Tabernanthe iboga
Howard S. Lotsof

Tabernanthe iboga
(plant source of ibogaine)
Howard S. Lotsof

Announcement – Howard Lotsof, father of ibogaine passed away on Sunday January 31st after some years of illness. He was active in promoting ibogaine right up until he left. Without Howard many people would likely never have beaten addiction and perhaps the world would still not know about this amazing natural substance. We all owe him an immense debt of gratitude – Nick Sandberg, website owner.

Ibogaine is a psychoactive indole alkaloid derived from the rootbark of an African plant – Tabernanthe iboga. In recent years it has been increasingly noted for its ability to treat both drug and alcohol addiction. Both scientific studies and widespread anecdotal reports appear to suggest that a single administration of ibogaine has the ability to both remove the symptoms of drug withdrawal and reduce drug-craving for a period of time after administration. In addition, the drug’s psychoactive properties (in large doses it can induce a dreamlike state for a period of hours) have been widely credited with helping users understand and reverse their drug-using behaviour.

Studies suggest that ibogaine has considerable potential in the treatment of addiction to heroin, cocaine, crack cocaine, methadone, and alcohol. There is also indication that it may be useful in treating tobacco dependence. It has also been suggested that the drug may have considerable potential in the field of psychotherapy, particularly as a treatment for the effects of trauma or conditioning.

A single administration of ibogaine typically has three effects useful in the treatment of drug dependence. Firstly, it causes a massive reduction in the symptoms of drug withdrawal, allowing relatively painless detoxification. Secondly, there is a marked lowering in the desire to use drugs for a period of time after taking ibogaine, typically between one week and several months. This has been confirmed by scientific studies. Finally, the drug’s psychoactive nature is reported to help many users understand and resolve the issues behind their addictive behaviour.

Ibogaine can be easily administered, in capsule form, and has no addictive effects itself. It is essentially a "one-shot" medication and, used in a fully clinical setting with proper advance medical screening, the drug thus far appears to be safe to use. Whilst it certainly happens that some individuals stop using drugs permanently from a single dose of ibogaine, for many the treatment should best be regarded as simply the initial component in an overall rehabilitation programme.

Although approved for clinical trials (trials on humans) for the treatment of addiction in the US in the early 1990s, problems with financial backing and other issues have so hindered the development of ibogaine that, as of early 2005, it remains undeveloped and thus unavailable to the majority of addicts worldwide. There are however now an increasing number of private clinics, located mostly around the Caribbean and Central and South America, that offer ibogaine treatment at prices starting around £2,000, (approx US$4000). Some lay treatment providers offer lower cost treatment, with varying levels of medical facilities, in Europe. In addition, ibogaine, either in pure form or as a plant extract, has become available from some lay sources on the internet.

Ibogaine’s current legal status in the UK, and much of the rest of the world, is that of an unlicensed, experimental medication, and it not therefore an offence to possess the drug, though to act as a distributor may be breaking the law. Ibogaine is a restricted substance (possession is illegal) in some countries, including the US, Switzerland, Denmark, Sweden and Belgium.

Promotional Link – Some treatment clinics use herbal remedies for addiction drugs such as heroin, cocaine and alcohol.

 

 

Ibogaine

From Wikipedia, the free encyclopedia

Ibogaine

Systematic (IUPAC) name

(–)-12-Methoxyibogamine

Identifiers

CAS number
83-74-9

ATC code
None

PubChem
CID 363272

ChemSpider
170667

Chemical data

Formula
C20H26N2O

Mol. mass
310.433 g/mol

SMILES
eMolecules & PubChem

Physical data

Melt. point
152–153 °C (306–307 °F)

Pharmacokinetic data

Half-life
2 hours

Therapeutic considerations

Pregnancy cat.
?

Legal status
Schedule I (US)

Routes
oral

Ibogaine

Ibogaine is a naturally occurring psychoactive substance found in a number of plants, principally in a member of the Apocynaceae family known as iboga (Tabernanthe iboga). Ibogaine-containing preparations are used in medicinal and ritual purposes within African spiritual traditions of the Bwiti, who claim to have learned it from the Pygmy. Although it was first commonly advertised as having anti-addictive properties in 1962 by Howard Lotsof, its western use predates that by at least a century. In France it was marketed a ‘Lambarene’, a medical drug used for dieting. Additionally FOIA documents released in the 1980’s show that the CIA studied the effects of ibogaine in the 1950’s. Ibogaine is an indole alkaloid that is obtained either by extraction from the iboga plant or by semi-synthesis from the precursor compound voacangine, another plant alkaloid. A full organic synthesis of ibogaine has been achieved but is too expensive and challenging to produce any commercially significant yield yet, primarily due to the need to conduct the synthesis in an anoxic environment.

In the early 1960s, anecdotal reports appeared concerning ibogaine’s effects.[1] Since that time, it has been the subject of investigation into its abilities to interrupt addictions to methadone, heroin, alcohol, andcocaine. It is thought that ibogaine may have potential to facilitate introspection, helping to elucidate the psychological issues and behavior patterns that drive addictions or other problems. However, ibogaine therapy for drug addiction is the subject of some controversy. Due to safety concerns, it has been placed in the strictest drug prohibition schedules in the United States and a handful of other countries. Canada and Mexico both allow ibogaine therapy facilities to operate and openly contribute to further understanding of the detoxification and therapeutic process that ibogaine has the potential to facilitate.

While ibogaine’s prohibition in the U.S. has slowed scientific research into its anti-addictive properties, the use of ibogaine for drug treatment has grown in the form of a large worldwide medical subculture.[2]Ibogaine is now used by treatment clinics in 12 countries on six continents to facilitate detoxification and relief of chemical dependence to substances such as methadone, heroin, alcohol, powder cocaine, crack cocaine, and methamphetamine, as well as to facilitate psychological introspection and spiritual exploration.

Psychoactive effects

At doses of around 3–5 mg/kg of body weight, ibogaine has a mild stimulant effect. The high-dose ibogaine experience of 10 mg/kg or greater most commonly occurs as two distinct phases: the visual phase and the introspective phase.[citation needed]

The visual phase is characterized by open-eye visuals, closed-eye visuals, and dreamlike sequences. Objects may be seen as distorted, projecting tracers, or having moving colors or textures. When the eyes are closed, extremely detailed and vivid geometric and fractal visions may be seen. Subjective reports often include a movie-like recollection of earlier life experiences as well as dreamlike sequences with symbolism of one’s present or anticipated future. Other effects in the visual phase may include laughing, sensations of euphoria or fear, and temporary short-term memory impairment. The visual phase usually ends after one to four hours, after which the introspective phase begins.[citation needed]

The introspective phase is typically reported to bring elevated mood, a sense of calm and euphoria, and a distinct intellectual and emotional clarity. Subjects often report being able to accomplish deep emotional and intellectual introspection into psychological and emotional concerns. It is also during this period that opioid addicts first notice the absence of withdrawal symptoms or cravings. The duration of the introspective phase is highly variable, usually lasting hours but sometimes lasting days.[citation needed]

Side effects and safety

One of the first noticeable effects of large-dose ibogaine ingestion is ataxia, a difficulty in coordinating muscle motion which makes standing and walking difficult without assistance. Xerostomia (dry mouth), nausea, and vomiting may follow. These symptoms may be long in duration, ranging from 4 to 24 hours in some cases. Ibogaine is sometimes administered by enema to help the subject avoid vomiting up the dose. Psychiatric medications are strongly contraindicated in ibogaine therapy due to adverse interactions. Some studies also suggest the possibility of adverse interaction with heart conditions. In one study of canine subjects, ibogaine was observed to increase sinus arrhythmia (the normal change in heart rate during respiration).[3] Ventricularectopy has been observed in a minority of patients during ibogaine therapy.[4] It has been proposed that there is a risk of QT-interval prolongation following ibogaine administration.[5] This risk was further demonstrated by a case reported in the New England Journal of Medicine documenting prolonged QT interval and ventricular tachycardia after initial use.[6]

There are 12 documented fatalities that have been loosely associated with ibogaine ingestion.[7] Exact determinations of the cause of death have proven elusive due to the quasi-legal status of ibogaine and the unfamiliarity of medical professionals with this relatively rare substance. No autopsy to date has implicated ibogaine as the sole cause of death. Causes given range from significant pre-existing medical problems to the co-consumption of drugs such as opiates which are potentiated by ibogaine. Also, because ibogaine is one of the many drugs that are partly metabolized by the cytochrome P450 complex, caution must be exercised to avoid foods or drugs that inhibit CP450, in particular foodstuffs containing bergamottin or bergamot oil, common ones being grapefruit juice and Earl Grey tea.

Therapeutic uses

Treatment for opiate addiction

The most-studied therapeutic effect of ibogaine is the reduction or elimination of addiction to opioids.[1] An integral effect is the alleviation of symptoms of opioid withdrawal. Research also suggests that ibogaine may be useful in treating dependence on other substances such as alcohol, methamphetamine, and nicotine and may affect compulsive behavioral patterns not involving substance abuse or chemical dependence.[1]

Proponents of ibogaine treatment for drug addiction have established formal and informal clinics or self-help groups in Canada, Mexico, the Caribbean, Costa Rica, the Czech Republic, France, Slovenia, the Netherlands, Brazil, South Africa, the United Kingdom and New Zealand, where ibogaine is administered as an experimental compound. Many users of ibogaine report experiencing visual phenomena during a waking dream state, such as instructive replays of life events that led to their addiction, while others report therapeutic shamanic visions that help them conquer the fears and negative emotions that might drive their addiction. It is proposed that intensive counseling, therapy and aftercare during the interruption period following treatment is of significant value. Some individuals require a second or third treatment session with ibogaine over the course of the next 12 to 18 months. A minority of individuals relapse completely into opiate addiction within days or weeks. A comprehensive article (Lotsof 1995) on the subject of ibogaine therapy detailing the procedure, effects and aftereffects is found in "Ibogaine in the Treatment of Chemical Dependence Disorders: Clinical Perspectives".[8] Ibogaine has also been reported in multiple small-study cohorts to reduce cravings for methamphetamine.[9]

Chronic pain management

In 1957, Jurg Schneider, a pharmacologist at CIBA, found that ibogaine potentiates morphine analgesia.[10] Further research was abandoned, and no additional data was ever published by Ciba researchers on ibogaine–opioid interactions. Almost 50 years later, Patrick Kroupa and Hattie Wells released the first treatment protocol for concomitant administration of ibogaine with opioids in human subjects, indicating ibogaine reduced tolerance to opioid drugs.[11] Kroupa et al. published their research in theMultidisciplinary Association for Psychedelic Studies Journal demonstrating that administration of low-"maintenance" doses of ibogaine HCl with opioids decreases tolerance. It should be noted however, that the potentiation action of ibogaine may make this a very risky procedure.Psychotherapy

Ibogaine has been used as an adjunct to psychotherapy by Claudio Naranjo, documented in his book The Healing Journey.[12]

Recreational use

Casual use of ibogaine in a social or entertainment context is nearly unknown due to its high cost, constrained availability, long duration of effects, and uncomfortable short-term side effects. In the clandestine markets, ibogaine is typically sought as a drug addiction treatment, for ritual spiritual purposes, or psychological introspection.

