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Home/Research/LSD/Schizophrenia

LSD for Schizophrenia

58 papers and 3 clinical trials exploring lsd as a treatment for schizophrenia.

Compoundclassic psychedelic

LSD

LSD is a classic psychedelic ergoline with high potency at microgram doses and an 8-12 hour duration of action, mediated primarily via 5-HT2A receptor agonism. Modern Phase IIb data in generalised anxiety disorder and FDA Breakthrough Therapy Designation for MM120 have reignited clinical development.

Full LSD profile
IndicationApproximately 24 million people worldwide are affected by schizophrenia.

Schizophrenia

Schizophrenia is a complex psychiatric disorder characterised by disruptions in thought processes and perception. Recent research into psychedelics has opened new avenues for understanding its neurobiology and exploring potential therapeutic mechanisms, particularly in addressing treatment-resistant symptoms.

Full Schizophrenia profile

Academic Research

58 papers
Open Accessmeta

Treatment approaches and efficacy in Psychedelic-Induced Psychosis: A systematic review

This systematic review (n=93 cases) found that psychedelic-induced psychosis, primarily caused by LSD and MDMA, lasted an average of 1.8 weeks and responded much better to second-generation antipsychotics (91% response rate) than first-generation antipsychotics (27% response rate), though one-third of patients later developed schizophrenia spectrum disorders.

Published
June 26, 2025
Journal
Asian Journal of Psychiatry
Authors
Sulstarova, A., Scheuerlein, L., Monari, S., Seragnoli, F., Gabriel, T., Preller, K., Böge, K., Sentissi, O., Kaiser, S., Solmi, M., Kirschner, M., Sabé, M.
Open Accessmeta

‘Equal-unblinding’ meta-analysis of psychedelic therapy vs. antidepressants for the treatment of depression

In a pre-registered meta-analysis of 8 PAT trials (548 patients) and 16 open‑label traditional antidepressant studies (9,751 patients), psychedelic-assisted therapy was not more effective than open‑label antidepressants on the 17‑item Hamilton Depression Rating Scale (difference 0.3 favouring tAD; 95% CI −1.39 to 1.98; p=0.73). This equal‑unblinding comparison emphasises that blinding integrity materially influences apparent treatment effects and that both PAT and tAD produced robust, clinically meaningful improvements.

Published
June 9, 2025
Journal
OSF Preprints
Authors
Williams, Z. J., Barnett, H., Szigeti, B.
Open Accessindividual

The Role of the Dorsolateral Prefrontal Cortex in Ego Dissolution and Emotional Arousal During the Psychedelic State

Using fMRI and MEG in healthy volunteers during acute LSD, the study shows that DLPFC functional connectivity—notably bilateral DLPFC–thalamus–FFA coupling—correlates with subjective ego dissolution, while right DLPFC–IPS–salience network coupling correlates with emotional arousal. MEG Granger causality further revealed increased theta‑band information flow between thalamus and DLPFC, consistent with disrupted thalamic gating during ego dissolution.

Published
April 9, 2025
Journal
Human Brain Mapping
Authors
Coleman, J. A., Shinozuka, K., Tromm, R., Dipasquale, O., Kaelen, M., Roseman, L., Muthukumaraswamy, S., Nutt, D. J., Barnett, L., Carhart-Harris, R. L.
Paywallmeta

Adverse Events in Studies of Classic Psychedelics: A Systematic Review and Meta-Analysis

This systematic review and meta‑analysis of 214 studies (3,504 participants with analysable adverse‑event data) found that high‑dose classic psychedelics were generally well tolerated in clinical/research settings, with serious adverse events occurring mainly in ~4% of participants who had preexisting neuropsychiatric disorders and no reports in contemporary trials of suicide, persistent psychotic disorder or hallucinogen‑persisting perception disorder. Common non‑serious adverse events (headache, anxiety, nausea, fatigue, dizziness) had similar prevalences for psilocybin and LSD, but substantial heterogeneity and limited systematic adverse‑event monitoring across studies highlight the need for improved pharmacovigilance.

