Neuroplasticity of Iboga and Ibogaine

Table of Contents

Iboga and Ibogaine are primarily known as a treatment for attenuating symptoms of addiction and withdrawal. Less-known benefits include improving mental health conditions, PTSD, trauma, traumatic brain injuries, autoimmune disease, Parkinson’s, and creating new healthy habits. 

Many of these surprising benefits are due to Iboga’s ability to rewire the brain. The underlying mechanism is called neuroplasticity, which involves the brain’s innate ability to change, repair, and adapt.

Unfortunately, our highly developed central nervous system has a limited ability to recover due to the complex mechanism and factors affecting neuroplasticity. However, Iboga may be able to stimulate the majority of these factors in different parts of the brain and boost neuroplasticity.

What is Iboga and Ibogaine?

Tabernanthe Iboga is a perennial shrub native to the equatorial parts of West Africa. The plant contains several alkaloids, which contribute to its psychoactive and medicinal properties.

The primary psychoactive alkaloid is called Ibogaine, and its concentrations are the highest in the roots, more specifically, the root bark. However, there are many other alkaloids found in Iboga besides Ibogaine that may contribute to its medicinal effects, including tabernanthine, ibogamine, coronaridine, voacangine, and harmaline.

For thousands of years, practitioners of the spiritual tradition known as Bwiti used Iboga. In recent years, Iboga has become more widely available to the general public for spiritual growth and physical and mental healing. 

Data on the benefits of Ibogaine dates back to 1962, with multiple case studies reporting successful treatments of addictions to heroin, cocaine, morphine, amphetamine, and alcohol (1).

People who have taken Ibogaine often report that they no longer desire to take drugs and got there without withdrawal symptoms. A life-changing psychedelic experience often accompanies this, healing the cause of the addictive behavior.

Despite being illegal in the United States and several other countries, Iboga retreats and Ibogaine Treatment Centers exist worldwide.

brain growth
neurons 1

What is Neuroplasticity?

Neuroplasticity is the capability of neurons to reorganize, adapt and even form anew. There are two main types of neuroplasticity – structural and functional.

Functional Neuroplasticity

Functional neuroplasticity is more common and involves forming new synapses (connections) between different brain cells. The process plays a crucial role in normal brain function, adaptation, and the formation of memories.

Structural Neuroplasticity

Structural neuroplasticity occurs more slowly and is often called “remapping.” It involves the anatomical reorganization of brain cells and even the formation of new ones. Previously, this process was believed to be inactive in adults.

Growth Factors

According to studies, several growth factors in the brain support the growth, survival, and adaptation of old neurons and the formation of new ones from progenitor cells (2). These growth factors include brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), glial cell-derived neurotrophic factor (GDNF), ciliary neurotrophic factor (CNTF), and others.

According to scientists, both BDNF and GDNF can induce remodeling in the nerve tissue and the formation of new connections (3).

BDNF might also stimulate neurogenesis, the formation of new neurons in parts of the adult brain that still retain stem cells (4).

Iboga & Ibogaine Increase Neuroplasticity

We know from scientific research that after administering Ibogaine, the alkaloid leads to a significant increase in the activity of these factors in different parts of the brain (5).

GDNF was significantly upregulated in areas rich in dopaminergic neurons in the midbrain, which are linked to reward-driven behavior and are often affected by drugs of abuse.

NGF and BDNF were upregulated in all areas linked to the reward systems in the brain as well.

Furthermore, they were activated in the prefrontal cortex, which is implicated in planning complex cognitive behavior, personality expression, decision-making, and moderating social behavior.

Ibogaine analogs ineffective 

Non-hallucinogenic analogs to Ibogaine are ineffective in activating neurotrophic factors such as GDNF (6).

What are the benefits of increasing neuroplasticity?

A primary mechanism by which Ibogaine attenuates drug-seeking behavior and helps treat mental health conditions, brain conditions, and neurological conditions is through its influence on several neurotransmitters. 

