Ibogaine is a naturally occurring psychoactive substance found in a variety of plant species in the Apocynaceae family, principally Tabernanthe iboga. It has demonstrated efficacy in the treatment of various substance use disorders (SUDs), particularly for detoxification for opioid used disorders and the reduction of the associated post acute withdrawal symptoms (PAWS) (Alper 1999, Brown 2013).
For this reason, ibogaine continues to generate a growing interest among medical professionals as well as the general public, especially those seeking alternatives to conventional modalities of treatment for SUDs.
This promise accompanies recognizable physical and psychological risks. Ibogaine has not yet been developed as a prescription medicine. However, some countries have explored or are exploring experimental prescription frameworks that make it available for use in detoxification. Other countries have implemented strict bans or restrictions against its use, largely without recognition of its potential medical benefit. In many other regions, ibogaine is used either under the auspices of “compassionate care,” or otherwise as an unapproved treatment.
It has been noted that the lack of standardized clinical practices in the experimental environments in which ibogaine therapy is generally practiced presents increased risks associated with its use (Alper 2007). The purpose of these guidelines is to consolidate existing knowledge gathered from thousands of treatments conducted since the early 1980s in a variety of medical and non-medical settings.
Most of the information presented in this document is supported by published research. Elsewhere, it is derived from a various clinical experiences, synthesized through extensive interviews with therapy providers.
It is our hope that the information presented herein will prove useful for medical professionals who wish to understand current clinical practices; in the development of protocols for clinical trials; and to policy makers who wish to review potential avenues for effective regulation of ibogaine-assisted detox as a prescription medicine. Finally, we hope that it will eventually lead to the development of comprehensive minimum standards of care in the future.
Risk Management
This methodology of risk management used in these guidelines is based on the International Standards Organization’s ISO31001: Enterprise Risk Management. This document uses a definition of risk outlined in ISO Guide 73, which calls it “the effect of uncertainty on objectives.” This effect has the potential to be positive or negative, but its effective management is crucial for ensuring positive outcomes.
Scope of this Document
This document was produced in an effort to identify the known risks associated with the use of ibogaine, and to present guidelines to manage its risks in a clinical setting. Although some other applications of iboga and ibogaine – as well as its metabolite noribogaine, and an ibogaine analog, 18-Methoxycoronaridine (18-MC) – are being explored, the scope of this document will refer specifically to the medical use of purified ibogaine hydrochloride as an aid in detoxification for opioid use disorders.
While this guide will focus on ibogaine’s ability to mitigate opiate withdrawal symptoms, it is practical to note that a significant number of patients with opioid use disorders are also polysubstance users and/or have other psychological or physical co-occurring disorders. Many of these issues are also discussed throughout this document.
A significant amount of further research is required in order to completely understand the nature of the ibogaine experience and its implications in the treatment of SUDs. This study will require comprehensive collaboration between various disciplines, including psychology, sociology, ethnopharmacology, philosophy, and comparative religion, amongst others. These guidelines do not function as a textbook or a manual, but the considerations outlined may be useful for medical professionals in the development of clinical protocols.
Context & Continuing Care
While the fields of psychiatry and allopathic medicine primarily focus on a biological foundation of SUDs, there are a complex bio-psycho-social phenomena affecting addiction that are crucial to consider in planning a complete recovery (Tatarsky 2007, Mate 2009, Alexander 2010).
Simply addressing a SUD with ibogaine can sometimes be enough to help a patient make desired changes in their lifestyle and drug use if and when they are ready and equipped for this change. But much more often further ongoing psychological support is necessary. There is evidence from observational research following ibogaine therapy that patients who were provided or sought out various forms of ibogaine aftercare and additional therapeutic support had improved rates in long-term sobriety from their primary substance of abuse (GITA 2014, Schenberg 2014).
Whenever possible, the detoxification guidelines outlined here should be considered as an elementary step in the larger SUD treatment process.
