Ibogaine

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Ibogaine
Chemical name (IUPAC)	10-Methoxyibogamine
Chemical name (CAS)	12-Methoxyibogamine
CAS number	83-74-9
Chemical formula	C20H26N2O
Molecular mass	310.44 g/mol

Ibogaine is an indole alkaloid, a long-acting hallucinogen which has gained attention due to its application in the treatment of opioid addiction and similar addiction syndromes. It occurs naturally in a number of dogbane plants, among them above all in Tabernanthe iboga.

Contents 1 Formulations 2 History 3 Effects 4 Pharmacology 4.1 Mechanism and Pharmacodynamics 4.2 Metabolites 4.3 Derivatives 5 Usage 5.1 Addiction Interruption 5.2 Chronic pain management 5.3 Degenerative neural diseases 6 Side effects 7 Research 8 Legal status 9 Arbitrary references in popular media 10 See also 11 External links 12 References

[edit] Formulations

In traditional use, ibogaine is consumed by chewing the root bark of Tabernanthe iboga. Commercially available formulations include crystalline ibogaine hydrochloride salt and the Indra plant extract. The single-alkaloid ibogaine hydrochloride salt is favored for research because its greater standardization allows for more consistent results. The Indra extract contains all 13 alkaloids of the Tabernanthe iboga rootbark and thus more closely resembles the native formulations used in African folk tradition.

[edit] History

Ibogaine was first isolated from Tabernanthe iboga in 1901 by Dybowski and Landrin^[1] and independently by Haller and Heckel in the same year. Samples of the plant were obtained from Gabon, Africa in the mid 1800s where it has been used in initiation rites of the Bwiti religion. The challenging total synthesis was accomplished by G. Büchi in 1966.^[2] Since then, several further totally synthetic routes have been developed.^[3] The use of ibogaine in treating substance use disorders in human subjects was first proposed by Howard Lotsof in a US Patent awarded in 1985.^[4] Ibogaine's ability to attenuate opioid withdrawal confirmed in the rat was first published by Dzoljic et al. (1988).^[5] Ibogaine's use in diminishing morphine self-administration in preclinical studies was shown by Glick et al. (1991)^[6] and ibogaine's capacity to reduce cocaine self-administration in the rat was shown by Cappendijk et al. (1993). ^[7] Animal model support for ibogaine claims to treat alcohol dependence were established by Rezvani (1995).^[8]

Data demonstrating ibogaine's efficacy in attenuating opioid withdrawal in drug dependent human subjects was published by Alper et al. (1999) ^[9] and Mash et al. (2000). ^[10] However, there have been as yet no peer-reviewed studies demonstrating any statistically significant long term improvement following ibogaine administration to humans with drug problems.

[edit] Effects

At low doses, ibogaine has a mild stimulant effect. At higher doses, temporary effects include hallucination and ataxia. The most studied long-term therapeutic effect is that ibogaine seems to catalyze partial or complete interruption of addiction to opioids. An integral effect is the alleviation of symptoms of opioid withdrawal. Research also suggests that ibogaine may be useful in treating dependence to other substances such as alcohol, methamphetamine, and nicotine, and may affect compulsive behavioral patterns not involving substance abuse or chemical dependence. Ibogaine has been used as an adjunct to psychotherapy by Claudio Naranjo some of whose work was published in The Healing Journey.^[11]

[edit] Pharmacology

The pharmacology of ibogaine is quite complex, affecting many different neurotransmitter systems simultaneously.^{[12] [13]} Because of its fairly low potency at any of its target sites, ibogaine is used in doses anywhere from 5 milligrams per kilogram of body weight for minor effect to 30 mg/kg in the cases of strong polysubstance addiction. It is unknown whether doses greater than 30mg/kg in humans produce effects that are therapeutically beneficial, medically risky, or simply prolonged in duration.

[edit] Mechanism and Pharmacodynamics

Among recent proposals for ibogaine mechanisms of action is activation of the glial cell line-derived neurotrophic factor (GDNF) pathway in the ventral tegmental area (VTA) of the brain. The work has principally been accomplished in preclinical ethanol research where 40 mg/kg of ibogaine caused increases of RNA expression of GDNF in keeping with reduction of ethanol intake in the rat, absent neurotoxicity or cell death.^[14]

Ibogaine is a noncompetitive antagonist at α3β4 nicotinic receptors, binding with moderate affinity. Several other α3β4 antagonists are known, and some of these such as bupropion (Zyban) and mecamylamine have been used for treating nicotine addiction. This α3β4-antagonism correlates quite well with the observed effect of interrupting addiction. Since α3β4 channels and NMDA channels are related to each other and their binding sites within the lumen bind a range of same ligands (e.g. DXM), some "older" sources suggested that ibogaine's anti-addictive properties may be (partly) due to it being an NMDA receptor antagonist.^[15] However, ligands, like 18-MC, selective for α3β4- vs. NMDA-channels showed no drop-off in activity.

It is suspected that ibogaine's actions on the opioid and glutamatergic systems are also involved in its anti-addictive effects. Persons treated with ibogaine report a cessation of opioid withdrawal signs generally within an hour of administration.

