Tabernanthe iboga

In Gabon, T. iboga is employed as an initiation rite of the cult of Bwiti (Schultes, 1977), a contemporary Neo-Christian religion practiced by the Fang peoples and other groups of equatorial Western Africa (Ott, 1995). Referred to as Eboka by the Fang (Fernandez, 1972), T. iboga, and its associated name are deeply rooted in the cultural identity of the Bwitist tradition, as the word Eboka is used as a metonymic for the entire cultural disposition of Bwiti (Fernandez, 1972). The process of Bwiti initiation involves the ingestion of large quantities of Eboka, which serves the purpose of “breaking open the head” to initiate communion with the ancestors of the spirit world (Furst, 1972). Thus, the use of T. Iboga is strictly entheogenic in its ritual methodology, as defined by Ott (1995). To the Bwitists among the Fang, Eboka allows participants to pass over into the afterlife, offering an opportunity to come to terms with the prospect of death (Fernandez, 1972).

The Eboka experience is accompanied by visions and perceptional abnormalities that include subjective sensations of physical elongation, floating, synesthesia, spectral hallucinations on the margins of perceived objects, and an alteration of the perception of time (Fernandez, 1972). The final stage of the Eboka experience is often accompanied by a physical collapse, which indicates that the soul of the participant has left the body to accompany the ancestors (Fernandez, 1982). In this process, the soul of the participant is thought by the Fang to be wending its way through a forest to a confirmational vision of a spiritual landscape that transcends beyond the land of the dead (a land beyond the land of the dead) (Fernandez, 1982). Thus, the visions associated with the Eboka experience have been described by the Fang as “wending through the forest” (Fernandez, 1982).

Pharmacology 

Data related to the human pharmacokinetics of ibogaine (10-methoxyibogamine) is limited and relies mostly on studies that have been conducted using drug-dependent subjects (Mačiulaitis et al., 2008). Ibogaine is known to be metabolized via cytochrome CYP2D6 into the biologically active metabolite noribogaine (Mačiulaitis et al., 2008). Additionally, contributing metabolic pathways include CYP2C9 and CYP3A4, both of which facilitate the metabolic conversion of ibogaine to noribogaine (Litjens & Brunt, 2016). Investigations carried out with human hepatic cells indicate that ibogaine undergoes metabolic demethylation, which is catalyzed by the cytochrome CYP2D6 pathway and to a lesser degree by CYP2C9 and CYP3A4 (Wasko et al., 2018).

According to Litjens and Brunt (2016), the few studies that have investigated the human pharmacokinetics of ibogaine indicate that enzymatic CYP2D6 polymorphism can influence systemic bioavailability of both ibogaine and its associated metabolite. Thus, the pharmacokinetics of ibogaine, as it relates to the metabolic conversion to noribogaine, is dependent on variants in enzymatic pathways associated with cytochrome P450.

The elimination half-life of ibogaine in rats equates to 1-3 h (Mačiulaitis et al., 2008), though half-life values in humans have been determined to approximate up to 7.47 h (Litjens & Brunt, 2016). It should be noted that a half-life approximation of 7.47 h is consistent with other reports, which highlight a half-life approximation of ibogaine in humans at 4-7 h (Alper et al., 2012). In human subjects, noribogaine has been shown to have a longer half-life than its nonmetabolized progenitor, as PO doses given at 3, 10, 30, and 60 mg have yielded a mean plasma elimination measurement of 28-49 h (Glue et al., 2014). I 

Pharmacodynamically, ibogaine and its metabolite have a robust receptor binding profile at a variety of locations, with affinities at glutamate NMDA (N-methyl-D-aspartate) receptor-coupled ion channels, and κ-opioid receptors (both κ1 and κ2) (Mačiulaitis et al., 2008). Additionally, ibogaine’s binding affinity extends to σ2 receptor sites and agonistically interacts with serotonergic subsites 5-HT2A, and 5-HT2C (Obembe, 2012). To add to the complicated pharmacology of ibogaine, muscarinic acetylcholine receptor sites (mAChRs subtypes M1 and M2), and nicotinic acetylcholine receptor sites (nAChRs) are susceptible to activation by ibogaine via agonistic receptor binding (Mačiulaitis et al., 2008).  

Ibogaine’s hallucinogenic effect is thought to be associated with 5-HT2A activation, as it exhibits an agonistic binding affinity at this serotonergic subsite (Alper et al., 2001). It should be noted that the serotonergic subsite 2A is associated with the effects of other psychedelic compounds, such as LSD-25 (Nichols, 2004). Additionally, ibogaine’s disposition as an agonist at μ-opioid receptors (MOR) is a likely mechanism for ibogaine’s purported efficacy at ameliorating opioid withdrawal symptoms (Alper et al., 2001).

Page Author: Ryan M. Teets (2020)