7-Hydroxymitragynine

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7-Hydroxymitragynine
Clinical data
Other names7-OH; 7α-Hydroxy-7H-mitragynine;[1] 9-Methoxycorynantheidine hydroxyindolenine[1]
Dependence
liability		Moderate
Addiction
liability		Moderate[2]
Routes of
administration		Oral
Drug classOpioid
ATC code
  • None
Legal status
Legal status
  • BR: Class F1 (Prohibited narcotics)
  • US: Unscheduled
Pharmacokinetic data
MetabolitesMitragynine pseudoindoxyl
Identifiers
  • Methyl (2E)-2-[(2S,3S,7aS,12bS)-3-ethyl-7a-hydroxy-8-methoxy-1,2,3,4,6,7,7a,12b-octahydroindolo[2,3-a]quinolizin-2-yl]-3-methoxyprop-2-enoate
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC23H30N2O5
Molar mass414.502 g·mol−1
3D model (JSmol)
  • CC[C@@H]1CN2CC[C@@]3(O)C(=Nc4cccc(OC)c34)[C@@H]2C[C@@H]1\C(=C/OC)C(=O)OC

  • CC[C@@H]1CN2CC[C@@]3(O)C(=NC4=CC=CC(OC)=C34)[C@@H]2C[C@@H]1\C(=C/OC)C(=O)OC
  • InChI=1S/C23H30N2O5/c1-5-14-12-25-10-9-23(27)20-17(7-6-8-19(20)29-3)24-21(23)18(25)11-15(14)16(13-28-2)22(26)30-4/h6-8,13-15,18,27H,5,9-12H2,1-4H3/b16-13+/t14-,15+,18+,23+/m1/s1 checkY
  • Key:RYENLSMHLCNXJT-CYXFISRXSA-N checkY

7-Hydroxymitragynine (7-OH-MIT, often simply referred to as 7-OH) is a terpenoid indole alkaloid present in the plant Mitragyna speciosa, commonly known as kratom.[3] It was first described in 1994.[4] In humans, it is produced as an active metabolite of mitragynine via hepatic oxidation.[5] 7-OH exhibits greater binding affinity to μ-opioid receptors (MOR) than mitragynine.[citation needed]

Frequent consumption of 7-OH is known to cause dependence, addiction, and—upon cessation of use—withdrawal symptoms similar to those caused by most opiates and opioids.[citation needed]

Pharmacology

[edit]

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.[6][7] Both 7-OH-MIT and mitragynine do not appear to activate the β-arrestin pathway, distinguishing it from traditional opiate and opioid chemicals.[6] 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.[8] 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.[9] Another study found the binding affinity of 7-OH-MIT to be MOR 13.5 nM, DOR 155 nM, and KOR 123 nM.[9] 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.[10]

Synthesis

[edit]

In natural kratom leaves, 7-hydroxymitragynine is only present in small amounts, comprising less than 2% of overall alkaloid content.[11] 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.[5]

Society and culture

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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.[12] 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.[11]

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.[13]

[edit]

United States

[edit]

In July 2025, the US Food and Drug Administration (FDA) formally recommended that the Drug Enforcement Administration (DEA) classify 7-hydroxymitragynine as a controlled substance, citing it as the newest wave in the opioid epidemic. There have been claims this action will not affect the legal status of Mitragyna speciosa itself but this would conflict with law if 7-hydroxymitragynine is made Schedule I or Schedule II then Kratom would be considered a container of a scheduled substance due to containing low amounts of 7-hydroxymitragnine, additionally Mitragynine would be illegal under the federal analog act as a structural analog. It would take an act of congress to then legalize Kratom if the DEA formally scheduled 7-hydroxymitragynine.[14] Despite many 7-OH products claiming that they can help with anxiety or pain relief, the drug is not approved by the FDA for any medical use or as a food supplement.[15]

On August 13, 2025, Florida attorney general James Uthmeier announced an emergency rule placing 7-hydroxymitragynine into Schedule I status under Florida state law.[16][17][18]

Research

[edit]

Studies on 7-hydroxymitragynines safety have been unable to identify an LD50 orally with no deaths occurring.[19] 7-hydroxymitragynine has been described as a "prototypical" compound to develop a new generation of opioids with a better safety profile.[20]