History

It is uncertain exactly how long iboga has been used in African spiritual practice, but its activity was first observed by French and Belgian explorers in the 19th century. The first botanical description of the Tabernanthe iboga plant was made in 1889. Ibogaine was first isolated from T. iboga in 1901 by Dybowski and Landrin[13] and independently by Haller and Heckel in the same year using T. iboga samples from Gabon. In the 1930s, ibogaine was sold in France in 8 mg tablets under the name "Lambarene". The total synthesis of ibogaine was accomplished by G. Büchi in 1966.[14] Since then, several further totally synthetic routes have been developed.[15] The use of ibogaine in treating substance use disorders in human subjects was first observed by Howard Lotsof in 1962, for which he was later awarded U.S. Patent 4,499,096 in 1985. In 1969, Claudio Naranjo was granted a French patent for the use of ibogaine in psychotherapy.

Ibogaine was placed in US Schedule 1 in 1967 as part of the US government’s strong response to the upswing in popularity of psychedelic substances, though iboga itself was scarcely known at the time. Ibogaine’s ability to attenuate opioid withdrawalconfirmed in the rat was first published by Dzoljic et al. (1988).[16] Ibogaine’s use in diminishing morphine self-administration in preclinical studies was shown by Glick et al. (1991)[17] and ibogaine’s capacity to reduce cocaine self-administration in the rat was shown by Cappendijk et al. (1993).[18] Animal model support for ibogaine claims to treat alcohol dependence were established by Rezvani (1995).[19]

The name "Indra extract", in strict terms, refers to 44 kg of an iboga extract manufactured by an unnamed European industrial manufacturer in 1981. This stock was later purchased by Carl Waltenburg, who distributed it under the name "Indra extract". Waltenburg used this extract to treat heroin addicts in Christiania, Denmark, a squatter village where heroin addiction was widespread in 1982.[20] Indra extract was offered for sale over the Internet until 2006, when the Indra web presence disappeared. It is unclear whether the extracts currently sold as "Indra extract" are actually from Waltenburg’s original stock, or whether any of that stock is even viable or in existence. Ibogaine and related indole compounds are susceptible to oxidation when exposed to oxygen[21] [22], as opposed to their salt form, which is stable. The exact methods and quality of the original Indra extraction was never documented, so the real composition of the product remains uncertain.

Data demonstrating ibogaine’s efficacy in attenuating opioid withdrawal in drug-dependent human subjects was published by Alper et al. (1999)[23] and Mash et al. (2000).[24]

In 1972, journalist Hunter S. Thompson accused democratic candidate Edmund Muskie of being addicted to ibogaine in a satirical piece. Many readers, and even other journalists, did not realize that Thompson was being facetious. The claim, of course, was completely unfounded, and Thompson himself is documented in the movie Gonzo: The Life and Work of Dr. Hunter S. Thompson discussing the self-fabricated joke of Muskie’s alleged ibogaine use and his surprise that anyone actually believed the claim.

Formulations

In Bwiti religious ceremonies, the rootbark is pulverized and swallowed in large amounts to produce intense psychoactive effects. In Africa, iboga rootbark is sometimes chewed, which releases small amounts of ibogaine to produce a stimulant effect. Ibogaine is also available in a total alkaloid extract of the Tabernanthe iboga plant, which also contains all the other iboga alkaloids and thus has only about one-fifth the potency by weight as standardized ibogaine hydrochloride.[25]

Total alkaloid extracts of T. iboga are often loosely called "Indra extract". However, that name actually refers to a particular stock of total alkaloid extract produced in Europe in 1981. The fate of that original stock (as well as its original quality) is unknown.

Currently, pure crystalline ibogaine hydrochloride is the most standardized formulation. It is typically produced by the semi-synthesis from voacangine in commercial laboratories. Ibogaine has two separate chiral centers which means that there a four different stereoisomers of ibogaine. These four isomers are difficult to resolve.[26]

A synthetic derivative of ibogaine, 18-methoxycoronaridine (18-MC), is a selective α3β4 antagonist that was developed collaboratively by the neurologist Stanley D. Glick (Albany) and the chemist Martin E. Kuehne (Vermont).[27] This discovery was stimulated by earlier studies on other naturally occurring analogues of ibogaine such as coronaridine and voacangine that showed these compounds also have anti-addictive properties.[28][29]

Pharmacology

The pharmacology of ibogaine is quite complex, affecting many different neurotransmitter systems simultaneously.[30][31] Because of its fairly low potency at any of its target sites, ibogaine is used in doses anywhere from 5 mg/kg of body weight for a minor effect to 30 mg/kg in the cases of strong polysubstance addiction. It is unknown whether doses greater than 30 mg/kg in humans produce effects that are therapeutically beneficial, medically risky, or simply prolonged in duration. In animal neurotoxicity studies, there was no observable neurotoxicity of ibogaine at 25 mg/kg, but at 50 mg/kg, one-third of the rats had developed patches of neurodegeneration, and at doses of 75 mg/kg or above, all rats showed a characteristic pattern of degeneration ofPurkinje neurons, mainly in the cerebellum.[32] While caution should be exercised when extrapolating animal studies to humans, these results suggest that neurotoxicity of ibogaine is likely to be minimal when ibogaine is used in the 10–20 mg/kg range typical of drug addiction interruption treatment regimes, and indeed death from the other pharmacological actions of the alkaloids is likely to occur by the time the dose is high enough to produce consistent neurotoxic changes.[22][33]

Metabolites

Ibogaine is metabolized in the human body by cytochrome P450 2D6, and the major metabolite is noribogaine (12-hydroxyibogamine). Noribogaine is most potent as a serotonin reuptake inhibitor and acts as a moderate κ- and weak µ-opioid receptor full agonist and therefore, also has an aspect of an opiate replacement similar to compounds like methadone. It is possible that this action of noribogaine at the kappa opioid receptor may indeed contribute significantly to the psychoactive effects attributed to ibogaine ingestion; salvia divinorum, another plant recognized for its strong hallucinogenic properties, contains the chemical salvinorin-A which is a highly selective kappa opioid agonist. Both ibogaine and noribogaine have a plasma half-life of around two hours in the rat[34], although the half-life of noribogaine is slightly longer than the parent compound. It is proposed that ibogaine is deposited in fat and metabolized into noribogaine as it is released.[35] Noribogaine shows higher plasma levels than ibogaine and may therefore be detected for longer periods of time than ibogaine. Noribogaine is also more potent than ibogaine in rat drug discrimination assays when tested for the subjective effects of ibogaine.[36] The Noribogaine differs from ibogaine in that it contains a hydroxy instead of a methoxy group at the 12 position.

Research

An ibogaine research project was funded by the US National Institute on Drug Abuse in the early 1990s. The National Institute on Drug Abuse (NIDA) abandoned efforts to continue this project into clinical studies in 1995, citing other reports that suggested a risk of brain damage with extremely high doses and fatal heart arrhythmia in patients having a history of health problems,[citation needed] as well as inadequate funding for ibogaine development within their budget. However, NIDA funding for ibogaine research continues in indirect grants often cited in peer-reviewed ibogaine publications.

In addition, after years of work and a number of significant changes to the original protocol, on August 17, 2006, a MAPS-sponsored research team received "unconditional approval" from a Canadian Institutional Review Board (IRB) to proceed with a long-term observational case study that will examine changes in substance use in 20 consecutive people seeking ibogaine-based therapy for opiate dependence at the Iboga Therapy House in British Columbia, Canada.

Legal status

Ibogaine and its salts were regulated by the U.S. Food and Drug Administration in 1967 pursuant to its enhanced authority to regulate stimulants, depressants, and hallucinogens granted by the 1965 Drug Abuse Control Amendments (DACA) to the Federal Food, Drug, and Cosmetic Act. In 1970, with the passage of the Controlled Substances Act, it was classified as a Schedule I-controlled substance in the United States, along with other psychedelics such as DMT and mescaline. Since that time, several other countries, including Sweden, Denmark, Belgium, and Switzerland, have also banned the sale and possession of ibogaine. Although illegal in these countries, ibogaine has been used by hundreds of drug dependents in the United States and abroad. Howard Lotsof, a pioneer in bringing awareness to ibogaine’s success in helping hardcore drug dependents to quit their addiction, and others have been offering willing persons the treatment. In the Czech Republic and Slovenia, taking advantage of less prohibitive legal systems, ibogaine has been applied to people coming from the U.S. and other countries seeking a safe haven.

Canada

Ibogaine is not the subject of any regulation in Canada.[37][38]

Sweden

In early 2006, a non-profit foundation addressing the issue of providing ibogaine for the purpose of addiction interruption within established drug treatment care was formed in Sweden.[39]

In popular culture

Ibogaine first[dubiousdiscuss] appeared in popular culture in the writings of Hunter S. Thompson. While covering the Wisconsin primaries of the 1972 U.S. Presidential primaries for Rolling Stone magazine, Thompson claimed that presidential candidateEdmund Muskie showed symptoms of being under the influence of Ibogaine. This assertion was later revealed by Thompson to be false, one that he had planted as media bait. He himself was surprised when the leading media outlets picked up the story and ran with it.[40]

It also appeared in the seventh episode of the eleventh season of Law & Order: Special Victims Unit. In the episode, Doctor Huang administers Ibogaine to a heroin addict so that he can testify against a therapist who raped a girl under his care.[41]

