Single-Dose Psilocybin Treatment for Major Depressive Disorder

作者：Charles L. Raison, Gerard Sanacora, Joshua Woolley, Keith G. Heinzerling, Boadie W. Dunlop, Randall Brown, Rishi Kakar, Michael Hassman, Rupal Trivedi, Reid Robison, Natalie Gukasyan, Sandeep M. Nayak, Xiaojue Hu, Kelley C. O’Donnell, Benjamin Kelmendi, Jordan Sloshower, Andrew 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 H Wilson, Carrie Brown, William Linton, Matthew W. Johnson, Stephen Ross, Roland R. Griffiths · 发表于：JAMA · 年份：2023 · DOI：10.1001/jama.2023.14530 · 被引用次数：507 · 研究领域：Psychedelics and Drug Studies、Pain Management and Placebo Effect、Forensic Toxicology and Drug Analysis

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 scor...