7-Hydroxymitragynine

Last updated

7-Hydroxymitragynine
7-hydroxymitragynine2DACS.svg
7-OH-mitragynine.png
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 class Opioid
ATC code
  • None
Legal status
Legal status
  • BR: Class F1 (Prohibited narcotics)
  • US:Unscheduled
Pharmacokinetic data
Metabolites Mitragynine 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
Formula C23H30N2O5
Molar mass 414.502 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 Yes check.svgY
  • Key:RYENLSMHLCNXJT-CYXFISRXSA-N Yes check.svgY

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 ]

Contents

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

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

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

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]

United States

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. [14] Despite claims by 7-OH products 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. [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

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

  1. 1 2 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. 1 2 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. Bibcode:2024PChRv.tmp..145G. doi:10.1007/s11101-024-10029-x. ISSN   1572-980X.{{cite journal}}: CS1 maint: bibcode (link)
  6. 1 2 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. 1 2 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. 1 2 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. ↑ "Attorney General James Uthmeier Files Emergency Rule; Immediately Removing Dangerous 7-OH from Store Shelves | My Florida Legal".
  17. ↑ "Florida AG announces ban on "7-OH" products".
  18. ↑ <https://www.fox13news.com/news/florida-ag-uthmeier-taking-emergency-action-against-new-synthetic-drug-7-oh
  19. ↑ Smith LC, Lin L, Hwang CS, Zhou B, Kubitz DM, Wang H, et al. (2019). "Lateral Flow Assessment and Unanticipated Toxicity of Kratom". Chemical Research in Toxicology. 32 (1): 113–121. doi:10.1021/acs.chemrestox.8b00218. PMC   6662923 . PMID   30380840.
  20. ↑ Matsumoto K, Narita M, Muramatsu N, Nakayama T, Misawa K, Kitajima M, et al. (2014). "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. doi:10.1124/jpet.113.208108. PMC   6067406 . PMID   24345467.


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