{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T02:11:15Z","timestamp":1793412675630,"version":"4.5.0"},"reference-count":121,"publisher":"SAGE Publications","issue":"7","license":[{"start":{"date-parts":[[2022,5,30]],"date-time":"2022-05-30T00:00:00Z","timestamp":1653868800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Psychopharmacol"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:p>Psilocybin is a naturally occurring psychedelic compound with profound perception-, emotion- and cognition-altering properties and great potential for treating brain disorders. However, the neural mechanisms mediating its effects require in-depth investigation as there is still much to learn about how psychedelic drugs produce their profound and long-lasting effects. In this review, we outline the current understanding of the neurophysiology of psilocybin\u2019s psychoactive properties, highlighting the need for additional preclinical studies to determine its effect on neural network dynamics. We first describe how psilocybin\u2019s effect on brain regions associated with the default-mode network (DMN), particularly the prefrontal cortex and hippocampus, likely plays a key role in mediating its consciousness-altering properties. We then outline the specific receptor and cell types involved and discuss contradictory evidence from neuroimaging studies regarding psilocybin\u2019s net effect on activity within these regions. We go on to argue that in vivo electrophysiology is ideally suited to provide a more holistic, neural network analysis approach to understand psilocybin\u2019s mode of action. Thus, we integrate information about the neural bases for oscillatory activity generation with the accumulating evidence about psychedelic drug effects on neural synchrony within DMN-associated areas. This approach will help to generate important questions for future preclinical and clinical studies. Answers to these questions are vital for determining the neural mechanisms mediating psilocybin\u2019s psychotherapeutic potential, which promises to improve outcomes for patients with severe depression and other difficulty to treat conditions.<\/jats:p>","DOI":"10.1177\/02698811221092508","type":"journal-article","created":{"date-parts":[[2022,5,31]],"date-time":"2022-05-31T02:41:50Z","timestamp":1653964910000},"page":"781-793","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":64,"title":["Neural mechanisms underlying psilocybin\u2019s therapeutic potential \u2013 the need for preclinical in vivo electrophysiology"],"prefix":"10.1177","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6557-9891","authenticated-orcid":false,"given":"Rebecca","family":"Smausz","sequence":"first","affiliation":[{"name":"Division of Neuroscience and Experimental Psychology, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2717-9739","authenticated-orcid":false,"given":"Joanna","family":"Neill","sequence":"additional","affiliation":[{"name":"Division of Pharmacy and Optometry, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK"},{"name":"Medical Psychedelics Working Group, Drug Science, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8253-1582","authenticated-orcid":false,"given":"John","family":"Gigg","sequence":"additional","affiliation":[{"name":"Division of Neuroscience and Experimental Psychology, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2022,5,30]]},"reference":[{"key":"bibr1-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1016\/S0893-133X(98)00046-3"},{"key":"bibr2-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2009.11.023"},{"key":"bibr3-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.06.014"},{"key":"bibr4-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-019-0611-3"},{"key":"bibr5-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhg128"},{"key":"bibr6-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2011.01.015"},{"key":"bibr7-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2010.02.005"},{"key":"bibr8-02698811221092508","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.31991"},{"key":"bibr9-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(02)03727-7"},{"key":"bibr10-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1525586113"},{"key":"bibr11-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2044"},{"key":"bibr12-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1110266108"},{"key":"bibr13-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0700436104"},{"key":"bibr14-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2018.02.018"},{"key":"bibr15-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2011.01.004"},{"key":"bibr16-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1177\/0269881114565144"},{"key":"bibr17-02698811221092508","doi-asserted-by":"publisher","DOI":"10.3389\/fnhum.2013.00647"},{"key":"bibr18-02698811221092508","author":"Buckholtz NS","year":"1990","journal-title":"Neuropsychopharmacology"},{"key":"bibr19-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1440.011"},{"key":"bibr20-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1126\/science.1099745"},{"key":"bibr21-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1038\/nature08002"},{"key":"bibr22-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1124\/pr.118.017160"},{"key":"bibr23-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1177\/0269881117725915"},{"key":"bibr24-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-017-4771-x"},{"key":"bibr25-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1016\/S2215-0366(16)30065-7"},{"key":"bibr26-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1119598109"},{"key":"bibr27-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2032994"},{"key":"bibr28-02698811221092508","doi-asserted-by":"publisher","DOI":"10.3389\/fnhum.2014.00020"},{"key":"bibr29-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1007\/s00221-013-3579-0"},{"key":"bibr30-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2008.03.013"},{"key":"bibr31-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-psych-113011-143750"},{"key":"bibr32-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-979351"},{"key":"bibr33-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1007\/s00429-008-0189-x"},{"key":"bibr34-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2010.01.004"},{"key":"bibr35-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1038\/35036213"},{"key":"bibr36-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1038\/nrn.2017.74"},{"key":"bibr37-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1038\/35094565"},{"key":"bibr38-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychires.2015.05.006"},{"key":"bibr39-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2015.09.034"},{"key":"bibr40-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(01)00285-9"},{"key":"bibr41-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-013-3057-1"},{"key":"bibr42-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1016\/j.euroneuro.2012.10.018"},{"key":"bibr43-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1017\/S1092852921000791"},{"key":"bibr44-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1021\/acsptsci.0c00164"},{"key":"bibr45-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0135058100"},{"key":"bibr46-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0308627101"},{"key":"bibr47-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1300711"},{"key":"bibr48-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1177\/0269881116675513"},{"key":"bibr49-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-006-0457-5"},{"key":"bibr50-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1001\/archgenpsychiatry.2010.116"},{"key":"bibr51-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.071043098"},{"key":"bibr52-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1016\/S0028-3908(03)00139-4"},{"key":"bibr53-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2014.07.016"},{"key":"bibr54-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2011.01.017"},{"key":"bibr55-02698811221092508","doi-asserted-by":"publisher","DOI":"10.3389\/fnint.2013.00083"},{"key":"bibr56-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1016\/S0031-6865(97)00014-9"},{"key":"bibr57-02698811221092508","unstructured":"Hofmann A (1980) LSD: My problem child. New York: McGraw-Hill Book Company, pp.6\u201316."