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LSD (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 25 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.

LSD is a classic psychedelic that produces profound alterations in consciousness, including visual hallucinations and ego dissolution, which are linked to increased brain signal diversity and changes in functional connectivity, particularly via the 5-HT2A receptor. Early and recent clinical trials suggest that LSD-assisted psychotherapy may reduce anxiety in life-threatening illness and decrease alcohol misuse, with effects lasting up to 12 months in small samples. However, evidence is limited by small sample sizes, open-label designs, and a lack of large-scale, rigorous controlled trials, and LSD can exacerbate psychosis in vulnerable individuals.

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 of a New Schizophrenomimetic Drug—Sernyl 1959
Unclear

This early paper discusses LSD as a model psychosis tool and notes objections to drawing analogies between drug-induced states and schizophrenia.

theoretical/review

Neural correlates of the LSD experience revealed by multimodal neuroimaging. 2016
Supports

LSD increased visual cortex blood flow and connectivity, which correlated with visual hallucinations, and decreased parahippocampal-retrosplenial connectivity correlated with ego dissolution.

observational (neuroimaging)

Safety and Efficacy of Lysergic Acid Diethylamide-Assisted Psychotherapy for Anxiety Associated With Life-threatening Diseases 2014
Supports

LSD-assisted psychotherapy (200 μg) significantly reduced trait and state anxiety at 2 months (effect sizes 1.1 and 1.2), with reductions sustained for 12 months and no serious adverse events.

RCT (double-blind, active placebo-controlled pilot) Sample size: 12

Structural Features for Functional Selectivity at Serotonin Receptors 2013
Unclear

This paper describes crystal structures of serotonin receptors bound to ligands including an LSD precursor, revealing how ligand binding can differentially activate signaling pathways.

theoretical (structural biology)

Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized controlled trials 2012
Supports

Meta-analysis of six RCTs found that a single dose of LSD was associated with a decrease in alcohol misuse (OR 1.96, 95% CI 1.36–2.84, p=0.0003) with negligible heterogeneity.

meta-analysis Sample size: 536

Increased Global Functional Connectivity Correlates with LSD-Induced Ego Dissolution. 2016
Supports

LSD-induced ego dissolution correlated with increased global functional connectivity in the brain.

observational (neuroimaging)

Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function. 2019
Supports

This integrative review notes that classic psychedelics including LSD have shown promising results for end-of-life distress and addiction, and that naturalistic use is associated with positive mental health outcomes.

review

Crystal structure of an LSD-bound human serotonin receptor 2017
Unclear

The crystal structure of LSD bound to the 5-HT2B receptor reveals a 'lid' mechanism for slow dissociation and provides molecular explanation for LSD's actions at serotonin receptors.

theoretical (structural biology)

The Pharmacology of Lysergic Acid Diethylamide: A Review 2008
Unclear

This comprehensive review states that LSD is physiologically well tolerated in controlled settings, but complications can arise from uncontrolled use, and its mechanisms of action remain incompletely understood.

review

LSD-assisted psychotherapy for anxiety associated with a life-threatening disease: A qualitative study of acute and sustained subjective effects 2014
Supports

Qualitative analysis at 12 months post-LSD psychotherapy found sustained anxiety reduction (77.8%) and improved quality of life (66.7%), with no lasting adverse reactions.

qualitative (prospective follow-up) Sample size: 10

Dose-Response Study of N,N-Dimethyltryptamine in Humans 1994
Unclear

This study describes the subjective effects of intravenous DMT, not LSD, and is therefore not directly relevant to the question.

observational (dose-response) Sample size: 12

Increased spontaneous MEG signal diversity for psychoactive doses of ketamine, LSD and psilocybin 2017
Supports

LSD, along with psilocybin and ketamine, increased spontaneous MEG signal diversity (entropy and Lempel-Ziv complexity) beyond normal waking consciousness, correlating with intensity of psychedelic experience.

observational (neuroimaging)

Changes in global and thalamic brain connectivity in LSD-induced altered states of consciousness are attributable to the 5-HT2A receptor 2018
Supports

LSD reduced associative and increased sensory-somatomotor brain connectivity; these effects were fully blocked by the 5-HT2A antagonist ketanserin, implicating the 5-HT2A receptor in LSD's neural effects.