Published
December 1, 2024
Journal
JAMA Psychiatry
Authors
Hinkle, J. T., Graziosi, M., Nayak, S., Yaden, D. B.
Open Accessmeta

Reconsidering evidence for psychedelic-induced psychosis: an overview of reviews, a systematic review, and meta-analysis of human studies

This systematic review (2024) and meta-analysis (s=131) examines the incidence of psychedelic-induced psychosis, focusing on individuals with schizophrenia. It finds an incidence of 0.002% in population studies, 0.2% in UCTs, and 0.6% in RCTs, with 3.8% of UCT participants with schizophrenia developing long-lasting psychotic symptoms. It also reports that 13.1% of those with psychedelic-induced psychosis later developed schizophrenia.

Published
November 27, 2024
Journal
Molecular Psychiatry
Authors
Sabé, M., Sulstarova, A., Glangetas, A., De Pieri, M., Mallet, L., Curtis, L., Richard-Lepouriel, H., Penzenstadler, L., Seragnoli, F., Thorens, G., Zullino, D., Preller, K., Böge, K., Leucht, S., Correll, C. U., Solmi, M., Kaiser, S., Kirschner, M.
Open Accessindividual

Inter-individual variability in neural response to low doses of LSD

In a placebo-controlled trial of repeated low-dose LSD (N = 53), acute effects included reduced resting EEG delta/theta/alpha power and enhanced pre-attentive processing, plus blunted visual LTP after repeated dosing, and these effects depended on baseline cognitive state — stimulatory effects were largest in participants with low baseline arousal/attention while inhibitory effects were greatest in high memory performers. Decreases in delta power and enhanced pre-attentive processing persisted at 1-week follow-up, suggesting short-term neuroadaptations beyond treatment.

Published
July 15, 2024
Journal
Translational Psychiatry
Authors
Hutten, N. R. P. W., Quaedflieg, C. W. E. M., Mason, N. L., Theunissen, E. L., Liechti, M. E., Duthaler, U., Kuypers, K. P. C., Bonnelle, V., Feilding, A., Ramaekers, J. G.

Clinical Trials

3 trials
Completed

Single Oral Lysergide (LSD 500 µg) in Inpatient Alcoholic Rehabilitation: Controlled Evaluation with Schizophrenic Sub-Analysis (Tomsovic & Edwards 1970)

This unregistered trial (n=75) was a partially randomised, placebo-controlled evaluation of a single 500 µg oral dose of LSD for alcohol use disorder in an inpatient rehabilitation setting, which found higher abstinence rates in non-schizophrenic participants at one year.

Started
January 1, 1966
Type
interventional
Blinding
single
Randomized
Yes
Registry ID
TOMSOVIC-1970-QJSTUDIALCOHOL-LYSERGIDE-ALCOHOLICS
Completed

LSD-25 in Autistic Schizophrenic Children: An Open Observational Study (Freedman 1962)

Open, observational study (Archives of General Psychiatry, March 1962; Freedman AM, Ebin EV, Wilson EA) at a day school for children with schizophrenia. From a total school population of 40, 12 well-known pupils were selected who met the authors' criteria for autistic schizophrenia: 10 boys and 2 girls aged 5 years 11 months to 11 years 10 months; 7 were essentially mute and the other 5 used words or phrases only occasionally. No control arm or randomisation. Intervention: d-lysergic acid diethylamide (LSD-25) administered in an open exploratory design; dose details and session structure not fully described in available methods extract. Outcomes: behavioural and developmental observations at the day school. No trial registry; pre-dates any formal registration requirement.

Started
January 1, 1960
Type
interventional
Randomized
No
Registry ID
FREEDMAN-1962-ARCHPSYC-LSD-AUTISTIC-CHILDREN
CompletedPhase NA

Clinical Studies of Lysergic Acid Diethylamide

Open-label phenomenological characterization study of LSD effects in 23 subjects (4 normal staff volunteers and 19 psychiatric inpatients) at the University of Manchester, UK. A total of 58 oral LSD administrations were given across a wide dose range (10–600 µg). The study documents perceptual, mood, ego, cognitive, and autonomic effects; 6 subjects showed prolonged clinical changes.

Started
January 1, 1952
Type
interventional
Blinding
none
Randomized
No

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