Ibogaine: Everything You Want to Know 

Overview: Ibogaine is a naturally occurring indole alkaloid derived from the roots of the Tabernanthe iboga plant, which has been used by indigenous peoples of Central West Africa for centuries. Ibogaine has shown promise as a treatment for addiction, with research suggesting its ability to interrupt addiction to opioids, stimulants, and other drugs. However, it remains a Schedule I controlled substance in the United States and other countries due to safety concerns and lack of regulatory approval. Further research is needed to understand ibogaine's anti-addictive effects and determine its safety and efficacy in larger patient populations.

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What is Ibogaine?

Ibogaine is a naturally occurring indole alkaloid derived from the roots of a perennial rainforest shrub called Tabernanthe iboga (Iboga). According to ethnobotanical literature, iboga, a chemically fascinating plant medicine bearing white tubular flowers and a yellow-orange fruit, has been used by the indigenous peoples of Central West Africa for centuries. 

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Iboga has become centrally integrated into a sophisticated, syncretic Christian religion called Bwiti in the countries of Gabon, Cameroon, and to a lesser extent in the Democratic Republic of the Congo. Followers of the Bwiti religion see the iboga shrub as the tree of knowledge as described in the Christian Bible.

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Throughout the 19th century, the use of iboga became a central feature of resistance against French colonization, and since then, it has become increasingly important and politically relevant.

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Since the 1960s, ibogaine has been shown to have potent anti-addictive properties. Research has demonstrated its ability to interrupt addiction to opioids, stimulants, and other drugs. Despite its therapeutic potential, ibogaine remains a Schedule I controlled substance in the United States and many other countries, largely due to safety concerns and a lack of regulatory approval.

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Ibogaine is illegal in the United States and is similarly scheduled in Canada, the UK, France, and the Scandinavian countries, but is unregulated in most countries.

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Traditional Usage of Iboga 

The root bark of the iboga plant is rich in approximately 80 indole alkaloids, the most abundant, most prominent, and most studied being ibogaine.

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According to American anthropologist James W. Fernandez in his book Bwiti: An Ethnography of the Religious Imagination in Africa, the people of Central West Africa mainly use iboga for two reasons: 

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At low doses, iboga has energizing, stimulant effects that are used to stave off hunger and thirst and prevent fatigue on hunting trips.

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On the other hand, high doses of iboga are used sacramentally to induce dream-like visionary experiences during religious “rebirth” ceremonies and rites of initiation, which are typically undertaken before one enters adolescence.

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To prepare iboga for ingestion, the root of the plant must first be dried. Once dried, the bark on the root is scraped off, sifted, and stored in a crystal goblet. In the Bwiti tradition, ceremony facilitators use a teaspoon to measure what they consider to be an appropriate dose. The facilitator then uses his fingers to carefully place the measured dose of iboga into the mouth of the receiver.

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Finally, the plant medicine is washed down with water. Smoked tobacco, whiskey, or honey may be offered to remedy its bitter taste.  

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The Surprising Journey of Ibogaine as an Anti-Addiction Agent

Ibogaine's journey as a potential anti-addiction agent began in 1962 in New York City when Howard Lotsof, a heroin-addicted teenager, consumed the substance in an attempt to alter his consciousness.

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To his surprise, he did not experience the typical symptoms of heroin withdrawal. Instead, he had intense psychedelic visions and underwent a profound introspection of his life, marked by hyper-logical interpretations of his experiences.

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Lotsof's experience paved the way for further exploration of ibogaine's potential therapeutic benefits in addiction treatment.

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Lotsof would go on to make important contributions to the world of ibogaine research, publishing hundreds of case reports showcasing people who had managed to break free from addiction. His findings and impassioned promotion of ibogaine turned scientists on to the possibility that ibogaine may possess anti-addictive properties.

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Evidence of Ibogaine’s Addiction Treatment Potential 

In 1991, behavioral pharmacologist Stanley Glick injected ibogaine into 13 morphine-addicted rats. In this study, ibogaine administered in 10mg/kg doses was shown to be effective in decreasing morphine self-administration, an effect that lasted several weeks. 

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Since then, observational studies have found that ibogaine treatment can induce opioid cessation and produce substantial reductions in opioid withdrawal symptoms and drug use in treatment-resistant opioid-dependent individuals. These results remain significant 12 months after treatment.

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In 2018, a systematic review of clinical trials on ibogaine found promising results. Three open-label clinical trials showed that ibogaine could reduce cocaine and heroin cravings in patients with Opioid Use Disorder or Cocaine Use Disorder. Additionally, one double-blind placebo-controlled trial demonstrated that ibogaine significantly reduced cocaine cravings and use in patients with Cocaine Use Disorder.

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Research to date suggests that ibogaine may be an effective tool for the treatment of opioid withdrawal and substance-related cravings. However, further research is needed to better understand the mechanisms underlying ibogaine's anti-addictive effects and to determine its safety and efficacy in a larger patient population. 

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How Does Ibogaine Work in the Brain?

The ibogaine molecule has an impressive 3-dimensional structure that is quite complex, making its synthesis a challenging task. In addition to its structural complexity, the pharmacology of ibogaine is also not yet fully understood.

