{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T23:33:11Z","timestamp":1793403191767,"version":"4.5.0"},"reference-count":43,"publisher":"American Medical Association (AMA)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Psychiatry"],"published-print":{"date-parts":[[2025,6,1]]},"abstract":"\n Importance<\/jats:title>\n Microdosing psychedelics, including lysergic acid diethylamide (LSD), has gained attention for its potential benefits in several psychiatric disorders, including attention-deficit\/hyperactivity disorder (ADHD). However, LSD\u2019s efficacy in reducing ADHD symptoms remains unknown.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To determine the safety and efficacy of repeated low doses of LSD in reducing ADHD symptoms compared with placebo.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This was a 6-week, multicenter, double-blind, placebo-controlled, parallel-group phase 2A randomized clinical trial conducted between December 17, 2021, and December 4, 2023. Data were analyzed from March 22, 2024, to August 19, 2024. Outpatient treatment was provided at 2 centers: University Hospital in Basel, Switzerland, and Maastricht University in the Netherlands. Adults aged 18 to 65 years with a prior ADHD diagnosis who presented with moderate to severe symptoms (Adult Investigator Symptom Rating Scale [AISRS] score \u226526 and Clinical Global Impression Severity score \u22654) were eligible for inclusion. Key exclusion criteria included selected current major psychiatric or somatic disorders and the use of potentially interacting medications.<\/jats:p>\n <\/jats:sec>\n \n Intervention<\/jats:title>\n Participants received either LSD (20 \u03bcg) or placebo twice weekly for 6 weeks (total of 12 doses).<\/jats:p>\n <\/jats:sec>\n \n Main Outcome and Measures<\/jats:title>\n The primary outcome was the change in ADHD symptoms from baseline to week 6, assessed by the AISRS and analyzed with a mixed-effects model for repeated measures.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n A total of 53 participants were randomized to LSD (n\u2009=\u200927) or placebo (n\u2009=\u200926). Mean (SD) participant age was 37 (12) years, and 22 participants (42%) were female. The LSD group presented a mean AISRS improvement of \u22127.1 points (95% CI, \u221210.1 to \u22124.0). The placebo group presented a mean AISRS improvement of \u22128.9 points (95% CI, \u221212.0 to \u22125.8), with no difference between groups. LSD was physically safe and psychologically well tolerated overall.<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n In this randomized clinical trial, repeated low-dose LSD administration was safe in an outpatient setting, but it was not more efficacious than placebo in reducing ADHD symptoms.<\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ClinicalTrials.gov Identifier:\n NCT05200936<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamapsychiatry.2025.0044","type":"journal-article","created":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T11:36:52Z","timestamp":1742384212000},"page":"555","source":"Crossref","is-referenced-by-count":22,"title":["Safety and Efficacy of Repeated Low-Dose LSD for ADHD Treatment in Adults"],"prefix":"10.1001","volume":"82","author":[{"given":"Lorenz","family":"Mueller","sequence":"first","affiliation":[{"name":"Division of Clinical Pharmacology and Toxicology, University Hospital Basel, Basel, Switzerland"},{"name":"Department of Clinical Research, University of Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce","family":"Santos de Jesus","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology and Toxicology, University Hospital Basel, Basel, Switzerland"},{"name":"Department of Clinical Research, University of Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasmin","family":"Schmid","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology and Toxicology, University Hospital Basel, Basel, Switzerland"},{"name":"Department of Clinical Research, University of Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology and Toxicology, University Hospital Basel, Basel, Switzerland"},{"name":"Department of Clinical Research, University of Basel, Basel, Switzerland"},{"name":"University Psychiatric Clinic Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Becker","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology and Toxicology, University Hospital Basel, Basel, Switzerland"},{"name":"Department of Clinical Research, University of Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Klaiber","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology and Toxicology, University Hospital Basel, Basel, Switzerland"},{"name":"Department of Clinical Research, University of Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Straumann","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology and Toxicology, University