Oral noribogaine shows high brain uptake and anti-withdrawal effects not associated with place preference in rodents
This vehicle-controlled rodent study (n=54) investigated the dose-dependent effects of noribogaine (10, 30, or 100mg/kg) on the uptake and anti-withdrawal symptoms of morphine. Results demonstrate the efficacy of noribogaine to reduce the somatic signs of morphine withdrawal up to 88% in mice two hours after oral administration and attenuates the negative signs of morphine withdrawal within substance-dependent mice, in a dose-dependent manner.
Authors
- Deborah Mash
Published
Abstract
Introduction
This study investigated the effects of noribogaine, the principal metabolite of the drug ibogaine, on substance-related disorders.
Methods
In the first experiment, mice chronically treated with morphine were subjected to naloxone-precipitated withdrawal two hours after oral administration of noribogaine. Oral noribogaine dose dependently decreased the global opiate withdrawal score by up to 88% of vehicle control with an ED50 of 13 mg/kg. In the second experiment, blood and brain levels of noribogaine showed a high brain penetration and a brain/blood ratio of 7±1 across all doses tested. In a third experiment, rats given oral noribogaine up to 100 mg/kg were tested for abuse liability using a standard biased conditioned place paradigm.
Results
Noribogaine-treated rats did not display place preference, suggesting that noribogaine is not perceived as a hedonic stimulus in rodents.
Discussion
Retrospective review of published studies assessing the efficacy of ibogaine on morphine withdrawal shows that the most likely cause of the discrepancies in the literature is the different routes of administration and time of testing following ibogaine administration. These results suggest that the metabolite noribogaine rather than the parent compound mediates the effects of ibogaine on blocking naloxone-precipitated withdrawal. Noribogaine may hold promise as a non-addicting alternative to standard opiate replacement therapies to transition patients to opiate abstinence.
Research Summary of 'Oral noribogaine shows high brain uptake and anti-withdrawal effects not associated with place preference in rodents'
Introduction
Mash and colleagues situate this work in a historical and pharmacological context in which ibogaine, an alkaloid used traditionally in Central Africa and explored clinically, has been reported to reduce opioid withdrawal and craving after single large doses. Early clinical and animal reports suggested durable effects of ibogaine despite its relatively short half-life in rodents, prompting the hypothesis that a long-lived metabolite mediates the sustained actions. Noribogaine, the principal o‑demethylated metabolite of ibogaine, has since been identified and shown to have distinct pharmacology, including higher affinity for the serotonin transporter and differential activity at opioid and nicotinic receptors relative to the parent compound. The study aimed to test whether noribogaine can attenuate the somatic signs of opioid withdrawal in a mouse model when given orally, to characterise its brain penetration (brain/blood ratio), and to assess abuse liability using a conditioned place preference (CPP) assay in rats. The investigators also performed a retrospective review of prior animal studies of ibogaine to explore whether differences in administration route and timing could explain inconsistent findings about ibogaine's effects on morphine withdrawal.
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Study Details
- Study Typeindividual
- Journal
- Compound
- Author
- APA Citation
Mash, D. C., Ameer, B., Prou, D., Howes, J. F., & Maillet, E. L. (2016). Oral noribogaine shows high brain uptake and anti-withdrawal effects not associated with place preference in rodents. Journal of Psychopharmacology, 30(7), 688-697. https://doi.org/10.1177/0269881116641331
References (3)
Papers cited by this study that are also in Blossom
Alper, K. R., Lotsof, H. S., Frenken, G. M. N. et al. · The American Journal on Addictions (2010)
Glue, P., Lockhart, M., Lam, F. et al. · Journal of Clinical Pharmacology (2014)
Maillet, E. L., Milon, N., Heghinian, M. D. et al. · Neuropharmacology (2015)
Cited By (8)
Papers in Blossom that reference this study
Fernandes-Nascimento, M. H., Negrão, A. B., Viana-Ferreira, K. et al. · Journal of Psychoactive Drugs (2023)
Mash, D. C. · Pharmacological Research (2023)
Rodríguez, P., Urbanavicius, J., Prieto, J. P. et al. · ACS Chemical Neuroscience (2020)
Wasko, M. J., Witt-Enderby, P. A., Surratt, C. K. · ACS Chemical Neuroscience (2018)
Logrip, M. L., Mash, D. C., Duque, L. et al. · Frontiers in Pharmacology (2018)
Camlin, T. J., Eulert, D., Horvath, A. T. et al. · Journal of Psychedelic Studies (2018)
Schenberg, E. E., de Castro Comis, M. A., Alexandre, J. F. M. et al. · Journal of Psychedelic Studies (2017)
Wilkins, C., Dos Santos, R. G., Solá, J. et al. · Journal of Psychedelic Studies (2017)
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