Chemistry:7-Hydroxymitragynine

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7-Hydroxymitragynine (7-OH-MIT, often simply referred to as 7-OH) is a terpenoid indole alkaloid present in the plant Mitragyna speciosa (the leaves of which are commonly known as kratom).[1] It was first described in 1994.[2] In humans, it is produced as an active metabolite of mitragynine via hepatic oxidation.[3] 7-OH exhibits greater binding affinity to μ-opioid receptors (MOR) than mitragynine.

Pharmacology

7-OH-MIT, like mitragynine, appears to be a mixed opioid receptor agonist/antagonist, with recent research indicating that it acts as a partial agonist at μ-opioid receptors and as a competitive antagonist at δ- and κ-opioid receptors.[4][5] Both 7-OH-MIT and mitragynine do not appear to activate the β-arrestin pathway, distinguishing it from traditional opiate and opioid chemicals.[4] A study has found the binding affinity of 7-OH-MIT to be μ-opioid receptor (MOR) 37 (± 4) nM and δ-opioid receptor (DOR) 91 (± 8) nM and κ-opioid receptor (KOR) 132 (± 7) nM.[6] Another study found the binding affinity of 7-OH-MIT to be MOR 16 (± 1) nM and DOR 137 (± 21) nM and KOR 133 (± 37) nM.[7] Another study found the binding affinity of 7-OH-MIT to be MOR 13.5 nM, DOR 155 nM, and KOR 123 nM.[7] Cross-tolerance to morphine was evident in mice rendered tolerant to 7-hydroxymitragynine and vice versa. Naloxone-induced withdrawal signs were elicited equally in mice chronically treated with 7-hydroxymitragynine or morphine.[8]

Synthesis

In natural kratom leaves, 7-hydroxymitragynine is only present in small amounts, comprising less than 2% of overall alkaloid content.[9] Therefore, extracting 7-OH-MIT in high concentrations directly from natural kratom leaves is not practical. Instead, 7-hydroxymitragynine can be produced semisynthetically via the oxidation of mitragynine.[3]

Society and culture

7-OH has been rising in popularity as a recreational drug, particularly in the United States. Its ability to bind to opioid receptors can cause addictive effects. In an electrical stimulation test using guinea-pig ileum, 7-OH performed 13 times greater pain relief than that of morphine.[10] The drug's novelty has meant that it has increasingly been sold unregulated over the counter in gas stations and smoke shops, often in highly concentrated "candy-like" or pill form alongside kratom powder and other supplements with little to no information provided to consumers about its effects.[9]

According to the United States Poison Control Center, the number of cases relating to kratom-based products such as 7-OH have increased from under 200 in 2014 to 1600 in 2024, with approximately 40% of 7-OH reports coming from individuals who were abusing the drug.[11]

United States

In July 2025, the Food and Drug Administration (FDA) formally recommended that the Drug Enforcement Administration (DEA) classify 7-hydroxymitragynine as a controlled substance.[12] This action is not directed toward Mitragyna speciosa itself, which will remain unaffected by regulation of 7-OH.[13] Despite claims by marketers for products that contain 7-OH that they can be used to treat anxiety and pain, the drug is not approved by the FDA for any medical use or as a food supplement.[14]

On August 13, 2025, Florida attorney general James Uthmeier announced an emergency rule placing 7-hydroxymitragynine into schedule I status under Florida state law, effectively outlawing the substance and removing it from all headshops and similar stores from the state.[15][16][17]

Research

Studies on 7-hydroxymitragynines safety have been unable to identify an LD50 orally with no deaths occurring.[18] 7-hydroxymitragynine has been described as a "prototypical" compound to develop a new generation of opioids with an improved safety profile.[19]

