Ascending Single-Dose, Double-Blind, Placebo-Controlled Safety Study of Noribogaine in Opioid-Dependent Patients.
Paul Glue, Gavin Cape, Donna Tunnicliff, Michelle Lockhart, Fred Lam, Noelyn Hung, Cheung-Tak Hung, Sarah Harland, Jane Devane, R S Crockett, John F Howes, Borje Darpo, Meijian Zhou, Holger Weis, Lawrence Friedhoff
Clinical Pharmacology in Drug Development November 1, 2016 DOI: 10.1002/cpdd.254 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Placebo-controlled Double-blind Peer reviewed |
|---|---|
| Sample size | 27 |
| Population | Patients on methadone opioid substitution therapy seeking to discontinue methadone |
| Intervention | Noribogaine |
| Dose | 60, 120, or 180 mg |
| Duration | Single ascending dose |
| Topics | Ibogaine |
| Keywords | Qtc Opioid withdrawal Pharmacokinetics First-in-patient trial |
| Citations | 66 |
| Key findings | Noribogaine was well tolerated but caused a concentration-dependent increase in QTcI, and showed a nonstatistically significant trend toward reducing opioid withdrawal symptoms. |
Abstract
Ibogaine is a psychoactive substance that may reduce opioid withdrawal symptoms. This was the first clinical trial of noribogaine, ibogaine's active metabolite, in patients established on methadone opioid substitution therapy (OST). In this randomized, double-blind, placebo-controlled single ascending-dose 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-emergent adverse events were noneuphoric changes in light perception ∼1 hour postdose, headache, and nausea. Noribogaine had dose-linear increases for AUC and Cmax and was slowly eliminated (mean t1/2 range, 24-30 hours). There was a concentration-dependent increase in QTcI (0.17 ms/ng/mL), with the largest observed mean effect of ∼16, 28, and 42 milliseconds in the 60-, 120-, and 180-mg groups, respectively. Noribogaine showed a nonstatistically significant trend toward decreased total score in opioid withdrawal ratings, most notably at the 120-mg dose; however, the study design may have confounded evaluations of time to resumption of OST. Future exposure-controlled multiple-dose noribogaine studies are planned that will address these safety and design issues.
Comparable studies
Other randomized controlled trials on ibogaine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Ascending-dose study of noribogaine in healthy volunteers: pharmacokinetics, pharmacodynamics, safety, and tolerability. Healthy drug-free male volunteers | 2015 | Randomized controlled trial | n = 36 |
| Influence of CYP2D6 activity on the pharmacokinetics and pharmacodynamics of a single 20 mg dose of ibogaine in healthy volunteers. Healthy subjects | 2015 | Randomized controlled trial | n = 21 |
Citations in the library
Cited by 52
- A systematic literature review of clinical trials and therapeutic applications of ibogaine. Journal of Substance Abuse Treatment July 1, 2022
- Subjective effectiveness of ibogaine treatment for problematic opioid consumption: Short- and long-term outcomes and current psychological functioning. Journal of Psychedelic Studies November 1, 2017
- Classic and non‐classic psychedelics for substance use disorder: A review of their historic, past and current research Addiction Neuroscience June 22, 2022
- The adverse events of ibogaine in humans: an updated systematic review of the literature (2015-2020). Psychopharmacology June 1, 2022
- IUPHAR - invited review - Ibogaine - A legacy within the current renaissance of psychedelic therapy. Pharmacological Research April 1, 2023
and 47 more in the library
Cites 7
- The ibogaine medical subculture. Journal of Ethnopharmacology January 4, 2008
- The Anti-Addiction Drug Ibogaine and the Heart: A Delicate Relation Molecules January 29, 2015
- Ascending-dose study of noribogaine in healthy volunteers: pharmacokinetics, pharmacodynamics, safety, and tolerability. The Journal of Clinical Pharmacology February 1, 2015
- Anti-addiction drug ibogaine inhibits voltage-gated ionic currents: a study to assess the drug's cardiac ion channel profile. Toxicology and Applied Pharmacology December 1, 2013
- Mechanism of hERG channel block by the psychoactive indole alkaloid ibogaine. Journal of Pharmacology and Experimental Therapeutics February 1, 2014
and 2 more in the library