See also

References

  1. ^ a b c K.R. Alper, H.S. Lotsof, G.M. Frenken , D.J. Luciano , J. Bastiaans (1999). "Treatment of Acute Opioid Withdrawal with Ibogaine". The American Journal on Addictions 8 (3): 234–42. doi:10.1080/105504999305848. PMID 10506904. Retrieved 2009-06-16.
  2. ^ K.R. Alper, H.S. Lotsof, C.D. Kaplan (2008). "The Ibogaine Medical Subculture". J. Ethnopharmacology 115 (1): 9–24. doi:10.1016/j.jep.2007.08.034. PMID 18029124. Retrieved 2008-02-22.
  3. ^ http://www.puzzlepiece.org/ibogaine/literature/gershon1962.pdf
  4. ^ Dora Weiner Foundation Conferences: 2004, Reports and Exhibits – AATOD and HRC
  5. ^ Maas U, Strubelt S (2006). "Fatalities after taking ibogaine in addiction treatment could be related to sudden cardiac death caused by autonomic dysfunction". Med. Hypotheses 67 (4): 960–4. doi:10.1016/j.mehy.2006.02.050. PMID 16698188.
  6. ^ Hoelen DW, Spiering W, Valk GD (January 2009). "Long-QT syndrome induced by the antiaddiction drug ibogaine". N. Engl. J. Med. 360 (3): 308–9. doi:10.1056/NEJMc0804248. PMID 19144953.
  7. ^ Ibogaine & Eboga (Related) Recorded Fatalities
  8. ^ H.S. Lotsof (1995). Ibogaine in the Treatment of Chemical Dependence Disorders: Clinical Perspectives (Originally published in MAPS Bulletin (1995) V(3):19-26)
  9. ^ Giannini, A. James (1997). Drugs of Abuse (2nd ed.). Practice Management Information Corporation. ISBN 1-57066-053-0.
  10. ^ Jurg Schneider (assignee: Ciba Pharmaceuticals), Tabernanthine, Ibogaine Containing Analgesic Compositions. US Patent No. 2,817,623 (1957) (pdf)
  11. ^ Patrick K. Kroupa, Hattie Wells (2005): Ibogaine in the 21st Century. Multidisciplinary Association for Psychedelic Studies. Volume XV, Number 1: 21-25 (pdf)
  12. ^ Naranjo, Claudio (1973). "V, Ibogaine: Fantasy and Reality". The healing journey: new approaches to consciousness. New York: Pantheon Books. pp. 197–231. ISBN 0-394-48826-1.
  13. ^ J. Dybowski, E. Landrin (1901). "PLANT CHEMISTRY. Concerning Iboga, its excitement-producing properties, its composition, and the new alkaloid it contains, ibogaine". C. R. Acad. Sci. 133: 748. Retrieved 2006-06-23.
  14. ^ G. Büchi, D.L. Coffen, Karoly Kocsis, P.E. Sonnet, and Frederick E. Ziegler (1966). "The Total Synthesis of Iboga Alkaloids" (pdf). J. Am. Chem. Soc. 88 (13): 3099–3109. doi:10.1021/ja00965a039. Retrieved 2006-06-23.
  15. ^ C. Frauenfelder (1999) Doctoral Thesis, page 24 (pdf)
  16. ^ Dzoljic ED, Kaplan CD, Dzoljic MR (1988). "Effect of ibogaine on naloxone-precipitated withdrawal syndrome in chronic morphine-dependent rats". Arch Int Pharmacodyn Ther 294: 64–70. PMID 3233054.
  17. ^ Glick SD, Rossman K, Steindorf S, Maisonneuve IM, Carlson JN (1991). "Effects and aftereffects of ibogaine on morphine self-administration in rats". Eur. J. Pharmacol 195 (3): 341–345. doi:10.1016/0014-2999(91)90474-5. PMID 1868880.
  18. ^ Cappendijk SLT, Dzoljic MR (1993). "Inhibitory effects of ibogaine on cocaine self-administration in rats". European Journal of Pharmacology 241 (2-3): 261–265. doi:10.1016/0014-2999(93)90212-Z. PMID 8243561.
  19. ^ Rezvani A, Overstreet D, Lee Y (1995). "Attenuation of alcohol intake by ibogaine in three strains of alcohol preferring rats.". Pharmacology, Biochemistry, and Behaviour 52 (3): 615–20. doi:10.1016/0091-3057(95)00152-M. PMID 8545483.
  20. ^ A Contemporary History of Ibogaine in the United States and Europe
  21. ^ a)Taylor WI (1965): "The Iboga and Voacanga Alkaloids" (Journal?), Pages 203, 207 and 208. Oxidation products: peroxides; indolenine, iboquine and iboluteine. pdf
  22. ^ a b Kontrimaviciūte V, Mathieu O, Mathieu-Daudé JC, et al. (September 2006). "Distribution of ibogaine and noribogaine in a man following a poisoning involving root bark of the Tabernanthe iboga shrub". J Anal Toxicol 30 (7): 434–40. PMID 16959135.
  23. ^ Alper KR, Lotsof HS, Frenken GM, Luciano DJ, Bastiaans J (1999). "Treatment of acute opioid withdrawal with ibogaine" (PDF). Am J Addict 8 (3): 234–42. doi:10.1080/105504999305848. PMID 10506904.
  24. ^ Mash DC, Kovera CA, Pablo J, et al. (September 2000). "Ibogaine: complex pharmacokinetics, concerns for safety, and preliminary efficacy measures". Ann. N. Y. Acad. Sci. 914: 394–401. PMID 11085338.
  25. ^ Jenks CW (2002)
  26. ^ Shulgin & Shulgin (1997), TiHKAL, p. 487.
  27. ^ Pace CJ, Glick SD, Maisonneuve IM, et al. (May 2004). "Novel iboga alkaloid congeners block nicotinic receptors and reduce drug self-administration". Eur. J. Pharmacol. 492 (2-3): 159–67. doi:10.1016/j.ejphar.2004.03.062. PMID 15178360.
  28. ^ Glick SD, Kuehne ME, Raucci J, et al. (September 1994). "Effects of iboga alkaloids on morphine and cocaine self-administration in rats: relationship to tremorigenic effects and to effects on dopamine release in nucleus accumbens and striatum". Brain Res.657 (1-2): 14–22. doi:10.1016/0006-8993(94)90948-2. PMID 7820611.
  29. ^ Tsing Hua. Antiaddictive indole alkaloids in Ervatamia yunnanensis and their bioactivity. Academic Journal of Second Military Medical University. January 28, 2006.
  30. ^ P. Popik, P. Skolnick (1998). Pharmacology of Ibogaine and Ibogaine-Related Alkaloids. The Alkaloids 52, Chapter 3, 197-231, Academic Press, Editor: G.A. Cordell
  31. ^ Kenneth R. Alper; Glick, Stanley D. (2001). "Ibogaine: A Review" (PDF). The alkaloids: chemistry and biology. 56. San Diego: Academic. pp. 1–38. ISBN 0-12-469556-6.
  32. ^ Xu Z, Chang LW, Slikker W, Ali SF, Rountree RL, Scallet AC (September 2000). "A dose-response study of ibogaine-induced neuropathology in the rat cerebellum". Toxicol. Sci. 57 (1): 95–101. doi:10.1093/toxsci/57.1.95. PMID 10966515.
  33. ^ Maciulaitis R, Kontrimaviciute V, Bressolle FM, Briedis V (March 2008). "Ibogaine, an anti-addictive drug: pharmacology and time to go further in development. A narrative review". Hum Exp Toxicol 27 (3): 181–94. doi:10.1177/0960327107087802.PMID 18650249.
  34. ^ Baumann MH, Rothman RB, Pablo JP, Mash DC (1 May 2001). "In vivo neurobiological effects of ibogaine and its O-desmethyl metabolite, 12-hydroxyibogamine (noribogaine), in rats". J. Pharmacol. Exp. Ther. 297 (2): 531–9. PMID 11303040.
  35. ^ Hough LB, Bagal AA, Glick SD (March 2000). "Pharmacokinetic characterization of the indole alkaloid ibogaine in rats". Methods Find Exp Clin Pharmacol 22 (2): 77–81. doi:10.1358/mf.2000.22.2.796066. PMID 10849889.
  36. ^ Zubaran C, Shoaib M, Stolerman IP, Pablo J, Mash DC (July 1999). "Noribogaine generalization to the ibogaine stimulus: correlation with noribogaine concentration in rat brain". Neuropsychopharmacology 21 (1): 119–26. doi:10.1016/S0893-133X(99)00003-2. PMID 10379526.
  37. ^ Johnson, Gail straight.com (January 2, 2003) Ibogaine: A one-way trip to sobriety, pot head says
  38. ^ Controlled Drugs and Substances Act (1996, c. 19), Canadian Department of Justice website. Accessed 5 November 2009.
  39. ^ Stiftelsen Iboga´s web site
  40. ^ The original article was republished as Fear and Loathing on the Campaign Trail ’72 (New York: Popular Library, 1973), pp. 150-154
  41. ^ TV.com, "Law & Order: SVU: Users Episode Recap Season 11 Episode Seven," CBS, 2010, http://www.tv.com/law-and-order-special-victims-unit/users/episode/1304610/recap.html?tag=episode_recap;recap
Further reading

 

 

Making a Tabernanthe iboga extract

DO NOT CONSIDER SELF-ADMINISTERING IBOGAINE OR RELATED IBOGA PRODUCTS WITHOUT MEDICAL APPROVAL

The following piece concerning the making of a T. iboga extract for consumption was forwarded to a foreign Internet list dealing with Ibogaine issues. We reproduce it here for interest value, not as a methodology for self-treatment.

Because of the problems of working with Tabernathe iboga rootbark in its natural form, namely it’s foul taste and the need for supervised hourly administrations, simple extraction processes have been devised which can render it easier to take.

We have no knowledge of anyone using the extraction detailed below to detoxify from drug usage, though it may be suitable for such a purpose.

Method

Put the rootbark into a large clean jar and add approx half a 70cl bottle of vodka, two cups of red wine and the juice of a lemon. Some users like to also add a half-teaspoon of vinegar.

Shake vigorously and then leave to stand for one week, shaking occasionally.

After one week has passed, empty the contents into a bowl or pan and place gently over boiling water. DO NOT DO THIS CLOSE TO A NAKED FLAME AS ALCOHOL IS HIGHLY FLAMMABLE. ENSURE THE AREA IS WELL VENTILATED.

Alcohol boils at around 80 degrees centigrade, (as opposed to water which boils at 100). When the alcohol has boiled gently away, remove the bowl and strain the contents through cloth. (The solid that remains should no longer have the bitter taste it did prior to beginning the extraction. If it does, mix everything back together and return it to the jar for another week. Then repeat the above.)

Assuming that the solid is not now distinctly bitter, discard it and allow the liquid that remains after straining to stand for about 12 hours.

The extract is now ready for consumption. For details on administration, obtain medical approval and consult one of the protocols on our treatment page.

Storage – It is recommended you consume the extract within a few days of making it. However, if necessary, it can be stored for about 2 – 3 weeks in a domestic refrigerator. After this period it will begin to brew, and the composition will be altered. Smelling the extract will tell you if it’s started to deteriorate.

 

Is This Root A Real Cure For Heroin Addiction?
by lain S. Bruce
Scotsman (UK)
March 31, 1999