RCT (double-blind, randomized, cross-over) Sample size: 24

Lysergic Acid Diethylamide: Sensitive Neuronal Units in the Midbrain Raphe 1968
Unclear

LSD inhibited spontaneous activity of serotonin-containing neurons in the midbrain raphe at doses below the threshold for behavioral effects.

observational (animal study)

Classic psychedelic use is associated with reduced psychological distress and suicidality in the United States adult population. 2015
Supports

Lifetime classic psychedelic use was associated with reduced odds of past-month psychological distress (OR 0.81), past-year suicidal thinking (OR 0.86), planning (OR 0.71), and attempt (OR 0.64).

observational (cross-sectional epidemiological) Sample size: 190000

Policy Considerations for Psychedelics in Research and Medicine – What’s Next on the Schedule? 2026
Unclear

This paper notes that LSD has received FDA Breakthrough Therapy designation for generalized anxiety disorder and that over 150 clinical trials are assessing psychedelic therapies.

review/policy analysis

The toxicity of psychedelic LSD derivatives: 1-acetyl-LSD (ALD-52), 1-propionyl-LSD (1P-LSD), 1-butyryl-LSD (1B-LSD), 1-valeryl-LSD (1V-LSD) and 1-cyclopropylmethanoyl-LSD (1cP-LSD)-prediction of toxicological parameters relevant to clinical and forensic toxicology using multi-in silico approach. 2026
Unclear

In silico predictions for LSD derivatives suggest varying toxicity profiles, with some compounds showing genotoxicity and cardiotoxicity alerts, but this does not directly address LSD's effects.

theoretical (in silico toxicology)

The intersection between psychedelics and schizophrenia spectrum disorders: Reevaluating risk and therapeutic potential. 2026
Mixed

This narrative review concludes that psychedelics can exacerbate pre-existing psychotic illness and may trigger psychosis in vulnerable individuals, but phenomenological and mechanistic distinctions suggest potential therapeutic applications for stable patients.

review

Effects of repeated low-dose LSD on neuropsychological functioning in adults with ADHD: a randomized placebo-controlled study 2026
Mixed

Six weeks of biweekly low-dose LSD (20 μg) improved temporal processing but left other neuropsychological domains (attention, inhibition, motivation) unaffected in adults with ADHD.

RCT (double-blind, placebo-controlled, parallel group) Sample size: 53

Acute and post-acute neurobehavioral responses to lysergic acid diethylamide in healthy subjects: a randomized controlled study 2026
Supports

A single 100 μg LSD dose improved offline motor learning the next day, reduced perceived stress, and increased cognitive flexibility one week later, with acute EEG and TMS changes.

RCT (randomized crossover) Sample size: 45

Characterizing non-hallucinogenic psychedelics beyond the head twitch response: phenotypic fingerprinting of lisuride and LSD 2026
Unclear

In mice, LSD produced a 5-HT2A-dependent head-twitch response but minimal effects on other behaviors, while lisuride (no head-twitch) caused broad disruptions, suggesting the head-twitch response alone is insufficient to predict psychoactivity.

observational (animal study)

The effects of psychedelics on attention deficit and hyperactivity disorder - a systematic review. 2026
No effect

This systematic review found only six studies on psychedelics for ADHD; one RCT showed no statistically significant difference versus placebo, and the evidence is insufficient to recommend psychedelic use for ADHD.

systematic review

Electrophysiological mechanisms of psychedelic drugs: A systematic review. 2026
Unclear

This systematic review of electrophysiological studies concludes that psychedelics exert complex, heterogeneous effects on neuronal excitability and synaptic transmission, challenging the view that they uniformly increase cortical excitability.

systematic review

Integrating the Mystical Experience Questionnaire Into a Broader Psychometric Framework: English Validation of the Psychedelic Experience Scale and Comparison of Psilocybin and LSD Sessions Across Two Controlled Settings. 2026
Unclear

This validation study of the Psychedelic Experience Scale included data from psilocybin sessions, not LSD, and is therefore not directly relevant to the question.

observational (psychometric validation) Sample size: 280

Who Keeps Using Lysergic Acid Diethylamide? Correlates of Past-Year Use in People Who Initiated Use at least Five Years Ago. 2026
Unclear