Hospital Basel, Basel, Switzerland"},{"name":"Department of Clinical Research, University of Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dino","family":"Luethi","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology and Toxicology, University Hospital Basel, Basel, Switzerland"},{"name":"Department of Clinical Research, University of Basel, Basel, Switzerland"},{"name":"Department of Biomedicine, University of Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eline C. H. M.","family":"Haijen","sequence":"additional","affiliation":[{"name":"Department of Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra P. M.","family":"Hurks","sequence":"additional","affiliation":[{"name":"Department of Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim P. C.","family":"Kuypers","sequence":"additional","affiliation":[{"name":"Department of Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias E.","family":"Liechti","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology and Toxicology, University Hospital Basel, Basel, Switzerland"},{"name":"Department of Clinical Research, University of Basel, Basel, Switzerland"},{"name":"Department of Biomedicine, University of Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"key":"yoi250003r1","doi-asserted-by":"publisher","first-page":"04009","DOI":"10.7189\/jogh.11.04009","article-title":"The prevalence of adult attention-deficit hyperactivity disorder: a global systematic review and meta-analysis.","volume":"11","author":"Song","year":"2021","journal-title":"J Glob Health"},{"issue":"4","key":"yoi250003r2","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1176\/ajp.2006.163.4.716","article-title":"The prevalence and correlates of adult ADHD in the United States: results from the National Comorbidity Survey Replication.","volume":"163","author":"Kessler","year":"2006","journal-title":"Am J Psychiatry"},{"key":"yoi250003r3","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.eurpsy.2018.11.001","article-title":"Updated European Consensus Statement on diagnosis and treatment of adult ADHD.","volume":"56","author":"Kooij","year":"2019","journal-title":"Eur Psychiatry"},{"issue":"2","key":"yoi250003r4","doi-asserted-by":"publisher","first-page":"66","DOI":"10.4103\/TPSY.TPSY_14_19","article-title":"Treatment-resistant attention-deficit hyperactivity disorder: clinical significance, concept, and management.","volume":"33","author":"Chen","year":"2019","journal-title":"Taiwanese J Psychiatry."},{"issue":"9","key":"yoi250003r5","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1016\/S2215-0366(18)30269-4","article-title":"Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis.","volume":"5","author":"Cortese","year":"2018","journal-title":"Lancet Psychiatry"},{"issue":"3","key":"yoi250003r6","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1007\/s00228-012-1390-7","article-title":"Treatment discontinuation with methylphenidate in adults with attention deficit hyperactivity disorder: a meta-analysis of randomized clinical trials.","volume":"69","author":"Castells","year":"2013","journal-title":"Eur J Clin Pharmacol"},{"issue":"4","key":"yoi250003r7","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1097\/JCP.0000000000000917","article-title":"Long-term tolerability and safety of pharmacological treatment of adult attention-deficit\/hyperactivity disorder: a 6-year prospective naturalistic study.","volume":"38","author":"Edvinsson","year":"2018","journal-title":"J Clin Psychopharmacol"},{"issue":"2","key":"yoi250003r8","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1080\/02791072.2019.1593561","article-title":"Might microdosing psychedelics be safe and beneficial? an initial exploration.","volume":"51","author":"Fadiman","year":"2019","journal-title":"J Psychoactive Drugs"},{"key":"yoi250003r10","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugpo.2019.11.008","article-title":"Microdosing psychedelics: motivations, subjective effects and harm reduction.","volume":"75","author":"Lea","year":"2020","journal-title":"Int J Drug Policy"},{"issue":"2","key":"yoi250003r11","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1080\/02791072.2020.1718250","article-title":"Psychedelic microdosing: prevalence and subjective effects.","volume":"52","author":"Cameron","year":"2020","journal-title":"J Psychoactive Drugs"},{"issue":"9","key":"yoi250003r12","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.1177\/0269881119857204","article-title":"Microdosing psychedelics: more questions than answers? an overview and suggestions for future research.","volume":"33","author":"Kuypers","year":"2019","journal-title":"J Psychopharmacol"},{"issue":"5","key":"yoi250003r13","doi-asserted-by":"publisher","first-page":"1521","DOI":"10.1007\/s00213-020-05477-0","article-title":"Perceived outcomes of psychedelic microdosing as self-managed therapies for mental and