This review of the History of Ibogaine, an African root, focuses on contextual aspects impinging upon its use in the treatment of substance abuse disorders. The focus on context and history intends to convey the message that Ibogaine properties and potential benefits have not found a place in the treatment of substance abuse disorders, in spite of substantial practice-based evidence supporting them. The focus of the article is on stimulating and/or rekindling some interest in this natural root, and at the same time, increasing awareness about alternative treatments for substance abuse disorders, which are often ignored by mainstream science.

Introduction

The use of Ibogaine, an alkaloid found in an African root, originated in some indigenous African cultures as a powerful healing tool for different types of physical and emotional discomfort. In the last three decades, it has gained popularity in the Western world because of its potential benefits in the treatment of substance abuse problems. Both clinical and research work have shown the benefits of Ibogaine in the treatment of opioids and, to some degree, cocaine and alcohol abuse. This article offers a review of the most salient aspects of the history of this natural remedy. It is also a testimony to the difficulties experienced by its proponents, who have faced ideological conflicts, economic problems, and social isolation, in proposing Ibogaine as a legitimate treatment for substance abuse problems. The goal of this narrative is to increase the level of curiosity about Ibogaine treatment in the professional who may focus predominately on mainstream therapies, while neglecting some promising alternative approaches.

History

Ibogaine is the name given to the alkaloid found in the root bark of the African plant Tabernanthe Iboga, well known to some Indigenous populations from unmemorable times. The populations following the Bwiti culture are probably the most jealous custodians of the tradition of Ibogaine rituals. Their relationship with the plant has been multidimensional, encompassing spiritual, political, and medicinal aspects. However, other groups on African soil have been using the plant for ceremonial and therapeutic uses. All these populations have a strong sense of community and spirituality in common.

The use of Ibogaine throughout the ages has expanded to about three million of Indigenous Africans. In general, they value it as a source of imagery and visions capable of triggering spiritual and social insights. The Indigenous manufacturing of the Ibogaine (essentially the same throughout the ages), consists of grinding the plant root bark which will be slowly chewed by the candidate for the rituals (Alpert .et al 2001; Fernadez, 1972; Fernandez, 1982). The use of ground bark is part of one of the most symbolic rituals in the Bwiti tradition. This ceremony marks the transition from adolescence into adulthood by promoting a deeper identification with the tribal culture and the development of the "adult persona" (Fernadez, 1972, Fernandez, 1982). In other rituals, Ibogaine facilitates the reawakening of a traditional spirit and the development of a personal renewal leading to a sense of continuity with the community. During all the events including the use of Ibogaine, the individual discloses his/her moral and emotional issues with the goal of developing renewed insights and a clearer sense of self. Although the rituals have assumed several anthropologic meanings, one of their essential roles is the attainment of a tribal identity in which the masculine and feminine aspects coalesce in a sort of "primordial essence" and re- emerge as a newfound identity. Usually, an experienced healer guides the spiritual aspects of the ceremony and, at the same time, helps in preventing the occurrence of possible physical side effects and unpleasant psychological experiences (Fernandez, 1982, Naranjio, 1974, Pope, 1969).

Although there is no documentation that the Bwiti have treated substance abuse problems, addicts, clinicians and researchers in the Western world have developed a keen interest in its potentials for ameliorating substance abuse problems (Alpert .et al, 2001, Alper et al., 2008).On the Western front, the U.S. drug subculture of the 1960s and 1970s was pivotal in acknowledging the positive effects of Ibogaine on substance abuse problems.