Among US adults who first used LSD ≥5 years ago, only 4.2% reported past-year use, and use declined with time since initiation; past-year use was associated with male sex, poverty, and other drug-related factors.

observational (cross-sectional epidemiological)

Points of agreement

  • LSD produces profound alterations in consciousness, including visual hallucinations and ego dissolution, which are linked to changes in brain connectivity and increased neural signal diversity.
  • The 5-HT2A receptor is a key mediator of LSD's subjective and neural effects, as shown by blockade with ketanserin.
  • LSD-assisted psychotherapy may reduce anxiety in patients with life-threatening illnesses and decrease alcohol misuse, with effects lasting up to 12 months in small studies.
  • LSD is generally well tolerated in controlled medical settings, but can exacerbate psychosis in vulnerable individuals.

Conflicts

  • One study found that LSD improved temporal processing in ADHD, while a systematic review concluded there is insufficient evidence for psychedelic use in ADHD and one RCT showed no significant effect.
  • Early research framed LSD as a psychotomimetic model of schizophrenia, but later work emphasizes qualitative differences between psychedelic and psychotic states.
  • Animal studies show dissociation between the head-twitch response and broader psychoactivity, challenging the use of this assay alone to predict hallucinogenic potential.

Gaps

  • Lack of large-scale, multi-site RCTs for LSD-assisted psychotherapy in anxiety, depression, and addiction.
  • Durability of therapeutic effects beyond 12 months is unknown.
  • Optimal dosing, frequency, and psychotherapeutic protocols for LSD-assisted therapy are not established.
  • Risks of LSD use in vulnerable populations (e.g., those with psychosis risk) are inadequately quantified.
  • Mechanisms of action beyond 5-HT2A receptor (e.g., role of other receptors, intracellular signaling) remain incompletely understood.
  • Evidence for LSD in ADHD is extremely limited, with only one small RCT and no controlled studies on microdosing.
Browse these studies in the library
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.

Ask your own question in the Research Synthesis Tool

Latest monthly recap: June 2026 →

2,554 articles · 602 from the last two years · 11,682,951 participants across 729 studies reporting sample size

Common study designs

review 516 systematic review 126 experimental study 229 historical analysis 102 theoretical or philosophical paper 141

Research

Synthesize the evidence → Search all →

The toxicity of psychedelic LSD derivatives: 1-acetyl-LSD (ALD-52), 1-propionyl-LSD (1P-LSD), 1-butyryl-LSD (1B-LSD), 1-valeryl-LSD (1V-LSD) and 1-cyclopropylmethanoyl-LSD (1cP-LSD)-prediction of toxicological parameters relevant to clinical and forensic toxicology using multi-in silico approach.

Archives of Toxicology July 1, 2026 Kamil Jurowski, Alicja Krośniak, Damian Kobylarz et al.

Lysergamide analogs such as ALD-52, 1P-LSD, 1B-LSD, 1 V-LSD, and 1cP-LSD are new psychoactive substances with hallucinogenic potential whose toxicological profiles are largely unknown. A comprehensive in silico assessment using multiple platforms predicted acute toxicity LD50 values in rats from 49 to 85 mg/kg. Organ-specific risks included elevated pulmonary risk for 1 V-LSD (92%) and 1cP-LSD (81%), and highest hematotoxicity for 1P-LSD (76%) and 1B-LSD (75%). Genotoxicity alerts were identified for ALD-52 and 1cP-LSD (up to 90% predicted probability), while all compounds were classified as non-mutagenic by OCHEM. Cardiotoxicity assessment showed strongest hERG channel inhibition for 1 V-LSD (IC50 = 1.4 µM), suggesting elevated proarrhythmic potential. Structural modifications at the N-1-acyl position influence toxicity patterns, particularly affecting cardiopulmonary and genotoxic endpoints.

DOI: 10.1007/s00204-025-04255-1 (opens in new tab) Full text (opens in new tab) Forensic toxicology Lysergamide analogs New psychoactive substance Toxicology in silico

Effects of repeated low-dose LSD on neuropsychological functioning in adults with ADHD: a randomized placebo-controlled study

Psychopharmacology June 20, 2026 E. C. H. M. Haijen-Bongers, P.p.m. Hurks, J. Schepers et al.

