Iboga Market Online
Ibogaine is a naturally occurring psychoactive substance found in plants in the Apocynaceae family such as Tabernanthe iboga, Voacanga africana and Tabernaemontana undulata.It is a psychedelic with dissociative properties.
Ibogaine is not currently approved for any medical uses in the United States. Preliminary research indicates that it may help with drug addiction; however, there is a lack of data in humans. Its use has been associated with serious side effects and death. It is used as an alternative medicine treatment for drug addiction in some countries. Its prohibition in other countries has slowed scientific research. Ibogaine is also used to facilitate psychological introspection and spiritual exploration. Derivatives of ibogaine that lack the substance's psychedelic properties are under development.
bogaine-containing preparations are used for medicinal and ritual purposes within African spiritual traditions of the Bwiti, who claim to have learned it from the Pygmy peoples. 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 as Lambarène and used as a stimulant. Additionally, the U.S. Central Intelligence Agency (CIA) studied the effects of ibogaine in the 1950s.
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. The total synthesis of ibogaine was described in 1956. Structural elucidation by X-ray crystallography was completed in 1960.
Psychoactive effects
Ibogaine is a psychedelic. The experience of Ibogaine is broken down in two phases, the visionary phase and the introspection phase. The visionary phase has been described as oneirogenic, referring to the dreamlike nature of its psychedelic effects, and lasts for 4 to 6 hours. The second phase, the introspection phase, is responsible for the psychotherapeutic effects. It can allow people to conquer their fears and negative emotions. Ibogaine catalyzes an altered state of consciousness reminiscent of dreaming while fully conscious and aware so that memories, life experiences, and issues of trauma can be processed.
Medical
Ibogaine is not currently approved for any medical uses. Clinical studies of ibogaine to treat drug addiction began in the early 1990s, but concerns about cardiotoxicity led to termination of those studies. There is currently insufficient data to determine whether it is useful in treating addiction. Nonetheless, some alternative medicine clinics administer ibogaine for this purpose, in what has been called a "vast, uncontrolled experiment.
Religious
In Bwiti religious ceremonies, the root bark is pulverized and swallowed in large amounts to produce intense psychoactive effects.
Immediate
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 per rectum to avoid nausea and vomiting.
Cardiovascular
Ibogaine causes long QT syndrome at therapeutic doses, apparently by blocking hERG potassium channels in the heart.
Neurotoxicity
Work in the laboratory of Mark Molliver at Johns Hopkins indicated degeneration of cerebellar Purkinje cells observed in rats given substantially larger dosages of ibogaine than those used to study drug self-administration and withdrawal. However, subsequent research found no evidence of neurotoxicity in the primate or mouse at dosages that produced cerebellar degeneration in the rat, and it has been suggested that cerebellar degeneration might be a phenomenon limited to a single species. The FDA was aware of Molliver’s work at the time it approved a Phase 1 study in which humans received ibogaine in 1993. Neuropathological examination revealed no evidence of degenerative changes in a woman who had received four separate doses of ibogaine ranging between 10 and 30 mg⁄ kg over a 15-month interval prior to her death due to a mesenteric artery thrombosis with small bowel infarction 25 days after her last ingestion of ibogaine. A published series of fatalities temporally associated with the ingestion of ibogaine found no evidence suggesting a characteristic syndrome of neurotoxicity.
Pharmacodynamics
Ibogaine affects many different neurotransmitter systems simultaneously.
Noribogaine is most potent as a serotonin reuptake inhibitor. It acts as a moderate κ-opioid receptor agonist and weak µ-opioid receptor agonist or weak partial agonist. It is possible that the action of ibogaine 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. Noribogaine is more potent than ibogaine in rat drug discrimination assays when tested for the subjective effects of ibogaine.
Pharmacokinetics
Ibogaine is metabolized in the human body by cytochrome P450 2D6 into noribogaine (12-hydroxyibogamine). Both ibogaine and noribogaine have a plasma half-life of around two hours in the rat, although the half-life of noribogaine is slightly longer than that of the parent compound. It is proposed that ibogaine is deposited in fat and metabolized into noribogaine as it is released. After ibogaine ingestion in humans, noribogaine shows higher plasma levels than ibogaine and is detected for a longer period of time than ibogaine.
Chemistry
Ibogaine is a tryptamine. It has two separate chiral centers, meaning that there are four different stereoisomers of ibogaine. These four isomers are difficult to resolve.
