Ascending Single‐Dose, Double‐Blind, Placebo‐Controlled Safety Study of Noribogaine in Opioid‐Dependent Patients

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 C and was slowly eliminated (mean t 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.

Pharmacochaperoning in a Drosophila model system rescues human dopamine transporter variants associated with infantile/juvenile parkinsonism

“…Finally, noribogaine restored trafficking of hDAT-V158F from the neuronal soma to the axonal territories, thus providing independent evidence for its pharmacochaperoning activity. The therapeutic implications of our findings are self-evident; phase I trials show that noribogaine is reasonably well tolerated up to doses of 180 mg/day by adults ( 38 , 39 ). A trial of noribogaine may be justified in children suffering infantile dystonia and parkinsonism, which is due to the mutations hDAT-V158F and hDAT-G327R.…”

The Effects of Ibogaine on Uterine Smooth Muscle Contractions: Relation to the Activity of Antioxidant Enzymes

“…During the early period of exploration, ibogaine was mostly known for its ability to inspire a sense of wellbeing both mentally and physically. Ibogaine has also been used for the treatment of substance abuse because it interrupts drug addiction, relieves withdrawal symptoms, and significantly decreases the desire for cocaine, heroin, alcohol, and most other mind-altering drugs [ 1 – 4 ]. The pharmacology of ibogaine is quite complex and affects many different neurotransmitter systems simultaneously.…”

Subjective effectiveness of ibogaine treatment for problematic opioid consumption: Short- and long-term outcomes and current psychological functioning

“…In 1993–1994, The National Institute on Drug Abuse (NIDA) developed a Phase I investigation to evaluate pharmacokinetic and safety data in a fixed dosage study for cocaine dependence, but they decided not to fund the implementation of the protocol ( Alper, 2001 ; Alper et al, 2001 ). In two Phase I studies, low doses of noribogaine (the active metabolite of ibogaine, which has a distinct pharmacological profile) was well tolerated ( Glue et al, 2015 ) and showed a trend toward reduction in opioid withdrawal ratings ( Glue et al, 2016 ).…”