In adults with attention-deficit hyperactivity disorder, six weeks of biweekly low-dose lysergic acid diethylamide (20 µg) produced a limited effect on temporal processing, specifically on a time reproduction task, but did not improve performance on other neuropsychological measures of attention, inhibition, or motivational processing. The finding was observed in a secondary analysis of a double-blind, placebo-controlled trial with 46 completers. Baseline performance predicted some treatment outcomes differently between the LSD and placebo groups. The authors caution that the single positive result should be interpreted cautiously, especially because the parent trial showed no corresponding improvements in clinical symptoms.

DOI: 10.1007/s00213-026-07107-7 (opens in new tab) Full text (opens in new tab) Neuropsychology Placebo Cognition Population +9

Acute and post-acute neurobehavioral responses to lysergic acid diethylamide in healthy subjects: a randomized controlled study

Neuropsychopharmacology June 18, 2026 Abigail E. Calder, Vincent J Diehl, Morten P. Lietz et al.

A single 100 µg dose of lysergic acid diethylamide (LSD) improved offline motor learning the next day and, one week later, reduced perceived stress and increased aspects of cognitive flexibility in 45 healthy adults. Electroencephalography showed that LSD acutely decreased N1 and P2 auditory event-related potential amplitudes, with P2 still modulated after one week. Transcranial magnetic stimulation revealed increased motor-evoked potential amplitude and faster latency under LSD. Brain-derived neurotrophic factor levels were unchanged. The findings suggest lasting effects of LSD on learning and neural signals, while highlighting challenges in measuring long-term potentiation in humans.

DOI: 10.1038/s41386-026-02454-7 (opens in new tab) Full text (opens in new tab) Lysergic acid diethylamide Transcranial magnetic stimulation Electroencephalography Crossover study +14

Characterizing non-hallucinogenic psychedelics beyond the head twitch response: phenotypic fingerprinting of lisuride and LSD

Translational Psychiatry June 13, 2026 Jillian L. King, Devin P. Effinger, Cameron Basquez-Pfeifer et al.

The head-twitch response (HTR) in mice, a standard test for hallucinogenic potential, fails to reliably indicate overall psychoactivity. Lisuride, which did not produce HTR, caused impaired movement, coordination, stress, cognitive disruption, and reduced prefrontal cortex EEG power. LSD, which triggered strong HTR, had minimal effects on these measures. Neither compound's effects beyond HTR depended on 5-HT₂A receptors. The HTR alone is insufficient and should be combined with other assessments.

DOI: 10.1038/s41398-026-04174-4 (opens in new tab) Full text (opens in new tab) Lisuride Phenotype Schizophrenia object-oriented programming Head geology +4

Synthetic Drugs and Behavioural Addictions: LSD, MDMA and Digital Toxicity

June 1, 2026 Sharda More-Pol

This chapter argues that modern psychological stressors, synthetic drug abuse (LSD, MDMA), and behavioral addictions such as gaming can be understood through ancient Ayurvedic concepts of Madya (intoxicants), Mada (intoxication), and Prajñāparādha (cognitive perversion). By examining classical texts from the Brihatrayi, it proposes that overstimulation from chemicals or screens causes deterioration of mental faculties, described as Ojas depletion and Manovaha Srotas vitiation. Drawing parallels with modern neurobiology—including 5-HT2A receptor agonism, monoamine depletion, and dopamine-driven reward-circuit changes—the authors present an integrative framework for emergency stabilization, behavioral modification, cognitive rehabilitation (Sattvāvajaya Cikitsā), and rasayana recovery protocols in integrative clinical psychiatry.

DOI: 10.63247/ayurveda360.cfa.agadatantra.c011 (opens in new tab) Lysergic acid diethylamide MDMA Cognition Parallels +9

Who Keeps Using Lysergic Acid Diethylamide? Correlates of Past-Year Use in People Who Initiated Use at least Five Years Ago.

Psychedelic medicine (New Rochelle, N.Y.) June 1, 2026 Brian S. Barnett, Akhil Anand, Jeremy Weleff et al.

Among US adults who first used LSD at least 5 years ago, only 4.2% reported using it in the past year. Past-year use dropped sharply with time since first use, from 14.4% among those who started 5 years ago to 0.1% among those who started 46–50 years ago. Factors linked to past-year use included being male, never married, living in poverty, higher education, lifetime stimulant use, recent contact with drug sellers, having sold illegal drugs, perceiving LSD as lower risk and more available, and a past-year suicide attempt. Having children at home, living in a small metro area, and more years since first use were linked to lower odds. Perceived risk and availability showed the strongest associations.

