Hello, and welcome to our new blog series where we will examine scientific studies related to kratom and summarize them into language that is accessible to all. There are numerous scientific and case studies that involve kratom, and much of the information is both enlightening and beneficial. Please take the time to read this series as it is published and utilize it to enhance the responsible and effective use of kratom.
The Science of Kratom Alkaloids
Mitragynine is the dominant player in kratom, but it’s only the beginning of the story. Once ingested, mitragynine converts to 7-HMG, a metabolite that is up to 22 times more potent as an opioid receptor agonist. However, researchers have discovered that in human plasma, 7-HMG doesn’t just linger—it morphs into a powerful new compound: mitragynine pseudoindoxyl.
This newly identified metabolite outclasses its predecessors in opioid potency, adding a new layer of complexity to kratom’s effects. What makes this discovery even more astonishing is that this transformation is unique to humans. Animal models, often used to predict human drug responses, don’t exhibit this metabolic pathway.
Why It Matters
The implications of this transformation are far-reaching:
• Enhanced Potency: Mitragynine pseudoindoxyl is a more potent opioid agonist than 7-HMG or mitragynine, potentially amplifying kratom’s effects.
• Abuse Potential: With increased potency comes increased risk. This novel metabolite may contribute to kratom’s appeal to some users but also raises red flags for regulators.
• Species-Specific Metabolism: Animal studies may not accurately reflect kratom’s behavior in humans, emphasizing the need for human-specific research.
Challenges and Questions Ahead
How and why does human plasma trigger this unique transformation? The answers could lie in our genetic makeup or specific plasma enzymes. These findings also hint at variability among individuals—some people may metabolize kratom into this potent compound more efficiently, experiencing stronger effects or higher risks.
Conclusion
As kratom continues to garner attention, this study highlights the importance of understanding its full pharmacological profile. The discovery of mitragynine pseudoindoxyl in human plasma doesn’t just change the conversation about kratom’s safety and efficacy—it revolutionizes it. Future research must unravel the mysteries of this transformation, ensuring that kratom can be used responsibly and safely.
Source:
Kamble, S. H., León, F., King, T. I., Berthold, E. C., Lopera-Londoño, C., Siva Rama Raju, K., Hampson, A. J., Sharma, A., Avery, B. A., McMahon, L. R., & McCurdy, C. R. (2020). Metabolism of a Kratom alkaloid metabolite in human plasma increases its opioid potency and efficacy. ACS Pharmacology & Translational Science, 3(6), 1063-1068. https://doi.org/10.1021/acsptsci.0c00075
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