Ibogaine for parkinsons and autoimmune - parkinsons patients

Potential for Ibogaine in The Treatment of Parkinson’s and Autoimmune Diseases

Ibogaine is an alkaloid derived from the African shrub Tabernanthe iboga. Aside from its psychoactive and anti-addiction properties, it has beneficial effects on certain neurotrophic factors and receptors in the brain. Targeting them has shown great potential for the future therapy of neurodegenerative and neuroinflammatory conditions such as Parkinson’s.

Parkinson’s disease is a crippling neurological disorder that affects more than 1 million people in the US. The number of people with the condition is expected to increase by more than 60% in the next 20 years [1]. Currently, its cause is unknown but new evidence suggests that its main pathogenetic mechanism might be related to an autoimmune reaction that is present even before the onset of the first symptoms. 

Autoimmune diseases are debilitating conditions that affect about 5% of the population. Currently, there is no cure for Parkinson’s or other autoimmune disorders. The treatment options aim at reducing symptoms, preventing complications, and prolonging life.

What is Parkinson’s

Parkinson’s disease is a progressive and degenerative brain disorder, caused by the death of dopamine-producing brain cells in the midbrain [2].

Its main pathogenetic mechanism is the dysfunction of a cell protein called alpha-synuclein. Normally, this protein has a critical role in DNA repair and cell survival. 

In Parkinson’s, the alpha-synuclein proteins become dysfunctional and aggregate together forming insoluble structures called Lewi bodies. Thus, they lose their protective role leading to the accumulation of DNA damage and nerve cell death [3].

Currently, the reason for this dysfunction is unknown which makes it impossible to prevent or treat it effectively. Preliminary studies have reported that the alpha-synuclein proteins in patients with Parkinson’s can trigger a specific autoimmune reaction [4].

A new human trial has revealed that the suspected autoimmune activation precedes the accumulation of neuronal damage and contributes to the etiology of the condition [5]. This is an indication of possible autoimmune mechanisms in the development of Parkinson’s.

Ibogaine for Parkinson’s

One of the options for the treatment of Parkinson’s is to protect the dopaminergic neurons against cell death by activating neurotrophic factors. Their function in the brain is to provide neuroprotective and nerve cell regenerating effects.

Glial Cell-Derived Neurotrophic Factor (GDNF) has a special role in protecting dopamine neurons. Its main function is to ensure neuron survival and stimulate the formation of new neuronal synapses.

Studies have revealed that GDNF has multiple benefits for the dopaminergic neurons in the midbrain and it’s widely investigated as a possible therapy for Parkinson’s [6]. Besides, experiments have shown that the administration of GDNF can suppress cell death in the brain of animal models [7].

Furthermore, there is a human trial that has reported almost 40% improvements in symptoms after induced Parkinson’s and no side effects after the therapy [8].

A case report on one of the participants reveals that GDNF infusion also stimulates the formation of new dopamine neurons in the human brain [9]. Thus, the Parkinson’s patient experienced significant clinical improvements.

However, the direct infusion into the brain is the only effective way to administer GDNF. This method is risky, invasive, and inconvenient. Any alternatives such as administration via blood or spinal fluid are not effective in reaching the midbrain.

On the other hand, Ibogaine is a well-known potent stimulator of GDNF. Tests in animal models report that the alkaloid is potent in upregulating the expression of GDNF in the central nervous system [10] [11].

Furthermore, another animal study reveals that this upregulation occurs specifically in the midbrain, where Parkinson’s pathology occurs [12]. There GDNF can effectively protect the dopaminergic neurons and even stimulate the formation of new ones. 

Thus, despite the lack of further evidence, it is likely that Ibogaine might provide effective alternative therapy for this debilitating condition.

What are Autoimmune Diseases

Autoimmune diseases are inflammatory conditions in which the immune system targets the healthy tissues of the host by mistake [13].

