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Initial trials suggested therapeutic effects of DMT in depressive disorders. However, systematic data on dose-dependent pharmacokinetics and acute effects of intravenous bolus DMT administration are currently lacking. We used a double-blind, randomized, placebo-controlled, crossover design in 20 healthy participants who received placebo and DMT (5, 10, 15, and 20\u2009mg) within a single test session. In a separate study arm, we used an open-label, DMT dose-escalation administration design where 16 participants received stepwise increases of 5\u2009mg DMT until reaching a maximally tolerated dose (max. 25\u2009mg). Outcome measures included subjective effects, autonomic effects, adverse effects, and pharmacokinetics that were assessed up to 55\u2009min after each bolus administration. Bolus DMT doses induced very strong subjective effects with a very rapid onset and peak within the first 2\u2009min after administration. Subjective effects declined quickly and subsided completely within 12\u201330\u2009min, consistent with the short elimination half-life of approximately 6\u20137\u2009min. A ceiling effect for peak subjective effects was reached at the 15\u2009mg dose. No tolerance was observed to acute effects of DMT. The tolerability markedly improved with open-label dose-escalation compared with double-blinded, randomized administration, and at equivalent dose levels, subjective effects were rated as less intense. These findings highlight the impact of blinding and expectancy on the subjective experience and suggest that individual dose-escalation may improve tolerability and help with dose selection for future DMT studies.\n                  <\/jats:p>","DOI":"10.1038\/s41398-026-03987-7","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T16:02:43Z","timestamp":1774627363000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Dose-dependent pharmacokinetics and acute effects of intravenous bolus N,N-dimethyltryptamine: double-blind, randomized versus open-label dose-escalation administration study in healthy participants"],"prefix":"10.1038","volume":"16","author":[{"given":"Livio","family":"Erne","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9155-1080","authenticated-orcid":false,"given":"Lorenz","family":"Mueller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2952-586X","authenticated-orcid":false,"given":"Isabelle","family":"Straumann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bislim","family":"Ademaj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9341-3669","authenticated-orcid":false,"given":"Anne","family":"Eckert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ina","family":"Vukalovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7040-1041","authenticated-orcid":false,"given":"Jan","family":"Valenta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0874-4875","authenticated-orcid":false,"given":"Dino","family":"Luethi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1765-9659","authenticated-orcid":false,"given":"Matthias E.","family":"Liechti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Severin B.","family":"Vogt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,27]]},"reference":[{"key":"3987_CR1","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1124\/jpet.103.049882","volume":"306","author":"J Riba","year":"2003","unstructured":"Riba J, Valle M, Urbano G, Yritia M, Morte A, Barbanoj MJ. 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