© 2019, Douglas Greene. All rights reserved. Used by Permission.
Ibogaine has shown great promise as an interrupter of substance use disorders (especially for opioid withdrawal management and opioid use disorders), but remains an obscure and misunderstood drug. Even in the world of psychedelics, far more attention is paid to LSD, ayahuasca and MDMA. There are many misconceptions about ibogaine, often due to its advocates, who tout it as a cure for substance use disorders, and the popular media, who turn to treatment professionals who have no experience with ibogaine to warn about hallucinations and possible death.
For the past 28 years, I’ve been advocating for more research into ibogaine’s use in treating substance use disorders. And more recently, I’ve become an aspiring substance use counselor, who wants to work with this powerful drug as part of a clinical team. Based on my work with ibogaine, including service with ibogaine providers in South Africa and Mexico, I’ve become convinced that ibogaine and related alkaloids such as noribogaine and 18-methoxycoronaridine (18-MC), along with integrative harm reduction psychotherapy, will eventually be key ingredients in many substance use disorder treatment plans.
Ibogaine is a monoterpene indole alkaloid that is derived from plant sources, principally from the endangered and protected perennial rain forest shrub Tabernanthe iboga, which is native to Central Africa (particularly Gabon and Cameroon). Traditional practitioners use the root bark of mature (7 to 10 years or older) iboga shrubs for fatigue, hunger and thirst. In the traditional animistic religion Bwiti, higher doses are used for healing and initiation rites. The root bark contains ibogaine and 11 other iboga alkaloids. Ibogaine was first extracted from iboga root bark in 1901. In the early years of the 20th century, French pharmacologists began to study ibogaine’s cardiovascular and central nervous system effects.
In France, Laboratoires Houdé marketed tablets containing five to eight milligrams of ibogaine as Lambarene for fatigue and depression. Lambarene was withdrawn from the market in 1967. In the 1950s, Dr. Harris Isbell, the Director of Research for the NIMH Addiction Research Center at the Public Health Service Hospital in Lexington, Kentucky, corresponded with CIBA’s United States subsidiary regarding his trials with ibogaine. Although these trials were intended to observe the effects of ibogaine, CIBA’s researchers were also aware of ibogaine’s ability to potentiate morphine’s analgesic effects, and it is conjectured that Isbell may have attempted to use ibogaine to interrupt patients’ opioid use disorders in Lexington.
In 1962, Howard Lotsof was a 19 year old NYU film student, living with his parents in New Jersey and using heroin and amphetamines. After taking ibogaine, he was dropped off at his psychologist’s office and began having a full blown ibogaine experience, which included Freudian visions of his birth and enhanced access to his memories and life experiences. At the end of his 36 hour experience, Lotsof had no desire to use more heroin and no withdrawal symptoms.
Over the course of eight months, Lotsof administered ibogaine to 20 people (including himself), seven of whom were using heroin and/or cocaine. Five of those seven stopped using their drug of choice, with no withdrawals, for periods ranging from six to 18 months of abstinence.
Unfortunately for Lotsof and other researchers, in 1965, Congress passed the Drug Abuse and Control Amendments to the Food, Drug and Cosmetics Act, which allowed the Secretary of the Department of Health, Education and Welfare to designate certain stimulant, depressant or hallucinogenic drugs as controlled substances, requiring licensing for sales or distribution. Sale and distribution of ibogaine became regulated in 1967, and it was placed in Schedule I under the Controlled Substances Act in 1970.
Development of ibogaine remained dormant throughout the 1970s. In 1981, Lotsof and his wife Norma Alexander teamed up with Yippie! activist Dana Beal to collect all the research to that point on ibogaine.
