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Arterial spin labeling perfusion and blood-oxygen level-dependent (BOLD) fMRI were used to map cerebral blood flow and changes in venous oxygenation before and after intravenous infusions of placebo and psilocybin. Fifteen healthy volunteers were scanned with arterial spin labeling and a separate 15 with BOLD. As predicted, profound changes in consciousness were observed after psilocybin, but surprisingly, only decreases in cerebral blood flow and BOLD signal were seen, and these were maximal in hub regions, such as the thalamus and anterior and posterior cingulate cortex (ACC and PCC). Decreased activity in the ACC\/medial prefrontal cortex (mPFC) was a consistent finding and the magnitude of this decrease predicted the intensity of the subjective effects. Based on these results, a seed-based pharmaco-physiological interaction\/functional connectivity analysis was performed using a medial prefrontal seed. Psilocybin caused a significant decrease in the positive coupling between the mPFC and PCC. These results strongly imply that the subjective effects of psychedelic drugs are caused by decreased activity and connectivity in the brain's key connector hubs, enabling a state of unconstrained cognition.<\/jats:p>","DOI":"10.1073\/pnas.1119598109","type":"journal-article","created":{"date-parts":[[2012,1,24]],"date-time":"2012-01-24T02:18:47Z","timestamp":1327371527000},"page":"2138-2143","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":1021,"title":["Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin"],"prefix":"10.1073","volume":"109","author":[{"given":"Robin L.","family":"Carhart-Harris","sequence":"first","affiliation":[{"name":"Neuropsychopharmacology Unit,"},{"name":"Academic Unit of Psychiatry, University of Bristol, Bristol BS8 2BN, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Erritzoe","sequence":"additional","affiliation":[{"name":"Neuropsychopharmacology Unit,"},{"name":"Neurobiology Research Unit, Rigshospitalet, and Center for Integrated Molecular Brain Imaging, University of Copenhagen, DK-2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Williams","sequence":"additional","affiliation":[{"name":"Academic Unit of Psychiatry, University of Bristol, Bristol BS8 2BN, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James M.","family":"Stone","sequence":"additional","affiliation":[{"name":"Neuropsychopharmacology Unit,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence J.","family":"Reed","sequence":"additional","affiliation":[{"name":"Neuropsychopharmacology Unit,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Colasanti","sequence":"additional","affiliation":[{"name":"Neuropsychopharmacology Unit,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin J.","family":"Tyacke","sequence":"additional","affiliation":[{"name":"Neuropsychopharmacology Unit,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Leech","sequence":"additional","affiliation":[{"name":"Imperial College London, London W12 0NN, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea L.","family":"Malizia","sequence":"additional","affiliation":[{"name":"Academic Unit of Psychiatry, University of Bristol, Bristol BS8 2BN, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Murphy","sequence":"additional","affiliation":[{"name":"Brain Research Imaging Centre, Cardiff University, Cardiff CF10 3AT, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Hobden","sequence":"additional","affiliation":[{"name":"Brain Research Imaging Centre, Cardiff University, Cardiff CF10 3AT, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Evans","sequence":"additional","affiliation":[{"name":"Brain Research Imaging Centre, Cardiff University, Cardiff CF10 3AT, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Feilding","sequence":"additional","affiliation":[{"name":"The Beckley Foundation, Beckley Park, Oxford OX3 9SY, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard G.","family":"Wise","sequence":"additional","affiliation":[{"name":"Brain Research Imaging Centre, Cardiff University, Cardiff CF10 3AT, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Nutt","sequence":"additional","affiliation":[{"name":"Neuropsychopharmacology Unit,"},{"name":"Academic Unit of Psychiatry, University of Bristol, Bristol BS8 2BN, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2012,1,23]]},"reference":[{"key":"e_1_3_3_1_2","article-title":"Seeking the magic mushroom","author":"Wasson GR","year":"1957","unstructured":"GR Wasson, Seeking the magic mushroom. 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