{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T10:22:19Z","timestamp":1792059739623,"version":"4.4.0"},"reference-count":50,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2024,3,22]],"date-time":"2024-03-22T00:00:00Z","timestamp":1711065600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2024,3,22]],"date-time":"2024-03-22T00:00:00Z","timestamp":1711065600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Stichting het Hoogeland"},{"name":"Di-AcetylM BV"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Psychopharmacol"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>Ibogaine is a hallucinogenic drug that may be used to treat opioid use disorder (OUD). The relationships between pharmacokinetics (PKs) of ibogaine and its metabolites and their clinical effects on side effects and opioid withdrawal severity are unknown. We aimed to study these relationships in patients with OUD undergoing detoxification supported by ibogaine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>The study was performed in 14 subjects with OUD. They received a single dose of 10mg\/kg ibogaine hydrochloride. Plasma PKs of ibogaine, noribogaine, and noribogaine glucuronide were obtained during 24 h. Cytochrome P450 isoenzyme 2D6 (CYP2D6) genotyping was performed. The PKs were analyzed by means of nonlinear mixed effects modeling and related with corrected QT interval (QTc) prolongation, cerebellar ataxia, and opioid withdrawal severity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      The PK of ibogaine were highly variable and significantly correlated to CYP2D6 genotype (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      &lt; 0.001). The basic clearance of ibogaine (at a CYP2D6 activity score (AS) of 0) was 0.82 L\/h. This increased with 30.7 L\/h for every point of AS. The relation between ibogaine plasma concentrations and QTc was best described by a sigmoid\n                      <jats:italic toggle=\"yes\">E<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      model. Spearman correlations were significant (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      &lt; 0.03) for ibogaine but not noribogaine with QTc (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      = 0.109) and cerebellar effects (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      = 0.668); neither correlated with the severity of opioid withdrawal symptoms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>The clearance of ibogaine is strongly related to CYPD2D6 genotype. Ibogaine cardiac side effects (QTc time) and cerebellar effects are most likely more driven by ibogaine rather than noribogaine. Future studies should aim at exploring lower doses and\/or applying individualized dosing based on CYP2D6 genotype.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/02698811241237873","type":"journal-article","created":{"date-parts":[[2024,3,22]],"date-time":"2024-03-22T23:13:50Z","timestamp":1711149230000},"page":"481-488","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":20,"title":["The pharmacokinetics and pharmacodynamics of ibogaine in opioid use disorder patients"],"prefix":"10.1177","volume":"38","author":[{"given":"Thomas","family":"Knuijver","sequence":"first","affiliation":[{"name":"IrisZorg, Nijmegen, The Netherlands"},{"name":"Nijmegen Institute for Scientist-Practitioners in Addiction, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2185-8201","authenticated-orcid":false,"given":"Rob","family":"ter Heine","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Research Institute for Medical Innovation, Radboudumc, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnt F. A.","family":"Schellekens","sequence":"additional","affiliation":[{"name":"Nijmegen Institute for Scientist-Practitioners in Addiction, Nijmegen, The Netherlands"},{"name":"Department of Psychiatry, Research Institute for Medical Innovation, Radboudumc, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paniz","family":"Heydari","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc","family":"Lucas","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sjoerd","family":"Westra","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Research Institute for Medical Innovation, Radboudumc, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maarten","family":"Belgers","sequence":"additional","affiliation":[{"name":"IrisZorg, Nijmegen, The Netherlands"},{"name":"Nijmegen Institute for Scientist-Practitioners in Addiction, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toon","family":"van Oosteren","sequence":"additional","affiliation":[{"name":"IrisZorg, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robbert Jan","family":"Verkes","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Research Institute for Medical Innovation, Radboudumc, Nijmegen, The Netherlands"},{"name":"Pompestichting, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelis","family":"Kramers","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Research Institute for Medical Innovation, Radboudumc, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2024,3,22]]},"reference":[{"key":"e_1_3_3_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2000.tb06687.x"},{"key":"e_1_3_3_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1556-4029.2011.02008.x"},{"key":"e_1_3_3_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3565(24)29567-7"},{"key":"e_1_3_3_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2016.71"},{"key":"e_1_3_3_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2011.04.016"},{"key":"e_1_3_3_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/00952990.2017.13208021-13."},{"key":"e_1_3_3_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/00952990.2017.1320802"},{"key":"e_1_3_3_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0376-8716(96)01331-2"},{"key":"e_1_3_3_10_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2036.2003.01641.x"},{"key":"e_1_3_3_11_1","unstructured":"EudraCT (2014) The Efficacy of Ibogaine in the Treatment of Addiction; an open label single fixed dose pilot-study of the efficacy of ibogaine in opioid-dependent subjects\u2013 EudraCT number 2014-000354-11. Available at: https:\/\/www.clinicaltrialsregister.eu\/ctr-search\/search?query=2014-000354-11."},{"key":"e_1_3_3_12_1","unstructured":"Flockhart DA Thacker D McDonald C et al. (2014) The Flockhart Cytochrome P450 Drug-Drug Interaction Table. Division of Clinical Pharmacology Indiana University School of Medicine. Updated 2021. Available at: https:\/\/drug-interactions.medicine.iu.edu (accessed 2014)."},{"key":"e_1_3_3_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.clpt.6100406"},{"key":"e_1_3_3_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.254"},{"key":"e_1_3_3_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.471"},{"key":"e_1_3_3_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jemermed.2019.06.052"},{"key":"e_1_3_3_17_1","doi-asserted-by":"crossref","unstructured":"Handelsman L Cochrane KJ Aronson MJ et al. (1987) Two new rating scales for opiate withdrawal. Am J Drug Alcohol Abuse 13(3): 293-308. https:\/\/crediblemeds.org\/TheArizonaQTdrugslist.","DOI":"10.3109\/00952998709001515"},{"key":"e_1_3_3_18_1","unstructured":"IBM Micromedex\u00ae (electronic version). IBM Watson Health Greenwood Village Colorado USA. Available at: https:\/\/www.micromedexsolutions.com\/ (cited: month\/day\/year)."},{"key":"e_1_3_3_19_1","unstructured":"inc. MefLEP (2014) Iboga\u00efne Alliance website with information Remogen Ibogaine. https:\/\/www.ibogainealliance.org\/conferences\/vancouver-2012\/archive\/bob-sisko\/."},{"key":"e_1_3_3_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac956"},{"key":"e_1_3_3_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/add.15448."},{"key":"e_1_3_3_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsat.2021.108717"},{"key":"e_1_3_3_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules20022208"},{"key":"e_1_3_3_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1369-1600.2012.00447.x"},{"key":"e_1_3_3_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2013.05.012"},{"key":"e_1_3_3_26_1","doi-asserted-by":"publisher","DOI":"10.3109\/15563650.2016.1138226"},{"key":"e_1_3_3_27_1","doi-asserted-by":"publisher","DOI":"10.3109\/00498254.2013.835885"},{"issue":"1","key":"e_1_3_3_28_1","doi-asserted-by":"crossref","first-page":"34","DOI":"10.18433\/J3GP53","article-title":"Understanding the hysteresis loop conundrum in pharmacokinetic\/pharmacodynamic relationships","volume":"17","author":"Louizos C","year":"2014","unstructured":"Louizos C, Y\u00e1\u00f1ez JA, Forrest L, et al. (2014) Understanding the hysteresis loop conundrum in pharmacokinetic\/pharmacodynamic relationships. Journal of pharmacy & pharmaceutical sciences: a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques 17(1): 34.","journal-title":"Journal of pharmacy & pharmaceutical sciences: a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques"},{"key":"e_1_3_3_29_1","doi-asserted-by":"publisher","DOI":"10.1177\/0960327107087802"},{"key":"e_1_3_3_30_1","doi-asserted-by":"publisher","DOI":"10.1080\/02791072.2018.1447175."},{"key":"e_1_3_3_31_1","doi-asserted-by":"publisher","DOI":"10.1097\/00008571-199706000-00004"},{"key":"e_1_3_3_32_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2018.00529"},{"key":"e_1_3_3_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0099-9598(01)56012-5"},{"key":"e_1_3_3_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2000.tb05213.x"},{"key":"e_1_3_3_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(96)00739-1"},{"key":"e_1_3_3_36_1","doi-asserted-by":"publisher","DOI":"10.1080\/00952990.2017.1310218."},{"key":"e_1_3_3_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(93)90500-F"},{"issue":"8","key":"e_1_3_3_38_1","first-page":"764","article-title":"Cytochrome P4502D6 catalyzes the O-demethylation of the psychoactive alkaloid ibogaine to 12-hydroxyibogamine","volume":"26","author":"Obach RS","year":"1998","unstructured":"Obach RS, Pablo J, Mash DC (1998) Cytochrome P4502D6 catalyzes the O-demethylation of the psychoactive alkaloid ibogaine to 12-hydroxyibogamine. Drug Metab Dispos 26(8): 764-768.","journal-title":"Drug Metab Dispos"},{"key":"e_1_3_3_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-021-05964-y"},{"key":"e_1_3_3_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jelectrocard.2020.01.003"},{"issue":"9","key":"e_1_3_3_41_1","first-page":"422","article-title":"Life-threatening complications of ibogaine: three case reports","volume":"70","author":"Paling FP","year":"2012","unstructured":"Paling FP, Andrews LM, Valk GD, et al. (2012) Life-threatening complications of ibogaine: three case reports. Neth J Med 70(9): 422-424.","journal-title":"Neth J Med"},{"key":"e_1_3_3_42_1","doi-asserted-by":"publisher","DOI":"10.2174\/1573403X10666140514103612"},{"key":"e_1_3_3_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/dar.13587"},{"key":"e_1_3_3_44_1","doi-asserted-by":"publisher","DOI":"10.1177\/0269881114552713"},{"key":"e_1_3_3_45_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000219042.60538.92"},{"key":"e_1_3_3_46_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181d1a6c9"},{"key":"e_1_3_3_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/0740-5472(94)90049-3"},{"key":"e_1_3_3_48_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.113.209643"},{"key":"e_1_3_3_49_1","doi-asserted-by":"publisher","DOI":"10.3109\/15563650.2014.927477"},{"key":"e_1_3_3_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.21544"},{"key":"e_1_3_3_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2007.09.021"}],"container-title":["Journal of Psychopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/02698811241237873","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/02698811241237873","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/02698811241237873","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:11:39Z","timestamp":1777507899000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/02698811241237873"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,22]]},"references-count":50,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,5]]}},"alternative-id":["10.1177\/02698811241237873"],"URL":"https:\/\/doi.org\/10.1177\/02698811241237873","relation":{},"ISSN":["0269-8811","1461-7285"],"issn-type":[{"value":"0269-8811","type":"print"},{"value":"1461-7285","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,22]]}}}