Ibogaine: America and Holland

Howard Lotsof, an addict himself, considered the father of the Ibogaine treatment in the Western world, became very interested in it after having experienced its beneficial benefits for his opioid abuse problem. He found it to be effective for his heroin withdrawal and craving. His addict friends, who, at least for a while, could stop the use of heroin after Ibogaine treatment, corroborated his views of its powerful and beneficial effects. However, it took him about twenty years to develop a viable plan to study the benefit of the drug. Even though, during this long period, Ibogaine had been declared illegal in the US, Lotsof did not give up, and decided to conduct his research abroad. In the 1990s, Lotsof set up a clinical trial in Holland, where, with the help of local clinicians, he treated a population of about thirty addicts, some of them with mixed substance abuse problems (e.g., heroin, cocaine) (Alpert,2001; Alpert .et al,2001). Unfortunately, the occurrence of a death during the research project caused the end of the Dutch experience.

The consequent negative propaganda originating from the most bureaucratic and conservative sectors of Dutch society, contributed to paint a dark and sinister picture of the effects of Ibogaine (Alpert .et al, 2001). It is worthwhile to state that the cause of death in the Lotsof study was not clear and that was probably due to a variety of factors, including hidden physical problems and concurrent drug abuse. In reality, the therapeutic outcome from the Dutch trials showed, in the overall, positive effects on craving and abstinence mainly for heroin and cocaine abuse and addiction (Alpert .et al, 2001; Alpert et al.,2008 ;Bastians, 2004).In the meantime, the U.S. National Institute on Drug Abuse(NIDA), which had shown some interest in getting involved in Ibogaine trials with Lotsof, decided to withdraw from the process, partially because of the negative publicity on its alleged lack of safety. This was a disastrous moment for the future of Ibogaine, since it established such a negative image, from which Ibogaine never fully recovered. As shown by history, when official science brands a therapeutic modality as ineffective and unsafe, the likelihood that it can regain popularity and status is, at best, minimal. (Alpert, 2001; Alpert .et al, 2001; Brother Shine et al., 1995).

Ibogaine and the Pharmaceutical Industry.

As stated, the developing controversy surrounding Ibogaine veered the interests of NIDA officials away from the development of scientific investigations and clinical trials regarding this drug. Not surprisingly, this lack of interest matched a similar neglect by the pharmaceutical industry, which expressed negative views about Ibogaine in treating substance abuse disorders. In reality, the industry was responding to the fact that Ibogaine is a natural compound and is, as such, not patentable. Also, its development would have been in potential competition with other established pharmacologic treatments, already a secure source of profit for the pharmaceutical industry (Alpert .et al, 2001; Alpert et al., 2008; Brother Shine et al, 1995).Moreover, the controversies surrounding Ibogaine, constituted a potential "image issue "for the industry, which could have been blamed for promoting an esoteric and potentially unsafe product. Indeed, similar concerns have tainted the therapeutic potentials of other hallucinogens (e.g. Peyote), which could have had a specific role in the treatment of substance abuse problems.

However, it would be erroneous to characterize the controversy surrounding the use of Ibogaine just in terms of profits or safety. A more comprehensive analysis shows that it is also about the quality and the ideology underlining its use and experience. Undeniably, the imagery and the mystical insights catalyzed by Ibogaine are alien to the Western healing paradigms. Moreover, the clinicians operating within a Western milieu approach the treatment of addiction problems as a tool for helping people in regaining their own ability to contribute to societal and industrial productivity, interpreted as Fordian/Calvinistic values of input-output measures (Wagner, 1997). On the contrary, the Ibogaine treatment strives to develop insights which could benefit the social, cultural, and spiritual well being of the community and does not focus on the reintegration of the individual in the cycles of Western capitalism (Alpert2001; Alpert .et al, 2001; Brother Shine et al.1995). In addition, although a period of political activism in favor of Ibogaine triggered some interest in its clinical use, it never reached a critical mass able to generate serious interest by public agencies, academia, and pharmaceutical industry. Actually, it could be argued, that its impact may have contributed to the strong and negative response within the scientific world (Alcoholism and Drug Abuse Weekly, 1995; Alpert .et al, 2001; Alpert et al., 2008). This comment does not imply that the "Ibogaine activists" have done anything wrong, just that their efforts did not find a receptive audience because of the socio-political climate already described. Moreover, the classification of the drug as Class I, and therefore illegal for any therapeutic use, has relegated it to a marginal status in the field of substance abuse. In addition, although there are private clinics around the world (e.g. South America), offering Ibogaine treatment, these operate with the support of a very limited subculture and are therefore emarginated from mainstream health care practice.

