Neuropharmacology
December 1, 2015
Emeline L Maillet, Nicolas Milon, Mari D Heghinian et al.
59 citations
Noribogaine, the main human metabolite of the anti-addictive substance ibogaine, reaches brain concentrations up to 20 μM after a therapeutic dose. Binding experiments and computational simulations indicate it may bind to the orthosteric morphinan site of opioid receptors. Noribogaine is a weak mu opioid receptor antagonist (Ke=20 μM at both G-protein and β-arrestin pathways) but a G-protein biased kappa opioid receptor agonist: 75% as efficacious as dynorphin A at stimulating GDP-GTP exchange (EC50=9 μM) yet only 12% as efficacious at recruiting β-arrestin. It also functionally inhibits dynorphin-induced kappa β-arrestin recruitment (IC50=1 μM), more potent than its G-protein agonism.
Journal of psychopharmacology (Oxford, England)
July 1, 2016
Deborah C Mash, Barbara Ameer, Delphine Prou et al.
29 citations
Oral noribogaine dose dependently reduced naloxone-precipitated morphine withdrawal signs in mice by up to 88% with an ED50 of 13 mg/kg. Noribogaine showed high brain penetration with a brain/blood ratio of 7±1 across all doses tested. In rats, noribogaine up to 100 mg/kg did not produce conditioned place preference, indicating it is not perceived as a hedonic stimulus. Retrospective review of ibogaine studies suggests that differences in route of administration and testing time explain literature discrepancies. Noribogaine, not ibogaine, likely mediates withdrawal-blocking effects and may offer a non-addictive alternative to opiate replacement therapies.
Journal of psychopharmacology (Oxford, England)
June 1, 2015
Qing Chang, Taleen Hanania, Deborah C Mash et al.
26 citations
Noribogaine, a drug that acts on opioid receptors, nicotinic receptors, and serotonin transporters, was tested for its ability to reduce nicotine self-administration in adult male rats. After training to self-administer nicotine intravenously, rats received oral doses of noribogaine (12.5, 25, or 50 mg/kg), vehicle, varenicline, or saline. Noribogaine dose-dependently decreased nicotine self-administration by up to 64% compared to saline-treated levels, matching the effectiveness of 1.7 mg/kg varenicline. At the highest dose, noribogaine reduced food pellet self-administration by only 23%, indicating greater specificity for nicotine. The findings suggest noribogaine may be a promising treatment for nicotine dependence.
Behavioural brain research
July 14, 2017
Allan V Kalueff, Aleksandra Kaluyeva, Emeline L Maillet
21 citations
Noribogaine, the main psychoactive metabolite of ibogaine, produces robust anxiolytic-like behavior in adult zebrafish without affecting locomotion. In a 5-minute novel tank test following acute 20-minute immersion in 1, 5, or 10 mg/L noribogaine, treated fish spent more time and made more transitions to the top half compartment and showed fewer freezing bouts compared to controls. These results indicate noribogaine modulates components of the acute stress response related to emotionality and anxiety, suggesting it may be a potentially useful non-sedative anxiolytic agent.