PMID- 37759038 OWN - NLM STAT- MEDLINE DCOM- 20231221 LR - 20231222 IS - 1476-5578 (Electronic) IS - 1359-4184 (Print) IS - 1359-4184 (Linking) VI - 28 IP - 9 DP - 2023 Sep TI - Neuroimaging in psychedelic drug development: past, present, and future. PG - 3573-3580 LID - 10.1038/s41380-023-02271-0 [doi] AB - Psychedelic therapy (PT) is an emerging paradigm with great transdiagnostic potential for treating psychiatric disorders, including depression, addiction, post-traumatic stress disorder, and potentially others. 'Classic' serotonergic psychedelics, such as psilocybin and lysergic acid diethylamide (LSD), which have a key locus of action at the 5-HT2A receptor, form the main focus of this movement, but substances including ketamine, 3,4-Methylenedioxymethamphetamine (MDMA) and ibogaine also hold promise. The modern phase of development of these treatment modalities in the early 21st century has occurred concurrently with the wider use of advanced human neuroscientific research methods; principally neuroimaging. This can potentially enable assessment of drug and therapy brain effects with greater precision and quantification than any previous novel development in psychiatric pharmacology. We outline the major trends in existing data and suggest the modern development of PT has benefitted greatly from the use of neuroimaging. Important gaps in existing knowledge are identified, namely: the relationship between acute drug effects and longer-term (clinically-relevant) effects, the precise characterisation of effects at the 5-HT2A receptor and relationships with functional/clinical effects, and the possible impact of these compounds on neuroplasticity. A road-map for future research is laid out, outlining clinical studies which will directly address these three questions, principally using combined Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI) methods, plus other adjunct techniques. Multimodal (PET/MRI) studies using modern PET techniques such as the 5-HT2A-selective ligand [11 C]Cimbi-36 (and other ligands sensitive to neuroplasticity changes) alongside MRI measures of brain function would provide a 'molecular-functional-clinical bridge' in understanding. Such results would help to resolve some of these questions and provide a firmer foundation for the ongoing development of PT. CI - (c) 2023. The Author(s). FAU - Wall, Matthew B AU - Wall MB AUID- ORCID: 0000-0002-0493-6274 AD - Invicro, London, UK. matthew.wall@imperial.ac.uk. AD - Faculty of Medicine, Imperial College London, London, UK. matthew.wall@imperial.ac.uk. AD - Centre for Psychedelic research and Neuropsychopharmacology, Imperial College London, London, UK. matthew.wall@imperial.ac.uk. FAU - Harding, Rebecca AU - Harding R AD - Clinical Psychopharmacology Unit, Faculty of Brain Sciences, University College London, London, UK. FAU - Zafar, Rayyan AU - Zafar R AD - Faculty of Medicine, Imperial College London, London, UK. AD - Centre for Psychedelic research and Neuropsychopharmacology, Imperial College London, London, UK. FAU - Rabiner, Eugenii A AU - Rabiner EA AUID- ORCID: 0000-0003-3612-6687 AD - Invicro, London, UK. FAU - Nutt, David J AU - Nutt DJ AUID- ORCID: 0000-0002-1286-1401 AD - Faculty of Medicine, Imperial College London, London, UK. AD - Centre for Psychedelic research and Neuropsychopharmacology, Imperial College London, London, UK. FAU - Erritzoe, David AU - Erritzoe D AUID- ORCID: 0000-0002-7022-6211 AD - Faculty of Medicine, Imperial College London, London, UK. AD - Centre for Psychedelic research and Neuropsychopharmacology, Imperial College London, London, UK. LA - eng PT - Journal Article PT - Review DEP - 20230927 PL - England TA - Mol Psychiatry JT - Molecular psychiatry JID - 9607835 RN - 0 (Hallucinogens) RN - 0 (Receptor, Serotonin, 5-HT2A) RN - 8NA5SWF92O (Lysergic Acid Diethylamide) RN - 2RV7212BP0 (Psilocybin) SB - IM MH - Humans MH - *Hallucinogens/pharmacology/history/therapeutic use MH - Receptor, Serotonin, 5-HT2A MH - Lysergic Acid Diethylamide/pharmacology/history/therapeutic use MH - Psilocybin/therapeutic use MH - Neuroimaging PMC - PMC10730398 COIS- MBW and ER's primary employer is Invicro LLC, a contract research organisation that provides research services to the pharmaceutical and biotechnology industries. DE has received consulting fees from Field Trip and Mydecine. DJN has received consulting fees from Algernon and H. Lundbeck and Beckley Psytech, advisory board fees from COMPASS Pathways and lecture fees from Takeda, Otsuka, and Janssen plus owns stock in Alcarelle, Awakn, and Psyched Wellness. The other authors declare no competing interests. EDAT- 2023/09/28 00:42 MHDA- 2023/12/21 06:43 PMCR- 2023/09/27 CRDT- 2023/09/27 23:36 PHST- 2022/11/29 00:00 [received] PHST- 2023/09/13 00:00 [accepted] PHST- 2023/12/21 06:43 [medline] PHST- 2023/09/28 00:42 [pubmed] PHST- 2023/09/27 23:36 [entrez] PHST- 2023/09/27 00:00 [pmc-release] AID - 10.1038/s41380-023-02271-0 [pii] AID - 2271 [pii] AID - 10.1038/s41380-023-02271-0 [doi] PST - ppublish SO - Mol Psychiatry. 2023 Sep;28(9):3573-3580. doi: 10.1038/s41380-023-02271-0. Epub 2023 Sep 27.