1 ) Addiction & Detox

According to researchers, the development of an addiction could be related to the dysfunction of the neurotrophic growth factors (7).

Long-term addictions lead to unfavorable neural remodeling combined with reduced neuroplasticity, which significantly complicates the treatment process.

Scientists suggest that activating these neurotrophic factors, especially GDNF restores normal neuroplasticity and plays a crucial role in Ibogaine’s long-lasting anti-addictive properties (8). 

By stimulating neuroplasticity and inducing favorable brain remodeling, Ibogaine may reverse the biochemical adaptations to chronic exposure to drugs of abuse in the reward system. 

Evidence also reveals that the induction of GDNF by Ibogaine may activate an autocrine loop, leading to a long-term synthesis and release of GDNF that persists beyond the short-term presence of Ibogaine after the therapy (9). 

2 ) Creating New Habits

The release of dopamine controls reward-driven behavior and plays a vital role in forming habits (10).

The formation of new habits is dependent on neuroplasticity, which lets the dopaminergic neurons form new connections and switch the release timing of dopamine. 

Furthermore, BDNF levels can dynamically impact reward-related decision-making and suppress unhealthy habits due to their role in neuroplasticity. 

For example, studies in mice reveal that reduced BDNF expression leads to a loss of control over unhealthy habits such as alcohol consumption (11).

iboga ibogaine neuroplasticity

3) Traumatic Brain Injuries

A Traumatic brain injury (TBI) is damage to the brain due to external factors such as sports and work traumas, accidents, violence, etc. The condition can lead to a progressive loss of brain cells and disability.

Neuroplasticity plays a critical role in the ability of the brain to recover different neurological functions after TBI.

The activation of BDNF may induce neuroplastic changes that lead to adaptive neural repair and may potentially reverse cognitive and emotional deficits in TBI patients (12).

Animal studies report that the extensive activation of BDNF in zebrafish can lead to complete brain repair after a TBI (13). 

The neurotrophic factor-induced both functional and structural neuroplasticity leading to the formation of new neurons.

4) Autoimmune Diseases

Research shows that BDNF increases nerve cell survival in autoimmune diseases that affect the human brain, such as autoimmune encephalomyelitis and multiple sclerosis (MS).

In a model of autoimmune encephalomyelitis in mice, experiments reveal that lack of BDNF reduces neuroplasticity and speeds up the brain cell death rate (14).

Furthermore, evidence suggests that increasing NGF and GDNF may protect brain cells against cell death and slow the progression of MS (15).

According to researchers, several lines of evidence, both from clinical research and animal models, suggest that neurotrophic factors play a pivotal role in neuroprotective and neuro-regenerative processes that are often defective in MS (16).

Therefore the scientists suggest that neuroprotective strategies could be used as valuable add-on therapies alongside traditional immunomodulatory treatment in this condition.

Neuroplasticity plays a critical role in the ability of the brain to recover different neurological functions after TBI.

The activation of BDNF may induce neuroplastic changes that lead to adaptive neural repair and may potentially reverse cognitive and emotional deficits in TBI patients (12).

Animal studies report that the extensive activation of BDNF in zebrafish can lead to complete brain repair after a TBI (13). 

The neurotrophic factor-induced both functional and structural neuroplasticity leading to the formation of new neurons.

neurons
Parkinsons Hand

5) Mental Health Conditions – Depression & Anxiety

Mental health conditions such as depression and anxiety disorders appear to be associated with changes in brain neuroplasticity.

For example, a study of almost 2000 individuals with depression reports that the participants had significantly reduced activity of BDNF and neuroplasticity (17).

BDNF was also low in patients with stress-related disorders such as anxiety and chronic fatigue (18).

Furthermore, individuals with genetically determined low expression of GDNF were much more likely to suffer from anxiety disorders (19).

Neuroplasticity plays a critical role in the ability of the brain to recover different neurological functions after TBI.

