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LSD

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.

Confidence in the evidence

Low-Moderate
  • Only one small (n=12) double-blind pilot RCT on LSD-assisted psychotherapy for anxiety, with positive but preliminary results.
  • A meta-analysis of six RCTs (n=536) on LSD for alcoholism shows a beneficial effect, but trials are older and have methodological limitations.
  • Neuroimaging studies (e.g., n=24, n=20) consistently link LSD to 5-HT2A receptor-mediated changes in brain connectivity, but sample sizes are small.
  • Large epidemiological studies (n>190,000) associate lifetime psychedelic use with reduced psychological distress, but are cross-sectional and cannot establish causality.
  • Evidence for LSD in ADHD is insufficient, with one RCT showing no significant effect and only observational reports suggesting benefit.
How we rate confidence

Confidence reflects the strength of the underlying evidence, not whether the result is favorable. It weighs the number and size of studies, their design (randomized trials count for more than observational or single-case work), how consistently they point the same way, and their risk of bias.

Tiers run from Insufficient to High. High is rare in this field: small, early, or open-label studies land lower even when their direction is encouraging.

Evidence by study

Direction is each study's finding relative to your question: Supports, Opposes, No effect, Mixed, or Unclear.

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

2,321 articles · 552 from the last two years · 8,501,679 participants across 625 studies reporting sample size

Common study designs

review 443 systematic review 116 experimental study 178 cross-sectional survey 93 theoretical or philosophical paper 120

Research

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The Birth of the Psychedelic Industry: Capitalizing on the Psychedelic Renaissance

Minsu Yoo, Sofia Sakopoulos

The commercialization of psychedelics like psilocybin, LSD, and MDMA for mental health treatment blurs the line between impartial science and profit-driven industry. Based on in-depth interviews with stakeholders, the study reveals how venture capitalists not only fund research but also provide regulatory and industry knowledge, creating ethical dilemmas for scientists. Researchers' reluctance to disclose personal psychedelic experiences during interviews signals a shift from an illegality paradigm to one of intellectual property. The findings suggest that ethical dynamics in scientific practice must be reconsidered, particularly how public and private funders shape researchers' priorities.

DOI: 10.22541/au.172496618.87990987/v1

Psychedelics and autobiographical memory – Six open questions

Samuli Kangaslampi, Morten P. Lietz preprint

Psychedelics have long been thought to enhance autobiographical memory, and revisiting such memories may be key to their therapeutic effects, yet modern research has largely overlooked this area. This review identifies six open questions: whether psychedelics boost autobiographical recall; whether recalling significant or traumatic memories is common during psychedelic experiences; whether they can produce false memories; how memories change when recalled and reconsolidated under psychedelics; what memories of the psychedelic experience itself are like; and whether autobiographical experiences under psychedelics are especially important for therapeutic outcomes. The authors present the limited current evidence for each question and propose how future studies could address them, emphasizing relevance for optimizing psychedelic-assisted therapies and avoiding harm.

DOI: 10.31234/osf.io/su7ch_v2

Psychedelics Use and the Risk of Reduced Formal Mental Health Care

Research Square • Sean Viña

People who use psychedelics are less likely to seek formal mental health care, including medication and outpatient treatment, even when experiencing high psychological distress. Analyzing data from over 458,000 participants in a national US survey between 2010 and 2018, the study found that as distress levels increase, psychedelic users become even less inclined to use formal care compared to non-users. This suggests a heightened risk of self-medication as psychedelics become more culturally and legally accepted.

DOI: 10.21203/rs.3.rs-4378944/v1

Lysergic acid diethylamide stimulates cardiac human H 2 histamine receptors

Research Square • Ulrich Gergs, Hannes Jacob, Pauline Braekow et al. • 1 citation

LSD increases the force and rate of heart muscle contraction by activating H2-histamine receptors in humans, and also acts as a partial agonist at 5-HT4 serotonin receptors in mice. In human atrial tissue from heart surgery patients, LSD's contractile effects were blocked by cimetidine, an H2-receptor antagonist. These findings clarify the cardiac effects of LSD, which is being studied again for psychiatric uses.

DOI: 10.21203/rs.3.rs-2898645/v1

Lysergic Acid Diethylamide Alters the Effects of Brain Stimulation in Rodents

bioRxiv (Cold Spring Harbor Laboratory) • Lucas Dwiel, Angela Henricks, Elise Bragg et al. • 1 citation preprint

Lysergic acid diethylamide (LSD) acutely reduces low-frequency electrical activity across the brain in rats, an effect that returns to normal after 24 hours. However, brain stimulation applied during a window of heightened neuroplasticity 24 hours after LSD produces larger and distinct changes in brain activity compared to stimulation after a placebo. This proof-of-concept finding suggests that psychedelic drugs may work in combination with brain stimulation to achieve enhanced effects on brain activity, with future work needed to assess impacts on behavior.

