Microdosing LSD and Psilocybin: The Placebo-Controlled Evidence

Short answer

Microdosing means repeated, sub-hallucinogenic doses of LSD or psilocybin. In placebo-controlled trials it has not beaten placebo for ADHD symptoms, depression, mood or cognition. A 2025 JAMA Psychiatry trial of 20 μg LSD in 53 adults with ADHD was null, three psilocybin trials were null, and a 60% depression-score drop in an open-label LSD study vanished in the controlled phase 2b trial (sponsor-reported). Microdoses do have measurable acute effects; they have not produced a clinical benefit.

Summary drafted from this entry’s sources; editorial review pending.

01Key questions

Does microdosing help ADHD?

Not in the only randomized trial. Adults with ADHD on 20 μg LSD twice a week for six weeks improved by 7.1 points on the AISRS, and those on placebo by 8.9 points, with no difference between groups. A 2026 systematic review concluded the evidence does not support psychedelics for ADHD.¹⁴

Does microdosing work for depression?

An open-label LSD study reported a 59.5% drop in depression scores, but it had no control group. The controlled phase 2b trial in 89 patients found no effect of LSD versus an active placebo (sponsor topline, November 2025; not yet peer-reviewed). Psilocybin microdosing trials also found no benefit on anxiety and depression symptoms versus placebo.⁸⁹⁶

Is microdosing just a placebo?

The controlled studies found no reliable advantage over placebo for the outcomes tested. They do not explain every person's reported improvement. In the largest placebo-controlled study, microdosers and placebo takers improved equally on well-being and mood. Low doses do cause measurable acute changes versus placebo, so the drug is not inert, but those effects have not added up to a clinical benefit.⁵¹⁰⁷

Is microdosing safe?

In screened adults in trials, low-dose LSD was well tolerated, and an eight-week heart-valve check in 19 people found no changes. People with major psychiatric or medical conditions were excluded, the studies were short, and street products are not dose-standardized.¹⁸

What would change this rating?

A peer-reviewed placebo-controlled trial showing a clinically meaningful benefit for ADHD, depression or cognition, with blinding checked.

Microdosing means taking repeated doses of LSD or psilocybin too small to cause a trip, usually a few times a week. On social media it is sold as a focus tool, an ADHD treatment and a mood fix. Since 2021, those claims have been tested in placebo-controlled trials lasting weeks. For ADHD symptoms, depression, mood and cognition, microdosing did no better than placebo. People taking placebo improved just as much.

That is a result about microdosing only. Full-dose psilocybin and MDMA given with psychotherapy are a different intervention with different results, covered on psychedelic-assisted therapy. LSD and psilocybin are controlled substances in most countries.

Not medical advice. The doses mentioned are the ones used in the cited trials, not a schedule.

02ADHD: the first real trial was null

Mueller et al. 2025, JAMA Psychiatry (PMID 40105807; NCT05200936). A phase 2A, double-blind, placebo-controlled trial at Basel and Maastricht. 53 adults with diagnosed, moderate-to-severe ADHD got 20 μg LSD or placebo twice a week for six weeks. The primary outcome was clinician-rated ADHD symptoms (AISRS):

LSD: −7.1 points (95% CI −10.1 to −4.0)
Placebo: −8.9 points (95% CI −12.0 to −5.8)
No difference between groups. On the point estimate, placebo did slightly better.

LSD was physically safe and psychologically well tolerated in this screened outpatient group. One author reported funding from Mind Medicine, the company developing LSD (MM120), during the study. Industry-linked trials tend to err toward positive results, which makes this null harder to dismiss. Liechti also disclosed consulting fees and grants from Mind Medicine outside this study.

Same trial, cognitive tests. Haijen-Bongers et al. 2026, Psychopharmacology (PMID 42322409). In the 46 completers, LSD changed one time-perception task (time reproduction). Attention, inhibition and motivation tasks did not change. The authors say this is not convincing evidence of a broad cognitive benefit.

2026 systematic review. Chmiel, Malinowska and Kurpas, Int J Mol Sci (PMID 42074098). Five studies in adults with ADHD: three online cohorts of self-selected microdosers, the Mueller trial and one ayahuasca retreat pilot. The online cohorts reported drops in ADHD ratings, but the review calls them highly vulnerable to self-selection, expectancy and drop-out. Its conclusion: the evidence does not support psychedelics as an ADHD treatment.