A Note About Traditional Use
The particularly narrow focus of these guidelines also takes into consideration that the ibogaine-containing plants – particularly the Tabernanthe iboga and Tabernanthe manii shrubs – have been used for millennia by traditional communities in Gabon and the surrounding regions of the West African rainforest as a sacrament in rituals of healing and spiritual initiation. In this context as well, adverse events and fatalities have been reported. In recent years these situations may be exacerbated by the fact that iboga is potentially threatened in its natural habitat, and other plants are sometimes used, whether mistakenly or intentionally, as substitutes, sometimes for economic advantage (GITA 2014). In other cases, these events have been attributed to unskilled practitioners.
It is hypothesized that aspects of the ritual and music employed by traditional communities are complexly arranged to both increase iboga’s effects (Mass 2006) as well as physical and psychological wellbeing (GITA 2014).
Use of iboga in these traditional contexts is protected by the 2007 United Nations Declaration on the Rights of Indigenous Peoples, which states in Article 24 the right of indigenous people, “to their traditional medicines and to maintain their health practices, including the conservation of their vital medicinal plants, animals and mineral.”
These guidelines can serve as a supplement to genuine spiritual practice, but in general this is beyond the scope of the considerations for risk management presented here.
Summary of Psychological Factors
For it’s psychological effects, ibogaine is best classified as an oneirogen, a substance that produces waking dreams (Naranjo 1974). For many ibogaine patients these effects are visual, and this visionary content is deeply subjective and personal, unfolding much the same way as dreams. The experience has also been likened to watching a film projected on an inner screen – often with a level of emotional detachment, even when the content is very emotional or graphic. This overall effect can evoke a state of profound contemplation and self-reflection.
It has been suggested that the experience is analogous to the kind of neurological and psychological integration that happens during a state of rapid eye movement (REM) sleep, but while the patient is fully conscious (Goutarel 1993).
These effects are distinct from classic psychedelic compounds, both subjectively and also because of the complex nature of the physiological effects that accompany them.
Onset, Phases & Duration of Effects
The onset of ibogaine’s effects is generally noticeable within 1-3 hours after administration. This includes both a marked decrease in physiological withdrawal symptoms as well as the subjective effects, which are divided by Dr. Kenneth Alper into three distinct phases (Alper 2001). The duration of the effects mentioned below will vary based on dosage, the timeframe over which the doses are administered, and also factors that affect individual metabolism, including CYP450-2D6 phenotype.
1. Acute
This phase generally lasts between 4 to 8 hours, and include the most intense and visual part of the experience that was described above as oneirogenic. During this phase the physiological effects, especially the mentioned ataxia, will be most pronounced.
2. Evaluative
The “evaluative” phase of the experience can last between 8 to 20 hours, and consists largely of a cognitive and more or less emotionally neutral review of material that was experienced in the acute phase. Patients generally prefer to be left undisturbed, and to lie mostly still and quietly during this integration phase.
3. Residual Stimulation
The final stage of effects generally last for another 24 to 72 hours. This period is usually accompanied by some level of exhaustion, and in some cases continued difficulty sleeping. Cognitive and introspective processes begin to relax and attention returns to the outer environment.
Management of Psychological Risk Factors
Conventional academic theories in the fields of psychology and psychiatry do not generally discuss the types of experiences that are commonly reported by ibogaine patients. When they do they are categorized broadly as forms of psychosis. However, transpersonal psychology and other similar experiential fields have established clear frameworks for understanding the nature and therapeutic value of these and other similar states. Rather than pathological, the natures of these states have been described by Stanislav Grof as holotropic, or “oriented towards wholeness” (Grof 1992). This field draws from millennia of human experience in accessing these states of consciousness for healing and rites of passage, and provides invaluable insights for integrating these types of experiences into contemporary therapeutic contexts.
It has been noted elsewhere that research using psychedelic contains rare but significant psychological risks, mostly involving “overwhelming distress” caused by a “bad trip” and resulting in the patient leaving the treatment site, or, less commonly, the manifestation of long-term psychosis (Johnson 2008). Unlike many conventional medical treatments, under the influence of ibogaine or other similar substances, it is difficult to overemphasize the importance of the treatment environment and the relationship that is formed between the patient and the caregivers, especially those who are present during administration and the acute period of integration following.
