Neuroimaging in psychedelic drug development: Past, present, and future
This review (2023) discusses the emerging field of psychedelic therapy for psychiatric disorders, emphasizing the potential of classic serotonergic psychedelics like psilocybin and LSD and substances like ketamine, MDMA, and ibogaine. It highlights the role of advanced neuroscientific research methods, particularly neuroimaging using Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI), in advancing the understanding of drug and therapy effects on the brain. The article identifies key knowledge gaps, including the relationship between acute and longer-term effects, the precise characterization of effects at the 5-HT2A receptor, and the impact of these compounds on neuroplasticity, and proposes a roadmap for future research to address these questions through multimodal PET/MRI studies.
Authors
- David Nutt
- David Erritzoe
- Matthew Wall
Published
Abstract
Psychedelic therapy (PT) is an emerging paradigm with great transdiagnostic potential for treating a range of psychiatric disorders, including depression, addiction, eating disorders, post-traumatic stress disorder, and others. ‘Classic’ serotonergic psychedelics, such as psilocybin, lysergic acid diethylamide (LSD), N, N-Dimethyltryptamine (DMT) and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), form the main focus of this movement, but other substances including ketamine, 3,4-Methylenedioxymethamphetamine (MDMA) and ibogaine also hold promise. The development of these novel treatment modalities in the early 21st century has occurred concurrently with the wider use of advanced human neuroscientific research methods; principally neuroimaging. This has enabled assessment of drug and therapy brain effects with greater precision and quantification than any previous novel development in psychiatric pharmacology. We outline some of the major trends in existing data and suggest that the modern development of PT has benefitted greatly from the use of neuroimaging. Important gaps in existing knowledge are identified which can be addressed by future neuroimaging work, principally using combined Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI) methods, plus other adjunct techniques. Suggestions for future multimodal imaging studies are discussed, which would resolve some of these questions and provide a firmer foundation for the development of PT.
Research Summary of 'Neuroimaging in psychedelic drug development: Past, present, and future'
Introduction
Wall and colleagues situate modern psychedelic research in a long historical context, noting early 20th century clinical interest, widespread therapeutic investigation in the 1950s–1960s, and the subsequent multi-decade hiatus caused by legal prohibition. They emphasise that this interruption occurred while neuroscience methods advanced considerably, so the current ‘‘second wave’’ of psychedelic science is unfolding alongside powerful molecular, structural and functional human neuroimaging techniques that were not previously available. This perspective piece aims to synthesise how neuroimaging has contributed to contemporary psychedelic drug development and to identify critical gaps. In particular, the authors highlight three outstanding questions: how acute brain effects relate to longer-term clinically relevant outcomes, the precise pharmacology and dose–effect relationships at the 5-HT2A receptor and their links to subjective and functional outcomes, and whether and how psychedelics induce neuroplasticity in humans. They propose a roadmap that places combined PET and MRI (multimodal) studies at the centre of future work to build a ‘‘molecular–functional–clinical bridge’’.
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Wall, M. B., Harding, R., Zafar, R., Rabiner, E. A., Nutt, D. J., & Erritzoe, D. (2023). Neuroimaging in psychedelic drug development: Past, present, and future. Molecular Psychiatry, 28(9), 3573-3580. https://doi.org/10.1038/s41380-023-02271-0
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Subramanian, S., Renau, R., Perry, D. et al. · Scientific Data (2025)
Nicol, G. E. · Nature (2024)
Erritzoe, D., Timmermann, C., Godfrey, K. et al. · Nature Mental Health (2024)
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