Over the course of the 1980s, Beal, Lotsof and Bob Sisko of the International Coalition for Addict Self-Help (ICASH) began a relentless campaign to inform the media and U.S government about ibogaine’s ability to interrupt substance use disorders. In 1983, Lotsof applied for a U.S. patent for ibogaine’s use as a rapid method for interrupting the narcotic addiction syndrome, which was granted in 1985. From 1986 to 1992, Lotsof and his company NDA International, Inc. received four more patents, for ibogaine’s use in interrupting cocaine and amphetamine abuse syndrome, attenuating alcohol dependency syndrome, interrupting or attenuating nicotine/tobacco dependency syndrome and interrupting or attenuating poly-drug dependency syndromes.
By May 1991, activists had succeeded in convincing the National Institute on Drug Abuse’s Medications Development Division (MDD) to start an ibogaine development project. In 1993 and 1994, NIDA held a total of four Phase I/II protocol development meetings for cocaine dependence. In March 1995, MDD held an ibogaine review meeting, and outside consultants convinced MDD to not proactively pursue clinical studies with ibogaine.
By the mid-1990s, ibogaine treatment was being provided in a variety of underground and medical settings. One of the most prominent treatment centers at this time was Healing Visions in St. Kitts, which was run by Dr. Deborah Mash of the University of Miami, who was an early ibogaine researcher.
Ibogaine is not controlled under the United Nations Single Convention on Narcotic Drugs of 1961 and other international drug control treaties. However, ibogaine is prohibited in several jurisdictions, including the United States, France, Sweden, Switzerland and Israel. A pending bill in Vermont would allow a pilot ibogaine treatment program, and has been referred to the House Committee on Human Services.
The Ibogaine Experience
Although some providers work with low doses of various iboga products over an extended period of time, and many providers create proprietary protocols based on the individual characteristics of the patient, including any substance use and co–occurring disorders, most providers usually administer a large dose (usually in the range of 12-24 mg/kg), which may be followed up with lower “booster doses.” Prior to arrival, various tests should be performed; primarily an EKG, a liver (hepatic) function panel and an electrolyte panel. When patients arrive, they may have their person and luggage searched, and urine toxicology may be performed. A test dose (2-3 mg/kg) is usually given prior to administration of a large dose in order to monitor for allergic reactions and observe metabolic reactions to ibogaine.
The classic high dose ibogaine experience involves four phases: the onset phase, the acute visionary or “waking dream” phase, the evaluative phase and the residual stimulation phase. In the onset phase, which can last for approximately one to three hours, the patient begins to experience perceptual changes, such as ataxia and an increased sensitivity to stimuli and may hear a buzzing sound or the sound of an airplane readying for takeoff.
In the visionary or “waking dream” phase, which lasts for approximately four to eight hours, the patient’s ataxia becomes overwhelming and he or she needs to lie down. Although not all patients have visionary experiences, many do, which include intense personal and transpersonal visions, which are enhanced by the use of an eye mask. Nausea and emesis are common. Some providers provide antiemetic medications, while others welcome the purging process as part of the healing experience.
In this phase of the ibogaine experience, the patient sometimes sees his or her life as a movie, including the factors and choices that led to the development of the patient’s substance use and other co-occurring disorders. Although ibogaine is typically described as a hallucinogen, its visual effects do not persist when the patient’s eyes are open, and it differs in others ways from classical hallucinogens such as LSD and psilocybin. Therefore, it is more aptly described as an oneirgenic (dream producing) drug than a hallucinogen.
In the evaluative phase, which lasts for approximately eight to 20 hours, the patient begins to return to normal psychological and physiological functioning. During this phase, the patient begins to process the insights and visions of the prior phase into abstract thought. In the residual stimulation phase, which lasts approximately 24 to 72 hours, fatigue and exhaustion are common, as patients return attention to their external environment.
Patients usually need a reduced amount of sleep (three to four hours per night for up to a month) after administration of a large dose of ibogaine, possibly due to its enhancement of REM activity. Ibogaine’s principal metabolite, noribogaine, has an extended half-life and is believed to be responsible for a pronounced antidepressant effect that persists for several months after administration, which provides a window of opportunity for patients to implement a plan for recovery and change.
