Topic starter
There is a new scientific article which looks at the effects of LSD microdosing in people with depression, with a special focus on mood, subjective perception and pharmacokinetics.
In it, we discuss:
The researchers conducted an open-label phase 2a study in 19 people with depressive disorder. Participants received a total of 16 sublingual LSD doses over eight weeks. The first dose was 8 micrograms under supervision, followed by further dosing at home twice a week with accrual between 6 and 20 micrograms.
The real focus of this paper is not on hard clinical efficacy compared to placebo, but on daily mood, perceived effects on dosing days and the pharmacokinetics of LSD in these low doses. The researchers saw that participants felt more creative and happy on dosing days, for example, but that daily depression scores themselves did not improve significantly at those same measurement times.
It is also notable that the researchers found no evidence of tolerance or sensitisation during the course. This means that the subjective effects of repeated microdoses in this study did not clearly diminish or become stronger over time, despite the gradual dose build-up.
In addition, this article provides pharmacokinetic data of 8 micrograms of LSD in people with depression. The mean exposure was 836 ± 319 pg.h/mL, the mean peak concentration 212 ± 77.7 pg/mL and the time to peak concentration about 1.17 ± 0.56 hours. This also makes this article especially technically relevant for future microdose research.
Importantly, however, this is a small open-label study without a placebo group. As a result, expectancy effects, natural fluctuations in mood and other confounding factors may play a major role. The authors themselves therefore stress that controlled follow-up studies are needed to determine whether microdosing LSD has real antidepressant value.
In one sentence, this article shows that LSD microdosing in people with depression on dosing days was associated with a temporary more positive mood, but that does not prove that it is actually an effective antidepressant treatment.
Spoiler
New article description
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 burden 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.
Keywords: LSD; Major depressive disorder; Microdosing; Pharmacokinetics; Psychedelics.
Posted : 18 March 2026 14:38