Progress in neuro-psychopharmacology & biological psychiatry · 2026
LSD microdosing for major depressive disorder: Mood and pharmacokinetic outcomes from a Phase 2a trial.
СтатьяКлиническое исследование II фазыНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Daldegan-Bueno Dimitri, Donegan Carina Joy, Sumner Rachael, Forsyth Anna, Jeong Soo Hee, Evans William, Alshakhouri Malak, Murphy Robin J, Reynolds Lisa, Hoeh Nicholas, Allen Nathan, Sundram Frederick, Menkes David B, Muthukumaraswamy Suresh
Аннотация
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.
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.