There are rare anecdotal reports of patients who experienced an acute confusional state after ingesting ibogaine that persisted from less than one hour up to several days. There are other very rare reports of symptoms of prolonged psychosis (Houenou 2011, Dyer 2011), as well as others of individuals who were diagnosed with mania following ingestion (Marta 2015).
However, to the extent ibogaine shares similar psychological risks to other psychedelic medicines, the psychological frameworks and therapeutic tools used when administering psychedelic medicines may also prove useful guides for psychological safety. Grof wrote that, “LSD subjects whose sessions terminate in a state of incomplete rebirth show all the typical signs of mania,” but that, “when individuals experiencing this state can be convinced to turn inward, face the difficult emotions that remained unresolved, and complete the (re)birth process, the manic quality disappears from their mood and behavior.”
A comprehensive psychological assessment (Ch. 2) should precede any administration of ibogaine. Further, during and after treatment, sensitivity on behalf of the practitioners to the nature of the oneirogenic state and focused attention to the set and setting (Ch. 1) should be paramount at all times.
Working with Spiritual Emergence
One of the most important implications of transpersonal psychology is the understanding that many commonly diagnosed psychiatric conditions are forms of “spiritual emergency” or psychospiritual crisis that can lead to personal breakthroughs (“emergence”) if properly managed. Stanislav Grof lists addiction itself as a form of spiritual emergency, healing through which has the power to be incredibly transformative for an individual.
It is important to be able to differentiate between a genuine spiritual emergency that may possess cathartic healing potential, and forms of psychosis and genuine medical emergencies that require acute medical interventions.
Implementing this model of practice in the case of an acute confusion state can be time and energy intensive for therapy providers, but, when fully understood, the benefits for the patients are difficult to overlook. In all known cases, those who experienced an acute confusional state following ibogaine administration and were cared for throughout the entirety of this episode later reported that the process was personally important and ultimately beneficial.
The most important implication here is in the strategy in regards to the use of prescription medications. In the treatment of spiritual emergencies, clinicians should avoid use of psychiatric medications that may interrupt the psychological process underway. Anti-psychotic medications such as haldol or thorazine, which are used to interrupt the effects of other psychedelic substances have been known to cause prolonged negative reactions in patients. When necessary, and in instances where insomnia threatens physical and psychological wellbeing, the judicious use of benzodiazepines can slow subjective effects and help to facilitate relaxation and sleep.
Treatment of spiritual emergencies is a field too vast to summarize in these guidelines, and strays from our intended focus. However, there is a sufficient amount of existing material to inform clinicians on the foundations of this work (Grof 1989, 1993, 2008).
Summary of Medical Factors
While ibogaine’s mechanisms of action are not fully understood, some aspects of its complicated pharmacodynamics have been summarized in scientific literature (Alper 2001). Here we will review some of the relevant aspects of ibogaine’s effects and neurotransmitter activity, as well as documented risk factors. These types of considerations are not common amongst psychedelic medicines, highlighting the unique physiological characteristics of ibogaine and the importance of its particular requirements for screening and monitoring.
Basic Pharmacodynamics
In addition to the psychological effects noted in the previous section, ibogaine presents some powerful physiological effects, including ataxia, tremor, nausea, vomiting, slowed breathing, heightened sensitivity to sensory stimuli, as well as bradycardia, hypotension and other changes to heart rhythms or blood pressure, including QT interval prolongation and t-wave morphology changes. As a result, unless necessary, patients generally prefer to be lying comfortably without a lot of agitation or movement.
Ibogaine’s physiological effects, particularly its cardiac effects, can present significant and potentially life threatening risk factors even within the therapeutic dose range in patients that have certain pre-existing heart conditions, electrolyte imbalance, or who are detoxifying from alcohol or benzodiazepines (Alper 2012).