Pharmacodynamics and Pharmacokinetics
Ibogaine is usually administered orally, though it occasionally has been administered rectally, and one Mexican provider claims to administer it intravenously. Most providers usually work with ibogaine, but some providers also work with iboga root bark and “total alkaloid” (“TA”), a mixture of ibogaine and other iboga alkaloids.
Ibogaine affects multiple neurotransmitter systems, including the serotonin system, the opioid system and the glutamatergic system. However, its mechanisms of actions are still not well known.
When taken orally, ibogaine is demethylated into noribogaine, its principal metabolite, which is primarily mediated by the CYP2D6 enzyme. Some providers and researchers have advocated CYP2D6 genotyping prior to administration of ibogaine to guide dosing, as some adverse events with ibogaine may be related to both poor and rapid CYP2D6 metabolization.
Ibogaine is also a proarrythmic drug, which regularly induces bradycardia and sometimes induces torsades de pointes, a polymorphic ventricular tachycardia that can be fatal. For this reason, candidates for ibogaine treatment must be carefully screened and monitored.
A 2012 Journal of Forensics Sciences article by Dr. Kenneth Alper of NYU and his coauthors reviewed fatalities temporally associated with ibogaine administration outside of West Central Africa from 1990 to 2008. The review found that:
“[A]dvanced preexisting medical comorbidities, which were mainly cardiovascular, and/or one or more commonly abused substances explained or contributed to the death in 12 of the 14 cases for which adequate postmortem data were available. Significant factors in this series appear to include preexisting medical, particularly cardiovascular disease, possible [pulmonary thromboembolism], drug use during treatment, seizures associated with withdrawal from alcohol and benzodiazepines, and the uninformed use of ethnopharmacological forms of ibogaine [i.e., root bark and TA].”
Current Uses of Ibogaine
Jonathan Dickinson, the executive director of the Global Ibogaine Therapy Alliance (GITA), estimates that there are about 75 to 100 individuals and entities around the world providing ibogaine treatments. Settings vary widely, from professional conventional medical models with licensed facilities and clinicians and continuous cardiac monitoring to lay providers conducting Bwiti ceremonies. The highest concentrations of providers are in Mexico, Brazil and Costa Rica. Ibogaine is being used not only for interruption of substance use disorders, but for co–occurring disorders such as depression and anxiety. An exciting new frontier for ibogaine is its possible use in low doses for neurodegenerative disorders such as Parkinson’s disease and Lou Gehrig’s disease (amyotrophic lateral sclerosis). Some providers, such as the Genesis Ibogaine Center in Baja California, Mexico, have been experimenting with ibogaine to treat these diseases. It’s hypothesized that the mechanism of action may involve ibogaine’s role in expression of glial cell–derived neurotrophic factor (GDNF). Researchers at Columbia University have begun a two year study to investigate ibogaine as an anti–Parkinsonian agent and its effects on GDNF production.
However, due to its costs and profound physiological and psychological potency, ibogaine is mostly used in the treatment of substance use disorders. While it has been successfully utilized for many types of substance use disorders, it is especially effective for opioid withdrawal management and treatment of opioid use disorders. For these patients, most providers usually begin ibogaine administration when the patient begins to feel withdrawal symptoms, which ibogaine completely interrupts in most people.
A 2014 Current Drug Abuse Reviews article on the use of psychedelics for treatment of substance use disorders concluded that, in regard to ibogaine “[m]any forms of information—including case reports, preclinical toxicological evaluations, initial Phase I trials of safety pharmacokinetics—provide a substantial body of evidence constituting preclinical proof of concept and the equivalence of Phase I and II trials.” Further evidence of ibogaine’s effectiveness in treating opioid use disorders may be forthcoming from two observational studies on the long term effectiveness of ibogaine for opioid use disorders funded by the Multidisciplinary Association for Psychedelic Studies in Mexico and New Zealand. Results from both studies are under preparation for publication.
