{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T11:12:03Z","timestamp":1788261123885,"version":"build-2803163510"},"reference-count":146,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,4,22]],"date-time":"2021-04-22T00:00:00Z","timestamp":1619049600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Hallucinogens are a loosely defined group of compounds including LSD, N,N-dimethyltryptamines, mescaline, psilocybin\/psilocin, and 2,5-dimethoxy-4-methamphetamine (DOM), which can evoke intense visual and emotional experiences. We are witnessing a renaissance of research interest in hallucinogens, driven by increasing awareness of their psychotherapeutic potential. As such, we now present a narrative review of the literature on hallucinogen binding in vitro and ex vivo, and the various molecular imaging studies with positron emission tomography (PET) or single photon emission computer tomography (SPECT). In general, molecular imaging can depict the uptake and binding distribution of labelled hallucinogenic compounds or their congeners in the brain, as was shown in an early PET study with N1-([11C]-methyl)-2-bromo-LSD ([11C]-MBL); displacement with the non-radioactive competitor ketanserin confirmed that the majority of [11C]-MBL specific binding was to serotonin 5-HT2A receptors. However, interactions at serotonin 5HT1A and other classes of receptors and pleotropic effects on second messenger pathways may contribute to the particular experiential phenomenologies of LSD and other hallucinogenic compounds. Other salient aspects of hallucinogen action include permeability to the blood\u2013brain barrier, the rates of metabolism and elimination, and the formation of active metabolites. Despite the maturation of radiochemistry and molecular imaging in recent years, there has been only a handful of PET or SPECT studies of radiolabeled hallucinogens, most recently using the 5-HT2A\/2C agonist N-(2[11CH3O]-methoxybenzyl)-2,5-dimethoxy- 4-bromophenethylamine ([11C]Cimbi-36). In addition to PET studies of target engagement at neuroreceptors and transporters, there is a small number of studies on the effects of hallucinogenic compounds on cerebral perfusion ([15O]-water) or metabolism ([18F]-fluorodeoxyglucose\/FDG). There remains considerable scope for basic imaging research on the sites of interaction of hallucinogens and their cerebrometabolic effects; we expect that hybrid imaging with PET in conjunction with functional magnetic resonance imaging (fMRI) should provide especially useful for the next phase of this research.<\/jats:p>","DOI":"10.3390\/molecules26092451","type":"journal-article","created":{"date-parts":[[2021,4,22]],"date-time":"2021-04-22T13:59:14Z","timestamp":1619099954000},"page":"2451","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0257-9621","authenticated-orcid":false,"given":"Paul","family":"Cumming","sequence":"first","affiliation":[{"name":"Department of Nuclear Medicine, Bern University Hospital, CH-3010 Bern, Switzerland"},{"name":"School of Psychology and Counselling, Queensland University of Technology, Brisbane 4059, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1313-2208","authenticated-orcid":false,"given":"Milan","family":"Scheidegger","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital of the University of Zurich, CH-8032 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dario","family":"Dornbierer","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital of the University of Zurich, CH-8032 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6014-2084","authenticated-orcid":false,"given":"Mikael","family":"Palner","sequence":"additional","affiliation":[{"name":"Odense Department of Clinical Research, University of Southern Denmark, DK-5000 Odense, Denmark"},{"name":"Department of Nuclear Medicine, Odense University Hospital, DK-5000 Odense, Denmark"},{"name":"Neurobiology Research Unit, Copenhagen University Hospital, DK-2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris B.","family":"Quednow","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital of the University of Zurich, CH-8032 Zurich, Switzerland"},{"name":"Neuroscience Center Zurich, University of Zurich and Swiss Federal Institute of Technology Zurich, CH-8058 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3859-9023","authenticated-orcid":false,"given":"Chantal","family":"Martin-Soelch","sequence":"additional","affiliation":[{"name":"Department of Psychology, University of Fribourg, CH-1700 Fribourg, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/bs.pbr.2018.08.004","article-title":"Advances and challenges in neuroimaging studies on the effects of serotonergic hallucinogens: Contributions of the resting brain","volume":"242","author":"Muller","year":"2018","journal-title":"Prog. 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