03Mood and depression

Self-blinding citizen-science trial. Szigeti et al. 2021, eLife (PMID 33648632). Microdosers mixed their own doses with placebo capsules using online instructions, without knowing which they took. 191 people completed four weeks. Well-being, mood and life-satisfaction scores improved in both groups, with no difference between them. Small acute differences on dosing days were explained by people guessing which capsule they had. The authors conclude that the anecdotal benefits can be explained by the placebo effect.

Psilocybin crossover. Marschall et al. 2022, J Psychopharmacol (PMID 34915762). Preregistered, double-blind, placebo-controlled. Psilocybin microdoses did not change emotion processing or anxiety and depression symptoms compared with placebo. Participants broke blind in the second block.

Psilocybin truffles, two trials. Prochazkova et al. 2026, Neuropharmacology (PMID 41110634). Two randomized, double-blind, placebo-controlled trials in everyday settings tested memory, cognitive control, social cognition and well-being. Nothing beat placebo after correction for multiple comparisons. Here blinding held, and unpleasant bodily feelings were more common on the active doses.

LSD for major depression: big open-label drop, then a null controlled trial.

LSDDEP1, Daldegan-Bueno et al. 2026 (PMID 41202873; ACTRN12623000486628). 19 people with depression, most already on an antidepressant, took 16 doses of 6–20 μg over eight weeks. Depression scores (MADRS) fell 59.5%, and no serious adverse events occurred, including on heart-valve checks. There was no control group. MindBio Therapeutics, which develops the LSD product, supported the trial.
LSDDEP2 (protocol PMID 39182140; ACTRN12624000128594) was the controlled follow-up: randomized, triple-blind, with caffeine as an active placebo. In November 2025 the sponsor reported topline results for 89 patients: MADRS fell 36.4% on placebo and 29.9% on LSD, with no effect of the drug (p=0.55). Its own conclusion was that repeated microdosed LSD is not effective for major depression. This is a company release and not yet a peer-reviewed paper.

The open-label 60% drop next to the controlled null is the clearest lesson in this field. The controlled trial found no advantage over placebo; it did not measure how much improvement came from expectation, attention or time.

04Is it all placebo?

Not quite. Polito and Liknaitzky's 2024 review (J Psychopharmacol, PMID 38877715) counted 19 placebo-controlled studies. Low doses do produce measurable acute changes against placebo in brain activity, physiology, mood and perception. The authors argued the "just placebo" verdict was premature: the trials were small, used few doses and mostly studied healthy volunteers. The ADHD, psilocybin and depression trials published since then addressed several of those gaps. The drug does something acutely, but that has not translated into a measurable benefit for ADHD, depression or cognition.

05Claims against the evidence

Claim	What the evidence shows
Microdosing treats adult ADHD	Not supported. The only randomized trial was null, and placebo did slightly better (PMID 40105807).
Microdosing sharpens focus and cognition	Not supported. Cognitive batteries in the ADHD trial and the psilocybin trials were null apart from one time-perception task (PMID 42322409, 41110634).
Microdosing treats depression	Not supported. A large open-label drop disappeared in the controlled phase 2b trial (PMID 41202873; sponsor topline, 2025).
Microdosers feel better	True, and so do people taking placebo who think they might be microdosing (PMID 33648632).
Microdoses do nothing at all	Not true. Acute effects versus placebo are measurable (PMID 38877715). They just have not produced a clinical benefit.

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06Safety

In the controlled trials, low-dose LSD was well tolerated in screened adults. People with major psychiatric or medical conditions and those on interacting medicines were excluded, so the safety data do not cover them.
The LSDDEP1 heart checks (ECG and echocardiography) found no valve changes over eight weeks in 19 people. That is too small and too short to rule out rare harms with long-term use.
Anxiety on dosing days led one LSDDEP1 participant to withdraw. Unpleasant bodily feelings were more common on active psilocybin doses.
Street products are unmeasured. Trial doses were standardized, and illicit blotters and mushrooms are not.

07What would change this rating

A peer-reviewed, placebo-controlled trial showing a clinically meaningful benefit for ADHD, depression or cognition, with blinding checked. As of October 2026 no controlled trial shows that, and the two largest trials designed to find it came out null: ADHD (published) and depression (sponsor-reported).

