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

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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