References

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  1. ^ a b Chemical Abstracts Service: Columbus, OH, 2004; RN 174418-82-7 (accessed via SciFinder Scholar, version 2007.3; November 30, 2011)
  2. ^ Matsumoto K, Horie S, Takayama H, Ishikawa H, Aimi N, Ponglux D, et al. (19 November 2005). "Antinociception, tolerance and withdrawal symptoms induced by 7-hydroxymitragynine, an alkaloid from the Thai medicinal herb Mitragyna speciosa". Life Sci. 78 (1): 2–7. doi:10.1016/j.lfs.2004.10.086. PMID 16169018.
  3. ^ Matsumoto K, Horie S, Ishikawa H, Takayama H, Aimi N, Ponglux D, et al. (March 2004). "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. doi:10.1016/j.lfs.2003.09.054. PMID 14969718.
  4. ^ Ponglux D, Wongseripipatana S, Takayama H, Kikuchi M, Kurihara M, Kitajima M, et al. (December 1994). "A New Indole Alkaloid, 7 alpha-Hydroxy-7H-mitragynine, from Mitragyna speciosa in Thailand". Planta Medica. 60 (6): 580–581. Bibcode:1994PlMed..60..580P. doi:10.1055/s-2006-959578. PMID 17236085. S2CID 260252538.
  5. ^ a b Karunakaran T, Marimuthu Y, Rusmadi NN, Firouz NS, Jenis J, Kumar US, et al. (2024-10-10). "Chemistry and toxicity of 7-hydroxymitragynine (7-OHMG): an updated review on the oxidized derivative of mitragynine". Phytochemistry Reviews. doi:10.1007/s11101-024-10029-x. ISSN 1572-980X.
  6. ^ a b Eastlack SC, Cornett EM, Kaye AD (June 2020). "Kratom-Pharmacology, Clinical Implications, and Outlook: A Comprehensive Review". Pain and Therapy. 9 (1): 55–69. doi:10.1007/s40122-020-00151-x. PMC 7203303. PMID 31994019.
  7. ^ Chang-Chien GC, Odonkor CA, Amorapanth P (2017). "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. doi:10.36076/ppj.2017.1.E195. PMID 28072812.
  8. ^ Váradi A, Marrone GF, Palmer TC, Narayan A, Szabó MR, Le Rouzic V, et al. (2016). "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. doi:10.1021/acs.jmedchem.6b00748. PMC 5344672. PMID 27556704.
  9. ^ a b Takayama H, Ishikawa H, Kurihara M, Kitajima M, Aimi N, Ponglux D, et al. (2002). "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. doi:10.1021/jm010576e. PMID 11960505.
  10. ^ Matsumoto K, Horie S, Takayama H, Ishikawa H, Aimi N, Ponglux D, et al. (2005). "Antinociception, tolerance and withdrawal symptoms induced by 7-hydroxymitragynine, an alkaloid from the Thai medicinal herb Mitragyna speciosa". Life Sciences. 78 (1): 2–7. doi:10.1016/j.lfs.2004.10.086. PMID 16169018.
  11. ^ a b Reissig CJ, Chiapperino D, Seitz A, Lee R, Radin R, McAninch J (2025). "7-Hydroxymitragynine (7-OH): An Assessment of the Scientific Data and Toxicological Concerns Around an Emerging Opioid Threat". Food and Drug Administration: 4. 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.
  12. ^ Reissig CJ, Chiapperino D, Seitz A, Lee R, Radin R, McAninch J. 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. 7-OH displayed approximately 13-fold greater potency than morphine
  13. ^ Office of the Commissioner (2025-07-30). "Hiding in Plain Sight: 7-OH Products". FDA. Retrieved 2025-08-05.
  14. ^ "US health officials crack down on kratom-related products after complaints from supplement industry". WHEC. Associated Press. 2025-07-29. Retrieved 2025-07-29.
  15. ^ "Products Containing 7-OH Can Cause Serious Harm". Drugs.com. Retrieved 2025-08-05.
  16. ^ https://www.myfloridalegal.com/newsrelease/attorney-general-james-uthmeier-files-emergency-rule-immediately-removing-dangerous-7
  17. ^ https://www.axios.com/local/tampa-bay/2025/08/13/florida-ag-ban-7-oh-kratom-products
  18. ^ <https://www.fox13news.com/news/florida-ag-uthmeier-taking-emergency-action-against-new-synthetic-drug-7-oh
  19. ^ https://pubs.acs.org/doi/10.1021/acs.chemrestox.8b00218
  20. ^ https://jpet.aspetjournals.org/article/S0022-3565(24)27223-2/abstract