Synthesis
One recent total synthesis of ibogaine and related drugs starts with 2-iodo-4-methoxyaniline which is reacted with triethyl((4-(triethylsilyl)but-3-yn-1-yl)oxy)silane using palladium acetate in DMF to form 2-(triethylsilyl)-3-(2-((triethylsilyl)oxy)ethyl)-1H-indole. This is converted using N-iodosuccinamide and then fluoride to form 2-(2-iodo-1H-indol-3-yl) ethanol. This is treated with iodine, triphenyl phosphine and imidazole to form 2-iodo-3-(2-iodoethyl)-1H-indole. Then using 7-ethyl-2-azabicyclo oct-5-ene and cesium carbonate in acetonitrile the ibogaine precursor 7-ethyl-2-(2-(2-iodo-1H-indol-3-yl)ethyl)-2-azabicyclo[2.2.2]oct-5-ene is obtained. Using palladium acetate in DMF the ibogaine is obtained. If the exo ethyl group on the 2-azabicyclo[2.2.2]octane system in ibogaine is replaced with an endo ethyl then epiibogaine is formed.
Crystalline ibogaine hydrochloride is typically produced by semi-synthesis from voacangine in commercial laboratories.
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). 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.
Atural occurrence
Ibogaine occurs naturally in iboga root bark. 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 half the potency by weight as standardized ibogaine hydrochloride.
History
The use of iboga in African spiritual ceremonies was first reported 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 and independently by Haller and Heckel in the same year using T. iboga samples from Gabon. Complete synthesis of ibogaine was accomplished by G. Büchi in 1966. Since then, several other synthesis methods have been developed.
From the 1930s to 1960s, ibogaine was sold in France in the form of Lambarène, an extract of the Tabernanthe manii plant, and promoted as a mental and physical stimulant. The drug enjoyed some popularity among post World War II athletes. Lambarène was withdrawn from the market in 1966 when the sale of ibogaine-containing products became illegal in France.
In the late 1960s the World Health Assembly classified ibogaine as a “substance likely to cause dependency or endanger human health,” the U.S. Food and Drug Administration (FDA) assigned it Schedule I classification, and the International Olympic Committee banned it as a potential doping agent.
Anecdotal reports concerning ibogaine's effects appeared in the early 1960s. Its anti-addictive properties were discovered accidentally by Howard Lotsof in 1962, at the age of 19, when he and five friends-all heroin addicts-noted subjective reduction of their craving and withdrawal symptoms while taking it. Further anecdotal observation convinced Lotsof of its potential usefulness in treating substance addictions. He contracted with a Belgian company to produce ibogaine in tablet form for clinical trials in the Netherlands, and was awarded a United States patent for the product in 1985. The first objective, placebo-controlled evidence of Ibogaine's ability to attenuate opioid withdrawal in rats was published by Dzoljic et al. in 1988. Diminution of morphine self-administration was reported in preclinical studies by Glick et al. in 1991. Cappendijk et al. demonstrated reduction in cocaine self-administration in rats in 1993, and Rezvani reported reduced alcohol dependence in three strains of "alcohol preferring" rats in 1995.
As the use of ibogaine spread, its administration varied widely; some groups administered it systematically using well developed methods and medical personnel, while others employed haphazard and possibly dangerous methodology. Lotsof and his colleagues, committed to the traditional administration of ibogaine, developed treatment regimens themselves. In 1992, Eric Taub brought ibogaine to an offshore location close to the United States, where he began providing treatments and popularizing its use. In Costa Rica Lex Kogan, another leading proponent, joined Taub in systematizing its administration. The two men established medically monitored treatment clinics in several countries.
In 1981 an unnamed European manufacturer produced 44 kg of iboga extract. The entire stock was purchased by Carl Waltenburg, who distributed it under the name "Indra extract" and used it in 1982 to treat heroin addicts in Christiania, Denmark, a squatter village where heroin addiction was widespread. Indra extract was available for sale over the Internet until 2006, when the Indra web presence disappeared. Various products are currently sold in a number of countries as "Indra extract", but it is unclear if any of them are derived from Waltenburg's original stock. Ibogaine and related indole compounds are susceptible to oxidation over time.
The National Institute on Drug Abuse (NIDA) began funding clinical studies of ibogaine in the United States in the early 1990s, but terminated the project in 1995. Data demonstrating ibogaine's efficacy in attenuating opioid withdrawal in drug-dependent human subjects was published by Alper et al. in 1999. A cohort of 33 patients were treated with 6 to 29 mg/kg of ibogaine; 25 displayed resolution of the signs of opioid withdrawal from 24 hours to 72 hours post-treatment, but one 24-year-old female, who received the highest dosage, died. Mash et al., (2000) using lower oral doses (10-12 mg/kg) in 27 patients, demonstrated significantly lower objective opiate withdrawal scores in heroin addicts 36 hours after treatment, with self-reports of decreased cocaine and opiate craving and alleviated depression symptoms. Many of these effects appeared sustainable over a one-month post-discharge follow-up.