},{"key":"bibr58-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1007\/BF02159243"},{"key":"bibr59-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09562-7"},{"key":"bibr60-02698811221092508","doi-asserted-by":"publisher","DOI":"10.21236\/AD0291057"},{"key":"bibr61-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1080\/17470919.2010.507948"},{"key":"bibr62-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1177\/0269881114548296"},{"key":"bibr63-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0704848104"},{"key":"bibr64-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2006.10.004"},{"key":"bibr65-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-015-4026-7"},{"key":"bibr66-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2004.10.011"},{"key":"bibr67-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1038\/srep25826"},{"key":"bibr68-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0315-18.2018"},{"key":"bibr69-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2017.07.020"},{"key":"bibr70-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1038\/nature06976"},{"key":"bibr71-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1200506109"},{"key":"bibr72-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2020.117653"},{"key":"bibr73-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-12658-9"},{"key":"bibr74-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2004.03.016"},{"key":"bibr75-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.05.022"},{"key":"bibr76-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.20.1.185"},{"key":"bibr77-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1007\/7854_2017_480"},{"key":"bibr78-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-020-0718-8"},{"key":"bibr79-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.160.1.90"},{"key":"bibr80-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0101-19.2019"},{"key":"bibr81-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.12.030"},{"key":"bibr82-02698811221092508","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.v67n1110"},{"key":"bibr83-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2004.07.044"},{"key":"bibr84-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2063-13.2013"},{"key":"bibr85-02698811221092508","doi-asserted-by":"publisher","DOI":"10.4103\/0976-0105.177703"},{"key":"bibr86-02698811221092508","volume-title":"Psychedelics as Psychiatric Medicines","author":"Neill JC"},{"key":"bibr87-02698811221092508","unstructured":"Ni J, Lewis CM, Wunderle T, et al. (2017) Gamma-band resonance of visual cortex to optogenetic stimulation. Available at: https:\/\/www.biorxiv.org\/content\/10.1101\/135467v1.article-info"},{"key":"bibr88-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2003.11.002"},{"key":"bibr89-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1038\/s41429-020-0311-8"},{"key":"bibr90-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1002047"},{"key":"bibr91-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.03.020"},{"key":"bibr92-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1098\/rsif.2014.0873"},{"key":"bibr93-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.24003"},{"key":"bibr94-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1021\/cn500350e"},{"key":"bibr95-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhh104"},{"key":"bibr96-02698811221092508","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22020835"},{"key":"bibr97-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4037-06.2007"},{"key":"bibr98-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2017.11.049"},{"key":"bibr99-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1017\/S1461145714000261"},{"key":"bibr100-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1177\/0269881119855974"},{"key":"bibr101-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhh070"},{"key":"bibr102-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1038\/srep46421"},{"key":"bibr103-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1101\/2021.02.17.431629"},{"key":"bibr104-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0812686106"},{"key":"bibr105-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2008.11.036"},{"key":"bibr106-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.02.028"},{"key":"bibr107-02698811221092508","doi-asserted-by":"publisher","DOI":"10.3389\/fnsys.2015.00190"},{"key":"bibr108-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1038\/nature07991"},{"key":"bibr109-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1126\/science.272.5259.225"},{"key":"bibr110-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1101\/2021.02.16.431276"},{"key":"bibr111-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1093\/ijnp\/pyw041.506"},{"key":"bibr112-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-08-02785.1997"},{"key":"bibr113-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2884"},{"key":"bibr114-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-020-0367-2"},{"key":"bibr115-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1016\/S0893-133X(96)00246-1"},{"key":"bibr116-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-199812010-00024"},{"key":"bibr117-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00035.2008"},{"key":"bibr118-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1126\/science.1123432"},{"key":"bibr119-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1038\/373612a0"},{"key":"bibr120-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.6377-11.2012"},{"key":"bibr121-02698811221092508","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2007.07.009"}],"container-title":["Journal of Psychopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/02698811221092508","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/02698811221092508","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/02698811221092508","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:11:01Z","timestamp":1777507861000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/02698811221092508"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,30]]},"references-count":121,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2022,7]]}},"alternative-id":["10.1177\/02698811221092508"],"URL":"https:\/\/doi.org\/10.1177\/02698811221092508","relation":{},"ISSN":["0269-8811","1461-7285"],"issn-type":[{"value":"0269-8811","type":"print"},{"value":"1461-7285","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,30]]}}}