LINDA Scott was a serious junkie with 25 years of drug addiction behind her – – then somebody gave her the most intense hallucinogenic trip she had ever experienced. By the time the Californian had emerged from the ordeal four days later she felt cleansed, liberated and that she had finally thrown off a dependency that had hounded her for decades. "I had a window of opportunity and I went through it," she explains. "I was fortunate enough to be on the receiving end of the gift of freedom – ibogaine."
A natural alkaloid compound extracted from the roots of a West African shrub, ibogaine has been a central plank of the Cameroon-based Bwiti religion for centuries, its potent hallucinogenic properties highly prized as an effective catalyst that allows tribesmen not only to achieve spiritual enlightenment but to enjoy a euphoric haze that bestows the ability to dance all night. Now Western researchers, who claim that the drug could cut the number of heroin addicts by a third inside three years, are bringing it to Scotland.
"There are no easy words to describe ibogaine, no convenient ways to explain," says Dan Leiberman, a South African ethno-botanist who brings the results of his 12-year study of the substance to Edinburgh next month. "Taking the substance is a powerful, intense and fundamental experience that has brought a massive response from many people seeking to deal with addiction to heroin. It takes strength and determination, but finally many psychologists are beginning to recognise the healing power it commands."
Since first learning of the drug’s existence from a Peruvian shaman in 1989, Leiberman has devoted most of his life to researching the effect it has had on followers of the Bwiti religion. He claims they are a people living out a completely peaceful, contented existence deep in the central African jungle and holds regular sessions on his South African farm where he introduces a collection of curious hippies and desperate heroin addicts to the drug. Although he says that many addicts have enjoyed remarkable recoveries, the sessions are never advertised and no claims are made that he offers a cure for addiction. "I facilitate the experience and monitor the events that follow," he says. "After that it is between them and the iboga."
Certainly, a growing army of ibogaine proponents is emerging to champion the drug as a major step forward in the fight to help recovering addicts. Howard Lotsof, the American researcher who has championed the drug as a detoxifying agent for over 30 years, says that experiences like those of Linda Scott, where addicts awake to find themselves completely untroubled by withdrawal symptoms, are the usual consequences of the treatment. "After a trip of 36 hours or more the subjects usually fall asleep, then wake up alert and ravenously hungry," he says. "It’s a miracle for a heroin addict of ten years, who has been shooting up a gram and a half a day, to wake up wanting steak and eggs for breakfast."
Lotsof discovered ibogaine’s allegedly miraculous properties in 1962, completely by accident, when as a New York film school student he was offered ibogaine. The 19-year-old hedonist – who was already using heroin regularly and had already experimented widely with hallucinogens such as mescaline, LSD and DMT – leapt at the chance. While the 33 hours that followed had only ever meant to be fun, Lotsof emerged from the party to discover that he no longer felt the need to take smack, and became immediately convinced that a radical new rapid detox method had just been uncovered.
As ibogaine is classified as an illegal stimulant in the US – so little is known about it in the UK that it does not feature on any official drugs register – Lotsof was forced to pursue unofficial research through tests on addicts over the next 22 years. In 1990 he began supervising trials on over 40 addicts in the Netherlands, with claimed results so successful that the American Federal Drug Administration expressed interest in a programme of ibogaine tests. Examples and apocryphal tales of addicts claiming to be cured by ibogaine continue to proliferate across the globe, and it would appear that some highly respected scientists share Lotsof’s belief that they are on the verge of a major breakthrough in addiction therapy. Professor Piotr Popik, of the US National Institute of Health, has called the treatment "a potentially life-saving new strategy for treating addiction to a diverse range of drugs".
Opponents of giving addicts methadone as a heroin substitute – the predominant detox method in the Edinburgh area – have demanded ibogaine’s use be investigated and widely promoted. While ibogaine would certainly seem to have great potential, the loud claims of its many proponents that the substance is a cure-all drug capable of combating any heavy addiction would seem extremely suspect. Linda Scott, whose personal testimony is frequently brandished as evidence of the cure’s potency, experienced a rapid return of her craving for drugs, an event that led to her suicide in December 1997, less than a month after she had believed herself cured forever. The only Briton known to have completed a course of treatment, Yorkshireman Richard Harper, similarly fell off the wagon after initially believing himself free of heroin’s hooks.
"It was certainly the best way of quitting I had ever come across," he said. "I was able to quit methadone without any cravings whatsoever. I don’t know what has changed, but I do know that my past is not such a burden now. Ibogaine has given me a new freedom. It isn’t a drug, it’s something divine – which sounds stupid, but it’s true."
Dan Leiberman points out that if an addict returns to his old haunts soon after the treatment he is sure to be tempted into his bad old ways. To illustrate, he describes a Johannesburg radio DJ who threw off a long-standing dependency to heroin but restarted his habit after a few months back in the social whirl. To cure himself this time, he is returning to spend many months working the ibogaine programme. "The drug will definitely get you through the withdrawal period painlessly," says Leiberman. "The problem comes later when you are still in the same environment that got you into drugs in the first place. That is the real problem, that is what Scotland must consider."
All is far from rosy, and there is still considerable concern from some researchers that ibogaine might have contributed to the deaths of addicts undergoing treatment. In 1994, Nicola, a 25-year-old German heroin addict, decided to undergo the treatment alongside her boyfriend Marcel, also a heavy drug user. At a discreet location in Amsterdam, the pair both took the substance and passed through the traditional sequence of events, an experience beginning with mild, LSD-like distortions of sound and light and ending after a three-day inner journey from which users regularly report having been transported down tunnels of light and "chanted clean" by groups of African people. As expected, Marcel awoke a new man, demanding a hearty breakfast to prepare him for the fresh, drug-free path that lay before him.
Just before dawn that day, however, Nicola suddenly gurgled, stopped breathing and died. The post-mortem that followed failed to pinpoint the exact reason for her death. It could well have been the ibogaine, but she had only taken 10 per cent of the known fatal dose. It could just have easily been the heroin that still coursed around a body still ravaged by the effects of prolonged opiate abuse. It could have been practically anything, but the real answer will never be known, argues Lotsof, until the FDA, or some other responsible body, completes the exhaustive programme of testing he believes ibogaine deserves.
To Lotsof, there are two reasons why ibogaine, despite 30 years of research, has failed to make a significant impact on the traditional medical establishment working in the field of drug addiction. First is an obvious reluctance on the part of men of science to embrace a practice only known due to its role in what is perceived to be a primitive, ignorant religion. Second, and perhaps most crucial, has been their dyed-in-the-wool conservatism. "Any new technology will be met by some resistance from the old guard," he says. "But even some of the methadone fans are finally starting to come around. The truly responsible researchers working out there want – and deserve – every possible tool at their disposal to help people dependent on drugs."
Dr Juan Sanchez-Ramos, the head of the University of Miami ibogaine research programme, is convinced that if ibogaine can throw off its common perception in the scientific community as an illegal drug similar in both use and effect to LSD, then such a tool will soon be available and a major breakthrough in narcotic treatment will have finally stepped out of the shadows.
"We have to take this out of the realm of mythology, he says. "A drug that is taboo can be extremely useful, but if it remains taboo then we will never find out."

ibogaine_story

An African Shrub that Got Him off Heroin and Cocaine

by Andrew Maykuth

Originally published in Philadelphia Inquirer, July 4, 1992

It’s from an African shrub. Howard Lotsof says it got him off heroin and cocaine.
To help battle addiction, he advocates the use of a drug
NEW YORK – Howard Lotsof was a 19-year old college dropout hungering for a new drug adventure in 1962 when somebody gave him a hallucinogen called ibogaine.
He sampled the drug, derived from the root of an African shrub, and experienced strange, colorful three-dimensional visualizations that kept him awake for more than a day.
In a sense, the trip has lasted for 30 years.
For what Lotsof said he discovered in 1962 is a drug that treats addiction. He said that ibogaine erased his dependency on heroin and cocaine without the agony of withdrawal– a claim endorsed by other addicts who have tried it.
Lotsof has become the guru of a small band of evangelists, who speak of the drug almost reverentially. They accompany addicts to the Netherlands for legal, experimental treatment. Lotsof says the drug’s effect "is like going through 10 years of psychoanalysis in three days."
Scientists regard the claims about ibogaine skeptically. But several studies have shown that Lotsof may be right.
"I decided to pursue a preliminary study as a lark, and it turned out it has some interesting effects," said Stanley D. Glick, chairman of the department of pharmacology and toxicology at Albany Medical Center.
"I think it merits further attention," said Patricia A. Broderick, a pharmacologist at the City University of New York Medical School, whose studies indicated that ibogaine inhibited the pleasurable effects of cocaine in laboratory rats.
The preliminary studies helped convince the National Institute on Drug Abuse (NIDA) to add ibogaine to its list of about two dozen drugs that merit research for addiction therapy. This year, NIDA is funding 10 studies to explore ibogaine’s potential.
"This drug at first I found a little hokey," said James W. Cornish, director of pharmacotherapy at University of Pennsylvania’s Treatement Research Center. "But the fact that NIDA is doing a study is very important."
The medical community’s interest has given a measure of legitimacy to a compound that the Drug Enforcement Administration lists as a dangerous controlled substance, although there is no record of ibogaine addiction.
"I don’t like to take it," said Lotsof, who formed a small company that operates out of his Staten Island home, which has obtained the patents to use ibogaine in addiction treatment.
"Ibogaine kind of knocks you on your butt, which is good because you can’t go out and get drugs," said Dana Beal, a former Yippie and smoke-in organizer, who has become the drug’s leading promoter. "By the time the ibogaine wears off, you don’t have any craving."
Getting mainstream medical laboratories to look at ibogaine is largely the work of Lotsof and his disciples in New York’s counterculture– an alliance of aging hipsters, Lower East Side political activists and drug-decrimnalization advocates.
Lotsof’s appearance is not outlandish. He has short, thinning gray hair and a trimmed mustache and wears conventional clothing. He speaks in humorless, measured, hushed tones. He accknowledges he has a history of drug abuse. He spent 18 months in jail in 1966 for conspiracy to sell LSD.
In the early 1980’s, after he was disabled with a back injury from his job as a film producer, Lotsof harkened back to his experience with ibogaine and decided to promote it as a treatement for addicts who were unable to cope with the debilitation of withdrawal.
Lotsof learned that ibogaine is derived from the iboga shrub, native to West Africa. Natives use it as a stimulant to keep hunters awake, and members of a religious sect in Gabon consume it in initiation rites, allowing them to speak with their ancestors.
Ibogaine had received little notice in the West, except for Hunter S. Thompson, the writer and noted drug sampler, who commented satirically that the statements of some candidates in 1972 presidential campaign were probably caused by ibogaine hallucinations.
Some pharmaceutical companies studied ibogaine over the years as a heart treatment or as a psychiatric medication, but they developed no drugs and their patents expired in the 1960s.
Lotsof got his friends to invest– he says that his company, NDA International, has spent about $1 million– and persuaded a few pharmacologists to study ibogaine’s effect on addiction.
While researchers are interested in ibogaine’s apparent ability to inhibit drug dependency and are leery of its hallucinogenic properties, Lotsof and his followers argue that the drug’s psychoactive nature is an essential part of its healing power. The "visions"– Lotsof denies they are hallucinations– help addicts deal with the underlying behavioral problems that cause their addiction.
"If people don’t see anything, you’re interrupting the therapy," said Bob Sisko, 46, a new York activist who kicked heroin with ibogaine and has helped promote its legalization. "Forget about that."
But the descriptions of ibogaine’s hallucinatory effect hardly appear to conform with conventional pharmacology’s preference for predictable results.
In a recent presentation to the AIDS Coalition to Unleash Power– ACT UP is interested in treating drug addiction because of its relation to the spread of AIDS– Lotsof described a two-day treatment of ibogaine as a kind of high speed home movie.
"You are literally speeding through your life’s decision-making history," he said. "Whoa! I did that and there were four other things I could have done. Zap. Next situation."
In an interview, Lotsof was more restrained in his description. He said that the release of memories is followed by "a period of intellectual evaluation," followed by "residual stimulation" and then sleep.
But not everybody gets the this-is-your-life treatment that Lotsof describes.
Carol– not her real name– is a 39 year old HIV-positive real estate saleswoman who has been addicted to heroin and methadone for 25 years. She recently paid about $5,000– the amount she would spend in a month on heroin– to travel to Amsterdam, Netherlands, with Lotsof to undergo a medically supervised ibogaine treatement.
"It’s like seeing a movie on your eyelids," said Carol, a plump woman who wore a black jumpsuit with an abundance of zippers. She said the visions– which appeared only when her eyes were closed– were mostly unfamiliar faces of medieval, mythological characters.
"If I would concentrate too long on one they would get ugly and I would get scared," she said.
But Carol said she saw no visions from her own life.
"I did have one vision that stuck with me," she said. "That was my brain, like a hand holding my brain, and this deep brown liquid dripping in thick oozy drops out of it. I felt in myself that my brain was soaked with ibogaine."
Carol said the 22 hours of visions were unpleasant– she vomited frequently and her legs were so wobbly she could not stand. For days afterward, she said, she had no appetite and suffered from hand tremors and sleep disruption.
But Carol said that as uncomfortable as the experience was, it was mild compared to her previous attempts at drug withdrawal, during which she was overcome with pain, weepy eyes and discomfort for weeks.
"There was no sweating, no sniffling, no diarrhea, no cramps," she said. She has not taken any narcotics wince the treatement in early April.
"This is like an amazing miracle."
Lotsof said that he and other ibogaine advocates have taken about 30 addicts to Amsterdam for treatment in recent years and few of them suffered withdrawal.
Lotsof has refused to make the drug available to desperate addicts in the United States because possission of ibogaine is illegal. "If we want to get this to the market, we have to do it properly," he said.
That is not entirely true.
"The people advocating ibogaine make it sound like the fact that NIDA is looking at, that’s a validation that the drug works," said Charles Grudzinskas, director of medications developement for NIDA. He said it could be years– if ever– before NIDA develops a useful drug from ibogaine.
"These claims are made about almost every drug," said Ronald Siegel, a UCLA psychopharmacoligist. "Cocaine was once promoted as a cure for morphine. Morphine was promoted as a cure for cocaine. Psychedelics, including ibogaine and LSD, were all promoted as psychotherapeutic cures for all kinds of ailments, including drug addictions."
Undeterred, Lotsof said physicians are envious that somebody outside the medical field devised a treatment.
"If you’re the person at the cutting edge," he said, "there’s very little training to be obtained."