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Although ibogaine has shown potential as a treatment for addiction, the exact mechanism of how it works remains a mystery to researchers. Ibogaine appears to exhibit a polypharmacy effect, whereby it uniquely acts on a cluster of different brain receptors. The effects of ibogaine may be associated with the following mechanisms of action:

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• Ibogaine’s inhibitory effect on serotonin and dopamine transporters
• Action at opioid receptors
• Action at N-methyl-d-aspartate (NMDA) receptors 
• Action at sigma receptors
• Action at nicotinic acetylcholine receptors
• The production of glial-derived neurotrophic factors (GDNF)
• The production of brain-derived neurotrophic factor (BDNF) 

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This polypharmacy effect has made it difficult for researchers to associate observed benefits with specific mechanisms of action, but some hypotheses have been put forward. 

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Ibogaine affects various brain structures and receptors to help reduce substance use. For example, it has been shown to increase the production of a protein called GDNF, which supports the survival of dopamine neurons and can lead to reduced alcohol intake. Ibogaine also blocks nicotinic receptors in the habenula, a brain structure involved in reward and punishment, which is associated with decreased alcohol and nicotine use.

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Another way that ibogaine works is by partially activating mu-opioid receptors, which decreases the desire to use opioids. Its active metabolite, noribogaine, acts on the kappa-opioid receptor, which is important in treating cocaine addiction.

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In addition to these mechanisms, ibogaine also interferes with the reuptake of dopamine and serotonin, and inhibits NMDA receptors that are involved in pain, analgesia, and memory formation. By targeting multiple brain systems, ibogaine can help reduce addiction and craving. However, further research is needed to fully understand how ibogaine works and to ensure its safety and effectiveness.

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Overall, ibogaine shows no clear preference for any particular receptor site. It appears likely that ibogaine’s targeting of multiple receptor systems and its long-lasting activity both play an instrumental role in treating substance use disorders.

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The Role of the Ibogaine Experience in Breaking the Cycle of Addiction

The Ibogaine experience has been reported to provide individuals with a sense of clarity and insight into their addiction, helping them to confront and process underlying emotional issues that may be contributing to their substance abuse.

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Additionally, the dreamlike psychedelic effects of ibogaine can provide a unique and profound experience that some individuals find transformative and helpful in breaking the cycle of addiction.

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However, it is important to note that the experience alone is not enough to ensure long-term recovery, and that ongoing support and therapy are often necessary for sustained sobriety.

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Understanding the Safety Profile of Ibogaine: A Review of the Evidence

The true safety profile of ibogaine remains unclear due to a lack of clinical research, and as such, the evidence regarding ibogaine's physiological effects should be viewed as preliminary.

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Despite promising preliminary research, progress in ibogaine-related research has been slowed down by a number of setbacks. One of the challenges is the reported deaths linked to cardiotoxicity, with 33 such cases reported in the literature.

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Specifically, ibogaine has been associated with prolongation of the QTc interval, which refers to the lengthening of the time it takes for the heart to depolarize and repolarize, potentially due to the drug’s action at the human ether-a-go-go-related gene (hERG) channel. The hERG channel is a gene that codes for a potassium ion channel found in the heart that plays an important role in the repolarization of the heart. 

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In addition, researchers sustained a blow after FDA-approved research to treat cocaine-dependent humans was stopped in its tracks after researchers discovered an association between ibogaine and cerebellar ataxia — a neurological disorder that affects movement and coordination. 

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These findings have led to hesitancy among the Food and Drug Administration (FDA) to approve ibogaine-related research.

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However, reviews suggest that unsafe settings, lack of medical supervision, toxic doses, and pre-existing heart conditions may be the main causes of these fatalities. 

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During an ibogaine experience, individuals may experience acute psychological distress, which may include feelings of anxiety, fear, or paranoia. However, it is important to note that the severity and duration of these distressing experiences can vary widely depending on factors such as the individual's psychological state, dose, and setting of administration.

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It is also worth mentioning that the risk of severe psychological distress can be mitigated through proper preparation and guidance from trained professionals in a controlled and supervised setting. Additionally, research conducted in controlled settings with fixed doses of ibogaine has reported lower rates of severe distress than anecdotal reports from non-medical settings where doses are often variable and uncontrolled.

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Limitations of Current Knowledge: The Need for Further Research on Ibogaine

In conclusion, while Ibogaine has shown promising results in the treatment of addiction, it is essential to note that further research is needed to fully understand its mechanisms of action, potential risks, and long-term effects. The current state of knowledge is still limited, and more rigorous scientific studies are required to ensure the safety and efficacy of Ibogaine as a therapeutic option.

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To better understand the therapeutic potential of ibogaine, larger clinical trials with randomized and controlled designs need to be conducted. These trials should have adequate sample sizes and be conducted in diverse populations with varying degrees of addiction severity. The use of standardized protocols for administering ibogaine and the careful monitoring of patients during and after treatment can help identify potential risks and adverse effects.

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Additionally, research on the long-term effects of ibogaine is crucial to assess its safety as a therapeutic option. Long-term follow-up studies can provide valuable information on the durability of the treatment effects and any potential adverse effects that may emerge over time.

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Overall, larger and more rigorous clinical trials, long-term follow-up studies, and mechanistic investigations are necessary to fully understand the therapeutic potential, risks, and long-term effects of ibogaine. These studies can help establish the safety and efficacy of ibogaine as a new and alternative option for addiction treatment.