Measurement of persisting changes in emotional brain functioning produced by psilocybin

项目摘要 迷幻剂(包括裸盖菇素和迷幻剂)的非医疗使用和滥用在过去一直保持稳定 12年。与典型滥用药物的滥用责任模式相反，在这种模式下，重新管理是驱动的 通过急性正强化和持续负强化机制，重复的自我强化 经典迷幻剂的使用可能是由长期持续的积极强化推动的。这 持续的积极强化可能是由负面情绪刺激的神经处理过程的改变所驱动的 在摄入一种经典的迷幻剂之后。我们提出了一项开放标签试点研究， 迷幻剂-天真的志愿者对大剂量经典迷幻剂裸盖菇素的持久影响 与情绪处理有关的行为和大脑功能。参与者将接受功能性磁化 完成情绪处理任务期间的磁共振成像(FMRI)(包括情绪识别， 情绪歧视和情绪冲突处理)在基线(大剂量裸盖菇素注射前一天) 会议)，裸盖菇素后一周，和裸盖菇素后一个月。参与者还将完成良好的- 建立有效的情绪和情绪自我报告测量方法，以及有效的虐待责任测量方法。我们的 目的是评估裸盖菇素对1)情绪处理的持续影响的时间-过程，通过测量 任务绩效，以及2)情绪处理的神经回路，通过静息状态和基于任务的方式来测量 功能磁共振成像。这项研究是研究经典之作非典型增强特性的合乎逻辑的第一步。 迷幻剂，它将为更全面的研究计划产生必要的初步数据 在这片区域。拟议的研究和后续的研究计划将对我们的 理解滥用的可能性和支持滥用经典的潜在机制 致幻剂，我们目前对此知之甚少。

Project Summary Nonmedical use and abuse of hallucinogens (including psilocybin and LSD) has remained stable over the past 12 years. Contrary to the model of abuse liability for typical drugs of abuse, where re-administration is driven by acute positive reinforcement and persistent negative reinforcement mechanisms, repeated self- administration of classic hallucinogens may be driven by long-term persisting positive reinforcement. This persisting positive reinforcement may be driven by alteration in neural processing of negative emotional stimuli subsequent to ingestion of a classic hallucinogen. We propose an open-label pilot study in healthy, hallucinogen-naïve volunteers of the persisting effects of a high dose of the classic hallucinogen psilocybin on behavior and brain function related to emotion processing. Participants will undergo functional magnetic resonance imaging (fMRI) during completion of emotional processing tasks (including emotion recognition, emotion discrimination, and emotional conflict processing) at baseline (one day before a high-dose psilocybin session), one week post-psilocybin, and one month post-psilocybin. Participants will also complete well- established, validated self-report measures of mood and emotion, and validated abuse liability measures. Our aims are to assess the time-course of persisting effects of psilocybin on 1) emotion processing as measured by task performance, and 2) neural circuitry of emotion processing as measured by resting state and task-based fMRI. This study is a logical first step in investigating the atypical reinforcing properties of classic hallucinogens, and it will generate necessary preliminary data for a more comprehensive program of research in this area. The proposed study and subsequent program of research will make critical contributions to our understanding of the potential for abuse and the underlying mechanisms supporting abuse of classic hallucinogens, for which we currently know very little.