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Exploring mechanisms of psychedelic action using neuroimaging

Abstract

Modern psychedelic research and clinical development is at a crucial inflection point, with great potential for the treatment of many mental illnesses demonstrated but significant questions that remain unresolved. Neuroimaging has been pivotal in the modern era of psychedelic research, providing crucial insights into the acute effects of these drugs that revealed translational, clinical potential. Here we review this evidence from functional magnetic resonance imaging, positron emission tomography and magnetoencephalography/electroencephalography studies and describe how these findings inform computational models of both the acute action of psychedelics and their longer-term therapeutic effects. This approach, based on multi-modal neuroimaging, provides a solid evidence base for these therapies as they move forwards, as well as a fuller understanding of the powerful effects of psychedelics on the phenomenology of human consciousness.

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Fig. 1: Overview of fMRI implementation, analysis methods and key findings relating to psychedelic drug administration.
Fig. 2: Overview of MEG/EEG implementation, analysis methods and key findings relating to acute psychedelic administration.
Fig. 3: Overview of PET method, examples of application in pharmacology research and key findings relating to psychedelic drug use.
Fig. 4: Model of the action of psychedelic therapy in the treatment of depression.

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Within the past two years D.E. has received fees for scientific advisory work from the following (novel psychedelic) companies: Mydecine, Field Trip Health, Entheon, SmallPharma Ltd, Aya Biosciences, Clerkenwell Health and Mindstate Design Lab; D.E. has also received an honorarium fee from each of COMPASS Pathways and H. Lundbeck for a talk about psychedelic science. The primary employer of M.B.W. is Invicro LLC, a contract research organization that provides research services to the pharmaceutical and biotechnology industries; M.B.W. has also benefitted from travel expenses provided by COMPASS Pathways. D.J.N. has received consulting fees from Algernon, H. Lundbeck and Beckley Psytech, advisory board fees from COMPASS Pathways and lecture fees from Takeda, and Otsuka and Janssen; D.J.N. also owns stock in Alcarelle, Awakn and Psyched Wellness. R.C.-H. is a scientific advisor to Usona Institute, Journey Colab, Osmind, Maya Health, Beckley Psytech, Anuma, MindState and Entheos Labs.

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Erritzoe, D., Timmermann, C., Godfrey, K. et al. Exploring mechanisms of psychedelic action using neuroimaging. Nat. Mental Health 2, 141–153 (2024). https://doi.org/10.1038/s44220-023-00172-3

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