7-Hydroxymitragynine Is an Active Metabolite of Mitragynine and a Key Mediator of Its Analgesic Effects

Kratom’s increase in popularity since the early 2000s has brought with it a great deal of misinformation and concern regarding “safe” use and “proper” dosage levels. This paper dives into the details, investigating how mitragynine and 7-hydroxymitragynine are metabolized and activated in mice. Thorough, detailed and a bit complicated, this paper describes the effects of different dosages of mitragynine, how it is processed by the body, and how different alkaloids work together on different receptors in the brain.

The researchers demonstrate both alkaloid’s affinities for mu-opioid receptors (MORs) as well as the importance of metabolism in relation to dosage and perceived effects. Finally, the dense medical jargon describes two key takeaways. The first is that even though kratom acts on the same channels as opioids, it does so without “depressing respiration”, the primary cause of opioid overdose deaths. Second, the kratom’s unique combination of alkaloids appear to work together as both agonists and antagonists on MORs, suggesting that the effects of kratom are self-limiting and altogether safe.

The American Kratom Association’s 2018 Policy Report, which runs to around 27 pages, clearly and concisely addresses the concerns surrounding overdose and abuse potential of kratom. The report cites an article in the June 2018 edition of the journal Addiction Biology that “…authoritatively addresses this issue and concludes that MG ‘does not have abuse potential and reduces morphine intake’3 and that 7-HMG potentially has abuse potential, but only in purified or concentrated adulterants.” (emphasis added).

Notable Quotes:

  • We believe mitragynine and related compounds have great potential as future therapeutics, but metabolic processes must be carefully considered as the field continues to advance.
  • We have thus classified the kratom alkaloids as “atypical opioids” and have postulated that these compounds may provide a greater therapeutic window between analgesia and classical opioid side effects.

Publication details: ACS Cent Sci. 2019 Jun 26;5(6):992-1001. doi: 10.1021/acscentsci.9b00141. Epub 2019 May 29. PMID: 31263758; PMCID: PMC6598159..

Read the full article here:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6598159/