{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T11:10:45Z","timestamp":1773054645122,"version":"3.50.1"},"reference-count":19,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T00:00:00Z","timestamp":1694044800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp; Syst Pharma"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>N,N\u2010dimethyltryptamine (DMT) is a psychedelic compound that is being studied as a therapeutic option in various psychiatric disorders. Due to its short half\u2010life, continuous infusion of DMT has been proposed to extend the psychedelic experience and potential therapeutic effects. The primary aim of this work was to design an infusion protocol for DMT based on a desired level of psychedelic intensity using population pharmacokinetic\/pharmacodynamic modeling. As a secondary aim, the impact of choosing a continuous variable or a bounded integer pharmacokinetic\/pharmacodynamic model to inform such an infusion protocol was investigated. A previously published continuous variable model and two newly developed bounded integer models were used to assess optimal doses for achieving a target response. Simulations were performed to identify an optimal combination of a bolus dose and an infusion rate. Based on the simulations, optimal doses to achieve intensity ratings between 7 and 9 (possible range\u2009=\u20090\u201310) were a bolus dose of 16\u2009mg DMT fumarate followed by an infusion rate of 1.4\u2009mg\/min based on the continuous variable model and 14\u2009mg with 1.2\u2009mg\/min for the two bounded integer models. However, the proportion within target was low (&lt;53%) for all models, indicating that individual dose adjustments would be necessary. Furthermore, some differences between the models were observed. The bounded integer models generally predicted lower proportions within a target of 7\u20139 with higher proportions exceeding target compared with the continuous variable model. However, results varied depending on target response with the major differences observed at the boundaries of the scale.<\/jats:p>","DOI":"10.1002\/psp4.13037","type":"journal-article","created":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T10:56:07Z","timestamp":1694084167000},"page":"1398-1410","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Optimized infusion rates for N,N\u2010dimethyltryptamine to achieve a target psychedelic intensity based on a modeling and simulation framework"],"prefix":"10.1002","volume":"12","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, Sahlgrenska Academy University of Gothenburg  Gothenburg Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeroen","family":"Koomen","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology University of Groningen, University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher","family":"Timmermann","sequence":"additional","affiliation":[{"name":"Centre for Psychedelic Research, Division of Psychiatry, Department of Brain Sciences Imperial College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robin","family":"Carhart\u2010Harris","sequence":"additional","affiliation":[{"name":"Psychedelics Division, Neuroscape, Department of Neurology University of California San Francisco  San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"R\u00f6shammar","sequence":"additional","affiliation":[{"name":"Pharmetheus AB  Uppsala Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Ashton","sequence":"additional","affiliation":[{"name":"Unit for Pharmacokinetics and Drug Metabolism, Sahlgrenska Academy University of Gothenburg  Gothenburg Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,9,7]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-017-4771-x"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/jcp.0000000000000436"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/0269881116675513"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-022-01344-y"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1017\/s0033291718001356"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsptsci.0c00194"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.13410"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-51974-4"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1994.03950020009001"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2016.00211"},{"key":"e_1_2_9_12_1","doi-asserted-by":"crossref","unstructured":"LuanLX Eckern\u00e4sE AshtonM et al.Psychological and physiological effects of extended DMT.PsyArXiv.2023. doi:10.31234\/osf.io\/vg4dp","DOI":"10.31234\/osf.io\/vg4dp"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13318-023-00822-y"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-019-0343-9"},{"key":"e_1_2_9_15_1","unstructured":"BealS SheinerL BoeckmannA LuddenT BachmanW BauerR.NONMEM users guide.1989."},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmpb.2005.04.005"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1023\/b:jopa.0000012998.04442.1f"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt1979253358"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-016-9487-8"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1080\/02791072.2019.1602291"}],"container-title":["CPT: Pharmacometrics &amp; 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