DOI: 10.1177/28314425251367321 (opens in new tab) Full text (opens in new tab) LSD Drug use Hallucinogen Psychedelics

Integrating the Mystical Experience Questionnaire Into a Broader Psychometric Framework: English Validation of the Psychedelic Experience Scale and Comparison of Psilocybin and LSD Sessions Across Two Controlled Settings.

International Journal of Methods in Psychiatric Research June 1, 2026 Kurt Stocker, Matthias Hartmann, Frederick S. Barrett et al.

The eight-factor structure of the Psychedelic Experience Scale (PES48), which includes the Mystical Experience Questionnaire (MEQ30) and additional factors for paradoxicality, connectedness, visual experience, and distressing experience, is valid for use in English. Analysis of 280 measurements from 145 healthy participants in four placebo-controlled psilocybin studies found that six subscales have high internal consistency, one good, and one acceptable. Both the MEQ30 and MEQ40 models show acceptable to good model fits, with better fits in English than in German. All six MEQ40 scale means were higher in English data, suggesting that the PES48 provides a broader conceptualization of mystical and non-mystical psychedelic experiences, and that setting may influence mystical experience.

DOI: 10.1002/mpr.70073 (opens in new tab) Full text (opens in new tab) Mystical experience Psychedelic experience Psychometrics Setting

Lysergic acid diethylamide reverses aging- and neurodegeneration-associated brain transcriptional programs

bioRxiv May 29, 2026 Aurora Savino, Carla Liaci, Ilaria Bertani et al.

LSD induces gene expression patterns that oppose the transcriptional signatures of brain aging and dementia. By comparing chronic LSD treatment in rodents with age- and dementia-related gene expression changes in the human prefrontal cortex, the authors show that LSD's effects are strongly anti-correlated with these disease programs, a reversal specific compared to other pharmacological perturbations and reproducible across datasets and species. LSD also counteracts amyloid-β-induced structural and molecular alterations in primary cortical neurons, linking transcriptomic opposition to functional rescue under neurodegenerative stress. These findings suggest LSD modulates molecular and cellular pathways associated with brain aging and neurodegeneration.

DOI: 10.64898/2026.05.26.727809 (opens in new tab)

Lysergic acid diethylamide pretreatment prolongs brain-stimulation induced neural activity changes.

Brain Stimulation May 21, 2026 Lucas Dwiel, Mackenzi L. Prina, Elise Bragg et al.

Pretreating rats with LSD before electrically stimulating the infralimbic cortex produces larger and longer-lasting changes in brain activity than stimulation alone. The combination activates the mTOR signaling pathway and alters perineuronal net integrity, suggesting a mechanism for enhanced neuroplasticity. Brain activity during stimulation did not predict the persistent changes seen minutes or days later. These findings support developing psychedelic-assisted brain stimulation approaches to improve durability of stimulation effects, potentially reducing relapse rates in clinical treatments.

DOI: 10.1016/j.brs.2026.103130 (opens in new tab) Full text (opens in new tab) Neuroplasticity Electrophysiology Neuromodulation Perineuronal nets +2

LSD persistently disrupts affective pain processing.

bioRxiv : the preprint server for biology May 11, 2026 Jared Plotkin, Elaine Zhu, Mélanie Druart et al.

A single dose of LSD in rats persistently reduces the emotional, or affective, component of pain, without altering basic sensation. This effect is produced by LSD acting directly in the anterior cingulate cortex (ACC), a brain region that assigns negative value to painful stimuli. Recordings of neural activity showed that LSD suppresses the ACC's responses to painful input, reducing how the brain encodes the unpleasantness of pain. Although LSD increased the intrinsic excitability of ACC neurons in isolated tissue, it paradoxically reduced their maximum firing in response to painful stimuli in living animals. These results suggest that psychedelics can disrupt the brain's transformation of a painful signal into an aversive experience.

DOI: 10.64898/2026.05.06.723205 (opens in new tab) Full text (opens in new tab)

Clinical trials

All LSD trials →