Tabernanthe Iboga

Ibogaine: A Novel Anti-Addictive Compound

A Comprehensive Literature Review

by Jonathan Freedlander, University of Maryland Baltimore County

Minor edits by Erowid. Originally published in Journal of Drug Education and Awareness, 2003; 1:79-98.

Erowid Note: The following was written as an undergraduate senior research project.

Tabernaemontana

Introduction and History:#

Ibogaine is a naturally occurring indole alkaloid, found in a variety of African shrubs of the Tabernanthe genus (Obach, Pablo, and Mash, 1998). The root of the Tabernanthe iboga plant (also known as eboga) is the most frequently cited source of ibogaine, and this plant contains 11 other known psychoactive constituents (Popik, and Skolnick, 1999). Chemically, ibogaine is classified as a tryptamine, being a rigid analogue of melatonin, and is structurally similar to harmaline, another natural alkaloid and psychedelic (Xu et al., 2000). Ibogaine was first extracted from the Tabernanthe iboga root in 1901 by Dybowsky and Landrin (Goutarel, Gollnhofer, and Sillans, 1993). It can also be synthesized from nicotinamide by way of a 13 or 14 step process, although extraction from the iboga root is a simpler method for obtaining the compound (Shulgin and Shulgin, 1997).
At low doses, ibogaine exerts primarily a stimulant effect, increasing alertness and reducing fatigue, hunger, and thirst (Rezavani, Overstreet, and Lee, 1995), though not in the manner of stereotypical CNS stimulants, such as amphetamine or cocaine (Da Costa, Sulklaper, and Naquet, 1908). At higher doses (typically above 3 mg/kg), ibogaine’s primary psychological effects include the retrieval of repressed memories, closed eye visual imagery (CEVs), and a state characterized as "waking dreaming" (Popik and Glick, 1996).
From anecdotal reports, it appears that memories are relived in a sense, primarily in a visual modality, but without the emotional weight they carried when the events occurred, allowing the individual to view them with greater insight (Naranjo, 1974; Alper et al., 1999). Subjectively, these effects have been described as fantasies, "as a movie run at high speed, or a slide show" (Lotsof, 1995). These fantasies are easy to manipulate by both the subjects and the clinician, and therefore this phenomenon has been sighted as a potentially valuable tool in psychotherapy (Naranjo, 1967, 1974). The imagery experienced under the effects of ibogaine is often largely Jungian in content, involving archetypes seemingly common across cultures; frequently animals, birth and rebirth sequences, and/or the subject with or without individuals (Popik and Glick, 1996). While ibogaine does share features common with many compounds labeled as hallucinogenic, it does not cause thought disturbances, alterations in reality testing, nor is it psychomimetic (Luciano, 1998; Goutarel, Gollnhofer, and Sillans 1993; Popik and Glick, 1996). Rather than classify ibogaine as a hallucinogen, it is suggested that the compound be termed oneirogenic, due to the "waking dream" state it induces, from the Greek, meaning "dream creator" (Naranjo, 1974; Goutarel, Gollnhofer, and Sillans, 1993).
In addition to ibogaine’s psychological effects, it elicits a number of physical effects, which include tremor, light sensitivity, nausea and vomiting, ataxia, and dystonia (Lotsof, 1994; Glick, Maisonneuve, and Szumlinski, 2000). All of these effects, psychological and physical, manifest in a dose-dependent fashion (Schechter and Gordon, 1993). In light of these properties, and that the sum effects of ibogaine can last up to 24-36 hours, ibogaine is not considered to have a high potential for abuse (Popik and Glick, 1996). Indeed, those who have experienced ibogaine, typically characterize its effects as a "rough trip;" one that is not suitable for recreational use (Shulgin and Shulgin, 1997).
Accordingly, when ibogaine was introduced to the United States’ black market in the 1960s, it showed little popularity, and subsequently has infrequently been seen sold illicitly (Goutarel, Gollnhofer, and Sillans, 1993). The U. S. Drug Enforcement Agency reports having encountered only a few illicit samples in their interdiction efforts (Cooper, 1988). According to Dharir (1971), ibogaine first appeared on the illegal drug market in 1967, and was reported in a handful of cases by the police of Suffolk County, NY and San Francisco, CA. Shortly thereafter, however, ibogaine suddenly disappeared from the black market, perhaps due to a lack of profit motive for drug dealers, resulting from ibogaine’s putative anti-addictive effects (which will be discussed later in this paper) (Goutarel, Gollnhofer, and Sillans, 1993).
Various preparations of plants containing ibogaine have been used for centuries in traditional African medicine, as first reported by French and Belgian explorers in the 19th century (Popik and Skolnick, 1999). The iboga root may be eaten whole, or crushed and ground and mixed with other ingredients, sometimes including other psychoactive compounds (Fernandez, 1982). These preparations, in varying quantities, have been used as a stimulant to battle hunger, thirst, and fatigue during hunting, as an aphrodisiac, and as a catalyst for spiritual discovery involved in the initiation rites of the Bouti (Stafford, 1983). The Bouti (also Bwiti) is a religious society found among the indigenous peoples of the Gabon and Cameroon nations of western Africa, and initiation into this society, involving the use of ibogaine containing substances, is central to their cultures (Fernandez, 1982; Goutarel, Gollnhofer, and Sillans, 1993).
Literally, Bouti means "those of the chapel." The primary purpose of these initiation rites, as described by the initiates, is to travel through the land of the tribal ancestors, and emerge in the "pristine uterine condition" (Fernandez, 1982). This ritual is referred to by its participants as "cracking the skull" (Sheppard, 1994). The initiate, in the ibogaine-induced state, makes contact with the ancestral spirits, under the guidance of those already initiated. After the ceremony, the initiate is reborn as an adult in the tribe, having previous transgressions and illnesses removed in the initiation process (Fernandez, 1982).
Ibogaine was first introduced as a pharmaceutical product to Western medicine in the form of Lamberene, an extract of the Tabernanthe manii plant (Popik and Skolnick, 1999). Advertised as a mental and physical stimulant, it contained about 8 mg of ibogaine and was "…indicated in cases of depression, asthenia, in convalescence, infectious disease, [and] greater than normal physical or mental efforts by healthy individuals" (Goutarel, Gollnhofer, and Sillans, 1993). The drug enjoyed some popularity among post World War II athletes, but was eventually removed from the market, when the sale of ibogaine-containing products was prohibited in 1966.
Dr. Claudio Naranjo, a Chilean psychiatrist, was the first to study ibogaine’s potential psychotherapeutic effects. In the early 1960s, Naranjo conducted a series of case studies (approximately 40 studies, with 30 patients) using doses of 4-5 mg/kg, in which he found that ibogaine had the ability to facilitate closure of unresolved emotional conflicts (Popik and Glick, 1996). This closure was mediated by ibogaine’s aforementioned ability to enhance retrieval of repressed memories. Naranjo found that ibogaine allowed his patients to view their past experiences in an objective manner, which enabled them to confront personal issues that were previously unapproachable (Naranjo 1974).
Around the same time that Dr. Naranjo was conducting his case studies, ibogaine’s anti-addictive effects were serendipitously discovered. In 1962, Howard Lotsof, addicted to heroin at the time, took a dose of ibogaine (estimated to be about 500 mg) that a chemist friend had given him, tantalized by the promise of a 32 hour trip (Goutarel, Gollnhofer, and Sillans, 1993, De Rienzo, Beal, et al., 1997). He woke up the next morning with the startling revelation that he no longer desired heroin; in fact he remained free of the drug for years to follow (Lotsof, 1990). Though Lotsof was not a doctor, nor a scientist, his personal experience with ibogaine led him to investigate the drug further.
Over the course of the next year, Lotsof led a series of non-clinical focus groups under the auspices of S & L Laboratories, which he set up "to procure drugs and administer them to interested persons" (Lotsof, Della Sera, and Kaplan, 1995, Alper, Beal, and Kaplan, 2001). At that time, psychedelics were not scheduled drugs, and were effectively available to anyone who started their own chemical "company", needing little more than an official looking letterhead (De Rienzo, Beal, et al., 1997). Between 1962 and 1963, Lotsof administered ibogaine to 20 individuals at a variety of doses, up to 19 mg/kg (Alper, Beal, and Kaplan, 2001). Of these 20 subjects, 7 were heroin dependent, and noted the alleviation of withdrawal symptoms and drug craving after ingesting ibogaine. Additionally, 5 of these 7 individuals were able to maintain abstinence from heroin for 6 months or longer.
Shortly thereafter in 1963, the Food and Drug Administration (FDA) noticed the large amount of psychedelics Lotsof was ordering, and tracked a shipment of 100 g of mescaline to the laboratory he had set up (De Rienzo, Beal, et al., 1997). Though psychedelics were not illegal at that time, unauthorized use of mescaline on humans was punishable by a six month sentence. The FDA’s search of his premises discovered no mescaline, but did find 2 g of ibogaine, which the FDA agents forced Lotsof to sell to them. Subsequently, the FDA cut off his access to controlled substances, despite the fact that they found nothing with which they could charge him.
However, in 1966, LSD, mescaline, and psilocybin were categorized by the U.S. federal government as Schedule I narcotics; drugs with no medicinal value and a high potential for abuse. Shortly thereafter, Assistant U.S. Attorney Robert Morenthau had Lotsof arrested on drug conspiracy charges. When Lotsof spoke about ibogaine’s anti-addictive effects in court, the judge had his testimony stricken from the record. Lotsof was found guilty on 4 misdemeanors, and sentenced to 14 months in prison. Upon release in 1968, Lotsof was "shattered". He traveled to Nepal, where, for the first time in five years, he ate opium, and became re-addicted. In 1969, he tried to locate some ibogaine with the hopes of breaking his addiction again, but discovered that it had been added to the list of Schedule I drugs, and was unable to find any. [[true? was it really called schedule I in 69? ]]
Upon returning to New York, Lotsof entered a methadone maintenance program, which he considered life saving. However, "the system of administering methadone was becoming more restrictive to patient life styles," and so with the knowledge he had gained from his experiences with ibogaine, Lotsof endeavored to wean himself off methadone (Lotsof, 2002). In December of 1973, just as he was coming off of methadone, Lotsof met Dana Beal, the then new leader of the Yippie movement. Beal and Lotsof "hit it off from the start", and over the next six years, collaborated on a variety of projects, including three films, a series of Rock Against Racism concerts, and further investigation of ibogaine.
In 1981, a Yippie subcommittee named Citizens Against Heroin began to fund Lotsof’s ibogaine research. He used the bulk of this funding to execute an exhaustive literature search in the New York University library (where he had previously been a film student). By late 1983, Lotsof believed he had enough information to back his claims of ibogaine’s anti-addictive effects, and initiated a series of patents for Endabuse (NIH 10567), an oral preparation of ibogaine hydrochloride in capsule form. These patents indicated Endabuse for the "rapid interruption" of opiate dependence disorders (U.S. Patent 4,99,096, 1985), cocaine dependence disorders (U.S. Patent 4,587,243, 1986), nicotine dependence disorders (U.S. Patent 5,026,697, 1991) and poly-substance abuse disorders (U.S. Patent 5,152,994 1992) (Lotsof, Della Sera, and Kaplan, 1995).
Lotsof first made contact with the conventional scientific community in 1986, when he contracted with a professor at McGill University in Montreal to study ibogaine’s effects on alcohol dependence. However, the professor turned the project over to a graduate student and never published the results. (Fortunately, the contract for the experiment specified that Lotsof owned the data, and in 1988 he discovered that the results showed a significant reduction in alcohol intake by rats after administration of ibogaine.) Also in 1986, Lotsof founded a New York based organization, NDA International, Inc., with the dual mission of furthering the humanitarian applications of ibogaine and marketing the proprietary preparation, Endabuse (Goutarel, Gollnhofer, and Sillans, 1993).
After that, Lotsof sent a sample of ibogaine to researchers in the Pharmacology Department at Erasmus University in Rotterdam, where the investigators published the first paper indicating the effectiveness of ibogaine in the reduction of opiate self-administration in an animal model University (Alper, Beal, and Kaplan, 2001). The team at Erasmus also furthered the development of a method of injecting it into the ventricles of rat brains, which was originally conceived by Konig and Klippel in 1963. This reduced the amount of ibogaine needed to produce the effects of regular intravenous or intraperitoneal administration (De Rienzo, Beal, et al., 1997).
In 1989, Lotsof contracted with Dr. Stanley Glick, head of the Department of Pharmacology and Toxicology at Albany College of Medicine. This was perhaps the most pivotal of Lotsof’s contacts with the scientific community. After examining ibogaine’s long lasting effects on morphine self administration in rats, Dr. Glick became keenly interested in furthering ibogaine research. Although Lotsof had run out of funding at the time, having to break his contract with Glick, Glick continued with his own research, and over the years produced a significant body of work on ibogaine and related compounds (De Rienzo, Beal, et al., 1997).
Lotsof and colleagues developed a specific procedure [aptly named the Lotsof Procedure ™] for the use of Endabuse, which involves comprehensive short and long term medical, psychological, and social care of the patient. Lotsof describes the procedure a single administration modality (SAM), and summarizes the primary obligations of the treatment team as:

