Ibogaine : A Novel Anti-Addictive Compound. A Comprehensive Literature Review

Jonathan Freedlander

Journal of Drug Education and Awareness, 2003

https://www.researchgate.net/publication/287670047_Ibogaine_A_novel_anti-addictive_compound

 

Introduction and History

Ibogaine is a naturally occurring indole alkaloid, found in a variety of African shrubs of the Tabernathe 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 synthesised 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, 1977).

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 characterised 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, 1994). 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 labelled 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 an 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). Goutarel et al define an oneirogen as a compound “which disconnects the ‘I’ from Exoreality to reconnect it within Endoreality.” Other oneirogenic compounds, as cited by Goutarel et al, include ketamine (an anaesthetic) and salvinorin (the primary psychoactive compound in Salvia divinorum, an herb used in healing and religious ceremonies of indigenous Mexican peoples).

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 characterise its effects as a “rough trip;” one that is not suitable for recreational use (Shulgin and Shulgin, 1977).

Accordingly, when ibogaine was introduced to the United States’ black market in the 1960’s, 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 of the Gabon, Metsogo, and Kameroon tribes ofwestern Africa, and initiation into this society, involving the use of ibogaine containingsubstances, is central to their cultures (Fernandez, 1982; Goutarel, Gollnhofer, and Sillans,1993).

Literally, Bouti means “those of the chapel”. The primary purpose of these initiationrites, as described by the initiates, is to travel through the land of the tribal ancestors, andemerge in the “pristine uterine condition” (Fernandez, 1982). This ritual is referred to by itsparticipants 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 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 1960’s, 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, tantalised 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, unauthorised 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 categorised 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 misdemeanours, and sentenced to 14 months in prison. Upon release in 1968, Lotsof was “shattered”. He travelled 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.

Upon returning to New York, Lotsof entered a methadone maintenance program, which he considered a “prison without walls”. Fortunately, he was able to remember what it was like to be drug-free, and endeavoured to slowly wean himself off the “orange handcuffs”. 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 organisation, 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 developed a method of injecting it into the ventricles of rat brains. 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).

(…)

Ibogaine_A_Novel_Anti-Addictive_Compound