Currently, the reasons for such dysregulated immune reactions are unknown [14]. When the autoimmune attack is mounted against the brain, it leads to the development of neurological disorders such as Multiple Sclerosis (MS). 

In the case of MS, immune T-cells attack the myelin sheath of the neurons in the brain, which damages their ability to transmit signals and function properly [15].

Treatment options are extremely limited and include medications that suppress the immune system or simply subdue the symptoms. Unfortunately, most of these medications have common side effects.

Ibogaine for Autoimmune Diseases

A novel approach towards reducing neuroinflammation and treating autoimmune diseases such as MS might be the activation of the sigma-1 receptors (Sig1R) in the brain.

They are one of the receptor types which regulate neuroinflammation. Currently, they have shown potential for the management of multiple neurodegenerative conditions such as Parkinson’s, brain injury, stroke, and sclerosis [16].

Animal studies using agonists of the Sig1R have shown success in reducing the clinical signs of experimental autoimmune encephalomyelitis (inflammation of the brain and the spinal cord) [17].

Ibogaine is a potent agonist of the Sig1R and may provide benefits for neuroinflammation and help the management of autoimmune neurological diseases [18].

Limitations for Further Research

The level of research is only preliminary, but studies are suggesting great potential for Ibogaine in the treatment of neuroinflammatory and neurodegenerative disorders, including Parkinson’s

Unfortunately, there are multiple limitations for future research on Ibogaine and its effect on these debilitating conditions. In the US, Ibogaine is classified as a Schedule I substance, which makes it illegal for use or possession. It is also banned in Australia and many European countries.

That is mainly because of the safety concerns with high dose Ibogaine use. The use of Ibogaine without medical supervision can be dangerous for people with preexisting cardiovascular conditions or those taking prescription medications.

However, Ibogaine can be used safely by patients who don’t have cardiovascular problems, prepare for the therapy and taper off their medications properly. All of these factors should be carefully evaluated and overseen by a team of experienced medical professionals. Ibogaine therapy is legal in Canada, Mexico, and New Zealand and currently, it is used successfully for the treatment of patients with addictions.

References:

