A short-acting psychedelic intervention for major depressive disorder: a phase IIa randomized placebo-controlled trial.

Dimethyltryptamine (DMT), a serotonergic psychedelic with rapid onset and short duration, shows promise as a potential antidepressant (AD), although clinical evidence in MDD remains limited.

二甲基色胺（DMT）是一种起效快、作用时间短的血清素能迷幻剂，作为一种潜在的抗抑郁药（AD）显示出希望，尽管在重度抑郁症（MDD）中的临床证据仍然有限。

We conducted a phase IIa, double-blind, placebo-controlled, randomized clinical trial to evaluate the efficacy and safety of intravenous DMT (SPL026; DMT fumarate) in adults with moderate-to-severe MDD.

我们开展了一项IIa期、双盲、安慰剂对照、随机临床试验，以评估静脉注射DMT（SPL026；富马酸DMT）在中度至重度MDD成人患者中的疗效和安全性。

Participants received a single 21.5-mg dose of DMT or placebo infused over 10 min, along with supportive psychotherapeutic support, followed by a 2-week assessment.

参与者接受单次21.5毫克剂量的DMT或安慰剂，输注时间为10分钟，并接受支持性心理治疗支持，随后进行为期2周的评估。

A subsequent open-label phase offered all participants a second DMT dose.

随后的开放标签阶段为所有参与者提供了第二次DMT剂量。

The primary outcome was the change in Montgomery-Åsberg Depression Rating Scale (MADRS) at 2 weeks.

主要结果是在2周时蒙哥马利-阿斯伯格抑郁评定量表（MADRS）的变化。

Secondary outcomes included response (≥50% reduction in MADRS score) and remission (MADRS ≤ 10).

次要结果包括反应（MADRS评分降低≥50%）和缓解（MADRS≤10）。

A total of 34 participants were randomized, 17 to placebo-active and 17 to active-active.

共有34名参与者被随机分配，其中17名接受安慰剂-活性药物，另外17名接受活性药物-活性药物。

At 2 weeks, the DMT group showed a significantly greater reduction in MADRS score than placebo (mean difference = -7.35; 95% CI = -13.62 to -1.08; P = 0.023).

在2周时，与安慰剂组相比，DMT组的MADRS评分显著降低（平均差异 = -7.35；95%置信区间 = -13.62至-1.08；P = 0.023）。

In the open-label phase, AD effects persisted up to 3 months, with no significant differences between those who received one versus two doses.

在开放标签阶段，抗抑郁（AD）效果持续至3个月，接受一次剂量与两次剂量的患者之间没有显著差异。

Adverse events were mostly mild to moderate, commonly infusion site pain, nausea and transient anxiety.

不良事件大多为轻度至中度，常见的有输液部位疼痛、恶心和短暂性焦虑。

No serious adverse events occurred.

未发生严重不良事件。

A single dose of DMT with psychotherapeutic support produced a rapid, significant reduction in depressive symptoms, sustained up to 3 months.

单剂量的DMT配合心理治疗支持，迅速显著地减少了抑郁症状，这种效果可持续至3个月。

The treatment was well-tolerated and safe.

该治疗耐受性良好且安全。

ClinicalTrials.gov registration: NCT04673383 .

临床试验注册：NCT04673383 .