美国Usona研究所Charles L. Raison团队研究了裸盖菇素治疗重度抑郁症的疗效与安全性。相关论文于2023年8月31日发表于《美国医学会杂志》。

裸盖菇素有望治疗重度抑郁症（MDD）。为了评估单剂量裸盖菇素对MDD患者抗抑郁作用的程度、时间和持久性以及安全性，研究组于2019年12月至2022年6月在美国11个研究机构进行了一项临床2期试验，参与者以1:1的比例随机接受单剂量裸盖菇素与烟酸安慰剂，并给予心理支持。

参与者为21至65岁的成年人，均患有《精神障碍诊断和统计手册》第五版诊断为持续时间至少60天的MDD，症状严重程度为中度或以上。排除标准包括精神病或躁狂史、活性物质使用障碍和有意向的主动自杀意念。服用其他符合纳入/排除标准精神药物的参与者在药物减量后符合资格。在基线（给药前7天内进行）和给药后2、8、15、29和43天评估主要和次要结局及不良事件（AE）。

干预措施为25毫克剂量的合成裸盖菇素或100毫克剂量的烟酸，均装在外观相同的胶囊中，均同时进行心理支持。主要结局为从基线到第43天，中心评分者评估的Montgomery-Asberg抑郁评分量表（MADRS）评分（范围为0-60；评分越高表示抑郁越严重）的变化。关键次要结局评估是从基线到第8天MADRS评分的变化。其他次要结局为Sheehan残疾量表评分从基线到第43天的变化，MADRS定义了持续反应和缓解。参与者、研究现场人员、研究发起人、结局评估员（评分员）和统计学家对治疗分配不知情。

共有104名参与者（平均年龄41.1岁；52名[50%]女性）被随机分配（裸盖菇素组51名，烟酸组53名）。与烟酸相比，从基线到第43天，裸盖菇素治疗与MADRS评分显著降低有关（平均差异为−12.3；P<.001），从基线到第8天亦是如此（平均差异为−12.0；P < .001）。与烟酸相比，裸盖菇素治疗也与Sheehan残疾量表评分显著降低有关（平均差异为−2.31；P < .001）。接受裸盖菇素治疗的参与者比接受烟酸治疗的参与者有FC碰碰胡老虎机法典-提高赢钱机率的下注技巧的持续反应（但没有缓解）。没有严重的治疗突发AE；然而，裸盖菇素治疗与更高的总体AE发生率和更高的严重AE发生率相关。

裸盖菇素治疗与抑郁症状和功能残疾的临床显著持续减轻有关，没有严重不良事件。这些发现进一步证明，裸盖菇素在给予心理支持的情况下，可能有望成为MDD的一种新的干预措施。

附：英文原文

Title: Single-Dose Psilocybin Treatment for Major Depressive Disorder: A Randomized Clinical Trial

Author: Charles L. Raison, Gerard Sanacora, Joshua Woolley, Keith Heinzerling, Boadie W. Dunlop, Randall T. Brown, Rishi Kakar, Michael Hassman, Rupal P. Trivedi, Reid Robison, Natalie Gukasyan, Sandeep M. Nayak, Xiaojue Hu, Kelley C. O’Donnell, Benjamin Kelmendi, Jordan Sloshower, Andrew D. Penn, Ellen Bradley, Daniel F. Kelly, Tanja Mletzko, Christopher R. Nicholas, Paul R. Hutson, Gary Tarpley, Malynn Utzinger, Kelsey Lenoch, Kasia Warchol, Theraysa Gapasin, Mike C. Davis, Courtney Nelson-Douthit, Steffanie Wilson, Carrie Brown, William Linton, Stephen Ross, Roland R. Griffiths

Issue&Volume: 2023-08-31

Abstract:

Importance  Psilocybin shows promise as a treatment for major depressive disorder (MDD).

Objective  To evaluate the magnitude, timing, and durability of antidepressant effects and safety of a single dose of psilocybin in patients with MDD.

Design, Setting, and Participants  In this phase 2 trial conducted between December 2019 and June 2022 at 11 research sites in the US, participants were randomized in a 1:1 ratio to receive a single dose of psilocybin vs niacin placebo administered with psychological support. Participants were adults aged 21 to 65 years with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnosis of MDD of at least 60 days’ duration and moderate or greater symptom severity. Exclusion criteria included history of psychosis or mania, active substance use disorder, and active suicidal ideation with intent. Participants taking psychotropic agents who otherwise met inclusion/exclusion criteria were eligible following medication taper. Primary and secondary outcomes and adverse events (AEs) were assessed at baseline (conducted within 7 days before dosing) and at 2, 8, 15, 29, and 43 days after dosing.

Interventions  Interventions were a 25-mg dose of synthetic psilocybin or a 100-mg dose of niacin in identical-appearing capsules, each administered with psychological support.

Main Outcomes and Measures  The primary outcome was change in central rater–assessed Montgomery-Asberg Depression Rating Scale (MADRS) score (range, 0-60; higher scores indicate more severe depression) from baseline to day 43. The key secondary outcome measure was change in MADRS score from baseline to day 8. Other secondary outcomes were change in Sheehan Disability Scale score from baseline to day 43 and MADRS-defined sustained response and remission. Participants, study site personnel, study sponsor, outcome assessors (raters), and statisticians were blinded to treatment assignment.

Results  A total of 104 participants (mean [SD] age, 41.1 [11.3] years; 52 [50%] women) were randomized (51 to the psilocybin group and 53 to the niacin group). Psilocybin treatment was associated with significantly reduced MADRS scores compared with niacin from baseline to day 43 (mean difference,12.3 [95% CI, 17.5 to 7.2]; P <.001) and from baseline to day 8 (mean difference, 12.0 [95% CI, 16.6 to 7.4]; P<.001). Psilocybin treatment was also associated with significantly reduced Sheehan Disability Scale scores compared with niacin (mean difference, 2.31 [95% CI, 3.50-1.11]; P<.001) from baseline to day 43. More participants receiving psilocybin had sustained response (but not remission) than those receiving niacin. There were no serious treatment-emergent AEs; however, psilocybin treatment was associated with a higher rate of overall AEs and a higher rate of severe AEs.

Conclusions and Relevance  Psilocybin treatment was associated with a clinically significant sustained reduction in depressive symptoms and functional disability, without serious adverse events. These findings add to increasing evidence that psilocybin—when administered with psychological support—may hold promise as a novel intervention for MDD.

DOI: 10.1001/jama.2023.14530

Source: https://jamanetwork.com/journals/jama/fullarticle/2808950