The activation of BDNF may induce neuroplastic changes that lead to adaptive neural repair and may potentially reverse cognitive and emotional deficits in TBI patients (12).

Animal studies report that the extensive activation of BDNF in zebrafish can lead to complete brain repair after a TBI (13). 

The neurotrophic factor-induced both functional and structural neuroplasticity leading to the formation of new neurons.

Parkinson's Disease

GDNF is investigated as a potential treatment for Parkinson’s since it may help protect and even repair the neurons that are otherwise damaged due to the condition.

Researchers reveal that the activation of GDNF may prevent the death of dopaminergic neurons, which can slow down the progression of the disease (20).

Furthermore, case reports suggest that it can induce the formation of new dopamine neurons – the ones damaged and lost in Parkinson’s. 

For example, infusion of GDNF into the posterior putamen of 62-year-old patients causes similar sprouting of dopaminergic fibers in association with clinical improvement in Parkinson’s disease symptoms by 38% (21).

Another trial in 5 patients supports these findings and reports over 60% improvement in some of the symptoms one year after the therapy (22).

Summary

There is substantial evidence that neuroplasticity may play a role in a wide range of neurological conditions.

Despite that, there are serious obstacles to future research. For example, scientists lack reliable and non-invasive methods to increase the levels of neurotrophic factors in the brain, such as GDNF and BDNF (23, 24).

This is due to the blood-brain barrier, which separates the brain from the rest of the body’s circulation, and the infusion of neurotrophic factors cannot reach the brain.

Meanwhile, Ibogaine and other alkaloids present in Iboga can easily pass through this barrier and reach all parts of the brain.

Ibogaine increases GDNF, BDNF, and NGF levels in the brain, including areas affected by specific neurological disorders such as addictions, withdrawal, mental health conditions, Parkinson’s, MS, and Encephalomyelitis.

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References:

  1. Lotsof, H. S., & Alexander, N. E. (2001). Case studies of ibogaine treatment: implications for patient management strategies. The Alkaloids. Chemistry and biology, 56, 293–313. https://doi.org/10.1016/s0099-9598(01)56020-4 
  2. Deister, C., & Schmidt, C. E. (2006). Optimizing neurotrophic factor combinations for neurite outgrowth. Journal of neural engineering, 3(2), 172–179. https://doi.org/10.1088/1741-2560/3/2/011 
  3. Lu,, B. & Figurov,, A. (1997). Role of Neurotrophins in Synapse Development and Plasticity. Reviews in the Neurosciences, 8(1), 1-12. https://doi.org/10.1515/REVNEURO.1997.8.1.1
  4. Zigova, T., Pencea, V., Wiegand, S. J., & Luskin, M. B. (1998). Intraventricular administration of BDNF increases the number of newly generated neurons in the adult olfactory bulb. Molecular and cellular neurosciences, 11(4), 234–245. https://doi.org/10.1006/mcne.1998.0684 
  5. Marton, S., González, B., Rodríguez-Bottero, S., Miquel, E., Martínez-Palma, L., Pazos, M., Prieto, J. P., Rodríguez, P., Sames, D., Seoane, G., Scorza, C., Cassina, P., & Carrera, I. (2019). Ibogaine Administration Modifies GDNF and BDNF Expression in Brain Regions Involved in Mesocorticolimbic and Nigral Dopaminergic Circuits. Frontiers in pharmacology, 10, 193. https://doi.org/10.3389/fphar.2019.00193
  6. 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 
  7. Angelucci, F., Ricci, V., Pomponi, M., Conte, G., Mathé, A. A., Attilio Tonali, P., & Bria, P. (2007). Chronic heroin and cocaine abuse is associated with decreased serum concentrations of the nerve growth factor and brain-derived neurotrophic factor. Journal of psychopharmacology (Oxford, England), 21(8), 820–825. https://doi.org/10.1177/0269881107078491 
  8. Corne, R., & Mongeau, R. (2019). Utilisation des psychédéliques en psychiatrie : lien avec les neurotrophines [Neurotrophic mechanisms of psychedelic therapy]. Biologie aujourd’hui, 213(3-4), 121–129. https://doi.org/10.1051/jbio/2019015 
  9. 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 
  10. Neal, D. T., Wood, W., & Quinn, J. M. (2006). Habits—A repeat performance. Current directions in psychological science, 15(4), 198-202. https://doi.org/10.1111/j.1467-8721.2006.00435.x
  11. Pitts, E. G., Li, D. C., & Gourley, S. L. (2018). Bidirectional coordination of actions and habits by TrkB in mice. Scientific reports, 8(1), 4495. https://doi.org/10.1038/s41598-018-22560-x 
  12. Kaplan, G. B., Vasterling, J. J., & Vedak, P. C. (2010). Brain-derived neurotrophic factor in traumatic brain injury, post-traumatic stress disorder, and their comorbid conditions: role in pathogenesis and treatment. Behavioral pharmacology, 21(5-6), 427–437. https://doi.org/10.1097/FBP.0b013e32833d8bc9 
  13. Cacialli, P., Palladino, A., & Lucini, C. (2018). Role of brain-derived neurotrophic factor during the regenerative response after traumatic brain injury in adult zebrafish. Neural regeneration research, 13(6), 941–944. https://doi.org/10.4103/1673-5374.233430 
  14. Linker, R. A., Lee, D. H., Demir, S., Wiese, S., Kruse, N., Siglienti, I., Gerhardt, E., Neumann, H., Sendtner, M., Lühder, F., & Gold, R. (2010). Functional role of brain-derived neurotrophic factor in neuroprotective autoimmunity: therapeutic implications in a model of multiple sclerosis. Brain: a journal of neurology, 133(Pt 8), 2248–2263. https://doi.org/10.1093/brain/awq179 
  15. Razavi, S., Nazem, G., Mardani, M., Esfandiari, E., Salehi, H., & Esfahani, S. H. (2015). Neurotrophic factors and their effects in the treatment of multiple sclerosis. Advanced biomedical research, 4, 53. https://doi.org/10.4103/2277-9175.151570
  16. Kalinowska-Lyszczarz, A., & Losy, J. (2012). The role of neurotrophins in multiple sclerosis-pathological and clinical implications. International journal of molecular sciences, 13(10), 13713–13725. https://doi.org/10.3390/ijms131013713
  17. Bus, B. A., Molendijk, M. L., Tendolkar, I., Penninx, B. W., Prickaerts, J., Elzinga, B. M., & Voshaar, R. C. (2015). Chronic depression is associated with a pronounced decrease in serum brain-derived neurotrophic factors over time. Molecular psychiatry, 20(5), 602–608. https://doi.org/10.1038/mp.2014.83 
  18. Sjörs Dahlman, A., Blennow, K., Zetterberg, H., Glise, K., & Jonsdottir, I. H. (2019). Growth factors and neurotrophins in patients with stress-related exhaustion disorder. Psychoneuroendocrinology, 109, 104415. https://doi.org/10.1016/j.psyneuen.2019.104415 
  19. Kotyuk, E., Keszler, G., Nemeth, N., Ronai, Z., Sasvari-Szekely, M., & Szekely, A. (2013). Glial cell line-derived neurotrophic factor (GDNF) as a novel candidate gene of anxiety. PloS one, 8(12), e80613. https://doi.org/10.1371/journal.pone.0080613 
  20. 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 
  21. 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 
  22. 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 Parkinsons disease. Nature medicine, 9(5), 589–595. https://doi.org/10.1038/nm850 
  23. 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 

Chan, S. J., Love, C., Spector, M., Cool, S. M., Nurcombe, V., & Lo, E. H. (2017). Endogenous regeneration: Engineering growth factors for stroke. Neurochemistry international, 107, 57–65. https://doi.org/10.1016/j.neuint.2017.03.024