Ibogaine Mechanism of Action

 As already stated, Ibogaine is an alkaloid present in relevant quantities in the Iboga African root. Ibogaine HCL, its pharmacologic derivative, has triggered the interest of both researchers and clinicians. Its classification as a Schedule I-Drug under the Controlled Substance Act, because of supposed abuse properties and lack of proven clinical efficacy, is arguably severe and punitive. For instance, no researcher, clinician, or patient has ever reported any problems typically seen with other potentially addictive drugs. In addition, as noted, there are encouraging findings about its therapeutic properties. Therefore, its inclusion in the Schedule-I Group seems to derive from ideological and political factors, which have played a historical role in the classification of pharmaceutical compounds.

Like for many hallucinogens (this term is very loosely used in this article), Ibogaine’s mechanism of action is still unclear, although animal studies indicate that the drug affects several neurotransmitters and binding sites. In essence, these studies propose that the symptoms related to substance withdrawal are blocked or ameliorated through the action on the NMDA ((N-methyl D-aspartate)system; the positive effect on craving is modulated by its influence on the dopaminergic system ; the imagery and insights are mediated by its serotonergic properties (Ali, 2000;Alper;2001;Glick,et al.,1996;Lieberman,1999;Mash, et al.,1995;Sershen,et.al,1997;Popik,et.al.,1995). These mechanisms may be partially responsible for its efficacy on opioid, cocaine, and alcohol dependence, (even though the more robust evidence seems to be for opioids-related problems). Gaining personal insights into a drug problem is one of the most valuable therapeutic effects of Ibogaine therapy and can be the catalyst to address other psychological issues frequently co morbid with addiction problems (i.e., trauma, depression). In the past, these properties have prompted the use of Ibogaine as an ancillary tool for psychotherapy. In this regard, the Chilean psychiatrist Claudio Naranjo describes the role of Ibogaine in developing awareness into the unconscious and in removing obstacles stunting individual psychological growth (Naranjo, 1969; Naranjo, 1974). A review of the literature indicates the use of Ibogaine may not be sufficient to bring about a process of deep personal transformation. Nevertheless, the drug can provide the biological basis for the development of insights pivotal to behavioral changes.

So far, we do not know which Western —based psychotherapeutic approaches may be more effective, since research on the subject has been very limited. However, it is clear that the psychotherapeutic/ritualistic work of Indigenous communities is much different from the one practiced in a Western oriented milieu. The most striking gap between the two approaches is that while the former puts an emphasis on the well-being of the community as a source of healing, the latter focuses on individual therapeutic strategies and goals (Alpert .et al, 2001; Goutarel,1993). The former views health as a community process, the latter as individual responsibility.

Overview of Treatment Guidelines

 The scope of this article is not to elucidate in detail the technical /clinical aspects of Ibogaine treatment, since they are already available in numerous publications. However, illustrating the main aspects of it will convey a more comprehensive view of its biological and psychological properties. Although the clinical experience with Ibogaine is quite substantial, the definition of its treatment modalities is still in progress. According to protocols and to clinical/ anecdotal information, Ibogaine is available in capsule form as Ibogaine HCL and, as already stated, it appears to be effective, safe, and not addictive. The beneficial effects of the drug may show just after one dose, with a lessening of withdrawal symptoms, craving, and the triggering of imagery and insights.

