Noribogaine, but not 18-MC, exhibits similar actions as ibogaine on GDNF expression and ethanol self-administration.
Sebastien Carnicella, Dao‐yao He, Quinn V Yowell, Stanley D Glick, Dorit Ron
Addiction Biology October 1, 2010 DOI: 10.1111/j.1369-1600.2010.00251.x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical study Peer reviewed |
|---|---|
| Population | SH-SY5Y cells and rats |
| Interventions | noribogaine 18-Methoxycoronaridine (18-MC) |
| Topics | Ibogaine |
| Keywords | Alcoholism Anti-addiction Drug addiction Dependency Recovery Therapy Medication Alcohol consumption Alcohol intake Noribogaine ibogaine metabolite 18-mc Natural metabolite Synthetic derivative Therapeutic compound Drug development Neuroscience brain research Neurobiology Neuropharmacology Brain mechanisms Neural pathways Site of action Brain protein Brain region Target brain area Rat experiments In vivo studies Drug testing Efficacy studies Research findings Rats |
| Citations | 49 |
| Key points | Noribogaine, but not 18-MC, increases GDNF expression and reduces alcohol self-administration when acting in the VTA, suggesting distinct mechanisms for these compounds. |
Abstract
Ibogaine is a naturally occurring alkaloid that has been reported to decrease various adverse phenotypes associated with exposure to drugs of abuse and alcohol in human and rodent models. Unfortunately, ibogaine cannot be used as a medication to treat addiction because of severe side effects. Previously, we reported that the desirable actions of ibogaine to reduce self-administration of, and relapse to, alcohol consumption are mediated via the upregulation of the expression of the glial cell line-derived neurotrophic factor (GDNF) in the midbrain ventral tegmental area (VTA), and the consequent activation of the GDNF pathway. The ibogaine metabolite, noribogaine, and a synthetic derivative of ibogaine, 18-Methoxycoronaridine (18-MC), possess a similar anti-addictive profile as ibogaine in rodent models, but without some of its adverse side effects. Here, we determined whether noribogaine and/or 18-MC, like ibogaine, increase GDNF expression, and whether their site of action to reduce alcohol consumption is the VTA. We used SH-SY5Y cells as a cell culture model and found that noribogaine, like ibogaine, but not 18-MC, induces a robust increase in GDNF mRNA levels. Next, we tested the effect of intra-VTA infusion of noribogaine and 18-MC on rat operant alcohol self-administration and found that noribogaine, but not 18-MC, in the VTA decreases responding for alcohol. Together, our results suggest that noribogaine and 18-MC have different mechanisms and sites of action.
Comparable studies
Other preclinical and animal studies on ibogaine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Noncompetitive Functional Inhibition at Diverse, Human Nicotinic Acetylcholine Receptor Subtypes by Bupropion, Phencyclidine, and Ibogaine TE671/RD cells (human muscle-type nAChR) and SH-SY5Y neuroblastoma cells (human... | 1999 | In vitro study | |
| Degeneration of Purkinje cells in parasagittal zones of the cerebellar vermis after treatment with ibogaine or harmaline. Ibogaine- or harmaline-treated rats | 1993 | Experimental animal study | |
| Effects and aftereffects of ibogaine on morphine self-administration in rats. Rats | 1991 | Preclinical experimental study | |
| Effects of iboga alkaloids on morphine and cocaine self-administration in rats: relationship to tremorigenic effects and to effects on dopamine release in nucleus accumbens and striatum. Rats | 1994 | Experimental study | |
| Glial Cell Line-Derived Neurotrophic Factor Mediates the Desirable Actions of the Anti-Addiction Drug Ibogaine against Alcohol Consumption Rats | 2005 | Experimental study |
Citations in the library
Cited by 36
- A non-hallucinogenic psychedelic analogue with therapeutic potential. Nature 2021
- Treatment of opioid use disorder with ibogaine: detoxification and drug use outcomes. The American Journal of Drug and Alcohol Abuse 2018
- Ibogaine in the treatment of substance dependence. Current Drug Abuse Reviews March 1, 2013
- Ibogaine Administration Modifies GDNF and BDNF Expression in Brain Regions Involved in Mesocorticolimbic and Nigral Dopaminergic Circuits. Frontiers in Pharmacology 2019
- A systematic literature review of clinical trials and therapeutic applications of ibogaine. Journal of Substance Abuse Treatment July 1, 2022
and 31 more in the library
Cites 33
- Degeneration of Purkinje cells in parasagittal zones of the cerebellar vermis after treatment with ibogaine or harmaline. Neuroscience July 1, 1993
- Effects of iboga alkaloids on morphine and cocaine self-administration in rats: relationship to tremorigenic effects and to effects on dopamine release in nucleus accumbens and striatum. Brain Research September 19, 1994
- The ibogaine medical subculture. Journal of Ethnopharmacology January 4, 2008
- Glial Cell Line-Derived Neurotrophic Factor Mediates the Desirable Actions of the Anti-Addiction Drug Ibogaine against Alcohol Consumption Journal of Neuroscience January 19, 2005
- Inhibitory effects of ibogaine on cocaine self-administration in rats. European Journal of Pharmacology September 14, 1993
and 28 more in the library