, the highest trial phase, and studies from the last two years. Most studies first.
Condition or practice Studies Meta-analyses and systematic reviews Registered trials Highest phase From the last two years
Anxiety 97 studies 13 meta-analyses and systematic reviews 6 registered trials up to Phase 2 22 from the last two years
Addiction 59 studies 11 meta-analyses and systematic reviews 2 registered trials up to Phase 2 17 from the last two years
Depression 58 studies 9 meta-analyses and systematic reviews 8 registered trials up to Phase 2 21 from the last two years
Psychedelic-assisted therapy 55 studies 5 meta-analyses and systematic reviews 2 registered trials up to Phase 2 16 from the last two years
Microdosing 48 studies 2 meta-analyses and systematic reviews 1 registered trial No phase listed 22 from the last two years

Research volume by year

Compare topics →

927 studies whose primary subject is LSD since 2002

Studies about LSD per year, 2002 to 2026, peaking at 120 in 2023 Bar chart: one bar per year, taller where more studies were published that year. 0 100 200 2005 2010 2015 2020 2025
2026 is partial
Show the numbers
Studies about LSD per year, 2002 to 2026, peaking at 120 in 2023
Year Studies
2002 9
2003 6
2004 4
2005 11
2006 6
2007 10
2008 13
2009 12
2010 14
2011 6
2012 13
2013 13
2014 16
2015 17
2016 39
2017 44
2018 33
2019 45
2020 52
2021 56
2022 85
2023 120
2024 91
2025 118
2026 94

Research

Synthesize the evidence → Search all →

Same Molecule, Different People: Selection, Substitution and Setting as Explanations for Divergent Perceptions of LSD Risk

Zenodo (CERN European Organization for Nuclear Research) October 24, 2026 Odin Loch preprint

Background. Clinical papers and street experience give different answers to how dangerous lysergic acid diethylamide (LSD) is. This preprint treats safety as a property of a drug in a population in a context, and asks why the two pictures diverge. Four explanations are kept separate: who is exposed, what they are actually exposed to, the conditions of exposure, and who gets measured....

DOI: 10.5281/zenodo.23612127 (opens in new tab)

Investigating molecular and hemodynamic effects of LSD in the human brain.

Nature Neuroscience October 12, 2026 Drummond E-Wen Mcculloch, Kristian Larsen, Annette Johansen et al.

Lysergic acid diethylamide (LSD) is a potent psychedelic with increasing therapeutic interest, yet qualification of target engagement using in vivo neuroimaging has not yet been performed. Using simultaneous positron emission tomography-magnetic resonance imaging technology, we describe multiple brain actions of LSD in seven healthy volunteers blinded to LSD dose received. Here we show that LSD...

DOI: 10.1038/s41593-026-02462-2 (opens in new tab) Full text (opens in new tab)

DT120 (MM120): a single-dose orally disintegrating formulation of lysergide tartrate for generalized anxiety disorder

Expert Review of Neurotherapeutics October 8, 2026 Wiesław Jerzy Cubała

Introduction Generalized anxiety disorder (GAD) is a chronic, disabling condition for which currently available pharmacotherapies have delayed onset, incomplete remission rates, treatment-emergent adverse effects and substantial real-world discontinuation. DT120, formerly MM120, is an investigational orally disintegrating tablet formulation of lysergide tartrate being developed as a single-dose...

DOI: 10.1080/14737175.2026.2744754 (opens in new tab)

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)

Adverse Health Outcomes of Psilocybin, LSD, MDMA, Ibogaine, and 5-MeO-DMT

JAMA Network Open September 29, 2026 Otto Simonsson, Melissa Bradley, Joshua Curtis Black et al.

This cross-sectional study describes health outcomes attributed to recent use of psilocybin, lysergic acid diethylamide (LSD), 3,4-methylenedioxymethamphetamine (MDMA), ibogaine, and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) in a nationally representative survey of US adults.

DOI: 10.1001/jamanetworkopen.2026.36756 (opens in new tab)

Prolonged Psychological Distress Following Recreational LSD Use in a Young Adult with Multiple Vulnerability Factors: A Case Report

Clinical Neuropsychopharmacology and Addiction September 24, 2026 Giacomo D’andrea, Antonio Inserra, Andrea Miuli et al.

While psychedelic experiences are often reported as positive, adverse psychological reactions can occur. We present the case of a 19-year-old Caucasian male who presented to the ER with suicidal thoughts after taking lysergic acid diethylamide (LSD) alone. He was diagnosed with anxious state associated with panic attacks, and suicidal thoughts without ideation or behaviors. He was admitted to...

DOI: 10.53941/cna.2026.100015 (opens in new tab)

Psychedelic Hormesis: LSD Activates Adaptive Stress Transcriptional Programs in the Prefrontal Cortex

bioRxiv (Cold Spring Harbor Laboratory) September 18, 2026 Aurora Savino, Carla Liaci, Giorgio R. Merlo et al. preprint

Background Classic psychedelics are serotonergic agents increasingly recognized for their ability to produce rapid and long-lasting therapeutic effects in several neuropsychiatric conditions, yet the molecular mechanisms that translate acute serotonergic perturbation into long-term brain adaptation remain poorly understood. Psychedelic action is commonly attributed to enhanced neuronal...

DOI: 10.64898/2026.09.11.751070 (opens in new tab)

Le LSD comme traitement de la dépendance à ­­l’alcool en France (1960-1967)

Psychotropes September 15, 2026 Zoë Dubus

Durant la première vague ­­d’études occidentales sur les propriétés thérapeutiques du LSD, ­­l’une de ses indications principales dans le modèle « psychédélique » (administration de fortes doses en une à trois séances, surtout utilisée en Amérique du Nord) concerne le traitement de la dépendance à ­­l’alcool. À ­­l’inverse, en Europe, où se développait le modèle « psycholytique » (faibles doses...

DOI: 10.3917/psyt.323.0035 (opens in new tab)

720. Unraveling anxiolytic and anti-addictive properties of lysergic acid diethylamide in a model of alcohol use disorder

The International Journal of Neuropsychopharmacology September 9, 2026 Todd M Solomon, Robert Barrow, Daniel R Karlin et al.

Abstract Background Effective and well-tolerated pharmacotherapies for generalized anxiety disorder (GAD), which is one of the most common psychiatric disorders, are needed. Aims & Objectives To determine the dose-response relationship of MM120 (lysergide D-tartrate) in adults with moderate to severe GAD. Method This phase 2b, multicenter, randomized, double-blind, placebo-controlled study...

DOI: 10.1093/ijnp/pyag040.492 (opens in new tab)

Clinical trials

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