Author Topic: Ibogaine, GDNF expression and neurodegenerative diseases  (Read 2667 times)

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Offline Bancopuma

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Ibogaine, GDNF expression and neurodegenerative diseases
« on: January 19, 2011, 08:48:04 AM »
The following is a summary on existing research looking at the influence of Ibogaine on glial cell line-derived neurotrophic factor (GDNF) levels in the brain, and the beneficial impact that an increase in this protein can have. While existing studies have examined these areas, very few have identified a possible link between Ibogaine, GDNF expression and neurodegenerative diseases, and I believe more research is warranted. I would appreciate feedback off anyone, particularly anyone with a background in neuroscience. Attached is a presentation examining the biochemical background of Ibogaine and GDNF in more detail.

One reason Ibogaine is so interesting is that it increases levels of glial cell line-derived neurotrophic factor (GDNF) in the brain (He & Ron 2006), and this in turn appears to be a potent survival factor for several different neuronal populations in different brain regions (Boscia et al. 2009) and has neuroprotective properties that promote the survival of both dopaminergic and motor neurons (Bermingham et al. 2004; He and Ron 2006), which may be one of the reasons for the prolonged afterglow often experienced following treatment with the drug. Furthermore, GDNF can cause sprouting of dopaminergic fibers and clinical improvement in experimental animal models of Parkinson’s disease, as well as a similar sprouting of dopaminergic fibers in humans with the disease, with the resultant clinical improvement in symptoms (Love et al. 2005). GDNF has also been identified as having anti-addictive properties (Ron & Janak 2005; Carnicella & Ron 2008.) This may be one of the reasons for Ibogaine’s effectiveness in treating drug addicts with impaired receptor function, but this drug may also be a considerable ally to those with degenerative neurological diseases.

Both Parkinson’s disease and Motor neuron disease are chronic disorders with no known cure, and require management with drugs that can have considerable side effects, causing a very poor quality of life for terminal stage sufferers of these diseases. By contrast, a low dose regime of Ibogaine or Iboga alkaloid extract would be of low toxicity and free of serious side effects.

GDNF has been shown to have potent neurotrophic factor in both rodent and primate models of Parkinson’s disease (Gill et al. 2003). Direct brain infusion of GDNF into the brains of five Parkinson sufferers resulted in a 39% improvement in the off-medication motor sub-score of the Unite Parkinson’s Disease Rating Scale (UPDRS) and a 61% improvement in the activities of daily living sub score (Gill et al. 2003). Positron emission tomography (PET) scans of dopamine uptake showed a significant 28% increase in putamen dopamine storage after 18 months, indicating a direct effect of GDNF on dopamine function. Furthermore, after one year, no serious clinical side effects were observed (Gill et al. 2003). The use of Iboga alkaloid extract or Ibogaine would provide a longer term and much less invasive method of GDNF administration than direct brain infusion. Thus, further research on Ibogaine and GDNF is certainly warranted.

Regarding motor neuron disease, the little research that has occurred in this area, such as gene transfer of neurotrophic factors, suggests potential in the treatment of motor neuron disease (Haase et al. 1997). Again, Ibogaine therapy may offer a straightforward, non-invasive, cheap, low-toxicity method of treatment for sufferers of this disease.

Thus based on this previous research, it seems clear to me that further research with Ibogaine, GDNF expression and neurodegenerative diseases is certainly warranted, despite the financial and political hurdles of working with Ibogaine, a largely scheduled yet natural alkaloid extract from the root bark of the West African shrub Iboga (Tabernanthe iboga). The drug is of little financial interest to pharmaceutical companies, and quite inaccurately deemed to be of “no medical value”. Legal red tape is less restrictive for Ibogaine here in the UK than it is in many other parts of the world.

Bermingham, N., Hillermann, R., Gilmour, F., Martin, J. E. and Fisher, E. M. C. (2004) Human glial cell line-derived neurotrophic factor (GDNF) maps to chromosome 5. Human Genetics, 96, (6), 671-673.

Boscia F, Esposito CL, Di Crisci A, de Franciscis V, Annunziato L, et al. (2009) GDNF Selectively Induces Microglial Activation and Neuronal Survival in CA1/CA3 Hippocampal Regions Exposed to NMDA Insult through Ret/ERK Signalling. PLoS ONE 4, 8, e6486. doi:10.1371/journal.pone.0006486

Carnicella, s. & Ron, D. 2008. GDNF – A potential target to treat addiction. Pharmacology & Therapeutics, 122, (1), 9-18.

Gill, S. S., Patel, N. K., Hotton, G. R., O’Sullivan, McCarter, R., Bunnage, M., Brooks, D. J., Svendsen, C. N. and Heywood, P. (2003) Direct brain infusion of glial cell-line derived neurotrophic factor in Parkinson disease. Nature Medicine, 9, 589-595.

Grondin, R., and D. M. Gash. 1998. Glial cell line-derived neurotrophic factor (GDNF): a drug candidate for the treatment of Parkinson's disease. Journal Of Neurology 245, 35-42.

Haase, G., Kennel, B., Pettmann, B., Vigne, E., Akil, S., Revah, F., Schmalbruch, H. and Kahn, A. (1997) Gene therapy of murine motor neuron disease using adenoviral vectors for neurotrophic factors. Nature Medicine, 3, 429-436.

He, D. Y. & Ron, D. (2006) Autoregulation of glial cell line-derived neurotrophic factor expression: implications for the long-lasting actions of the anti-addiction drug, Ibogaine. The FASEB Journal, 20, 2420-2422.

Kirik, D., B. Georgievska, and A. Bjorklund. (2004) Localized striatal delivery of GDNF as a treatment for Parkinson disease. Nature Neuroscience 7:105-110.

Love, S., P. Plaha, N. K. Patel, G. R. Hotton, D. J. Brooks, and Gill, S. S. (2005) Glial cell line-derived neurotrophic factor induces neuronal sprouting in human brain. Nature Medicine 11:703-704.

Ron, D. & Janak, P. H. (2005) GDNF and addiction. Reviews in the Neurosciences, 16, (4), 277-285.