substance use disorders.","volume":"237","author":"Lea","year":"2020","journal-title":"Psychopharmacology (Berl)"},{"key":"yoi250003r14","doi-asserted-by":"publisher","DOI":"10.1016\/j.nsa.2022.101012","article-title":"Microdosing with psychedelics to self-medicate for ADHD symptoms in adults: a prospective naturalistic study.","volume":"1","author":"Haijen","year":"2022","journal-title":"Neurosci Applied"},{"key":"yoi250003r15","doi-asserted-by":"publisher","first-page":"672","DOI":"10.3389\/fpsyt.2019.00672","article-title":"Self-rated effectiveness of microdosing with psychedelics for mental and physical health problems among microdosers.","volume":"10","author":"Hutten","year":"2019","journal-title":"Front Psychiatry"},{"issue":"5","key":"yoi250003r16","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1016\/j.bpsc.2024.01.002","article-title":"Microdosing psychedelics: current evidence from controlled studies.","volume":"9","author":"Murphy","year":"2024","journal-title":"Biol Psychiatry Cogn Neurosci Neuroimaging"},{"issue":"1","key":"yoi250003r17","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1177\/1087054709347435","article-title":"Validation of the adult ADHD Investigator Symptom Rating Scale (AISRS).","volume":"14","author":"Spencer","year":"2010","journal-title":"J Atten Disord"},{"key":"yoi250003r19","first-page":"22","article-title":"The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10.","volume":"59","author":"Sheehan","year":"1998","journal-title":"J Clin Psychiatry"},{"issue":"12","key":"yoi250003r20","doi-asserted-by":"publisher","first-page":"1266","DOI":"10.1176\/appi.ajp.2011.10111704","article-title":"The Columbia-Suicide Severity Rating Scale: initial validity and internal consistency findings from three multisite studies with adolescents and adults.","volume":"168","author":"Posner","year":"2011","journal-title":"Am J Psychiatry"},{"issue":"3","key":"yoi250003r22","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1080\/10401230600801077","article-title":"Validity of pilot Adult ADHD Self- Report Scale (ASRS) to rate adult ADHD symptoms.","volume":"18","author":"Adler","year":"2006","journal-title":"Ann Clin Psychiatry"},{"key":"yoi250003r23","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1055\/s-2007-979351","article-title":"The standardized psychometric assessment of altered states of consciousness (ASCs) in humans.","volume":"31","author":"Dittrich","year":"1998","journal-title":"Pharmacopsychiatry"},{"issue":"8","key":"yoi250003r24","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0012412","article-title":"Psychometric evaluation of the altered states of consciousness rating scale (OAV).","volume":"5","author":"Studerus","year":"2010","journal-title":"PLoS One"},{"issue":"4","key":"yoi250003r25","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1111\/j.1468-5906.2012.01685.x","article-title":"Factor analysis of the Mystical Experience Questionnaire: a study of experiences occasioned by the hallucinogen psilocybin.","volume":"51","author":"Maclean","year":"2012","journal-title":"J Sci Study Relig"},{"issue":"6","key":"yoi250003r28","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1016\/j.biopsych.2023.03.013","article-title":"Acute mood-elevating properties of microdosed lysergic acid diethylamide in healthy volunteers: a home-administered randomized controlled trial.","volume":"94","author":"Murphy","year":"2023","journal-title":"Biol Psychiatry"},{"issue":"3","key":"yoi250003r29","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1002\/cpt.2057","article-title":"Pharmacokinetics and pharmacodynamics of lysergic acid diethylamide microdoses in healthy participants.","volume":"109","author":"Holze","year":"2021","journal-title":"Clin Pharmacol Ther"},{"issue":"3","key":"yoi250003r30","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1038\/s41386-020-00883-6","article-title":"Acute dose-dependent effects of lysergic acid diethylamide in a double-blind placebo-controlled study in healthy subjects.","volume":"46","author":"Holze","year":"2021","journal-title":"Neuropsychopharmacology"},{"issue":"3","key":"yoi250003r31","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1007\/s00213-019-05417-7","article-title":"Safety, tolerability, pharmacokinetics, and pharmacodynamics of low dose lysergic acid diethylamide (LSD) in healthy older volunteers.","volume":"237","author":"Family","year":"2020","journal-title":"Psychopharmacology (Berl)"},{"issue":"2","key":"yoi250003r32","doi-asserted-by":"publisher","DOI":"10.1111\/adb.13143","article-title":"Repeated low doses of LSD in healthy adults: a placebo-controlled, dose-response study.","volume":"27","author":"de Wit","year":"2022","journal-title":"Addict Biol"},{"issue":"10","key":"yoi250003r33","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1016\/j.biopsych.2019.05.019","article-title":"Acute