08Who paid, and how it got here

Who funded the key studies on this page, the favourable and the unfavourable alike, and how its legal status came about. From each paper’s funding and conflict-of-interest statements, trial registries and official documents; checked 1 Nov 2026. Why we show this

How it got here

LSD and psilocybin are Schedule I substances under US federal law. Szigeti and colleagues described restrictive drug policies as making conventional microdosing trials difficult and expensive, which motivated their low-cost self-blinding study. DEA: LSD DEA: psilocybin Szigeti study

Who paid for the key studies

Mueller 2025, placebo-controlled ADHD RCT, n=53ADHD symptom improvement did not exceed placebo.Funding and interests: Mind Medicine funded Mueller during the study; Liechti reported outside consulting and grants from Mind Medicine; Kuypers reported outside Clerkenwell support. Conflict-of-interest statement
LSDDEP1, open-label depression trial, n=19Depression scores fell 59.5%; no control group.Funding and interests: Health Research Council of New Zealand (public funding) and MindBio Therapeutics provided financial and material support. Conflict-of-interest statement
Szigeti 2021, self-blinding placebo-controlled study, n=191 completersWell-being improved similarly with microdoses and placebo.Funding and interests: No external funding reported. Paper's funding statement
Polito and Liknaitzky 2024, rapid review, 19 controlled studiesAcute effects detected; authors disputed an exclusively placebo explanation.Funding and interests: Polito disclosed Mydecine/Woke funding; Liknaitzky disclosed Incannex/MAPS/Beckley funding and Incannex/MIND advisory roles. Conflict-of-interest statement
Polito and Liknaitzky 2024, rapid review, 19 controlled studies; paper fundingAcute effects detected; authors disputed an exclusively placebo explanation.Funding and interests: No financial support for this review reported. Paper's funding statement

What studies and practitioners report

Amounts as reported in the cited sources: trial doses with the population studied, and practitioner-reported ranges marked as such. Not medical advice.

Trial 20 μg LSD, twice weekly for 6 weeks · LSD, ADHD trial (no benefit over placebo) adults with ADHD, n=53 PMID 40105807
Trial 6–20 μg LSD, 16 doses over 8 weeks · LSD, open-label depression study (no control group) adults with major depression, n=19 PMID 41202873
Trial 4–20 μg LSD, 16 doses over 8 weeks · LSD, controlled phase 2b depression trial (null, sponsor topline) adults with major depression, n=89 PMID 39182140 (protocol)

09Connections

Neighborhood · 3 linked entriesOpen full map →

10Sources

Mueller L, et al. Safety and Efficacy of Repeated Low-Dose LSD for ADHD Treatment in Adults: A Randomized Clinical Trial. JAMA Psychiatry. 2025;82(6):555-562. PMID 40105807 .PubMed 40105807
NCT05200936NCT05200936
Haijen-Bongers ECHM, et al. Effects of repeated low-dose LSD on neuropsychological functioning in adults with ADHD: a randomized placebo-controlled study. Psychopharmacology. 2026. PMID 42322409 .PubMed 42322409
Chmiel J, Malinowska A, Kurpas D. The Use of Psychedelics in the Treatment of Adult ADHD: A Systematic and Mechanistic Review. Int J Mol Sci. 2026;27(8):3453. PMID 42074098 .PubMed 42074098
Szigeti B, et al. Self-blinding citizen science to explore psychedelic microdosing. eLife. 2021;10:e62878. PMID 33648632 .PubMed 33648632
Marschall J, et al. Psilocybin microdosing does not affect emotion-related symptoms and processing. J Psychopharmacol. 2022;36(1):97-113. PMID 34915762 .PubMed 34915762
Prochazkova L, et al. Cognitive and subjective effects of psilocybin microdosing: Results from two double-blind placebo-controlled longitudinal trials. Neuropharmacology. 2026;283:110722. PMID 41110634 .PubMed 41110634
Daldegan-Bueno D, et al. LSD microdosing in major depressive disorder: results from an open-label trial. Neuropharmacology. 2026;283:110762. PMID 41202873 .PubMed 41202873
Daldegan-Bueno D, et al. LSDDEP2: study protocol for a randomised, double-dummy, triple-blind, active placebo-controlled trial of LSD microdosing in major depressive disorder. Trials. 2024;25:560. PMID 39182140 .PubMed 39182140
Polito V, Liknaitzky P. Is microdosing a placebo? A rapid review of low-dose LSD and psilocybin research. J Psychopharmacol. 2024;38(8):701-711. PMID 38877715 .PubMed 38877715
Daldegan-Bueno D, et al. LSD microdosing for major depressive disorder: Mood and pharmacokinetic outcomes from a Phase 2a trial. Prog Neuropsychopharmacol Biol Psychiatry. 2026;145:111645. PMID 41713673 .PubMed 41713673

11Entry history

1 Nov 2026

Psychedelic microdosing