Safety and Efficacy of Repeated Low-Dose LSD for ADHD Treatment in Adults A Randomized Clinical Trial
In a 6‑week, multicentre, double‑blind randomised phase 2A trial of 53 adults with moderate–severe ADHD, twice‑weekly low‑dose LSD (20 μg) was physically safe and psychologically well tolerated. However, LSD did not reduce ADHD symptoms more than placebo on the AISRS.
Authors
- Yasmin Schmid
- Felix Müller
- Matthias Liechti
Published
Abstract
Importance
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’s efficacy in reducing ADHD symptoms remains unknown.
Objective
To determine the safety and efficacy of repeated low doses of LSD in reducing ADHD symptoms compared with placebo.
Design, Setting, and Participants
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 ≥26 and Clinical Global Impression Severity score ≥4) were eligible for inclusion. Key exclusion criteria included selected current major psychiatric or somatic disorders and the use of potentially interacting medications.
Intervention
Participants received either LSD (20 μg) or placebo twice weekly for 6 weeks (total of 12 doses).
Main Outcome and Measures
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.
Results
A total of 53 participants were randomized to LSD (n = 27) or placebo (n = 26). Mean (SD) participant age was 37 (12) years, and 22 participants (42%) were female. The LSD group presented a mean AISRS improvement of −7.1 points (95% CI, −10.1 to −4.0). The placebo group presented a mean AISRS improvement of −8.9 points (95% CI, −12.0 to −5.8), with no difference between groups. LSD was physically safe and psychologically well tolerated overall.
Conclusions and Relevance
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.
Research Summary of 'Safety and Efficacy of Repeated Low-Dose LSD for ADHD Treatment in Adults A Randomized Clinical Trial'
Introduction
Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental condition in adults, characterised by inattention and/or hyperactivity–impulsivity and associated with substantial functional impairment and frequent psychiatric comorbidity. Standard pharmacotherapies—stimulants (eg, methylphenidate, amphetamines) and nonstimulants (eg, atomoxetine)—are effective for many patients but leave approximately 20% to 40% with an inadequate response and face problems with adverse effects and long‑term adherence. In parallel, microdosing of psychedelics such as LSD has gained popular and scientific interest, with surveys and naturalistic studies reporting perceived benefits for mood, cognition, and self‑treatment of disorders including ADHD, but randomised clinical evidence in patient populations is lacking. Mueller and colleagues therefore undertook a multicentre, double‑blind, placebo‑controlled Phase 2A randomised clinical trial to test whether repeated low doses of LSD reduce ADHD symptoms in adults with moderate to severe ADHD. The intervention was a 20 μg LSD dose administered twice weekly for 6 weeks (12 doses total); the primary aim was to compare change in ADHD symptoms (observer‑rated AISRS) from baseline to week 6 versus placebo, while also assessing safety, pharmacokinetics, acute subjective effects, and blinding.
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Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
- Authors
- APA Citation
Mueller, L., Santos de Jesus, J., Schmid, Y., Müller, F., Becker, A., Klaiber, A., Straumann, I., Luethi, D., Haijen, E. C. H. M., Hurks, P. P. M., Kuypers, K. P. C., & Liechti, M. E. (2025). Safety and Efficacy of Repeated Low-Dose LSD for ADHD Treatment in Adults A Randomized Clinical Trial. JAMA Psychiatry, 82(6), 555. https://doi.org/10.1001/jamapsychiatry.2025.0044
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