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The British Journal of Psychiatry (2006) 188: 587. doi: 10.1192/bjp.188.6.587-a
© 2006 The Royal College of Psychiatrists
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Correspondence

Psychotropic complementary medicines

K. R. Alper

Departments of Psychiatry and Neurology, New York University School of Medicine, New York, NY 10016, USA.

S. D. Glick

Center for Neuropharmacology and Neuroscience, Albany Medical College, Albany, New York, USA

Correspondence: E-mail: kral{at}nyu.edu

EDITED BY KIRIAKOS XENITIDIS and COLIN CAMPBELL

The recent review by Werneke et al (2006) 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 (Mash et al, 2001) and 33 patients (Alper 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 (Alper, 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 (1995) 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 {alpha}3ß4 nicotinic receptor (Maisonneuve & 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 (Maisonneuve 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 (Alper & 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.

REFERENCES

Alper, K. R. (2001) Ibogaine: a review. Alkaloids – Chemistry and Biology, 56, 1 –38.

Alper, K. R. & Cordell, G. (eds) (2001) Ibogaine: Proceedings from the First International Conference. San Diego, CA: Academic Press.

Alper, K. R., Lotsof, H. S., Frenken, G. M., et al (1999) Treatment of acute opioid withdrawal with ibogaine. American Journal of Addiction, 8, 234 –242.[CrossRef][Medline]

Maisonneuve, I. M. & Glick, S. D. (2003) Anti-addictive actions of an iboga alkaloid congener: a novel mechanism for a novel treatment. Pharmacology, Biochemistry and Behavior, 75, 607 –618.[CrossRef][Medline]

Maisonneuve, I. M., Keller, R. W. & Glick, S. D. (1991) Interactions between ibogaine, a potential anti-addictive agent, and morphine: an in vivo microdialysis study. European Journal of Pharmacology, 199, 35 –42.[CrossRef][Medline]

Mash, D. C., Staley, J. K., Pablo, J. P., et al (1995) Properties of ibogaine and its principal metabolite (12-hydroxyibogamine) at the MK-801 binding site of the NMDA receptor complex. Neuroscience Letters, 192, 53 –56.[CrossRef][Medline]

Mash, D. C., Kovera, C. A., Pablo, J., et al (2001) Ibogaine in the treatment of heroin withdrawal. Alkaloids – Chemistry and Biology, 56, 155 –171.

Werneke, U., Turner, T. & Priebe, S. (2006) Complementary medicines in psychiatry. Review of effectiveness and safety. British Journal of Psychiatry, 188, 109 –121.[Abstract/Free Full Text]





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