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Several studies have investigated the administration of intravenous boluses or combinations of a bolus and a subsequent continuous infusion. However, data on dose-dependent acute effects and pharmacokinetics of continuous DMT infusions are lacking. We used a double-blind, randomized, placebo-controlled, crossover design in 22 healthy participants (11 women, 11 men) who received placebo and DMT (0.6, 1.2, 1.8, and 2.4\u2009mg\/min) over an infusion duration of 120\u2009min. We also tested a self-guided titration scheme that allowed participants to adjust the DMT dose rate at prespecified time points to achieve their desired level of subjective effects. Outcome measures included subjective effects, autonomic effects, adverse effects, plasma hormone concentrations, and pharmacokinetics up to 3\u2009h after starting the infusion. DMT infusions exhibited dose-proportional pharmacokinetics and rapidly induced dose-dependent subjective effects that reached a plateau after 30\u2009min. A ceiling effect was observed for \u201cgood drug effect\u201d at 1.8\u2009mg\/min. The 2.4\u2009mg\/min dose of DMT induced greater anxious ego dissolution than the 1.8\u2009mg\/min dose and induced significant anxiety compared with placebo. We observed moderate acute tolerance to acute effects of DMT. In the self-guided titration session, the participants opted for moderate to strong psychedelic effects, comparable in intensity to the 1.8\u2009mg\/min DMT dose rate in the randomized dosing sessions. These results may assist with dose finding for future DMT research and demonstrate that acute subjective effects of DMT can be rapidly adjusted through dose titration.<\/jats:p>","DOI":"10.1038\/s41386-024-02041-8","type":"journal-article","created":{"date-parts":[[2024,12,19]],"date-time":"2024-12-19T14:02:21Z","timestamp":1734616941000},"page":"1008-1016","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Acute dose-dependent effects and self-guided titration of continuous N,N-dimethyltryptamine infusions in a double-blind placebo-controlled study in healthy participants"],"prefix":"10.1038","volume":"50","author":[{"given":"Livio","family":"Erne","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Severin B.","family":"Vogt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9155-1080","authenticated-orcid":false,"given":"Lorenz","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albiona","family":"Nuraj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5308-7945","authenticated-orcid":false,"given":"Anna","family":"Becker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Klaiber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melani","family":"Zuparic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nimmy","family":"Varghese","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":"Deborah","family":"Rudin","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"}]}],"member":"297","published-online":{"date-parts":[[2024,12,19]]},"reference":[{"key":"2041_CR1","doi-asserted-by":"publisher","first-page":"1327","DOI":"10.1016\/j.euroneuro.2016.05.001","volume":"26","author":"A Rickli","year":"2016","unstructured":"Rickli A, Moning OD, Hoener MC, Liechti ME. 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The other authors declare no conflicts of interests. Knowhow and data associated with this work and owned by the University Hospital Basel were licensed by Mind Medicine, Inc. Mind Medicine, Inc., had no role in financing, planning, or conducting the present study or the present publication.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}