The available data indicate that clinicians should follow specific steps when screening candidates for Ibogaine therapy: It is essential that the individual assumes an active role in treatment, meaning that he/she is responsible for the entire process leading to the development of insights and behavioral changes. The candidate should make an effort in observing abstinence for at least 24 hours before initiating treatment. Additional time may be necessary for drugs with a longer half-life (e.g. methadone) ( Alper et. al.,1999; Lotsof ,1985;Lotsof1986; Lotsof,1989; Lotsof,1992 ; Lotsof,1995).Although the risk for severe adverse effects (i.e. substantial withdrawal symptoms, sudden death) is a theoretical possibility, the evidence for these is rather weak. However, the message from most authors is that the clinician should be extremely cautious in initiating treatment with a patient who may be still metabolizing any psychotropic drugs. Unfortunately, we cannot ignore that the deaths occurred during the Dutch trials were attributed by some clinicians and researchers to the synergistic effects of opioids and Ibogaine. A physical exam and possibly an ECG (Electrocardiogram) would be advisable for all the candidates, with the possibility of other tests (i.e.: CBC (Complete Blood Count), liver functions), according to the assessed clinical needs (Lotsof, 1995; Lotsof .et. al., 2003).

The modality of dosing Ibogaine is also pivotal to a good outcome. Experience shows that doses within the range of 10 -20 mgs /kg are safe and effective. However, female patients usually require lower amounts. From experience, it is advisable to induce the patient with a moderate dose of Ibogaine (e.g. 100mg) before beginning treatment. This procedure will show clinical evidence of heightened sensitivity to treatment and therefore may be helpful in avoiding side effects (i.e. sedation, unsteadiness). After having established an effective and safe initial regimen, the clinician can safely start treatment. Although it is possible to give additional doses during treatment, this would require extreme caution since data on multiple dosing are quite sparse.

In addition, it is crucial to stress the importance of the psychological status and the social setting surrounding the experience both in terms of safety and therapeutic outcome .Ideally, treatment will take place in an environment sheltered from noise and providing a sense of "interior peace" to the individual. The presence of experienced medical personnel is pivotal for avoiding and/or lessening possible unwanted effects and for guiding the individual towards a rewarding and insightful experience, as is the case for rituals including other hallucinogens (e.g., Peyote) (Lotsof,1995; Lotsof et al., 2003; Lotsof, 2007;Luciano,1998.). Moreover, it is worthwhile to stress again that clear life threatening side effects from the clinical use of Ibogaine have not been definitely proven and that, when used appropriately, the drug shows very little, if any, toxicity.

Clinical Response

 Clinicians guiding the experience (including the original African healers which are probably the main experts in the Ibogaine treatment) pay attention to the individual response to treatment which, as expectable, shows a potential wide range of symptoms and signs. Usually, the effects are visible after thirty minutes from dosing, although in some cases, it may take up to two hours. The most common side effects seem to be ataxia, anxiety, peculiar acoustic experiences, and extreme sensitivity and reactivity to light. Some subject may also show nausea and vomiting which, in some cases, may interfere with the absorption of the drug, and potentially jeopardize treatment. Additionally, a slight elevation in blood pressure is common, particularly during the first few hours after dosing. These signs and symptoms may be potentially confused with a withdrawal process. Therefore, clinicians with experience in the field of substance abuse can be helpful in distinguishing signs of Ibogaine toxicity from those related to withdrawal (Lotsof et. al, 2003; Lotsof, 2007; Luciano, 1998).

The psychological and emotional effects become visible in two main phases: The first, which unveils visions of complex nature and content running through the mind. Individuals describe it as a film of earlier experiences running through the mind. During this phase, they may experience intense emotions, requiring, at times, supportive intervention by clinicians. The subsequent stage is characterized by a lessening of the vivid imagery and the development of a cognitive state, which could last over ten hours, characterized by moments of insight about personal drug habits and mixed with mystical themes, contributing to the development of a narrative of the personal drug and life experiences. If during these two phases the individual will experience peaks of emotional intensity, the clinicians will support him. Usually, when emotionally charged responses happen, an experienced clinician will be able to bring the patient back to a more balanced state (Lotsof et. al, 2003; Lotsof, 2007; Luciano, 1998)

Impact on the treatment of substance abuse disorders.

