Negative Affect Circuit Subtypes and Neural, Behavioral, and Affective Responses to MDMA

作者：Xue Zhang, Laura M. Hack, Claire Bertrand, Rachel Hilton, Nancy Gray, Leyla Boyar, Jessica Laudie, Boris D. Heifets, Trisha Suppes, Peter van Roessel, Carolyn I. Rodríguez, Karl Deisseroth, Brian Knutson, Leanne M. Williams · 发表于：JAMA Network Open · 年份：2025 · DOI：10.1001/jamanetworkopen.2025.7803 · 被引用次数：11 · 研究领域：Psychedelics and Drug Studies、Forensic Toxicology and Drug Analysis、Cannabis and Cannabinoid Research

Importance: Rapidly acting therapeutics like 3,4-methylenedioxymethamphetamine (MDMA) are promising treatments for disorders such as posttraumatic stress disorder (PTSD). However, understanding who benefits most and the underlying neural mechanisms remains a critical gap. Stratifying individuals by neural circuit profiles could help differentiate neural, behavioral, and affective responses to MDMA, enabling personalized treatment strategies. Objective: To investigate whether baseline stratification of individuals based on negative affect circuit profiles, particularly in response to nonconscious threat stimuli, can differentiate acute responses to MDMA. Design, Setting, and Participants: This randomized clinical trial, implementing a double-blinded, within-participant, placebo- and baseline-controlled design, was conducted at Stanford University School of Medicine between November 2, 2021, and November 9, 2022, for wave 1 data collection. Participants had used MDMA on at least 2 prior occasions, but not in the past 6 months, and had subthreshold PTSD symptoms and early life trauma but no current psychiatric disorders. Data were analyzed from March 1, 2023, to January 1, 2024. Interventions: Participants completed 4 visits: 1 baseline session followed by 1 placebo session and 2 MDMA sessions in a randomized order, totaling 64 visits. Baseline functional magnetic resonance imaging (fMRI) assessed the negative affect circuit using a nonconscious threat processing task (NTN). Mai...