Measurement of persisting changes in emotional brain functioning produced by psilocybin

项目摘要 致幻剂（包括裸盖菇素和LSD）的非医疗使用和滥用在过去一直保持稳定 12年与典型药物滥用的滥用责任模式相反， 通过急性正强化和持续负强化机制，重复自我- 经典致幻剂的施用可能是由长期持续的正强化驱动的。这 持续的正强化可能是由负面情绪刺激的神经处理改变驱动的 是因为摄入了典型的致幻剂我们提出了一项开放标签的试点研究， 高剂量的经典致幻剂裸盖菇素的持续作用， 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 在完成情绪处理任务（包括情绪识别， 情绪辨别和情绪冲突处理）在基线（高剂量裸盖菇素前一天 期）、裸盖菇素后一周和裸盖菇素后一个月。参与者也将完成良好的- 建立并验证了情绪和情感的自我报告措施，并验证了虐待责任措施。我们 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， 任务表现，以及2）通过静息状态和基于任务的测量的情绪处理的神经回路 功能磁共振成像。这项研究是调查经典的非典型强化特性的逻辑第一步。 它将为更全面的研究计划提供必要的初步数据 在这个领域。拟议的研究和随后的研究计划将为我们的研究做出重要贡献。 了解滥用的可能性和支持滥用经典药物的潜在机制 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.