The Principal Investigator for the Mexico study, Thomas Kinsgley Brown, Ph.D. reported promising improvement in subjects’ ASI Lite drug use composite score during the 12-month follow up in a sample of 12 participants. The Principal Investigator for the New Zealand study, Geoff Noller, Ph.D., also reported promising reductions in opiate withdrawal symptoms and improvements in drug use and medical composite scores in 11 participants.
Noller also noted that Professor Paul Glue, Head of Department of Psychological Medicine at the University of Otago has found a dose response relationship with ibogaine and QT interval prolongation, which is problematic for general use of ibogaine. However, he also noted the urgency and high level of risk of street drug use. He suggested that ibogaine prohibition is not a factor for people with substance use disorders who want ibogaine assisted treatment–but it will shift the setting of treatment to non-clinicians or self–treatment with materials of uncertain potency and purity. Noller hypothesized that that the differences between the results of the Mexico and the New Zealand studies could be attributed to: (1) the comprehensive assessments administered by the New Zealand providers; (2) their treatment modalities; (3) a very different drug use environment between native New Zealanders and primarily Americans engaging in medical tourism in Mexico; and (4) ibogaine’s status as a non-approved prescription medicine in New Zealand, which allows for an integrated system of care between physicians, pharmacists, ibogaine treatment providers and continuing care providers.
It is important to stress that these are observational studies, not randomized controlled trials. However, these results should encourage governments and other entities to consider approving or funding large scale randomized controlled trials of ibogaine’s effictiveness.
Recapitulation of the Development of the Minnesota Model and Therapeutic Communities in Ibogaine–Assisted Treatment
Ibogaine’s acceptance as a medication assisted treatment (MAT) for substance use disorders has been hindered by a wide variety of factors, including: (1) its profound physiological and psychological effects, which require medical screening and monitoring; (2) its unregulated status in the jurisdictions where most ibogaine providers are located; (3) a lack of licensed clinics in these jurisdictions; (4) its use as a standalone detox without integration into a continuum of care; and (5) a provider population that includes many lay people with substance use disorders who have been helped by ibogaine, but are still affected by substance use disorders, trauma and other co–occurring disorders.
In Slaying the Dragon: The History of Addiction Treatment and Recovery in America, Bill White describes how both centers based on the Minnesota model and therapeutic communities employed a workforce that largely consisted of “professionals by experience”–people in various stages of recovery from substance use disorders. The development of ibogaine treatment has followed a similar path–people with substance use disorders are treated with ibogaine, experience some benefit and then decide to become ibogaine providers, often without an extended amount of time in recovery.
Those who are called to become ibogaine providers also don’t always make the effort to gain the medical, psychological, legal and ethical skills, knowledge and attitudes required to be a safe and successful provider. Fortunately, ibogaine treatment is becoming increasingly professionalized, with the publication in September 2015 of the first edition of GITA’s Clinical Guidelines for Ibogaine–Assisted Detoxification and increased interest from clinicians. Some are established clinicians who are became convinced of ibogaine’s potential and others are people with substance use disorders who were treated with ibogaine and realized they needed clinical skills to work safely and effectively with this powerful drug. All three clinicians profiled below will be presenting at GITA’s Global Ibogaine Conference in Tepotzlan, Mexico from March 14th to 16th, 2016.
Jeffrey D. Kamlet, M.D.
Dr. Kamlet is a Miami Beach based cardiologist and a Fellow of the American Society of Addiction Medicine since 2006. He has been researching ibogaine for over 20 years, and worked closely with Dr. Mash at Healing Visions, with whom he coauthored “Ibogaine in the Treatment of Heroin Withdrawal” in 2001. According to Dr. Kamlet, “[i]bogaine is the most important discovery in the field of opiate dependency in the history of addiction medicines, and I’m confident that it will one day be a main stay treatment for many addictions.”