"four-fold: 1) to earn the trust of the patient, 2) to maintain the comfort of the patient, 3) to assist the patient in interrupting their chemical dependency, and 4) to supply the psychosocial support network needed by the majority of patients to enable them to develop a sense of personal accomplishment and the ability to function as productive members of society" (Lotsof, 1994).

One of the differences between the Lotsof Procedure and conventional addiction treatment that it stressed most is the level and nature of the rapport between the clinicians and the patient. As Lotsof describes (1994), "…the sense of conflict seen in most treatment modalities between the doctor and patient over the immediate ceasing of drug use does not exist". Treatment is approached with a "pro-choice attitude" by the caregivers, where abstinence is not demanded (Frenken, 1998). Rather, the patient is allowed to continue using drugs until a certain time before the procedure, based on the amount of time needed for the given drug to clear the body. The position of the treatment team is "that ibogaine will either work to interrupt chemical dependence or it will not" (Lotsof, 1994).
Another noteworthy difference of the Lotsof Procedure is the rapidity with which psychosocial support needs to be provided to the patient. "Ibogaine presents a symptom-free window of opportunity which the patient and therapist must take advantage of" (Lotsof, 1994). Because ibogaine (putatively) allows for an immediate interruption in the patient’s addiction, the patient is generally found to be in a receptive psychological state earlier in the course of therapy. Therefore "they will require faster intervention to learn societal skills and to overcome and objectively understand various traumas experienced during their lives" (Lotsof, 1994). Additionally, Lotsof asserts that many of the accepted boundaries between the therapist and patient can hinder ibogaine treatment, that patients will require a closer and more intensive guidance.
As word of Lotsof’s discovery gradually spread across the world, an unofficial global network of ibogaine therapy providers developed (Alper et al., 1999). This network was largely supported by the efforts of the New York based International Coalition for Addict Self-Help (ICASH), founded by Robert Sisko. ICASH is described "as having a self-help orientation in the tradition of European user self-help organizations, such as the Junkiebond in the Netherlands" (Alper, Beal, and Kaplan, 2001). This is not surprising, as ICASH often acted in partnership with the Dutch Addict Self Help group (DASH, now known as International Addict Self-Help, or INTASH). Together, these groups are estimated to have treated 40 to 45 individuals between 1989 and 1993. Though not officially sanctioned, the results of these treatments were reported in publications from Erasmus University. Self-help groups for the use of ibogaine also developed in the U. K., Slovenia, Italy, the Czech Republic, and France.
Professionals from various disciplines also became interested in examining ibogaine’s potential. Deborah Mash, professor of neurology at the University of Miami, became interested in ibogaine research after hearing a presentation on it at a conference in 1991 (Alper, Beal, and Kaplan, 2001). In 1992, NDA International and the University of Miami collaborated to organize a clinical trial of ibogaine. The following year, Mash received approval for an Investigational New Drug Application from the FDA. The study was not completed, however, due to lack of funds, and NDA International and the University of Miami commenced litigation of intellectual property rights. Since 1996, Mash has operated an ibogaine treatment center on the Caribbean island of St. Kitts.
Therapist Eric Taub also relocated from Florida to the Caribbean in order to establish an ibogaine therapy program. Since 1992, Taub has treated approximately 310 patients, 130 of which sought treatment for chemical dependency (Alper, Beal, and Kaplan, 2001). Through ibogaine therapy, Taub aides the patient in changing patterns of "reactive" or subconsciously determined behavior, including, but not limited to substance addiction. Ibogaine’s role in this psychotherapy is to facilitate a reduction of "pathologically acquired or learned" associations of cues or internal representations with corresponding motivational states and behavior. In accord with Lotsof’s methods, Taub stresses the rapidity and intensity with which support must be provided following the administration of ibogaine for successful treatment.
Dr. Jan Bastiaans was the president of the Psychoanalytic Institute in Amsterdam from 1954 to 1961, professor of psychiatry at the State University of Leiden from 1963 to 1985, and a major figure in the history of the psychotherapeutic use of psychedelics (Grof, 2001). Bastiaans work with psychedelics was sparked by his interest in the use of pharmacological methods in the treatment of war related trauma in the wake of World War II. In particular, his work focused on the treatment of concentration camp survivors, often using LSD or psilocybin to facilitate therapy (Snelders, 1998). Over time, Bastiaans began to develop the methods he used in therapy with war survivors to treat survivors of other traumas. In 1992, Bastiaans collaborated with NDA international, adapting his methods to treat those with substance addictions (Alper, Beal, and Kaplan, 2001). However in 1993, one of the few known ibogaine related fatalities occurred under his supervision. Although the official Dutch inquiry found no evidence to suggest wrongdoing on the part of Bastiaans, he was forced to give up his practice by the Medische Tuchtraad, the Dutch medical supervisory board. In his last years, Bastiaans became bitter over the lack of recognition for his contributions to psychotherapy and died in 1997.

