Journal of Ethnophamacology, 25 (1989) 123- 124 Elsevier Scientific Publishers Ireland Ltd.

Letters to the Editors

ETHNOPHARMACOLOGY OF KRATOM AND THE MITRAGYNA ALKALOIDS

Sirs,

The letter from Karl L.R. Jansen and Colin J. Priest (19881 regarding the pharmacological effects of Mitragyna speciosa Korth. raises a number of interesting points. In the first place it cannot be concluded that because mitragynine has a methoxy substitution at C(9) corresponding to a hydroxy substitution at C(4) in the indole unit of psilocybin and lysergic acid amide that the pharmacological actions must be similar. This was never suggested by Beckett et al. (1965). It should be noted that there are no C(9)_OH indole alkaloids in any of the species of Mitragynu although there are C(9)_OH oxidole alkaloids. None of these alkaloids are reported to have any analgesic activity although, as reported by Zarembo et al. (19741 mitragynine pseudoindoxyl does. However, this compound does not occur naturally and the A and B corresponding oxindole isomers are only found in traces, the former only during some months (Shellard et al., 19781. The pharmacological activity of mitragynine must obviously depend upon its configuration.

Mitragynine

has the allo configuration but speciociliatine (epiallol, speciogynine (normal) and mitraciliatine (pseudo) have no reported analgesic properties. Nevertheless, there is this contradiction between the activity of “kratom” leaves which are chewed as a stimulant and the depressant activity of mitragynine which is the main alkaloid found in “kratom” leaves but which is not found in any of the other species of Mitragyna But this is not an unknown feature of many plants, e.g. Panax ginseng CA. Meyer. Medical herbalists could give examples of many more such as Filipendula ulmariu and it is clear evidence of their claim that the therapeutic effect of plant extracts can be quite different from that of isolated constituents. It may be that the other alkaloids present in Mitragynu speciosa have a marked stimulant effect but this is most unlikely.

However, there is a possible explanation. In 1963 when our group at Chelsea College (now King’s College), University of London, was trying to isolate large amounts of mitragynine from “kratom” leaves it was found that when the powdered leaf was extracted with ethanol it was never possible to obtain a clean, white sample, whether the hemi-alcoholate or a salt. This was overcome by extracting the plant material with ethyl acetate which left behind a dark, sticky residue which because of its non-alkaloidal nature was ignored by us at the time. It was always my intention to return to this but the 124 opportunity never materialised. Evidence for the presence of latex in this leaf was substantiated by the anatomical study of the leaf which showed laticiferous cells particularly in the mid-rib (Shellard et al., 1965). It might well be that a study of this latex would be useful. I would like to mention one historical fact which could have some bearing on the question of finding a suitable treatment for addiction to opiates. When I was in Bristol in 1956-1957 a pharmacist friend purchased an old, historic pharmacy and found in the cellar hundreds of bottles of a reddishbrown liquid clearly labelled as an “Opium substitute”. They had obviously been in the cellar since 1924 when the Dangerous Drugs regulations came into force and, of course, they were destroyed. But I did have the opportunity of testing for alkaloids which were absent and I noted that the label indicated that the preparation was based on an extract of a species of Uncati. Unfortunately I cannot now remember the name of the species or find the notes I made at the time, but the close botanical relationship between the genera Uncaria and Mitragyna may not be without significance.

References

Beckett, A.H., Shellard, E.J. and Tackie, A.N. (1965) The Mitrugynu species of Asia. Part IV: The alkaloids of the leaves of M. speciosa Korth. Isolation of mitragynine and speciofoline. Planta Medica 13, 241-245. Shellard, E.J. and Lees, Margaret, D. (1965) The Mitmgm species of Asia. Part V: The anatomy of the leaves of Mitragynu speciosa Korth. Planta Medica 13, 280 – 290. Shellard, E.J., Houghton, P.J. and Resha Masechaba (1978) The Mitragynu species of Asia. Part XxX1: The alkaloids of Mitragyna speciosa Korth. from Thailand. Plunta Medica 34, 26-36. Zarembo, J.E., Douglas, B., Valenta, J. and Weisback, J.A. (1974) Metabolites of mitragynine. Journul of Pharmaceutical Sciences, 63,1409- 1415. E.J. Shellmd Emeritus Professor of Pharmacognosy University of London July 23, 1988