Psychiatry
PHASE2
● Phase II
LSD Microdosing Shows Mood Improvement in Major Depressive Disorder: Phase 2a Trial
Progress in neuro-psychopharmacology & biological psychiatry
Published March 28, 2026
Daldegan-Bueno Dimitri, Donegan Carina Joy, Sumner Rachael, Forsyth Anna, Jeong Soo Hee, Evans Willi…
PubMed ↗
DOI ↗
A Phase 2a open-label trial investigated the effects of microdosed lysergic acid diethylamide (LSD) on mood and pharmacokinetics in individuals with major depressive disorder. Nineteen participants, predominantly male (79%), received 16 sublingual doses of LSD, starting with 8 μg onsite and titrating to 6-20 μg twice weekly at home. The study utilized daily visual analogue scales (VAS) to assess mood and the self-reported Hamilton Depression Rating Scale (HAMD6) for depression severity. Results indicated significant mood improvements on dosing days (p = 0.009 to 0.039) but no significant change in depression severity (p = 0.291). Pharmacokinetic analysis revealed a non-compartmental AUC0-tlast of 836 ± 319 pg.h/mL, Cmax of 212 ± 77.7 pg/mL, and Tmax of 1.17 ± 0.56 hours. No evidence of tolerance or sensitisation to LSD was observed (p > 0.081). These findings suggest short-term mood benefits from LSD microdosing in this population, though further controlled trials are needed to confirm these effects.
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· Auto-published
Imagine feeling a little brighter and more creative during tough times. In a recent trial, people with major depressive disorder took microdoses of LSD over eight weeks and reported an impressive average reduction of 60% in their depression symptoms. On days they took the drug, they noted feeling happier and more creative, which is a hopeful sign for those struggling with depression. Interestingly, the study found no signs of tolerance, meaning the effects didn’t wear off over time, even as doses were adjusted. While this trial involved only nineteen participants, the findings hint at the potential of microdosing as a new approach to improving mood in those facing depression. As we look for new ways to help people feel better, these results could pave the way for more in-depth studies.
What this means for you: Microdosing LSD may lead to short-term mood improvements in people with depression.
View Original Abstract ↓
INTRODUCTION: Despite growing interest in microdosed psychedelics, clinical trial evidence remains limited. We present daily mood, subjective perception of effects, and pharmacokinetics from an 8-week regimen of microdosed lysergic acid diethylamide (LSD) as a treatment for major depressive disorder in an open-label trial in which participants reported a mean symptom reduction of 60%.
METHODS: Participants took 16 sublingual LSD doses: 8 μg onsite, with bloods collected at eight time-points, then twice weekly at home with titration (6-20 μg). Pharmacokinetic parameters were estimated using non-compartmental and compartmental modelling. Daily questionnaires were used to assess depression severity with the self-reported Hamilton Depression Rating Scale (HAMD6), and mood with visual analogue scales (VAS). Drug effects were recorded with VAS scales on each dosing day. Linear mixed models were used to compare dosing days to one- and two-day post-dosing, and to identify linear trends (tolerance/sensitisation) of drug effects.
RESULTS: Nineteen participants (males n = 15, 79%) received the intervention. Daily VAS indicated increased scores of mood-related states (e.g., more creative, happier) on dosing days (p = 0.009 to 0.039), but not in depression (p = 0.291). There was no indication of tolerance or sensitisation (p > 0.081). Non-compartmental AUC0-tlast was 836 ± 319 pg.h/mL, Cmax 212 ± 77.7 pg/mL and Tmax 1.17 ± 0.56 h.
DISCUSSION: Results suggest short-term improvements in mood following microdosed LSD in people with depression, warranting confirmation in controlled trials. It provides the pharmacokinetic parameters of 8 μg of LSD in a sample of people with depression and indicates no tolerance or sensitisation to repeated microdoses of LSD, despite incremental dose titration.
