Investigating long-term, post-acute effects of psychedelics on cognitive function: neurobiological and psychological mechanisms

牛津大学实验心理学 COMPASS Pathways 该项目旨在为更好地理解血清素药理学（特别是血清素迷幻药）与啮齿动物的灵活行为和认知之间关系的机制奠定基础。认知灵活性被认为在发展轨迹、人生成功和健康老龄化中发挥着重要作用（Uddin Nat Rev Neurosci 2021），而灵活性缺陷是多种神经和精神疾病的核心组成部分。此外，血清素信号与灵活认知密切相关，而血清素靶向药物已成为治疗一系列脑部疾病的既定疗法。因此，这项研究可能会对多个不同学科（例如心理学、神经生理学、精神病学、神经病学）产生广泛的影响。然而，重要的是，对于不同的血清素药物如何发挥其治疗作用，目前还没有达成共识。对于传统的抗抑郁药物如血清素再摄取抑制剂（SSRI）和新型血清素能致幻药物来说都是如此。采用系统神经科学方法来了解血清素能致幻剂如何影响灵活行为，并将其与 SSRI 的影响进行对比，可能会引起包括 COMPASS Pathways 在内的公司对投资研究新有效疗法的预测因子的高度兴趣。此外，学生还将受益于项目中只有少数英国机构才有的想法、体内技术和分析方法。这将使他们能够在未来将这些技能传播到其他学术或工业职位。我们致力于根据 BBSRC 政策免费提供我们研究中产生的所有数据，从而使各个领域的学者获得最大利益。特别是，电生理数据集将引起计算建模领域的浓厚兴趣，允许测试现有模型并为后续测试开发新假设。 BBSRC 主题 - 生物科学对健康的综合理解

Experimental Psychology, University of Oxford COMPASS Pathways This project aims to lay the foundations for a better understanding of the mechanisms underlying the relationship between serotonergic pharmacology - particularly serotonin psychedelics - and flexible behaviour and cognition in the rodent. Cognitive flexibility is thought to play an important role in developmental trajectories, life success and healthy ageing (Uddin Nat Rev Neurosci 2021), and deficits in flexibility form a core component of several neurological and psychiatric diseases. Moreover, serotonergic signalling is strongly implicated in flexible cognition, and serotonin-targeting drugs are established therapies for a range of these brain disorders. Therefore, the research will likely have a wide sphere of influence across several different disciplines (e.g., psychology, neurophysiology, psychiatry, neurology). Importantly, however, there is still little consensus as to how different serotonergic drugs exert their therapeutic effects. This is the case both for conventional anti-depressant medications such as serotonin reuptake inhibitors (SSRIs) and also for novel serotonergic psychedelic drugs. Taking a systems neuroscience approach to understanding how serotonergic psychedelics influence flexible behaviour, and contrasting this with the influence of SSRIs, is potentially of high interest to companies - including COMPASS Pathways - investing in researching predictors of new effective therapies. In addition, the student will benefit by exposure to ideas, in vivo techniques and analytical approaches in the project that are only available in a few UK institutes. This will allow them to propagate these skills to other academic or industrial positions in the future. We are committed to make all data arising from our studies freely available, in line with the BBSRC policy, enabling maximum benefit to academics across a range of fields. In particular, the electrophysiological data set will be of strong interest to the computational modelling field, allowing testing of existing models and the development of new hypotheses for subsequent testing.BBSRC theme - Bioscience for an integrated understanding of health