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Microdosing LSD for ADHD: Hype, hope, and the power of placebo: results from a randomised controlled trial
Published:
April 8, 2025
Updated:
Time to read:
7 MIN
Table of Contents
Odyssey Take
This landmark trial disrupts the narrative surrounding psychedelic microdosing by showing that, despite widespread anecdotal enthusiasm and promising observational data, low-dose LSD offers no measurable clinical benefit for ADHD. While well-tolerated physically, the intervention failed to outperform placebo across all efficacy metrics. The robust improvements in both groups—coupled with high rates of guessed treatment allocation—highlight expectancy as a likely driver. These findings underscore the importance of placebo-controlled designs in psychedelic research and raise important questions about the therapeutic validity and functional practicality of microdosing, especially when even “sub-perceptual” doses can elicit noticeable effects.
Title: Safety and Efficacy of Repeated Low-Dose LSD for ADHD Treatment in Adults: A Randomized Clinical Trial
Summary
A phase 2A double-blind, placebo-controlled trial published in the prestigious journal Jama Psychiatry tested whether twice-weekly low-dose LSD (20 μg) over six weeks could reduce ADHD symptoms in adults. The rationale was based on growing interest in psychedelic microdosing for mental health, including self-reported improvements in attention, emotional regulation, and productivity. Observational studies and surveys had suggested potential benefits of LSD microdosing for ADHD, but no controlled trials had been conducted until now. In this study, both LSD and placebo groups showed significant symptom reduction, but LSD did not outperform placebo. Still, the treatment was physically safe and well tolerated.
What was the goal?
The study aimed to answer:
- Can repeated low-dose LSD reduce ADHD symptoms in adults with moderate-to-severe ADHD?
- Is microdosing LSD safe and tolerable in this population?
- How do the acute subjective effects compare to placebo?
What happened in the study?
Fifty-three adults with moderate-to-severe ADHD were randomized to receive LSD or placebo twice weekly for six weeks. ADHD symptoms were assessed using:
- AISRS (Adult ADHD Investigator Symptom Rating Scale) – Clinician-rated scale based on DSM criteria, evaluating core symptoms like inattention and hyperactivity.
- CGI (Clinical Global Impression) – Clinician’s overall rating of illness severity and improvement.
- CAARS (Conners’ Adult ADHD Rating Scale) – Self-report scale measuring inattention, hyperactivity, impulsivity, and self-concept problems.
- ASRS (Adult ADHD Self-Report Scale) – Screening and severity tool for inattention and hyperactivity symptoms.
Acute effects were evaluated with visual analog scales and altered states questionnaires (5D-ASC, MEQ), and safety was monitored with ECGs, blood work, and adverse event tracking.
Key findings
- No difference in efficacy:
- AISRS scores improved by 7.1 points (LSD) and 8.9 (placebo), with no significant group difference.
- All the other symptom scales showed improvements over time in both groups without differences between them.
- Strong placebo and expectancy effects:
- 80% of participants guessed they were in the LSD group, regardless of allocation.
- Those who believed they received LSD reported greater symptom improvements, regardless of treatment.
- Acute effects were present at 20 μg:
- LSD caused stronger subjective effects than placebo, including mild perceptual and emotional changes.
- Two participants discontinued due to interference with daily functioning.
- Safe and well-tolerated:
- No serious adverse events.
- Most common side effects: headache, nausea, fatigue, insomnia, mild visual alterations.
- No ECG or lab abnormalities.
Why is this important?
This is the first placebo-controlled clinical trial to rigorously test repeated low-dose LSD in a clinical population, offering a necessary counterpoint to the wave of anecdotal enthusiasm and observational reports surrounding microdosing. For years, popular media and self-experimentation communities have touted microdosing psychedelics, especially LSD, as a promising strategy for enhancing focus, productivity, and emotional regulation in ADHD. Surveys and naturalistic studies have even reported perceived symptom improvements. But these reports lacked proper controls, and this trial shows how powerful placebo and expectancy effects can be. The fact that both LSD and placebo groups improved, and that most participants believed they were receiving LSD, highlights just how much therapeutic outcomes can be shaped by mindset, context, and belief.
These results emphasize that self-reported benefits from microdosing may be due more to expectation than pharmacological action. As psychedelic therapies move toward clinical adoption, this trial underscores the need for rigorous evaluation, not only to assess safety and efficacy but to disentangle genuine drug effects from powerful psychological factors like expectancy and setting. It also highlights that “harmless” self-experimentation may carry underestimated risks, especially if the dose is not as subtle as users believe.
Limitations
- Powered to detect only large effects.
- One site recruited the majority of participants.
- Only one dose and schedule tested.
- High expectancy not formally controlled.
Conclusion
Low-dose LSD (20 μg) was safe in adults with ADHD but did not reduce symptoms more than placebo. While the theoretical rationale remains intriguing, these results highlight the need for rigorous trials before clinical use.
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