Voacanga africana

Pharmacology:#

The principle method of ibogaine metabolism is O-demethylation by the liver, which yields O-desmethylibogaine (also known as 12-hydroxyibogaimine or, most commonly, noribogaine) and perhaps other, as of yet undetected, metabolites (Popik and Skolnik, 1999; Mash et al., 2000). Obach et al. (1998) found that, of ibogaine consumed, 75-80% was accounted for as noribogaine. Hough et al. (1996) reported that ibogaine, when administered intraperitoneally in rats, is subject to a significant "first pass" effect; that is its pharmacological actions begin before it is metabolized. They also found that ibogaine has a high propensity to be deposited in adipose tissue, showing high levels in fat for at least 12 hours after administration. It is hypothesized that this quality may enable a single dose of ibogaine to provide a long acting "depot-like time course of action" (Popik and Glick, 1996).
Additionally, noribogaine has a longer half-life than ibogaine, and is also psychoactive; therefore it is possible that this metabolite may play a role in ibogaine’s long-term effects (Mash et al., 2000). Pearl et al. (1997) detected presence of noribogaine in rodent brains up to 19 hours after an intraperitoneal administration of 40 mg/kg of ibogaine, while the half-life of ibogaine has been established to be 60 minutes (Dhahir, 1971; Zetler, Singbarth, and Schlosser, 1972). Oral administration of ibogaine in rabbits (10 mg/kg) yielded peak urine concentrations at a maximum of 4-5 hours, rapidly decreasing thereafter, until complete absence at 6 hours (Dhahir, 1971; Cartoni and Giarusso, 1972). In addition to urine, both ibogaine and noribogaine are detectable in many other bodily materials, including blood, liver, and brain (Cartoni and Giarusso, 1972; Bertol, Mari, and Froldi, 1976).
The O-demethylation of ibogaine in the liver is catalyzed by the P4502d6 cytochrome, which has important clinical implications (Obach, Pablo, and Mash, 1998). Approximately 5-10% of Caucasians lack the gene needed to produce this enzyme, and are therefore more prone to adverse reactions from drugs metabolized by it (Gonzalez and Meyer, 1991). In addition, this cytochrome is involved in the metabolism of a number of pharmacological compounds, including neuroleptics, beta-blockers, tricyclic antidepressants, and opioids, raising possible issues of adverse interactions with ibogaine (Eichelbaum and Gross, 1990; Fromm, Kroemer, and Eichelbaum, 1997). Furthermore, individuals lacking this gene are less likely to benefit from the therapeutic effects of drugs metabolized by P4502d6 (Obach, Pablo, and Mash, 1998).
Like many tryptamines (e.g. serotonin, melatonin, d-lysergic acid diethylamide or LSD, psilocybin, N,N-dimethyltryptamine or DMT), the pharmacodynamics of ibogaine are particularly complex, involving multiple sites of action. Ibogaine affects, both directly and indirectly, dopaminergic, glutamatergic, serotonergic, opioid, nicotinic, sigma, gamma-aminobutrylic acidergic (GABA), nicotinic, cholingeric, and muscarinic pathways, as well as calcium regulation and voltage-dependent sodium channels (Popik and Glick, 1996; Glick and Maisonneuve, 1998; Alper et al., 1999; Popik and Skolnik, 1999). It is therefore thought that ibogaine’s effects are a product of a combination of its interactions with these systems. However, there have been a number of discrepancies reported with regard to the specific manners in which ibogaine exerts its pharmacological actions (Popik and Skolnick, 1999). Additionally, noribogaine affects many of the same neural components as ibogaine, which further complicates the study of its pharmacological profile (Mash et al., 2000).
A great deal of attention has been paid to ibogaine’s effects on the dopaminergic system, as dopamine is theorized to play a primary role in the sensitization, reinforcing, and motivational properties of drugs of abuse (Fibiger and Phillips, 1986; Berrige and Robinson, 1998). Robinson and Berrige (1993) proposed that the incentive salience of drug-taking behaviors is related to neurotransmission in mesotelencephalic dopamine pathways, in which the repeated administration of addictive drugs sensitizes the incentive salience of drug related cues. Compared to drug-naïve individuals, drug addicts have increased sensitivity to both the positive (Grant et al. 1996; Ligouri, Hughes, Goldberg, and Callas, 1997) and negative (Ellinwood 1968; Angrist, 1983) reinforcing effects of drugs of abuse. These reinforcements are apparently mediated through enhanced brain activity in brain regions innervated by the mesolimbic dopamine system, including the frontal cortex (Alper et al., 1999) and the amygdala (Childress et al., 1999). According to this theory, if activity in sensitized dopamine pathways is decreased, it should alleviate addictive drug craving (Blackburn and Szumlinski, 1997).
Though ibogaine does not appear to affect binding at dopamine receptors or transporters (Broderick, Phelan, and Berger, 1992), it has been found to reduce extracellular levels of dopamine in the nucleus accumbens (Glick and Maisonneuve, 1998; Glick et al., 1999). Ibogaine effects on dopamine metabolites appear to be inconsistent. When measurements are taken shortly after administration (within 2 hours), or when high concentrations are used (greater than 100 uM), increases in dihydroxyphenyl-acetic acid (DOPAC) and homovanilic acid (HVA) are seen (Maisonneuve, Keller, and Glick, 1991; Maisonneuve, Rossman, Keller and Glick, 1992; Sershen, Hashim, Harsing, and Lajtha, 1992). However, when lower concentrations are used (e.g. 10 uM) or measurements are taken after a longer period of time (up to a week), dopamine brain concentrations remain unchanged, and metabolite concentrations decrease (Maisonneuve, Keller, and Glick, 1991; Shershen, Hashim, Harsing, and Lajtha, 1992).
Sershen et al. (1994) reported that ibogaine’s effects on dopaminergic function are largely regulated by its interactions with serotonin receptors. This was inferred from their finding that ibogaine inhibited the ability of the 5-HT1b agonist CGS-12066A to increase stimulation induced dopamine release in rat and mouse striatal slices. It has also been demonstrated that ibogaine increased the ability of the 5-HT3 agonist phenylbiguanide to produce stimulation evoked dopamine release in mouse striatal slices (Sershen, Hashim, and Lajtha, 1995). Taken together, these findings support the notion that ibogaine’s effects on serotonin have a role in determining its dopaminergic effects, but the specific nature of this role has yet to be determined.
Ibogaine has been found to increase 5-HT concentrations in both the nucleus accumbens and striatum of the rat (Broderick, Phelan, Eng, and Wechsler, 1994; Ali et al., 1996). However, Benwell et al. (1996) found that ibogaine reduced serotonin levels in the medial prefrontal cortex. Furthermore, studies of ibogaine’s specific actions at serotonin receptors have been inconclusive. Deecher et al. (1992) found that ibogaine did not displace ligands acting at 5-HT1a, 5-HT1b, 5-HT1c, 5-HT1d, 5-HT2, or 5-HT3 receptors, while Repke et al. (1994) found that it did inhibit binding of 5-HT1a, 5-HT2a, and 5-HT3 ligands with low affinity (>100, 12.5, and >100 uM). Additionally, Sweetnam et al. showed that ibogaine inhibits radioligand binding to both 5-HT2 and 5-HT3 receptors, with considerably higher affinity (approximately 4 uM), while Helsley et al. (1998) found that ibogaine bound to 5-HT2 receptors with low affinity in vitro ( > 40 uM), but occupied this receptor in vivo following systemic administration.
It is postulated that ibogaine may act as a reversible inhibitor of serotonin transporters, as concluded from the observation that it inhibited transporters in the isolated kidney cells of pigs (Popik and Skolnick, 1999). Sershen et al. (1994) found that, at doses of 40-50 mg/kg, ibogaine decreased levels of 5-hydroxyindoleacetic acid [5-HIAA] in the frontal cortex, hippocampus and olfactory tubercle of the mouse. Ibogaine was also found to decrease 5-HIAA levels in the nucleus accumbens and striatum of the rat, but to increase 5-HIAA levels in the medial prefrontal cortex (Benwell, Holtom, Moran, and Balfour, 1996; Ali et al., 1996). The differing effects of ibogaine on serotonergic function in different areas of the brain have yet to be explained. Indeed, this is the case with most psychedelic compounds, making a strong case for the further scientific study of these substances.
Like dopamine systems, the glutamatergic pathway has often been implicated in drug abuse and addiction, specifically N-methyl D-aspartate (NMDA) channel receptors. Preclinical data have consistently indicated that NMDA antagonists interfere with sensitization, tolerance, and dependence related to stimulant, alcohol, benzodiazepine, barbiturate, and opiate use (Trujillo and Akil, 1991; Wolf and Khansa, 1991; Khanna, Kalant, Shah, and Chau, 1993; File and Fernandez, 1994; Popik and Skolnik, 1996). Furthermore, blockers of NDMA receptors have been show to reduce nalaxone-induced jumping in morphine-dependent mice (Layer et al., 1996; Popik and Skolnick, 1996). NMDA antagonists act by occupying a binding site within a calcium channel, which is normally gated by glutamate, the brain’s principle excitatory neurotransmitter (Helsley, Rabin, and Winter, 2001).
Ibogaine has been found to act as a non-competitive antagonist at NDMA receptor channels (Popik et al., 1995), which is supported by the finding that ibogaine has a high affinity for NDMA site binding (Glick and Maisonneuve, 1998; Helsey, Rabin, and Winter, 2001). Popik et al. (1994) showed that ibogaine substituted for MK-801 (dizocilipine, a known NMDA antagonist) at a rate of approximately 70% in drug discrimination studies in mice. In addition, ibogaine has been shown to inhibit binding of both MK-801 (an NDMA antagonist) and PCP at NDMA receptors (Layer et al., 1996; Helsley et al., 1998). Ibogaine, at 80 mg/kg, also blocked NMDA-induced convulsions in mice for up to 72 hours after administration (Leal, de Souza, and Elisabetsky, 2000).
It has been demonstrated that certain sigma ligands may be effective in the treatment of drug abuse, due to their ability to block the behavioral effects of cocaine and amphetamine in non-human subjects (Helsley et al., 1998). Of all binding sites that have been studied thus far, ibogaine shows the greatest affinity for sigma-2 receptors, with reported K1 values ranging from 90-201 nM (Bowen et al., 1995; Mach, Smith, and Childers, 1995). Because of its high affinity for mu 2 receptors, ibogaine has been proposed to act as a mu 2 agonist (Bowen, Vilner, Bandarage, and Keuhne, 1996). Studies have also shown that ibogaine also binds to mu 1 receptors with an affinity of less than 10 uM (Mach, Smith, and Childers, 1995). In support of this finding, ibogaine was shown to inhibit [3H]pentazocine (a mu 1 receptor ligand) binding to high and low affinity sites in the mouse cerebellum (Popik and Skolnick, 1999).
Bowen et al. (1995) hypothesized that ibogaine’s interaction with sigma receptors, particularly sigma-2 receptors, may be responsible for its effects on the regulation of calcium release from intracellular stores. They found that ibogaine produced a concentration dependent increase of 13-45% in intracellular calcium levels. Additionally, ibogaine was shown to non-competitively antagonize calcium-induced contraction of the aorta and mesenteric artery in the rat (Hajo-Tello et al., 1985). The practical implications, however, of ibogaine’s effects on calcium regulation are not yet clear.
Of particular interest with regards to its putative role in interrupting opiate dependence are ibogaine’s effects on the opioid system. Ibogaine does not appear to be a conventional opioid agonist or antagonist (Alper et al., 1999). Bhargava et al. (1997) found that ibogaine bound to mu-, delta-, and kappa-opioid receptors low affinity, 11.0, > 100, and 3.77 uM, respectively. However, they did find that noribogaine had considerably higher affinities for these receptors; 2.66 uM for mu-, 24.72 uM for delta-, and 0.96 uM for kappa-opioid receptors. These findings have been supported by results showing even higher affinities for noribogaine binding, with affinities of up to 160 nM at the mu-opioid receptor (Pablo and Mash, 1998). It is therefore hypothesized that noribogaine may play a significant role in ibogaine’s effects on opiate dependency (Bhargava, Cao, Zhao, 1997; Mash et al., 2000).
While ibogaine does not show high affinity for opioid receptor binding, it has been shown to exert some less direct effects on the opioid system. Ibogaine inhibits the binding of [3h]U-69593 to kappa-opioid receptors, with a Ki value of 2-4 uM (Repke, Artis, Nelson, and Wong, 1994). However this inhibition is reversible, and therefore is not likely to contribute to ibogaine’s long-term effects (Popick and Skolnick, 1999). Additionally, it has been shown, through a two-site model, that ibogaine inhibits naloxone binding at mu-opioid receptors in the forebrain of mice with a Ki value of 130 nM (Codd, 1995). This suggests that ibogaine may act as mu-opioid agonist of a novel type (Bhargava, Cao, and Zhao, 1997).
Ibogaine, at concentrations less than 10 uM, has been shown to selectively inhibit nicotinic receptor mediated catecholamine release in the mesolimbic system (Mah et al., 1998). This inhibition was reversible at low doses (10 uM), but persisted for at least 19 hours with washout at higher doses. Like NDMA and dopaminergic systems, the mesolimbic catecholamine system is implicated in the addictive process. It is considered to be a part of the reward pathway that mediates positive reinforcement in drug addiction (Di Chiara and Imperato, 1988).
A recent study by Glick, Maisonneuve, Kitchen, and Fleck (2002) asserts that, although ibogaine and noribogaine exhibit low to moderate binding affinities at many sites, the most critical site of action for the modulation of drug self-administration may be the alpha3 beta4 nicotinic receptor. They found that both ibogaine and its synthetic analogue 18-methoxycoronaridine exhibit a more potent antagonism at this site than at alpha4 beta2 nicotinic receptors, or at NMDA or 5-HT3 receptors. Additionally, co-administration of either ibogaine or 18-methoxycoronaridine at sub-therapeutic doses with another alpha3beta4 antagonist (either mecamyline or dextromethorphan) produced a significant therapeutic response. Because alpha3beta4 receptors are mainly located in the medial habenula and the interpeduncular nucleus, and exist in the dopaminergic nuclei of the ventral tegmental area in only low densities, these researchers suggest that the dopaminergic mesolimbic pathway may not be directly involved in mediating ibogaine’s anti-addictive effects. It is hoped that further study will reveal these mechanisms in more detail.