 After treatment, the addict may experience very little signs and symptoms of withdrawal and limited or absent drug craving for at least several weeks. The length of these gains is variable, according to the experience of addicts who went through treatment (Lotsof, 2007; Luciano, 1998;Sisko ,1993).Unfortunately, because of the reason previously reviewed, no solid clinical trials have taken place yet. Moreover, there are methodological questions about the effective elements in the Ibogaine treatment and their respective and specific efficacy (i.e. biological factors versus psychological, cultural aspects of treatment). Hopefully, the awareness of these issues will help avoiding a biological/ reductionist bias in the investigation of this drug, as frequently happens in Western science. We should not forget that originally on African soil, the drug functioned as a biological trigger to stimulate psychological, spiritual, cultural, and social transformations, and therefore just as a step of the overall healing practice( Fernandez,1972;Fernandez, 1982; Naranjo,1969). Following the initial stage of treatment, the individual in recovery, has a window of opportunity for initiating additional, long-term psychosocial interventions. For now there is no clear evidence about the efficacy of any specific treatment in the follow up phase; therefore, the clinician will try to define the most appropriate follow up for the individual by paying attention to his/her cognitive, psychological, ethnic, social, and spiritual background and inclinations, as it should be done, in any optimal clinical situation.

In considering the possibility of an Ibogaine HCL re-administration during the follow up period, it is worthwhile to remember that its metabolites linger in the blood stream for several weeks, raising the possibility of side effects, if a new dose is given. Presently, we do not know if multiple treatment episodes are more effective than just one single dose. In addition, we do not have proof that shifting to any other medications (i.e. naltrexone, buprenorphine) improves outcomes. Having stated all these limitations in our knowledge, it remains clear that there are many clinical and research indications for continuing to study this drug. Presently, there are few groups around the world trying to set up clinical trials including Ibogaine. Among the main issues related to Ibogaine research are those about efficacy and safety and the identification of specific groups more likely to benefit from it (Alper ,2001;Alpert K.et al.,2001, ;Alpert et. al,2008). However, we seem to be far away from a cultural and political environment open to address the problem of substance abuse more comprehensively than the established biological and cognitive behavioral paradigms( Mental Health: A Report Of The Surgeon General,1999;Sturm,1995, Sweetnam et.al,1995,Williams,1995;Tucker,1985).

It is evident that there is not enough emphasis on societal and cultural issues in both clinical and research work in the field of substance abuse. Moreover, methodological issues are paramount to conducting studies including personal, societal, and cultural aspects of individual struggling with disorders of any kind and in particular with substance abuse problems. Although quantitative methodologies can be useful to assess aspects of the substance abusers experience, qualitative approaches can provide a personal and "intimate" views capable of unveiling insights into real and unexplored meaning of addiction and drug abuse.

Discussion

There is substantial clinical, and some research-based evidence that Ibogaine has properties favoring a positive outcome in treating certain substance abuse problems. Unfortunately, the progress of research involving this natural compound, has been severely slowed down, if not irreparably compromised, by concerns about its safety, negative ideological propaganda , and total neglect by pharmaceutical companies , not willing to invest in treatments with limited potentials for profit. Experience with Ibogaine has shown efficacy in treating opioid abuse and addiction, and to be helpful to people struggling with cocaine and alcohol problems. It seems to facilitate the therapeutic process by fostering insights and what could be defined as moments of "higher consciousness", pivotal in modifying pathological behaviors. Therefore, ignoring the potential benefits of this drug would constitute a scientific fallacy. Indeed, any reasonable professional should acknowledge that such robust preliminary findings as those available for Ibogaine should prompt additional scientific investigations. Moreover, qualitative approaches could capture the quintessence of the Ibogaine experience. Unfortunately, for the time being, the future of Ibogaine remains uncertain.