Molecular Formula: C20H26N2O
Molecular Weight: 310.433g/mol
Ibogaine is a psychoactive indole alkaloid of natural occurrence, derived from the root of the rainforest shrub tabernanthe iboga. Its historical use arises from shamanistic rituals in the African Bwiti religion, to bring on a trance-like state. More recently, ibogaine has been utilized in a medical setting from as early as the 1950’s as an adjunctive-use psychotherapy. In a timeline developed by Dr. Kenneth Apler, it is possible to trace the history of both the iboga shrub and the use of ibogaine as an isolated compound. In ~1864, T.iboga was introduced to the western world, as samples of the shrub were transported to France from Gabon in Western Africa. Ibogaine itself was first crystallized from the T.iboga root bark in 1901, with research into its potential pharmacological properties taking place soon after. It was finally marketed in France as “Lambarene” (named so after the town in which explorers first discovered it) in the 1930’s as a neuromuscular stimulant, taken orally as ~8mg tablets. In the 1950’s and 1960’s, ibogaine began to be used as an adjunct to psychotherapy. In 1969, Naranjo – a Chilean psychiatrist – obtained a French patent for the use of ibogaine in a psychotherapeutic setting, at a dosage range of ~4-5mg/kg. Naranjo determined that ibogaine allowed for enhanced retrieval of personal subjective memories, alongside archetypal imagery that founds the basis of the human psyche. These visions were used to facilitate mitigation of emotional conflicts, forming the basis of its therapeutic effects. As well as this, its anti-addictive effects were also of note. In 1989, ibogaine was utilized as an unofficial treatment in the Netherlands for drug dependence, in a non-medical setting. Since then, there have been many further studies detailing the therapeutic effects of ibogaine in the treatment of opioid addiction, yielding positive results.
Most studies detailing the pharmacodynamics and pharmacokinetics of ibogaine are preclinical, meaning that its effects have been observed in animal models and extrapolated to determine its potential mechanism of action in humans. The exact pharmacological profile of ibogaine is still relatively unclear, however it has been shown to rapidly demethylate to the metabolite ‘noribogaine’ via first pass metabolism in the liver in several in vivo studies. Several other in vivo studies show ibogaine to exert its effects through mediation of NMDA (N-methyl-D-aspartate) receptors, κ1, κ2 & σ2 opioid receptors, 5-HT2 & 5-HT3 serotonin receptors, M1 & M2 muscarinic receptors and nicotinic acetylcholine receptors. The neuropharmacology is therefore incredibly complex, with various agonistic and antagonistic affinities for each receptor type. The highest affinity interactions observed were agonistically at the σ2 receptor and antagonistically at the a3ß4 nicotinic acetylcholine receptor types. Noribogaine has shown increased affinity for both µ-opioid and κ1 receptor binding, although lower binding affinity for κ2receptors. Some clinical effects of ibogaine are theorized to involve the ventral tegmental area of the brain which is largely associated with the ‘reward’ circuit. This neurological region typically becomes altered following drug dependency. This is likely to be involved in the therapeutic efficacy of ibogaine, when observed attenuating alcohol & opiate dependency in previous studies. Further clinical trials are currently being conducted, investigating the use of ibogaine as a treatment for alcoholism and methadone dependency. Preclinical trials are also attempting to develop a safety/toxilogy profile, a link to these can be found below: