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
Journal of clinical pharmacology February 1, 2015 DOI: 10.1002/jcph.404 via PubMed
Summary
AI-generated from the abstractNoribogaine, the active metabolite of ibogaine, may help suppress withdrawal symptoms in opioid-dependent people. In a Phase I ascending single-dose, placebo-controlled, randomized, double-blind, parallel-group study in 36 healthy drug-free male volunteers, oral doses of 3, 10, 30, or 60 mg were given. Noribogaine was rapidly absorbed, reaching peak concentrations 2-3 hours after dosing, and showed dose-linear increases in exposure between 3 and 60 mg. The drug was slowly eliminated, with mean half-lives of 28-49 hours and a high volume of distribution (mean 1417-3086 L). No safety or tolerability issues were identified, and no mu-opioid agonist effects were observed in pupillometry or cold-pressor testing. Single oral doses of 3-60 mg were safe and well tolerated.
Study at a glance
| 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 finding | 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.