The QT interval prolongation associated with ibogaine may have several causes. The primary factor is changes to the way that cardiac cells utilize potassium to repolarize their electrical charge. This repolarization reserve is also affected by bradycardia and the blockage of the hERG channel, which modulates the bioavailability of potassium. As addressed later, this presents concerns in patients who are hypo or hyperkolemic.
Other factors also play a role in depleting repolarization reserves and causing QT prolongation. These include low levels of magnesium; other QT prolonging medications, foods and supplements; withdrawal from cocaine, alcohol, or amphetamines; and many of the risk factors outlined in Chapter 2.
In many cases, during the acute period of ibogaine metabolism, bizarre t-wave morphology may be noted. These changes may include flattening of the t-wave, biphasic t-waves, and initial decrease in the anterior slope of the t-wave. These changes have been postulated to be attributed to changes in intercellular potassium exchange caused by blockage of the hERG channel (Thurner 2013, Alper 2015).
Ibogaine is metabolized via liver enzyme CYP450-2D6 into its primary metabolite, noribogaine. There may be clinically significant variability in the initial phases of ibogaine’s effects based on a patients CYP2D6 metabolism phenotype, particularly at the extreme ends of the spectrum for poor and ultra-rapid metabolizers (Glue 2015).
Ibogaine is also known to cause a level of restlessness and sleeplessness in the days following administration in some cases. This is especially the case for patients who use benzodiazepines or other sleep inducing medications.
Seizures under the influence of ibogaine can induce lethal arrhythmias, and have led to fatalities as well as permanent injury. Ibogaine itself has not been known to induce seizures, however, this is a concern in regards to withdrawals from alcohol or benzodiazepines, as well as for epileptics.
Clinical Pharmacokinetics
Ibogaine saturation peaks at 2 hours after administration and has a half-life of up to 7 hours in human plasma (Koenig 2015). It is metabolized into noribogaine, which, it is believed, is stored in fat tissue and released over the course of the following weeks or months. Noribogaine possesses some of the same effects as ibogaine, which may account for the prolonged reported benefits.
In those patients who experience t-wave changes they generally last between 12-14 hours, but can persist for as long as 24 hours. Cardiac concerns decrease after t-wave stabilizes.
Some adverse events have been reported as late as 76 hours after administration (Alper 2012), however the factors in these instances generally can be addressed with proper screening and preparation.
Neurotransmitter Activity
In animal models, ibogaine has demonstrated action at various neurotransmitter sites, including the glutamate, opioid, dopamine, serotonin, and acetylcholine systems (Popik 1999). Its effects may be the result of a complex interaction between these systems, rather than the result of an effect on a single neurotransmitter system (Alper 2001).
The accumulation of these effects has been shown to mitigate withdrawal symptoms from opioids. Some suggest this to be up to 90% effective based on subjective reports. Ibogaine has also been shown to reduce the accumulated tolerance to opioids, and to increase the central nervous systems sensitivity to opioids (Parker 2001), which has implications in the case of relapse post-treatment. Patients need to be made acutely aware that their tolerance is reset to that of an opioid naïve person in order to avoid accidental overdose.
Ibogaine has also been shown to potentiate the effects of opioids and stimulants, with some gender variation in the case of cocaine. It is important for clinicians to be aware of these interactions in order to effectively facilitate detoxification. Especially in cases where long-acting opioids are considered, potentiation of opioid analgesia can result in simply delaying the onset of withdrawals until the effects of the ibogaine have subsided.
Methodology
Prior to this publication, the most significant precedent document to outline strategies for use of ibogaine in detoxification was the Manual for Ibogaine Therapy (Lotsof and Wachtel, 2006).
The current guidelines were drafted and edited by a panel of authors with extensive clinical and research experience. It was refined through a series of proposals and extensive interviews with medical professionals, practicing ibogaine therapy providers and researchers.
Proposals were presented during a series of public consultation periods, during which input was collected through in-person, electronic interviews, and written correspondence with members of the broader community of ibogaine therapy providers and medical professionals. The first completed version of this document is scheduled for publication in September 2015.
