Annals of the New York Academy of Sciences
May 1, 1998
Deborah C Mash, Craig A Kovera, Billy E Buck et al.
111 citations
Ibogaine, an indole alkaloid from the rain forest shrub Tabernanthe iboga, has been used by indigenous peoples in equatorial Africa to combat fatigue and hunger and as a religious sacrament. Anecdotal reports from addict self-help groups claim a single dose eliminates withdrawal symptoms and reduces drug cravings for extended periods, but these purported antiaddictive properties require rigorous validation. A rising tolerance study with single administration has been initiated to assess ibogaine's safety for treating cocaine dependency, with primary objectives to determine safety, pharmacokinetics, dose effects, and relevant efficacy parameters. Pharmacokinetic and pharmacodynamic characteristics are assessed via concentration-time data from the Phase I trial and in vitro experiments on metabolism.
Frontiers in pharmacology
January 1, 2018
Deborah C Mash, Linda Duque, Bryan Page et al.
109 citations
A single oral dose of ibogaine, administered under medical supervision, diminishes opioid withdrawal symptoms and reduces drug cravings in people seeking to detoxify from opioids or cocaine. In an open-label case series of 191 human volunteers, no significant adverse events occurred at doses effective for blocking withdrawal. Pharmacokinetic measures from whole blood assays tracked ibogaine's metabolism and clearance. Multi-dimensional craving questionnaires showed reduced heroin and cocaine cravings during inpatient detoxification. One-month follow-up data suggested some persistence of craving reduction outside the inpatient setting. The results support developing ibogaine as a treatment for opioid withdrawal during medically supervised detoxification to transition individuals toward abstinence.
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.
Bioorganic & medicinal chemistry
March 20, 2003
Daniele Passarella, Raffaele Favia, Alessandra Giardini et al.
23 citations
A method to synthesize 7-heteroaryl-2-azabicyclo[2.2.2]oct-7-enes using cycloaddition followed by cross-coupling is described. The binding affinity of these new compounds to the receptor targets characteristic of ibogaine is reported.
Frontiers in cellular neuroscience
January 1, 2022
Charles Sutton, Erin Q Williams, Hoomam Homsi et al.
13 citations
Mutations in the dopamine transporter gene cause Dopamine Transporter Deficiency Syndrome (DTDS), a fatal infantile parkinsonism-dystonia with no current treatment. Pharmacological chaperones can rescue some disease-causing variants. This study examined structure-activity relationships for two known chaperones, bupropion and ibogaine. The isoquinuclidine substituent of ibogaine and its analogs is important for chaperone efficacy. For bupropion, the secondary amine group is essential. Additional analogs with varying chemical modifications showed variable chaperone efficacies, contributing to the design of improved dopamine transporter pharmacological chaperones.