Ibogaine administration following repeated morphine administration upregulates myelination markers 2', 3'-cyclic nucleotide 3'-phosphodiesterase (CNP) and myelin basic protein (MBP) mRNA and protein expression in the internal capsule of Sprague Dawley rats.
Demi Govender, Leila Moloko, Maria Papathanasopoulos, Nancy Tumba, Gavin Owen, Tanya Calvey
Frontiers in Neuroscience 2024 DOI: 10.3389/fnins.2024.1378841 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Sample size | 50 |
| Population | Sprague Dawley rats |
| Interventions | Ibogaine hydrochloride Morphine |
| Dose | 50 mg/kg ibogaine hydrochloride; escalating morphine doses from 5 to 15 mg/kg |
| Duration | 10-day intervention; groups terminated at 24 h or 72 h after ibogaine administration |
| Topics | Addiction Ibogaine |
| Keywords | Oligodendrocytes Psychedelic medicine ibogaine Psychedelic drug Hallucinogenic medicine Psychotropic substance Opioid addiction therapy Opioid dependence therapy Brain repair neurorepair White matter repair Myelin regeneration Oligodendrocyte function Brain damage reversal Neural regeneration |
| Citations | 10 |
| Key findings | Ibogaine administration following repeated morphine administration upregulates CNP and MBP mRNA and protein expression in the internal capsule of rats, indicating a potential mechanism for remyelination after opioid use. |
Abstract
Ibogaine is a psychedelic alkaloid being investigated as a possible treatment for opioid use disorder. Ibogaine has a multi-receptor profile with affinities for mu and kappa opioid as well as NMDA receptors amongst others. Due to the sparsity of research into ibogaine's effects on white matter integrity and given the growing evidence that opioid use disorder is characterized by white matter pathology, we set out to investigate ibogaine's effects on two markers of myelination, 2', 3'-cyclic nucleotide 3'-phosphodiesterase (CNP) and myelin basic protein (MBP). Fifty Sprague Dawley rats were randomly assigned to five experimental groups of n = 10; (1) a saline control group received daily saline injections for 10 days, (2) a morphine control group received escalating morphine doses from 5 to 15 mg/kg over 10 days, (3) an ibogaine control group that received 10 days of saline followed by 50 mg/kg ibogaine hydrochloride, (4) a combination morphine and ibogaine group 1 that received the escalating morphine regime followed by 50 mg/kg ibogaine hydrochloride and (5) a second combination morphine and ibogaine group 2 which followed the same morphine and ibogaine regimen yet was terminated 72 h after administration compared to 24 h in the other groups. White matter from the internal capsule was dissected and qPCR and western blotting determined protein and gene expression of CNP and MBP. Morphine upregulated CNPase whereas ibogaine alone had no effect on CNP mRNA or protein expression. However, ibogaine administration following repeated morphine administration had an immediate effect by increasing CNP mRNA expression. This effect diminished after 72 h and resulted in a highly significant upregulation of CNPase protein at 72 h post administration. Ibogaine administration alone significantly upregulated protein expression yet downregulated MBP mRNA expression. Ibogaine administration following repeated morphine administration significantly upregulated MBP mRNA expression which increased at 72 h post administration resulting in a highly significant upregulation of MBP protein expression at 72 h post administration. These findings indicate that ibogaine is able to upregulate genes and proteins involved in the process of remyelination following opioid use and highlights an important mechanism of action of ibogaine's ability to treat substance use disorders.
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 |
| Oral noribogaine shows high brain uptake and anti-withdrawal effects not associated with place preference in rodents. Mice and rats | 2016 | Experimental study with three experiments |
Citations in the library
Cited by 9
- Psychedelic Drugs in Mental Disorders: Current Clinical Scope and Deep Learning‐Based Advanced Perspectives Advanced Science March 20, 2025
- Case report: Significant lesion reduction and neural structural changes following ibogaine treatments for multiple sclerosis. Frontiers in Immunology 2025
- Deciphering Ibogaine’s Matrix Pharmacology: Multiple Transporter Modulation at Serotonin Synapses Journal of the American Chemical Society December 26, 2025
- Psychedelics in Multiple Sclerosis: Mechanisms, Challenges, and Prospects for Neuroimmune Modulation and Repair. Cells November 26, 2025
- Toward a nuanced framework for the medical development of ibogaine and its analogues and derivatives: implications for psychopharmacology Expert Opinion on Drug Discovery July 4, 2026
and 4 more in the library
Cites 23
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- A non-hallucinogenic psychedelic analogue with therapeutic potential. Nature 2021
- Treatment of acute opioid withdrawal with ibogaine. American Journal on Addictions 1999
- 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
and 18 more in the library