Ibogaine is a weak 5HT_2A receptor ligand^[16] and a sigma₂ receptor agonist.^[17]

[edit] Metabolites

Ibogaine is rapidly metabolized in the human body by cytochrome P450 2D6. Effects after ibogaine treatment lasting longer than 48 hours are therefore not likely to be caused by the initial administration of ibogaine itself. The main metabolite in humans is noribogaine (12-hydroxyibogamine) which contains a phenolic hydroxy instead of a methoxy group. Both ibogaine and noribogaine have a plasma half-life of approximately thirty minutes. It is proposed that ibogaine is deposited in fat and metabolized into noribogaine as it is released.^[18] Noribogaine throws higher plasma levels than ibogaine and may therefore be detected for longer periods of time than ibogaine. The metabolite is somewhat more active at several receptors and transporters. Noribogaine is most potent as a serotonin reuptake inhibitor and acts as moderate κ- and weak µ-opioid receptor full agonist and has therefore also an aspect of an opiate replacement similar to compounds like methadone. Noribogaine is also more potent than ibogaine in rat drug discrimination assays when tested for the subjective effects of ibogaine.^{[citation needed]}

[edit] Derivatives

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).^[19]

[edit] Usage

[edit] Addiction Interruption

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 drug. Although the full nature of Ibogaine is still emerging, it appears that the most effective treatment paradigm involves visionary doses of ibogaine of 10 to 20 mg/kg, producing an interruption of opiate withdrawal and craving. 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 and therapy during the interruption period following treatment is of significant value. Some patients require a second or third treatment session with ibogaine over the course of the next 12 to 18 months as it will provide a greater efficacy in extinguishing the opiate addiction or other drug dependence syndrome. A minority of patients 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".^[20]

[edit] Chronic pain management

In 1957, Jurg Schneider, a pharmacologist at CIBA, found that ibogaine potentiates morphine analgesia ^[21]. 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^[22]. Kroupa, et al., published their research in the Multidisciplinary Association for Psychedelic Studies Journal demonstrating that administration of low "maintenance" doses of ibogaine HCl with opioids decreases tolerance.

[edit] Degenerative neural diseases

Substances that promote the expression of GDNF, such as ibogaine, are known to provide benefit in treating neurodegenerative diseases such as Parkinson's disease. Other ligands in the GDNF family may hold promise for treating related neurodegenerative diseases such as ALS and Alzheimer's disease. ^[23]

[edit] Side effects

At therapeutic doses, ibogaine has an active window of 24 to 48 hours, is often physically and mentally exhausting and produces ataxia for as long as twelve hours, in some cases even longer. Nausea that may lead to vomiting is not uncommon throughout the experience. Such unpleasant symptoms tend to reduce the attractiveness of ibogaine as a recreational drug at therapeutic doses, however, at lower doses ibogaine is known to have stimulant effects. Some users administer ibogaine by enema and report no gastrointernal side effects.

The drug is experimental and controversial, and isolated cases of fatal cardiac arrhythmias during treatment are proposed to have occurred. In such cases there has yet to be a firmly established causal link between mortality and ibogaine administration, because it is unclear whether or not other drugs (such as heroin) were co-administered against indication by the patient himself and because the autopsies have not been conclusive. Arrhythmias have been observed in EKGs to appear following ibogaine ingestion.

[edit] Research

An ibogaine research project was funded by the US National Institute on Drug Abuse in the early 1990's. 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, 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 addiction treatment for opiate dependence at Iboga Therapy House in Vancouver.

[edit] Legal status

In 1966 ibogaine was classified as a Schedule I Controlled Substance in the United States, along with other psychedelics such as LSD and mescaline. Since that time, several other countries, including Sweden, Denmark, Belgium, and Switzerland, have also banned the sale and possession of ibogaine.

In early 2006, the creation of a non-profit foundation addressing the issue of providing ibogaine for the purpose addiction interruption within establishment drug treatment care was formed in Sweden. ^[24]

[edit] Arbitrary references in popular media

Ibogaine was the topic of one show in the American public radio series This American Life, Week of December 1, 2006. The show called "Sink or Swim" documented the story of a former addict who opened an underground addiction treatment service using Ibogaine.

However, the treatment of ibogaine in popular media has also been the subject of utter misrepresentation of its properties:

• The X-Files, Season 8, Episode 7, "Via Negativa". Originally aired: 12/17/2000. Summary: a serial killer/cult leader uses Ibogaine to astral-project and kill his victims.
• CSI, Season 2, Episode 4, "Getting Off". Originally aired: 1/1/2004. Summary: The victim dealt ibogaine and the prime suspect was intoxicated on ibogaine when he assaulted and robbed the victim.

There is also an allegation from infamous gonzo journalist Hunter S Thompson^[25] that United States Democratic Party presidential hopeful Edmund Muskie used ibogaine during his 1972 campaign. This is also voiced in 1972 articles in Rolling Stone magazine. Thompson also claims to have used ibogaine himself.

[edit] See also

• Psychedelic drug
• Dissociative drug
• Psychoactive drug
• Oneirophrenia
• Deborah Mash

[edit] External links

• Ibogaine Dossier
• Ibogaine UK
• MindVox Ibogaine Site and Forums
• The Ibogaine Research Project
• Audio segment on This American Life, Week of December 1, 2006, "Sink or Swim" documents the story of a former addict who opens an underground addiction treatment service using Ibogaine.
• The Staten Island Project: The Ibogaine Story
• Ibogaine Patients' Bill of Rights
• Ibogaine & Addiction
• Ibogaine on CBS Channel 5; February, 2005
• Ten years of therapy in one night
• Ibogaine: A Novel Anti-Addictive Compound - A Comprehensive Literature Review

• Links to external chemical sources.

[edit] References