See also

  • Deuterated mitragynine

References

  1. ↑ "Antinociceptive effect of 7-hydroxymitragynine in mice: Discovery of an orally active atypical opioid analgesic from the Thai medicinal herb Mitragyna speciosa". Life Sciences 74 (17): 2143–2155. March 2004. doi:10.1016/j.lfs.2003.09.054. PMID 14969718. 
  2. ↑ "A New Indole Alkaloid, 7 alpha-Hydroxy-7H-mitragynine, from Mitragyna speciosa in Thailand". Planta Medica 60 (6): 580–581. December 1994. doi:10.1055/s-2006-959578. PMID 17236085. Bibcode: 1994PlMed..60..580P. 
  3. ↑ 3.0 3.1 "Chemistry and toxicity of 7-hydroxymitragynine (7-OHMG): an updated review on the oxidized derivative of mitragynine" (in en). Phytochemistry Reviews 24 (5): 4051–4064. 2024-10-10. doi:10.1007/s11101-024-10029-x. ISSN 1572-980X. Bibcode: 2024PChRv.tmp..145G. 
  4. ↑ 4.0 4.1 "Kratom-Pharmacology, Clinical Implications, and Outlook: A Comprehensive Review". Pain and Therapy 9 (1): 55–69. June 2020. doi:10.1007/s40122-020-00151-x. PMID 31994019. 
  5. ↑ "Is Kratom the New 'Legal High' on the Block?: The Case of an Emerging Opioid Receptor Agonist with Substance Abuse Potential". Pain Physician 20 (1): E195–E198. 2017. doi:10.36076/ppj.2017.1.E195. PMID 28072812. 
  6. ↑ "Mitragynine/Corynantheidine Pseudoindoxyls as Opioid Analgesics with Mu Agonism and Delta Antagonism, Which do Not Recruit β-Arrestin-2". Journal of Medicinal Chemistry 59 (18): 8381–8397. 2016. doi:10.1021/acs.jmedchem.6b00748. PMID 27556704. 
  7. ↑ 7.0 7.1 "Studies on the Synthesis and Opioid Agonistic Activities of Mitragynine-Related Indole Alkaloids: Discovery of Opioid Agonists Structurally Different from Other Opioid Ligands". Journal of Medicinal Chemistry 45 (9): 1949–1956. 2002. doi:10.1021/jm010576e. PMID 11960505. https://pubs.acs.org/doi/10.1021/jm010576e. 
  8. ↑ "Antinociception, tolerance and withdrawal symptoms induced by 7-hydroxymitragynine, an alkaloid from the Thai medicinal herb Mitragyna speciosa". Life Sciences 78 (1): 2–7. 2005. doi:10.1016/j.lfs.2004.10.086. PMID 16169018. 
  9. ↑ 9.0 9.1 "7-Hydroxymitragynine (7-OH): An Assessment of the Scientific Data and Toxicological Concerns Around an Emerging Opioid Threat". Food and Drug Administration: 4. 2025. https://www.fda.gov/media/187899/download?attachment. "7-OH is a naturally occurring substance in the kratom plant (Mitragyna speciosa), but only a minor constituent that comprises less than 2% of the total alkaloid content in natural kratom leaves.". 
  10. ↑ 7-Hydroxymitragynine (7-OH): An Assessment of the Scientific Data and Toxicological Concerns Around an Emerging Opioid Threat (Report). U.S. Drug and Food Administration (FDA) Center for Drug Evaluation and Research (CDER). p. 14. https://www.fda.gov/media/187899/download?attachment. "7-OH displayed approximately 13-fold greater potency than morphine" 
  11. ↑ Office of the Commissioner (2025-07-30). "Hiding in Plain Sight: 7-OH Products" (in en). https://www.fda.gov/drugs/information-consumers-and-patients-drugs/hiding-plain-sight-7-oh-products. 
  12. ↑ "US health officials crack down on kratom-related products after complaints from supplement industry". 2025-07-29. https://www.whec.com/ap-top-news/us-health-officials-crack-down-on-kratom-related-products-after-complaints-from-supplement-industry/. 
  13. ↑ U.S. Food and Drug Administration (July 29, 2025). "FDA Takes Steps to Restrict 7-OH Opioid Products Threatening American Consumers". https://www.fda.gov/news-events/press-announcements/fda-takes-steps-restrict-7-oh-opioid-products-threatening-american-consumers. 
  14. ↑ "Products Containing 7-OH Can Cause Serious Harm" (in en). https://www.drugs.com/fda-consumer/products-containing-7-oh-can-cause-serious-harm-439.html. 
  15. ↑ "Attorney General James Uthmeier Files Emergency Rule; Immediately Removing Dangerous 7-OH from Store Shelves | My Florida Legal". https://www.myfloridalegal.com/newsrelease/attorney-general-james-uthmeier-files-emergency-rule-immediately-removing-dangerous-7. 
  16. ↑ "Florida AG announces ban on "7-OH" products". 13 August 2025. https://www.axios.com/local/tampa-bay/2025/08/13/florida-ag-ban-7-oh-kratom-products. 
  17. ↑ <https://www.fox13news.com/news/florida-ag-uthmeier-taking-emergency-action-against-new-synthetic-drug-7-oh
  18. ↑ "Lateral Flow Assessment and Unanticipated Toxicity of Kratom". Chemical Research in Toxicology 32 (1): 113–121. 2019. doi:10.1021/acs.chemrestox.8b00218. PMID 30380840. 
  19. ↑ "Orally active opioid μ/δ dual agonist MGM-16, a derivative of the indole alkaloid mitragynine, exhibits potent antiallodynic effect on neuropathic pain in mice". The Journal of Pharmacology and Experimental Therapeutics 348 (3): 383–392. 2014. doi:10.1124/jpet.113.208108. PMID 24345467. PMC 6067406. https://jpet.aspetjournals.org/article/S0022-3565(24)27223-2/abstract. 




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