School of Pharmacy, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Road, Grafton, Auckland, 1023, New Zealand.
Department of Psychological Medicine, Faculty of Medical and Health Sciences, University of Auckland, 22 Park Avenue, Grafton, Auckland, 1023, New Zealand.
Trials. 2024 Aug 24;25(1):560. doi: 10.1186/s13063-024-08384-3.
Major depressive disorder (MDD) poses a significant global health burden with available treatments limited by inconsistent efficacy and notable side effects. Classic psychedelics, including lysergic acid diethylamide (LSD), have garnered attention for their potential in treating psychiatric disorders. Microdosing, the repeated consumption of sub-hallucinogenic doses of psychedelics, has emerged as a self-treatment approach for depression within lay communities. Building upon preliminary evidence and the successful completion of an open-label pilot trial of microdosing LSD for depression (LSDDEP1), this protocol outlines a phase 2b randomised controlled trial (LSDDEP2). The main objective of LSDDEP2 is to assess the modification of depressive symptoms, measured by the Montgomery-Åsberg Depression Rating Scale (MADRS), following a regimen of LSD microdoses versus placebo.
This is a randomised, double-dummy, triple-blind, active placebo-controlled, parallel groups trial of LSD microdosing in patients meeting DSM-5 criteria for major depressive disorder. Participants will undergo an 8-week LSD microdosing regimen using the titratable MB-22001 formulation taking two doses a week. All doses will be self-administered at home and will be titratable from 4 to 20 μg based on subjective perception and tolerability. In addition to depression symptoms, outcome will include psychiatric and personality inventories, sleep and activity tracking, electroencephalography (EEG), blood biomarkers, semi-structured interviews, and safety (e.g. adverse event, laboratory exam) measures.
This study will be the first randomised controlled trial to administer controlled microdoses of LSD for treatment of MDD in participants' naturalistic environment. The measures included are designed to assess the drug's safety, mechanism, and treatment efficacy over placebo in this population. The results of this study will be important for assessing the viability of psychedelic microdosing as an additional treatment option and for informing the direction of future clinical trials.
ANZCTR, ACTRN12624000128594. Prospectively Registered on 13 February 2024.
重度抑郁症（MDD）是全球范围内的一个重大健康负担，现有的治疗方法疗效不一致且存在明显副作用。经典迷幻剂，包括麦角酸二乙酰胺（LSD），因其在治疗精神疾病方面的潜力而备受关注。微剂量是指重复摄入低致幻剂量的迷幻剂，已成为非专业社区中治疗抑郁症的一种自我治疗方法。在初步证据的基础上，以及 LSD 治疗抑郁症的开放性试验（LSDDEP1）成功完成后，本方案概述了一项 2b 期随机对照试验（LSDDEP2）。LSDDEP2 的主要目的是评估 LSD 微剂量与安慰剂相比，对符合 DSM-5 重度抑郁症标准的患者的抑郁症状（用蒙哥马利-阿斯伯格抑郁评定量表（MADRS）测量）的改变。
这是一项在符合 DSM-5 重度抑郁症标准的患者中进行的 LSD 微剂量随机、双盲、三盲、活性安慰剂对照、平行组试验。参与者将接受为期 8 周的 LSD 微剂量治疗方案，使用可滴定的 MB-22001 制剂，每周服用两次。所有剂量都将在家中自行服用，并根据主观感知和耐受性从 4 至 20μg 进行滴定。除了抑郁症状外，结果还将包括精神病学和人格量表、睡眠和活动跟踪、脑电图（EEG）、血液生物标志物、半结构化访谈以及安全性（例如不良事件、实验室检查）措施。
这将是第一项在参与者的自然环境中给予 LSD 受控微剂量治疗 MDD 的随机对照试验。纳入的措施旨在评估该药物在该人群中的安全性、机制和相对于安慰剂的治疗效果。该研究的结果对于评估迷幻剂微剂量作为一种额外治疗选择的可行性以及为未来临床试验指明方向将非常重要。
澳大利亚新西兰临床试验注册中心，ACTRN12624000128594。2024 年 2 月 13 日前瞻性注册。