Andrew Tatarsky, Ph.D.
Dr. Tatarsky is the Founder and Director of the Center for Optimal Living (CFOL), a New York City based psychology practice specializing in treating substance use disorders using integrative harm reduction psychotherapy. He is the author of Harm Reduction Psychotherapy: A New Treatment for Drug and Alcohol Problems and co–teacher of the Integrative Harm Reduction Psychotherapy Certificate Program at the New School for Social Research. In November 2015, with Katherine MacLean, Ph.D., a former instructor and researcher in the Department of Psychiatry and Behavioral Sciences at Johns Hopkins University School of Medicine and others, he launched a Psychedelic Education and Continuing Care Program at CFOL. The program will help clients speak about their experiences and gain psychotherapeutic support. These clients may include research study subjects, people who have experienced ibogaine therapy and people who are currently using psychedelics to self–medicate. Clinicians can also utilize the program to learn how to work best with clients with a history of psychedelic use, to understand the potential harms and benefits associated with psychedelics and provide optimal client care.
Tanea Paterson, Applied Addiction Practitioner
After seven years in a methadone program, Ms. Paterson, a single mother, successfully undertook ibogaine therapy and ceased reliance on opiates in 2006. The treatment experience moved her to initiate a series of public forums across New Zealand in late 2009, which brought ibogaine to the attention of Medsafe, New Zealand’s drug regulatory agency. In 2012, she graduated as an Applied Addiction Practitioner from Moana House Training Institute. She has concentrated on developing ibogaine therapy into a legitimate part of a client’s existing treatment plan concentrating on risk management, whanau (family) inclusion and harm minimization.
Alternative Iboga–Related Alkaloids: Noribogaine and 18-MC
Many clinicians who have worked with ibogaine have sought alternatives that lacked ibogaine’s proarrythmic effects, tremors, ataxia and visions. Ibogaine’s principal metabolite, noribogaine, is being researched as a safer, non–visionary MAT for pain and substance use disorders. Noribogaine is a G-Protein biased kappa opioid receptor agonist. A study has demonstrated its ability to reduce nicotine self–administration in rats, and further research is currently being conducted in New Zealand.
18-MC is a synthetic non–psychoactive ibogaine congener that was developed in 1996 by researchers affiliated with Stanley D. Glick from the Albany Medical College (who claims that “ibogaine [will never be] an approvable drug in the United States”) and Martin E. Kuehne from the University of Vermont. Like ibogaine, administration of 18-MC results in long–lasting decreases in self–administration of ethanol, morphine, cocaine, nicotine and methamphetamine, as well as attenuation of opioid withdrawal symptoms.
In September 2012, Savant HWP, Inc. (“Savant”) received a $6.5M grant from NIDA for preclinical development of 18-MC for cocaine use disorders, and is also planning to study its effects on withdrawal and craving in nicotine, cocaine, opioid and methamphetamine users. Savant has received approval from the United States Food and Drug Administration and is seeking funding to start Phase I clinical trials in late 2015 or early 2016. However, unlike ibogaine and noribogaine, 18-MC does not increase expression of glial cell line-derived neurotrophic factor (GDNF) in a dopaminergic–like cell line, which some ibogaine advocates, like Dana Beal, consider essential to ibogaine’s mechanism of action in treating substance use disorders.
Like the substances it treats, ibogaine is here to stay. However, its expense, lack of regulation of providers and need for medical screening and monitoring of patients have produced a network of providers that often lack the ethical, psychological and medical skills to safely and effectively work with ibogaine. Even worse, the Internet is rife with online merchants who sell various forms of iboga products to all comers for self–administration, with often catastrophic results due to a lack of medical screening and monitoring. Since iboga and ibogaine are not regulated under international drug control treaties, the governments of the world need to fund more research and provide access to ibogaine–assisted withdrawal management and treatment as part of the continuum of care for substance use disorders. The people we serve deserve no less.