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August 13, 2020

Kratom Alkaloid “Even More Potent” in Humans Compared to Animals

Kratom leaves contain dozens of naturally-occurring alkaloids, which are responsible for the plant’s many properties. Historically, 7-hydroxymitragynine (7-HMG) has been considered the most powerful kratom alkaloid. But a new study suggests that there are other forces at play.

The study, conducted by American researchers, found that 7-HMG is stable in the blood plasma of tested animals (namely, rodents and monkeys). However, when humans ingest 7-HMG, the alkaloid converts to mitragynine pseudoindoxyl, becoming “yet more potent and at least as efficacious as 7-HMG.”

Despite the fact that the study was performed in vitro — or outside of a natural environment — the authors claim that this conversion reaction might be chiefly responsible for kratom’s pain-relieving effectiveness in humans. Scientists have already observed that 7-HMG is 22 times more potent than mitragynine as an opioid agonist. But 7-HMG’s conversion to mitragynine pseudoindoxyl could amplify kratom’s pain-relieving properties even further.

Although mitragynine pseudoindoxyl may have benefits for humans, the researchers also warned of its abuse potential: “7-HMG has been reported to have high abuse potential, and given that mitragynine pseudoindoxyl is an even more potent opioid agonist, it is likely to also be highly abusable.”

The study has also given its authors a new perspective on current research. Having observed that kratom is metabolized differently by various species, the authors noted that the results of kratom alkaloid mice studies might no longer translate to humans. “The discovery … is … not only unexpected but also may significantly alter our conclusions about the translatability of mitragynine findings using rodent models to the human condition,” they wrote.

Despite the significance of their findings, the team stressed that there’s more to learn. While they may have identified the conversion reaction of 7-HMG to mitragynine pseudoindoxyl, the exact mechanism for that conversion remains unknown. The study notes that the conversion could be determined by genetic enzymes, “which would potentially lead to substantial variability in an individual’s relative exposure to 7-HMG and mitragynine pseudoindoxyl.” But ultimately, “Further research is required.”

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