subjective and behavioral effects of microdoses of lysergic acid diethylamide in healthy human volunteers.","volume":"86","author":"Bershad","year":"2019","journal-title":"Biol Psychiatry"},{"issue":"5","key":"yoi250003r34","doi-asserted-by":"publisher","first-page":"774","DOI":"10.1038\/s41386-023-01772-4","article-title":"Greater subjective effects of a low dose of LSD in participants with depressed mood.","volume":"49","author":"Molla","year":"2024","journal-title":"Neuropsychopharmacology"},{"key":"yoi250003r35","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.euroneuro.2020.10.002","article-title":"Mood and cognition after administration of low LSD doses in healthy volunteers: a placebo controlled dose-effect finding study.","volume":"41","author":"Hutten","year":"2020","journal-title":"Eur Neuropsychopharmacol"},{"issue":"5","key":"yoi250003r36","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1016\/j.biopsych.2004.11.043","article-title":"A large, double-blind, randomized clinical trial of methylphenidate in the treatment of adults with attention-deficit\/hyperactivity disorder.","volume":"57","author":"Spencer","year":"2005","journal-title":"Biol Psychiatry"},{"issue":"2","key":"yoi250003r37","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1016\/S0006-3223(02)01671-2","article-title":"Atomoxetine in adults with ADHD: two randomized, placebo-controlled studies.","volume":"53","author":"Michelson","year":"2003","journal-title":"Biol Psychiatry"},{"issue":"8","key":"yoi250003r38","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1001\/jamapsychiatry.2024.0994","article-title":"Differential outcomes of placebo treatment across 9 psychiatric disorders: a systematic review and meta-analysis.","volume":"81","author":"Bschor","year":"2024","journal-title":"JAMA Psychiatry"},{"issue":"1","key":"yoi250003r39","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1093\/ijnp\/pyab054","article-title":"Placebo response and its predictors in attention deficit hyperactivity disorder: a meta-analysis and comparison of meta-regression and MetaForest.","volume":"25","author":"Castells","year":"2022","journal-title":"Int J Neuropsychopharmacol"},{"issue":"3","key":"yoi250003r40","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1177\/1087054718780328","article-title":"Characterizing the placebo response in adults with ADHD.","volume":"24","author":"Ben-Sheetrit","year":"2020","journal-title":"J Atten Disord"},{"issue":"12","key":"yoi250003r41","doi-asserted-by":"publisher","first-page":"3915","DOI":"10.1038\/s41380-024-02638-x","article-title":"Placebo effects in randomized trials of pharmacological and neurostimulation interventions for mental disorders: an umbrella review.","volume":"29","author":"Huneke","year":"2024","journal-title":"Mol Psychiatry"},{"key":"yoi250003r42","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.62878","article-title":"Self-blinding citizen science to explore psychedelic microdosing.","volume":"10","author":"Szigeti","year":"2021","journal-title":"Elife"},{"issue":"1","key":"yoi250003r43","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1186\/s40814-023-01399-8","article-title":"An open-label pilot trial assessing tolerability and feasibility of LSD microdosing in patients with major depressive disorder (LSDDEP1).","volume":"9","author":"Donegan","year":"2023","journal-title":"Pilot Feasibility Stud"},{"key":"yoi250003r9","volume-title":"The Science of Microdosing Psychedelics","author":"Passie","year":"2019"},{"key":"yoi250003r18","volume-title":"ECDEU Assessment Manual for Psychopharmacology","author":"Guy","year":"1976"},{"key":"yoi250003r21","volume-title":"Conners\u2019 Adult ADHD Rating Scale (CAARS)","author":"Conners","year":"1999"},{"key":"yoi250003r26","unstructured":"mmrm: Mixed Models for Repeated Measures. The Comprehensive R Network. Accessed September 26, 2024. https:\/\/cran.r-project.org\/web\/packages\/mmrm\/index.html"},{"key":"yoi250003r27","unstructured":"rbmi: Reference Based Multiple Imputation. The Comprehensive R Network. Accessed September 26, 2024. https:\/\/cran.r-project.org\/web\/packages\/rbmi\/rbmi.pdf"}],"container-title":["JAMA Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamapsychiatry\/articlepdf\/2831639\/jamapsychiatry_mueller_2025_oi_250003_1747773874.62143.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T11:00:39Z","timestamp":1749034839000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamapsychiatry\/fullarticle\/2831639"}},"subtitle":["A Randomized Clinical Trial"],"short-title":[],"issued":{"date-parts":[[2025,6,1]]},"references-count":43,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,6,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamapsychiatry.2025.0044","relation":{},"ISSN":["2168-622X"],"issn-type":[{"value":"2168-622X","type":"print"}],"subject":[],"published":{"date-parts":[[2025,6,1]]}}}