Toxicology:#

The LD50 of ibogaine seems to vary depending on the animal, and the route of administration. When administered intraperitoneally in the guinea pig, the LD50 was shown to be 82 mg/kg (Dhahir, 1971). In the rat, the LD50 was shown to be 145 mg/kg when administered intraperitoneally, but 327 mg/kg when administered intragastrically (Popick and Skolnik, 1999). Thus, ibogaine does not seem to have a great liability for lethality.
There have been, however, three recorded human deaths related to the intake of ibogaine, reported by Lotsof et al. (2002). The first, in 1989, was a 40 year old woman, administered 8 mg/kg for the purpose of psychotherapy. This is the lowest dose known to precipitate an ibogaine related death. Four hours into the session, she suffered cardiac arrest, and an autopsy showed significant blockage of the main arteries to the heart. Thus, should ibogaine prove to be a viable therapy, contraindications for patients with cardiovascular problems would most likely be necessary.
The second fatality (the fatality that led to Dr. Jan Bastiaans dismissal) occurred in 1993, a 24 year old Dutch woman being treated for heroin dependency. She received 29 mg/kg in a split dose of 23 mg/kg followed by an additional dose of 6 mg/kg 3 hours later. The patient died 16 hours later of unknown causes; an autopsy did not reveal any specific pathology. However, a sheet of charred tinfoil was found in her personal affects, indicating the possibility that she had consumed heroin during the course of her ibogaine treatment. (A popular method of heroin administration among Dutch addicts is to heat the heroin on a sheet of tinfoil and inhale the vapors, sometimes known as "chasing the dragon"). It is conceivable then, that a heroin-ibogaine interaction may have been the cause of death, as ibogaine has been shown to increase the effects and toxicity of opiates (Popick and Glick, 1996).
The third recorded fatality occurred in 2000, in the U.K. The patient was a 38 year old male, and suffered from hepatitis C. He was administered a total of approximately 5 grams of a total iboga extract standardized to 15% ibogaine. This was a most peculiar case, as the fatality did not occur until after the effects of ibogaine had subsided, 38 hours after initial administration. Police toxicologist Dr. John Taylor told testified that the level of ibogaine in the dead man’s blood was "well below the normal toxic dose" (Kerr, 2001). According to writer Nick Sandberg (2002), the official inquest named the primary cause of death as asphyxiation due to vomit clogging airways, with liver failure as a secondary cause.
Of more importance to the general population than these isolated incidents, are recent reports of ibogaine neurotoxicity. There are, however, some discrepancies among these reports. Dhahir (1971) found no pathological changes in the liver, kidney, heart or brain of the rat following chronic intraperitoneal ibogaine administration (10 mg/kg for 30 days, and 40 mg/kg for 12 days.) Likewise, Sanchez-Ramos and Mash (1994) found no evidence of gross pathology in African green monkeys given ibogaine in oral doses of 5-25 mg/kg for four consecutive days.
In higher doses, though, ibogaine has been shown to cause definitive neurotoxic effects. At a single intraperitoneal dose of 100 mg/kg, ibogaine was shown to cause marked degeneration of Purkinje cells and activation of microglia in discrete radial bands of the rat cerebellar cortex (O’Hearn and Molliver, 1997). In support of these findings, Xu et al. (2000) found that degeneration of Purkinje cells was visible at intraperitoneal doses beginning at 75 mg/kg, showing increasing damage at 100 mg/kg. This study revealed that the neurotoxicity of ibogaine is dose-dependent, a finding also supported by other investigations (Molinari, Maisonneuve, and Glick, 1996).
O’Hearn and Molliver (1997) propose that ibogaine is not directly toxic to Purkinje cells, but rather causes Purkinje cell degeneration through sustained activation of the olivocerebellar projection. Scallet et al. (1996) reported that activation of serotonin receptors in the forebrain is the initial site of ibogaine neurotoxicity. Cortifugal axons could then stimulate the inferior olive and its excitotoxic climbiner-fiber pathway to the cerebellum (Xu et al., 2000). This lends support to O’Hearn and Molliver’s theory of trans-synaptic excitoxicity mediated by the olivocerebllar projection.
In light of these findings, a number of researchers have recently been studying the effects of a synthetic congener of ibogaine, 18-methoxycoronaradine, more commonly known as 18-MC. Similar to ibogaine, 18-MC decreases levels of extracellular dopamine in the nucleus accumbens (Szumlinksi, Maisonneuve, and Glick, 2000). Likewise, 18-MC has similar effects to ibogaine on the attenuation of morphine and cocaine self-administration (Glick et al., 1996) and alcohol intake (Rezvani et al., 1997). However, unlike ibogaine, 18-MC is non-tremorigenic, does not induce brachycardia, nor does it cause damage to Purkinje cells, or the brain in general (Glick et al., 1996; Molinari, Maisonneuve, and Glick, 1996; Glick, Maisonneuve, and Szumlinski, 2000). FDA protocol studies of human toxicity are currently underway at the University of Miami, under the direction of neurologist Deborah Mash. Should these studies deem ibogaine too hazardous for clinical use, 18-MC could represent a viable alternative.

Use as an Anti-Addictive:#

Currently pharmacological treatments for substance addiction disorders can be broadly defined as falling two categories; replacement therapy and aversion therapy (Barber and O’Brien, 1999). 1) Replacement therapy includes treatments such as methadone maintenance and non-tobacco nicotine drugs. These therapies replace the drug of abuse with a theoretically safer drug. 2) Aversion therapy includes drugs such as naltrexone and antabuse, which interact with the drug of abuse, causing unpleasant effects such as physical pain, nausea, and vomited. The hope is that while on these drugs, the patient will avoid use of the drug of abuse, out of desire to avoid the painful side effects.
Ibogaine has distinct advantages over both these models of treatments. Both replacement and aversion therapies are long-term treatments, requiring frequent visits to the clinician over an extended period of time. Contra wise, ibogaine therapy, as described previously, involves more intensive intervention over a shorter time frame (Lotsof, 1994). Unlike the drugs used in replacement therapies, ibogaine itself does not appear to be addictive. Repeated administration of ibogaine, at doses of 10 and 40 mg/kg, did not result in dependence in rats as measured by the Primary Physical Dependence test (Aceto, Bowman, and Harris, 1990). A large concern with methadone treatment is its potential for illicit use; it is not uncommon for patients to sell their supply of methadone on the black market, and revert to heroin use (Barber and O’Brien, 1999). As noted earlier, ibogaine is considered to have a low potential for abuse. Aversion therapies, due to their unpleasant nature, often show high incidences of patient-non-compliance, and subsequent relapse (Barber and O’Brien, 1999). This is generally not an issue with ibogaine therapy; patients treated with ibogaine tend to be more receptive to intervention (Lotsof, 1994).
There is a significant body of evidence supporting ibogaine’s efficacy in the treatment of substance addition disorders. Case studies and anecdotal reports of humans have sighted ibogaine’s ability to interrupt opiate and cocaine addictions for 6 months or longer (Goutarel, Gollnhofer, and Sillans, 1993; Judd, 1994; Sheppard, 1994; Luciano, 1998; Alper et al., 1999). Clinical trials with non-human subjects have substantiated these results. A single intraperitoneal dose of 40 mg/kg reduced self-administration of cocaine for up to 5 days in cocaine-preferring rats (Cappenijk and Dzoljic, 1994). In support of this finding, intraperitoneal doses of ibogaine at 20-40 mg/kg reduced cocaine-induced hypermotility (Sershen, Hashim, Harsing, and Lajtha, 1992; Broderick, Phelan, Eng, and Wechsler, 1994; Maisonneuve et al., 1997). Some studies, however, have shown increased locomotor activity induced by ibogaine in non-human cocaine and amphetamine dependent subjects (Maisonneuve, Keller, and Glick, 1992; Maisonneuve and Glick, 1992). Maisonneuve et al. (1997) propose that these differences are a result of the time interval between the injections of ibogaine and the given stimulant. Furthermore, ibogaine’s effects on stimulant-induced locomotion, as well as on reduction of cocaine self-administration, appear to be dose-dependent (Glick et al., 1994).
Ibogaine has also been shown to reduce morphine self-administration in clinical trials using non-human subjects. In rats, ibogaine dose dependently reduced intravenous morphine self-administration both immediately after injection and the next day, at doses of 2.5-40 mg/kg (Glick et al., 1991). Dworkin et al. (1995) found that intraperitoneal doses of ibogaine at 40 and 80 mg/kg reduced heroin self-administration in rats, but only on the day it was administered. The reason for this discrepancy is not yet clear. In human users of heroin (with a daily average use of 0.64 g), oral ibogaine doses of 6-29 mg/kg eliminated heroin seeking behavior for at least 72 hours in 76% of patients treated (Alper et al., 1999).
In addition to reducing opiate self-administration, ibogaine has been shown to reduce symptoms of opiate withdrawal. In rats, intraperitoneal doses of 40 and 80 mg/kg dose-dependently reduced naloxone-induced withdrawal symptoms; including rearing, head hiding, chewing, teeth chattering, writhing, and penile licking (Glick et al., 1992, Parker et al., 2002). In morphine dependent rhesus monkeys, subcutaneous injections of ibogaine (2 and 8 mg/kg) partially suppressed the total number of withdrawal signs (Aceto, Bowman, and Harris, 1990). Alper et al. (1999) found that, out of 33 human patients treated with ibogaine, 25 reported no subjective complaints of withdrawal symptoms at 24 and 48 hours post-treatment. Ibogaine has also been shown to interfere with both alcohol and nicotine dependency. When administered intraperitoneally or intragastrically, but not subcutaneously, ibogaine dose-dependently reduced alcohol intake in rats, without altering blood alcohol levels or food intake (Rezvani, Overstreet, and Lee, 1995). The difference in effects of route of administration may reflect a role of noribogaine in mediating ibogaine’s reduction of alcohol intake. Glick et al. (1998) found that intraperitoneal ibogaine pretreatment (19 hours beforehand) of 40 mg/kg significantly decreased oral nicotine self-administration in rats for at least 24 hours. Additionally, this ibogaine pre-treatment significantly attenuated nicotine-induced dopamine release in the nucleus accumbens (Benwell, Holtom, Moran, and Balfour, 1996).

Conclusion and Commentary:#

Ibogaine could represent a truly novel approach to addiction treatment. Very loosely, ibogaine seems to "reset" the neural pathways and behavioral phenomena that comprise substance addiction, directly addressing the etiology of the disorder. Though the specific pharmacological actions of ibogaine are not yet clear, the evidence thus far seems to suggest such a hypothesis, at least in its broadest sense, and clearly warrants further investigation. This notion is also reflected in the theme of rebirth seen in the religious use of the iboga root by the indigenous peoples of western Africa.
Should further study replicate the results found thus far, and find ibogaine safe for use in clinical practice, this would be a major step forward in addiction treatment. Current methods of therapy, particularly in the United States, are often ineffectual, typically it takes an addict 4 to 7 times through conventional rehabilitation before abstinence is achieved (Anderson, 1996; Finney, Moos, and Timko, 1999). Ibogaine therapy represents a possibility to significantly reduce the length of time needed to break the addictive cycle In addition to the amount of effort and time needed, current rehabilitation programs are often degrading to the individual, perpetuating the stigma that addicts are somehow "bad people" (Luciano, 1998). As one patient stated, "ibogaine is a much more humane and dignified approach to detox [sic]" (Judd, 1994). Ibogaine treatment involves a more intimate relationship between the patient and the clinician (or, more appropriately, the team of clinicians), involving a greater level of trust and compassion than is generally seen in typical addiction counseling (Lotsof, 1995). Judd (1994) observed that ibogaine has significant advantages over traditional treatment methods with respect to what she considers the three major obstacles in addiction treatment; fear of detoxification, lack of insight, and the inability of addicts to control their urges to use drugs. The potential benefits of this compound necessitate a greater amount of clinical research. Should further studies suggest that the risks of ibogaine are too great for general use, research on the compound’s effects may nevertheless elucidate unknown aspects of the psychophysiological basis of substance addiction.
While it is fortuitous that serious scientific inquiry into ibogaine’s potential has begun, it is unfortunate that it took such a length of time from the initial discovery of its therapeutic properties. It is unfortunate that politics continue to impede the progress of science. There is a great need for a return of objectivity to science, as far too often today biases and self-serving interests are the driving forces behind scientific exploration.

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Iboga, spiritual ally of African shamans since antiquity, yields ibogaine, a powerful psychotropic substance. It is used mainly in Gabon and Cameroon in a secret initiatory tradition called bwiti-ngenza, in which physical and psychological illnesses can be rooted out and cured. Intense psychological conditioning that includes the rites of confession, contacting and honoring one’s ancestors, and construction of an in-depth psychological inventory are all part of the initiate’s encounter with this sacred root.
Like many visionary and initiatory plants, iboga is a key that gives access to other modes of being and consciousness. Despite its suppression by the FDA since the 1960s, and more recently by the DEA, researchers have shown that ibogaine provides a powerful adjunct to psychology due to its miraculous ability to break addictions–most notably to heroin. To the followers of the Bwiti religion, ibogaine is the indispensable means by which humans can truly communicate with the deepest reaches of their soul and with the spirits of their ancestors. This book details the traditions and techniques of iboga’s use by African shamans and the essential role it occupies in that community in order to preserve this knowledge and show how ibogaine may have an important role to play in our modern world

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A revealing documentary about the use of Ibogaine for the treatment of addiction and it’s spiritual background.

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