OPEN Foundation

F. Lam

Ascending single-dose, double-blind, placebo-controlled safety study of noribogaine in opioid-dependent patients

February 10, 2016 / Addiction, Iboga / Ibogaine, Papers, Psychiatry, Psychopharmacology, Publications / By / , , , , , ,

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 180mg (n = 6/dose level) or matching placebo (n = 3/dose level). Noribogaine was well tolerated. The most frequent treatment-emergent adverse events were non-euphoric changes in light perception at ∼1h post dose, headache and nausea. Noribogaine had dose-linear increases for AUC and Cmax, and was slowly eliminated (mean t1/2 range 24–30h). There was a concentration-dependent increase in QTcI (0.17msec/ng/mL) with largest observed mean effect of ∼16msec, 28msec, and 42msec in the 60mg, 120mg, and 180mg groups, respectively. Noribogaine showed a non-statistically significant trend to decrease total scores in opioid withdrawal ratings, most notably at the 120mg 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.

Glue, P., Cape, G., Tunnicliff, D., Lockhart, M., Lam, F., Hung, N., … & Howes, J. (2016). Ascending single‐dose, double‐blind, placebo‐controlled safety study of noribogaine in opioid‐dependent patients. Clinical Pharmacology in Drug Development. http://dx.doi.org/10.1002/cpdd.254
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Ascending-dose study of noribogaine in healthy volunteers: Pharmacokinetics, pharmacodynamics, safety, and tolerability

December 22, 2014 / Iboga / Ibogaine, Papers, Psychopharmacology, Publications, Safety, Toxicology / By / , , , , ,

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.

Glue, P., Lockhart, M., Lam, F., Hung, N., Hung, C. T., & Friedhoff, L. (2014). Ascending‐dose study of noribogaine in healthy volunteers: Pharmacokinetics, pharmacodynamics, safety, and tolerability. The Journal of Clinical Pharmacology. https://dx.doi.org/10.1002/jcph.404

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30 April - Q&A with Rick Strassman

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