Oral noribogaine shows high brain uptake and anti-withdrawal effects not associated with place preference in rodents.
Deborah C. Mash, Barbara Ameer, Delphine Prou, John F Howes, Émeline L. Maillet
Journal of Psychopharmacology July 1, 2016 DOI: 10.1177/0269881116641331 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study with three experiments Peer reviewed |
|---|---|
| Population | Mice and rats |
| Intervention | noribogaine |
| Dose | 13 mg/kg (ED50), up to 100 mg/kg |
| Topics | Addiction Ibogaine |
| Keywords | Cns drugs Blood–brain barrier Conditioned place preference Drug brain penetration Noribogaine research noribogaine Opioid addiction abstinence Opioid withdrawal symptoms Morphine withdrawal signs High brain uptake |
| Citations | 29 |
| Key findings | Oral noribogaine dose dependently reduces naloxone-precipitated morphine withdrawal in mice, shows high brain penetration, and does not produce conditioned place preference in rats. |
Abstract
This study investigated the effects of noribogaine, the principal metabolite of the drug ibogaine, on substance-related disorders. 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. Noribogaine-treated rats did not display place preference, suggesting that noribogaine is not perceived as a hedonic stimulus in rodents. 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.
Comparable studies
Other preclinical and animal studies on ibogaine for addiction, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Glial Cell Line-Derived Neurotrophic Factor Mediates the Desirable Actions of the Anti-Addiction Drug Ibogaine against Alcohol Consumption Rats | 2005 | Experimental study | |
| Effects of ibogaine on acute signs of morphine withdrawal in rats: independence from tremor. Morphine-dependent rats | 1992 | Randomized controlled trial | |
| Autoregulation of glial cell line-derived neurotrophic factor expression: implications for the long-lasting actions of the anti-addiction drug, Ibogaine. Dopaminergic-like SHSY5Y cell line | 2006 | In vitro cell culture study | |
| A dose-response study of ibogaine-induced neuropathology in the rat cerebellum. Rats | 2000 | Dose-response study | n = 30 |
| Noribogaine reduces nicotine self-administration in rats. Adult male Sprague-Dawley rats | 2015 | Within-subject design with a Latin square test schedule |
Citations in the library
Cited by 23
- Treatment of opioid use disorder with ibogaine: detoxification and drug use outcomes. The American Journal of Drug and Alcohol Abuse 2018
- Ibogaine treatment outcomes for opioid dependence from a twelve-month follow-up observational study. The American Journal of Drug and Alcohol Abuse 2018
- Ibogaine Detoxification Transitions Opioid and Cocaine Abusers Between Dependence and Abstinence: Clinical Observations and Treatment Outcomes. Frontiers in Pharmacology 2018
- DARK Classics in Chemical Neuroscience: Ibogaine ACS Chemical Neuroscience September 14, 2018
- Classic and non‐classic psychedelics for substance use disorder: A review of their historic, past and current research Addiction Neuroscience June 22, 2022
and 18 more in the library
Cites 25
- Treatment of acute opioid withdrawal with ibogaine. American Journal on Addictions 1999
- Effects and aftereffects of ibogaine on morphine self-administration in rats. European Journal of Pharmacology April 3, 1991
- A preliminary investigation of ibogaine: case reports and recommendations for further study. Journal of Substance Abuse Treatment 1994
- Ibogaine: complex pharmacokinetics, concerns for safety, and preliminary efficacy measures. Annals of the New York Academy of Sciences September 1, 2000
- Attenuation of alcohol intake by ibogaine in three strains of alcohol-preferring rats. Pharmacology, Biochemistry, and Behavior November 1, 1995
and 20 more in the library