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However, very little is known about the pharmacokinetic properties of DMT as well as any relationship between its exposure and effects. This study aimed to characterize population pharmacokinetics of DMT as well as the relationship between DMT plasma concentrations and its psychedelic effects as measured through subjective intensity ratings. Data were obtained from 13 healthy subjects after intravenous administration of DMT. The data were analyzed using nonlinear mixed\u2010effects modeling in NONMEM. DMT plasma concentrations were described by a two\u2010compartment model with first\u2010order elimination leading to formation of the major metabolite indole 3\u2010acetic acid. The relationship between plasma concentrations and psychedelic intensity was described by an effect site compartment model with a sigmoid maximum effect (<jats:italic>E<\/jats:italic><jats:sub>max<\/jats:sub>) response. DMT clearance was estimated at 26\u2009L\/min, a high value indicating elimination of DMT to be independent of blood flow. Higher concentrations of DMT were associated with a more intense experience with the concentration of DMT at the effect site required to produce half of the maximum response estimated at 95\u2009nM. The maximum achievable intensity rating was 10 and the simulated median maximum rating was zero, 2, 4, 8, and 9 after doses of 1, 4, 7, 14, and 20\u2009mg, respectively. The model can be useful in predicting suitable doses for clinical investigations of DMT based on the desired intensity of the subjective experience.<\/jats:p>","DOI":"10.1111\/cts.13410","type":"journal-article","created":{"date-parts":[[2022,9,11]],"date-time":"2022-09-11T20:03:25Z","timestamp":1662926605000},"page":"2928-2937","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Population pharmacokinetic\/pharmacodynamic modeling of the psychedelic experience induced by N,N\u2010dimethyltryptamine \u2013 Implications for dose considerations"],"prefix":"10.1111","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0625-5616","authenticated-orcid":false,"given":"Emma","family":"Eckern\u00e4s","sequence":"first","affiliation":[{"name":"Unit for Pharmacokinetics and Drug Metabolism, Department of Pharmacology Sahlgrenska Academy at University of Gothenburg  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Timmermann","sequence":"additional","affiliation":[{"name":"Division of Psychiatry, Department of Brain Sciences, Centre for Psychedelic Research Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Carhart\u2010Harris","sequence":"additional","affiliation":[{"name":"Division of Psychiatry, Department of Brain Sciences, Centre for Psychedelic Research Imperial College London  London UK"},{"name":"Psychedelics Division, Neuroscape, Department of Neurology University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"R\u00f6shammar","sequence":"additional","affiliation":[{"name":"Pharmetheus AB  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Ashton","sequence":"additional","affiliation":[{"name":"Unit for Pharmacokinetics and Drug Metabolism, Department of Pharmacology Sahlgrenska Academy at University of Gothenburg  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,9,27]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"Institute of Health Metrics and Evaluation.Global Health Data Exchange (GHDx). 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