{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:47:42Z","timestamp":1787014062829,"version":"build-2736575974"},"reference-count":50,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T00:00:00Z","timestamp":1747094400000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The serotonergic psychedelic\n                    <jats:italic>N<\/jats:italic>\n                    ,\n                    <jats:italic>N<\/jats:italic>\n                    \u2010dimethyltryptamine (DMT) presumably stimulates neuroplasticity in\u00a0vitro and in\u00a0vivo, by which it may exert neuroprotective effects during acute ischemic stroke. Since neuroplasticity has been implicated in the mechanism of action of rehabilitative therapy in stroke recovery, a pharmacological augmentation strategy facilitating neuroplasticity could be beneficial. To optimize this treatment strategy, a detailed understanding of the safety, pharmacokinetics, and pharmacodynamics of prolonged DMT administration is required. This randomized, double\u2010blind, placebo\u2010controlled, single ascending dose study administered three intravenous doses of DMT as a 30\u2010s bolus followed by a 6\u2010h infusion: 1.5\u2009mg\u2009+\u20090.105\u2009mg\/min, 7.5\u2009mg\u2009+\u20090.525\u2009mg\/min, and 5.0\u2009mg\u2009+\u20090.7875\u2009mg\/min. Twelve female and seventeen male psychedelic\u2010experienced and na\u00efve healthy participants, with a mean age of 27.3 (SD 10.2, range 19\u201357) years, were included. No serious adverse events occurred, and all adverse events were mild in intensity and self\u2010limiting. No significant abnormalities in vital signs or 12\u2010lead electrocardiography, and no suicidality or treatment\u2010emergent psychopathology occurred. Moderate interindividual pharmacokinetic variability was observed. Mild psychedelic effects were accompanied by decreases in sustained attention, postural stability, and occipital alpha electroencephalographic power at the highest dose, which peaked rapidly after bolus administration and remained relatively stable or decreased over time. Together, DMT administered intravenously as a 30\u2010s bolus followed by a 6\u2010h infusion and reaching maximal exposures of approximately 35\u2009ng\/mL in healthy volunteers was safe and demonstrated rapidly occurring but mild psychedelic effects, providing the basis for future proof\u2010of\u2010mechanism studies in patient populations.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Trial Registration:<\/jats:bold>\n                    ClinicalTrial.gov identifier: NCT05559931\n                  <\/jats:p>","DOI":"10.1111\/cts.70234","type":"journal-article","created":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T04:24:43Z","timestamp":1747110283000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Safety, Pharmacokinetics, and Pharmacodynamics of a 6\u2010h\n                    <i>N<\/i>\n                    ,\n                    <i>N<\/i>\n                    \u2010Dimethyltryptamine (DMT) Infusion in Healthy Volunteers: A Randomized, Double\u2010Blind, Placebo\u2010Controlled Trial"],"prefix":"10.1111","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-1783-357X","authenticated-orcid":false,"given":"Katelijne V.","family":"van der Heijden","sequence":"first","affiliation":[{"name":"Centre for Human Drug Research  Leiden the Netherlands"},{"name":"Leiden University Medical Centre  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5604-0157","authenticated-orcid":false,"given":"Rob G. 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