Ascending-dose study of noribogaine in healthy volunteers: pharmacokinetics, pharmacodynamics, safety, and tolerability.
Paul Glue, Michelle Lockhart, Fred Lam, Noelyn Hung, Cheung-Tak Hung, Lawrence Friedhoff
The Journal of Clinical Pharmacology February 1, 2015 DOI: 10.1002/jcph.404 (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 | 36 |
| Population | Healthy drug-free male volunteers |
| Intervention | Noribogaine |
| Dose | 3, 10, 30, or 60 mg |
| Duration | 216 hours |
| Topics | Ibogaine |
| Keywords | Pharmacodynamics Pharmacokinetics First-in-man study Drug safety |
| Citations | 61 |
| Key findings | Single oral doses of noribogaine 3-60 mg were safe and well tolerated in healthy volunteers, with no mu-opioid agonist pharmacodynamic effects observed. |
Abstract
Noribogaine is the active metabolite of the naturally occurring psychoactive substance ibogaine, and may help suppress withdrawal symptoms in opioid-dependent subjects. The objectives of this Phase I study were to assess the safety, tolerability, pharmacokinetic, and pharmacodynamic profiles of noribogaine. In this ascending single-dose, placebo-controlled, randomized, double-blind, parallel-group study in 36 healthy drug-free male volunteers, 4 cohorts (n = 9) received oral doses of 3, 10, 30, or 60 mg or matching placebo, with intensive safety and pharmacokinetic assessments out to 216 hours, along with pharmacodynamic assessments sensitive to the effects of mu-opioid agonists. Noribogaine was rapidly absorbed, with peak concentrations occurring 2-3 hours after oral dosing, and showed dose-linear increases of area under the concentration-time curve (AUC) and Cmax between 3 and 60 mg. The drug was slowly eliminated, with mean half-life estimates of 28-49 hours across dose groups. Apparent volume of distribution was high (mean 1417-3086 L across dose groups). No safety or tolerability issues were identified in any cohort. No mu-opioid agonist pharmacodynamic effects were noted in pupillometry or cold-pressor testing. Single oral doses of noribogaine 3-60 mg were safe and well tolerated in healthy volunteers.
Comparable studies
Other randomized controlled trials on ibogaine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Ascending Single-Dose, Double-Blind, Placebo-Controlled Safety Study of Noribogaine in Opioid-Dependent Patients. Patients on methadone opioid substitution therapy seeking to discontinue methadone | 2016 | Randomized controlled trial | n = 27 |
| 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 49
- Treatment of opioid use disorder with ibogaine: detoxification and drug use outcomes. The American Journal of Drug and Alcohol Abuse 2018
- Ibogaine treatment outcomes for opioid dependence from a twelve-month follow-up observational study. The American Journal of Drug and Alcohol Abuse 2018
- The Anti-Addiction Drug Ibogaine and the Heart: A Delicate Relation Molecules January 29, 2015
- Ibogaine Detoxification Transitions Opioid and Cocaine Abusers Between Dependence and Abstinence: Clinical Observations and Treatment Outcomes. Frontiers in Pharmacology 2018
- Intensity of Mystical Experiences Occasioned by 5-MeO-DMT and Comparison With a Prior Psilocybin Study Frontiers in Psychology December 6, 2018
and 44 more in the library
Cites 9
- The ibogaine medical subculture. Journal of Ethnopharmacology January 4, 2008
- Identification of a primary metabolite of ibogaine that targets serotonin transporters and elevates serotonin. Life Sciences 1995
- Ibogaine, an anti-addictive drug: pharmacology and time to go further in development. A narrative review. Human & Experimental Toxicology March 1, 2008
- Radioligand-binding study of noribogaine, a likely metabolite of ibogaine. Brain Research March 27, 1995
- Noribogaine (12-hydroxyibogamine): a biologically active metabolite of the antiaddictive drug ibogaine. Annals of the New York Academy of Sciences September 1, 2000
and 4 more in the library