DOI: 10.1101/2022.10.31.514588

Effect of LSD and music on the time-varying brain dynamics

bioRxiv (Cold Spring Harbor Laboratory) • Iga Adamska, Karolina Finc • 1 citation preprint

Listening to music while under the influence of LSD alters the brain's moment-to-moment patterns of activity, particularly in networks linked to attention and task performance. In a study of 15 participants who underwent functional MRI scans after taking LSD or a placebo, the combination of music and LSD changed how long the brain stayed in a task-positive state. LSD alone, regardless of music, affected the dynamics of a state involving the default mode, somatomotor, and visual networks. Music itself appeared to have a lingering effect on resting-state brain activity, especially on networks associated with tasks. These findings suggest that music, as part of the setting, can shape the psychedelic experience at a neural level.

DOI: 10.1101/2022.04.04.486673

Effect of Liner Properties on the Analysis of Lysergic Acid Diethylamide (LSD) Analogs

ChemRxiv • Sarah Shuda • 1 citation

LSD and related psychedelic drugs are often present at low concentrations on forensic evidence, requiring sensitive detection. The liner inside the injection port of a gas chromatograph (GC) affects how well these compounds are vaporized and transferred to the column. Testing twelve different liners—varying in shape, packing material, and chemical deactivation—showed that liners containing packing material (like glass wool) produced significantly higher peak areas than unpacked liners. Liner geometry had a smaller effect, only mattering with one deactivation type when glass wool was absent. Base deactivation improved peak area compared to standard and Topaz deactivation in straight liners with packing. Over seventy sample runs, base-deactivated and standard liners maintained consistent response, while Topaz-deactivated liners lost 52–68% response after the first injection and 30–54% from first to last injection.

DOI: 10.26434/chemrxiv-2025-q7jm0

Psychedelic Therapy: A Primer for Primary Care Clinicians – Part II. Lysergic acid diethylamide (LSD)

Bryce D. Beutler, Kenneth Shinozuka, Burton J. Tabaac et al. preprint

Lysergic acid diethylamide (LSD) shows promise for treating alcohol use disorder, anxiety, and depression, though its therapeutic potential remains incompletely understood. In clinical trials, adverse events have almost always been mild and transient, with serious events reported in none or very few participants. For anxiety and depression associated with life-threatening illnesses, 77% of participants demonstrate durable relief at one year post-treatment. A meta-analysis of randomized controlled trials found that single-dose LSD significantly improves alcohol use disorder with an odds ratio of 1.96. Large-scale prospective studies are needed to explore potential clinical applications.

DOI: 10.31234/osf.io/km7nu

A cross-national comparison of nonmedical and medical use of psychedelic drugs in the international cannabis policy study.

The International journal on drug policy • August 1, 2026 • Myfanwy Graham, Yimin Ge, Rosalie Liccardo Pacula et al. • 1 citation

An estimated 19% of adults in Canada, the United States, Australia, and New Zealand have used psilocybin, LSD, MDMA, or ketamine at some point in their lives. Psilocybin was the most commonly used substance, with lifetime use highest in Canada (16.3%), followed by the US (13.0%) and New Zealand (12.1%), and lowest in Australia (7.8%). Among those who had ever used a psychedelic, 10-20% had asked their medical provider about medical use, and over a third of past-year users reported experiencing an adverse health effect. Past-month use was low across all countries. Consumer interest in therapeutic use has outpaced clinical trials and therapeutic provisions, and many people use these substances outside regulated pathways, which may increase the risk of adverse events.

DOI: 10.1016/j.drugpo.2026.105348 Full text Adverse events Drug policy Nonmedical use Psychedelics

Sex Differences in Acute Responses to Psychedelics: Evidence for Greater Subjective Intensity and Impairment in Female Participants

bioRxiv (Cold Spring Harbor Laboratory) • July 13, 2026 • Natasha L. Mason, Eline Chm Haijen-bongers, Kim P. C. Kuypers et al.

Female participants reported more intense subjective effects from psilocybin, 2C-B, and LSD than male participants, including feeling more strongly under the drug's influence, reduced vigilance, and impaired control and cognition, with medium-to-large effects consistent across the three drugs. No sex differences were found in empathy measures or peak drug concentrations in blood. These findings suggest pharmacodynamic mechanisms—how the body responds to the drug—rather than pharmacokinetic differences in drug exposure explain the sex differences. The results have implications for dosing, informed consent, and safety monitoring in psychedelic research.

DOI: 10.64898/2026.07.08.737179 Empathy Feeling Psilocybin Interpersonal reactivity index +11

Clinical trials

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