The recent review by Werneke et al (Reference Werneke, Turner and Priebe2006) contains substantive errors and omissions regarding the iboga alkaloid ibogaine and its synthetic congener 18-methoxycoronaridine (18-MC). The review cites a single paper published in 1994 consisting of seven case reports and overlooks two larger studies on the use of ibogaine for the treatment of opioid withdrawal in 32 (Reference Mash, Kovera and PabloMash et al, 2001) and 33 patients (Reference Alper, Lotsof and FrenkenAlper et al, 1999). These were retrieved on Medline using the search terms stated by Werneke et al. The authors incorrectly state that clinical trials of ibogaine were abandoned because of cerebellar toxicity: this has been limited to the rat at higher doses than those that diminish drug self-administration and opioid withdrawal, and has not been evident in primate or mouse models (Reference AlperAlper, 2001). In 1993 the US Food and Drug Administration authorised Phase I clinical studies in which humans were given ibogaine. These studies were halted only because of a contractual dispute among the study sponsors and not because of safety issues.
Table 6 of Werneke et al's review states that ‘18-MC binds to the NMDA [N-methyl-d-aspartate] receptor’ and that this is because of its putative anti-addictive mechanism of action. Mash et al (Reference Mash, Staley and Pablo1995) is cited but this paper makes no mention of 18-MC, which lacks significant affinity for the NMDA receptor but is a potent antagonist at the α3β4 nicotinic receptor (Reference Maisonneuve and GlickMaisonneuve & Glick, 2003). The statement that ibogaine blocks ‘the dopamine response in general’ is inaccurate, as ibogaine does not have the properties of a dopamine receptor antagonist and does not decrease dopamine release in all brain regions (Reference Maisonneuve, Keller and GlickMaisonneuve et al, 1991).
Werneke et al stated that ‘All recovered papers were reviewed for further relevant references’, which would have led, among other sources, to an entire volume devoted to ibogaine of the Medline-indexed serial The Alkaloids (Reference Alper and CordellAlper & Cordell, 2001) and the additional references cited here. Systematic implementation of the stated search strategy and careful and accurate reading of the papers that were retrieved would have provided a far more credible evidence basis regarding the use of iboga alkaloids for the pharmacotherapy of addiction.
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