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In this randomized, double\u2010blind, placebo\u2010controlled single ascending\u2010dose study, we evaluated the safety, tolerability, and pharmacokinetics of noribogaine in 27 patients seeking to discontinue methadone OST who had been switched to morphine during the previous week. Noribogaine doses were 60, 120, or 180 mg (n = 6\/dose level) or matching placebo (n = 3\/dose level). Noribogaine was well tolerated. The most frequent treatment\u2010emergent adverse events were noneuphoric changes in light perception \u223c1 hour postdose, headache, and nausea. Noribogaine had dose\u2010linear increases for AUC and C<jats:sub>max<\/jats:sub> and was slowly eliminated (mean t<jats:sub>1\/2<\/jats:sub> range, 24\u201330 hours). There was a concentration\u2010dependent increase in QTcI (0.17 ms\/ng\/mL), with the largest observed mean effect of \u223c16, 28, and 42 milliseconds in the 60\u2010, 120\u2010, and 180\u2010mg groups, respectively. Noribogaine showed a nonstatistically significant trend toward decreased total score in opioid withdrawal ratings, most notably at the 120\u2010mg dose; however, the study design may have confounded evaluations of time to resumption of OST. Future exposure\u2010controlled multiple\u2010dose noribogaine studies are planned that will address these safety and design issues.<\/jats:p>","DOI":"10.1002\/cpdd.254","type":"journal-article","created":{"date-parts":[[2016,2,10]],"date-time":"2016-02-10T10:23:30Z","timestamp":1455099810000},"page":"460-468","source":"Crossref","is-referenced-by-count":62,"title":["Ascending Single\u2010Dose, Double\u2010Blind, Placebo\u2010Controlled Safety Study of Noribogaine in Opioid\u2010Dependent Patients"],"prefix":"10.1002","volume":"5","author":[{"given":"Paul","family":"Glue","sequence":"first","affiliation":[{"name":"University of Otago  Dunedin New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gavin","family":"Cape","sequence":"additional","affiliation":[{"name":"Southern District Health Board  Dunedin New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna","family":"Tunnicliff","sequence":"additional","affiliation":[{"name":"Southern District Health Board  Dunedin New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Lockhart","sequence":"additional","affiliation":[{"name":"University of Auckland  Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fred","family":"Lam","sequence":"additional","affiliation":[{"name":"Zenith Technology Ltd  Dunedin New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noelyn","family":"Hung","sequence":"additional","affiliation":[{"name":"University of Otago  Dunedin New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. 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