Ibogaine: Psychadelic’s journey from ceremonial to anti-addictive therapeutic

By Robert Taylor from the 2018 Archive

Ibogaine is a naturally occurring tryptamine derivative found in high concentrations in the root of Tabernanthe iboga – a plant found primarily in the northern forests of Gabon. Its favour in popular science has grown recently due to miraculous accounts of administration curing opioid and cocaine addictions. Furthermore, popular internet personalities such as Tim Ferriss profess to self-administer the substance to gain mental clarity and become more in-touch with his own psyche.

“Tabernanthe iboga Baill. (APOCYNACEAE)” by Scamperdale is licensed under CC BY-NC 2.0

Its indole structure, similar to that of N, N- Dimethyltryptamine, is an interesting case of functional conservation within biology, with indole structures being used in a plethora of signalling structures both in prokaryotic and eukaryotic systems.

“…ibogaine has a rich history of use in religious ceremonies of tribes in the Northern forests of Gabon and West Africa.”

Ibogaine is shown to be metabolised in the liver by CP4502D6 soon after ingestion in humans into 12-hydroxyibogamine, more commonly known as noribogaine. This metabolite is shown to be persistent in the plasma for much longer than ibogaine itself, and has been shown in ligand binding assays to have its own pharmacodynamic properties at neurochemical receptors. Notably, noribogaine has been shown to be more potent at the Δ-opioid and SERT serotonin transporter than ibogaine itself. This could be a reason for the perceived two step effect administration that ibogaine has, which is described regularly in subjective accounts of the effects of ibogaine.

As with most naturally occurring psychedelics, ibogaine has a rich history of use in religious ceremonies of tribes in the northern forests of Gabon in West Africa. The root of this plant in particular is very high in ibogaine, as well as other alkaloid substances, and has historically been ingested in high quantities to elucidate rather intense visual hallucinations in particular. The first western accounts of these Iboga rituals involved transcendent stories of the Bwiti tribe in equatorial Africa utilising the powerful effects of this root as a rite of passage ritual for adolescents on their path to adulthood. This tribe was described as having synergised with the tales told to them by Catholic missionaries, with the Iboga plant replacing the Tree of Knowledge of Good and Evil in their religious doctrine, and taking many other aspects of western monotheism with them.

The French colonisers were so fascinated by the effects of this plant, that they brought it back to France and were able to extract the ibogaine from the root directly, selling it as a narcoleptic and antidepressant. Today, ibogaine is considered a Schedule 1 drug in the United States of America, meaning it has no known clinical properties and has potential to cause the self and society great harm. In the UK, it is not specifically mentioned by any legislation, however, it is covered under the Psychoactive Substances Act of 2015, which bans the possession and distribution of any psychoactive substances unless you are prescribed them.

In the early 1960’s, subjective reports of the anti-addictive properties of ibogaine began surfacing, most notably by a young heroin addict Howard Lotsof. Lotsof was born in the Bronx in 1943 and was severely addicted to heroin by the time he was 19, and was searching for an ever-greater high.

By Lotsof’s own account, his, and six of his friends desire to take heroin was extinguished almost immediately after self administration of an exotic white powder that was the extract of the T. iboga root. This is not an isolated case. Subjective reports described the curing of addictions ranging from cocaine to sugar, and with ibogaine being chemically synthesised soon after this event in 1966, Lotsof became one of the most vocal advocates of ibogaine use for the treatment of addiction, and held a patent for the treatment of cocaine and heroin addiction using ibogaine.

“ibogaine” by fekaylius is licensed under CC BY 2.0

Currently, there are 21.5 million people in the United States with a substance use disorder, which is costing the economy over $200 billion in health-care costs and lost productivity as of 2014, according to the National survey of Drug Use and Health. Traditional methods of addiction treatment, especially in terms of opioid treatment, utilises pharmacologically active substances such as methadone to reduce physical dependence, but these drugs do not target the behavioural and social mechanisms behind the reason why users turn to opioids in the first place. Studies on rats showed decreased self administration of cocaine after a single high dose injection of ibogaine, with an even lower rate of relapse in rats who were treated for three consecutive weeks. In human studies, 12 of 14 patients in a New Zealand trial had a significant and sustained reduction or cessation of heroin self administration 12 months after treatment.

A mirror trial in Mexico yielded similar highly effective results. This purely biochemical effect is thought to occur due to the competitive binding of ibogaine and noribogaine to the Kappa opioid receptor in the central nervous system. It must be mentioned that the mechanism for the action is relatively unknown due to the restrictions on research on Schedule 1 substances, and the lack of radioligand binding experiments showing receptor agonism. Despite the success of human trials, it must also be noted that currently the mortality rate for ibogaine administration is between 1 in 300 to 1 in 4,007 due to a variety of factors. Dangerously low heart rate, liver failure and dangerous interactions with other administered drugs are just some of the deadly potential effects of ibogaine administration. It was found that while ibogaine did not have a direct interaction with the GABA system, effects of benzodiazepines, barbiturates and ethanol, all known to act on this inhibitory neurotransmitter system could cause side effects that could lead to death. The New Zealand human study run by the Multidisciplinary Association for Psychedelics Studies (MAPS) in fact contained a subject who had died during ibogaine treatment. MAPS has completed two human trials, utilising ibogaine to great effect in the curing of addiction both biochemically and behaviourally.

Underground providers in Mexico and other Latin American countries continue to offer week-long opioid curing rehabilitation clinics, utilising ibogaine in a number of therapeutic scenarios which are varied in their success and efficacy, but ultimately are prohibitively expensive and potentially dangerous due to the lack of government oversight. Methods include everything from coupling ibogaine administration with cognitive behavioural therapy, to administering ibogaine to blindfolded patients over the course of a week.

The current immediate objective is therefore to selectively purify this rather complex molecule to determine which aspects of its pharmacology cause the clinical effects, and to control any potential confounds of metabolite effects.

“Iboga” by The Drug Users Bible is licensed under CC BY 2.0

Furthermore, it is vital to understand if there are any alkaloids in the unpurified traditional administration that could contribute to the efficacy of ibogaine via the entourage effect, something that has not been achieved thus far as the efficacy of the purified product over the crude root has not been determined, and both are used in human trials. Acceptance of ibogaine as a drug with genuine clinical potential will open the doors to life-saving treatment that would allow healthcare providers to reduce the risks to some of the most vulnerable people in the country, and greatly increase understanding of the pharmacology of addiction. Ibogaine has the potential to cure more than just the pharmacology behind addiction- an outdated ideology- but rather target the psychosocial dependency that malign people afflicted by addiction. This presents a clear advantage over current drugs such as methadone, which has a very high relapse rate and does not target the underlying social schism affecting communities afflicted with opioid abuse and addiction.

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