  1. Kowal, S. L., Dall, T. M., Chakrabarti, R., Storm, M. V., & Jain, A. (2013). The current and projected economic burden of Parkinson’s disease in the United States. Movement disorders : official journal of the Movement Disorder Society, 28(3), 311–318. https://doi.org/10.1002/mds.25292 
  2. Davie C. A. (2008). A review of Parkinson’s disease. British medical bulletin, 86, 109–127. https://doi.org/10.1093/bmb/ldn013 
  3. Schaser, A. J., Osterberg, V. R., Dent, S. E., Stackhouse, T. L., Wakeham, C. M., Boutros, S. W., Weston, L. J., Owen, N., Weissman, T. A., Luna, E., Raber, J., Luk, K. C., McCullough, A. K., Woltjer, R. L., & Unni, V. K. (2019). Alpha-synuclein is a DNA binding protein that modulates DNA repair with implications for Lewy body disorders. Scientific reports, 9(1), 10919. https://doi.org/10.1038/s41598-019-47227-z 
  4. Sulzer, D., Alcalay, R. N., Garretti, F., Cote, L., Kanter, E., Agin-Liebes, J., Liong, C., McMurtrey, C., Hildebrand, W. H., Mao, X., Dawson, V. L., Dawson, T. M., Oseroff, C., Pham, J., Sidney, J., Dillon, M. B., Carpenter, C., Weiskopf, D., Phillips, E., Mallal, S., … Sette, A. (2017). T cells from patients with Parkinson’s disease recognize α-synuclein peptides. Nature, 546(7660), 656–661. https://doi.org/10.1038/nature22815 
  5. Lindestam Arlehamn, C. S., Dhanwani, R., Pham, J., Kuan, R., Frazier, A., Rezende Dutra, J., Phillips, E., Mallal, S., Roederer, M., Marder, K. S., Amara, A. W., Standaert, D. G., Goldman, J. G., Litvan, I., Peters, B., Sulzer, D., & Sette, A. (2020). α-Synuclein-specific T cell reactivity is associated with preclinical and early Parkinson’s disease. Nature communications, 11(1), 1875. https://doi.org/10.1038/s41467-020-15626-w 
  6. Peterson, A. L., & Nutt, J. G. (2008). Treatment of Parkinson’s disease with trophic factors. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 5(2), 270–280. https://doi.org/10.1016/j.nurt.2008.02.003
  7. Oo, T. F., Kholodilov, N., & Burke, R. E. (2003). Regulation of natural cell death in dopaminergic neurons of the substantia nigra by striatal glial cell line-derived neurotrophic factor in vivo. The Journal of neuroscience : the official journal of the Society for Neuroscience, 23(12), 5141–5148. https://doi.org/10.1523/JNEUROSCI.23-12-05141.2003
  8. Gill, S. S., Patel, N. K., Hotton, G. R., O’Sullivan, K., McCarter, R., Bunnage, M., Brooks, D. J., Svendsen, C. N., & Heywood, P. (2003). Direct brain infusion of glial cell line-derived neurotrophic factor in Parkinson disease. Nature medicine, 9(5), 589–595. https://doi.org/10.1038/nm850 
  9. Love, S., Plaha, P., Patel, N. K., Hotton, G. R., Brooks, D. J., & Gill, S. S. (2005). Glial cell line-derived neurotrophic factor induces neuronal sprouting in human brain. Nature medicine, 11(7), 703–704. https://doi.org/10.1038/nm0705-703 
  10. Carnicella, S., He, D. Y., Yowell, Q. V., Glick, S. D., & Ron, D. (2010). Noribogaine, but not 18-MC, exhibits similar actions as ibogaine on GDNF expression and ethanol self-administration. Addiction biology, 15(4), 424–433. https://doi.org/10.1111/j.1369-1600.2010.00251.x 
  11. 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. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 20(13), 2420–2422. https://doi.org/10.1096/fj.06-6394fje 
  12. 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. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 20(13), 2420–2422. https://doi.org/10.1096/fj.06-6394fje 
  13. Smith, D. A., & Germolec, D. R. (1999). Introduction to immunology and autoimmunity. Environmental health perspectives, 107 Suppl 5(Suppl 5), 661–665. https://doi.org/10.1289/ehp.99107s5661 
  14. Wang, L., Wang, F. S., & Gershwin, M. E. (2015). Human autoimmune diseases: a comprehensive update. Journal of internal medicine, 278(4), 369–395. https://doi.org/10.1111/joim.12395 
  15. Hohlfeld, R., Dornmair, K., Meinl, E., & Wekerle, H. (2016). The search for the target antigens of multiple sclerosis, part 1: autoreactive CD4+ T lymphocytes as pathogenic effectors and therapeutic targets. The Lancet. Neurology, 15(2), 198–209. https://doi.org/10.1016/S1474-4422(15)00334-8 
  16. Jia, J., Cheng, J., Wang, C., & Zhen, X. (2018). Sigma-1 Receptor-Modulated Neuroinflammation in Neurological Diseases. Frontiers in cellular neuroscience, 12, 314. https://doi.org/10.3389/fncel.2018.00314
  17. Oxombre, B., Lee-Chang, C., Duhamel, A., Toussaint, M., Giroux, M., Donnier-Maréchal, M., Carato, P., Lefranc, D., Zéphir, H., Prin, L., Melnyk, P., & Vermersch, P. (2015). High-affinity σ1 protein agonist reduces clinical and pathological signs of experimental autoimmune encephalomyelitis. British journal of pharmacology, 172(7), 1769–1782. https://doi.org/10.1111/bph.13037 
  18. Thompson, C., & Szabo, A. (2020). Psychedelics as a novel approach to treating autoimmune conditions. Immunology letters, 228, 45–54. https://doi.org/10.1016/j.imlet.2020.10.001 

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