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When combined with the monoamine oxidase A (MAO-A) inhibitor harmine\u2014mimicking the pharmacological profile of ayahuasca\u2014oral DMT induces a psychedelic experience lasting 4\u20135\u2009h. While some neuroimaging studies have characterized effects of DMT on functional connectivity and electroencephalography its impact on cerebral energy metabolism remains largely unexplored. We assessed the cerebral metabolic rate for glucose consumption (CMRglc) with [\n                    <jats:sup>18<\/jats:sup>\n                    F]fluorodeoxyglucose positron emission tomography ([\n                    <jats:sup>18<\/jats:sup>\n                    F]FDG-PET) and linear graphic analysis following buccal DMT\u2009+\u2009harmine (90\u2009mg DMT, 120\u2009mg harmine) versus placebo in a single-blind, crossover design in 14 healthy males. Scans were acquired during peak drug effects (100\u2013170\u2009min post-administration). Global CMRglc increased by 12.5% under DMT+harmine versus placebo (\n                    <jats:italic toggle=\"yes\">t<\/jats:italic>\n                    \u2009=\u20092.58,\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009=\u20090.011). Vertex- and network-wise analyses revealed widespread cortical increases, particularly in higher-order brain networks. Exploratory analyses found a significant positive correlation between global CMRglc and harmine plasma levels, but not with DMT plasma levels, subjective intensity ratings. A psychedelic dose of DMT\u2009+\u2009harmine globally increased cerebral glucose metabolism, recapitulating a classic finding for psilocybin, and suggesting a potential metabolic signature of the psychedelic state. Clinical trial registry name and URL incl. registration number: Molecular Imaging Study of Harmine\/DMT: a Basic Research Approach (HaD-PET)\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT06252506\">https:\/\/clinicaltrials.gov\/study\/NCT06252506<\/jats:ext-link>\n                    .\n                  <\/jats:p>","DOI":"10.1177\/0271678x261454172","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T07:05:41Z","timestamp":1780297541000},"page":"2411-2425","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Global increases in brain glucose metabolism following acute N,N-dimethyltryptamine and harmine administration in healthy volunteers: A randomized [\n                    <sup>18<\/sup>\n                    F]FDG-PET 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Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chantal","family":"Martin-Soelch","sequence":"additional","affiliation":[{"name":"Department of Psychology, University of Fribourg, Fribourg, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John W.","family":"Smallridge","sequence":"additional","affiliation":[{"name":"Reconnect Labs AG, Spin-Off of the University of Zurich, Winterthur, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dario","family":"Dornbierer","sequence":"additional","affiliation":[{"name":"Reconnect Labs AG, Spin-Off of the University of Zurich, Winterthur, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris B.","family":"Quednow","sequence":"additional","affiliation":[{"name":"Department of Adult Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Zurich, Switzerland"},{"name":"Neuroscience Center Zurich, University of Zurich and Swiss Federal Institute of Technology Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milan","family":"Scheidegger","sequence":"additional","affiliation":[{"name":"Department of Adult Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Zurich, Switzerland"},{"name":"Neuroscience Center Zurich, University of Zurich and Swiss Federal Institute of Technology Zurich, Zurich, Switzerland"},{"name":"Reconnect Labs AG, Spin-Off of the University of Zurich, Winterthur, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0257-9621","authenticated-orcid":false,"given":"Paul","family":"Cumming","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Bern University Hospital, Bern, Switzerland"},{"name":"School of Psychology and Counselling, Queensland University of Technology, Brisbane, QLD, 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