Tramadol; a natural product or not?

Last year a multi-national group discussed the isolation of tramadol from the roots of  the African peach or pincushion tree.

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This compound is a synthetic analgesic, which was first made and marketed in the 1970’s by a German company, is now used worldwide for the treatment of moderate to severe pain.

The isolation procedure and measurements of the compounds’ concentration in the plant roots were confirmed by other laboratories. Interestingly the compound was obtained as a racemate. This is unusual for natural products which are normally chiral. Speculation was made concerning the biosynthesis of such a compound.

However, a new paper, has appeared by a German group collaborating with a Cameroonian team comes to a different conclusion. They sampled the roots of the plant from different regions of Cameroon and showed that the samples collected from the original area of the country did indeed contain tramadol, however in very amounts, about 0.0001466 w/w% (the original isolation measured 0.4 w/w%). The levels of tramadol in the plant samples from other areas was below the limit of detection.  Now that is quite a difference. And the proposed biosynthetic pathway also flies out of the window.

To cut the story short it turns out that the occurrence of this compound in the roots of the plant are due to anthropogenic contamination with the synthetic material. I quote ” An extensive off-label use of synthetic tramadol both by the farmers as well as their farm animals occurs only in the Far North region (Houdouvou). The farmers, who have to work throughout the day under the sun in extremely high temperatures, buy tramadol from the local market or from local street sellers (twelve pills cost less than one Euro). They consume around two to three pills, which is much higher than the daily recommended dosage, with their morning cup of tea. They report that this allows them to work all day without feeling tired. 

Tramadol is further fed to cattle (but not to goats and sheep) as capsules when working them in their farms (as draft animals) so that the animals do not get tired quickly. As a consequence of the high day temperatures and the strong sun, the farm animals often choose the shade of trees to relax and also excrete their urine and feces.

Tramadol is also administered to horses prior to horse racing and is given only on the day of the competition. Generally around five capsules of tramadol (100 mg each) are mixed with flour and water to prepare a small cake, which is then fed to the horses before the race. Then, at the end of the day, the horses are “detoxified” by being fed milk.

In the southern region (Bafia), the use of tramadol is not known to farmers.”

So there we have it,  more direct proof of our  impact on the environment. Tramadol has several nasty side effects for example, seizures, organ problems up to and including death. The contamination of the plant root therefore precludes its role in the traditional medicine of this part of the world. This has been documented before with diclofenac seriously affecting the health of Indian vultures.

So we need to much more careful with such pharmaceuticals (and other things) and ensure that less privileged persons are provided with adequate, understandable training on the proper use and disposal of these “beneficial” compounds. Control procedures need to be established to monitor such events and provide corrective measures to prevent this sort of thing from occurring. Although ecological impact is measured and submitted with the compound NDA perhaps the standard screens need to be re-thought, however, you can’t think of everything.

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Prof. dangerdackel (199 Posts)


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