7-Hydroxymitragynine
Atypical Opioid analgesic compound
From Wikipedia, the free encyclopedia
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).[3] It was first described in 1994.[4] In humans, it is produced as an active metabolite of mitragynine via hepatic oxidation.[5]
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| Other names | 7-OH; 7α-Hydroxy-7H-mitragynine;[1] 9-Methoxycorynantheidine hydroxyindolenine[1] |
| Dependence liability | High |
| Addiction liability | High[2] |
| Routes of administration | Oral |
| Drug class | Opioid |
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| Pharmacokinetic data | |
| Metabolites | Mitragynine pseudoindoxyl |
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| Formula | C23H30N2O5 |
| Molar mass | 414.502 g·mol−1 |
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7-OH exhibits greater binding affinity to μ-opioid receptors (MOR) than mitragynine.[6] It acts primarily as a partial agonist at μ-opioid receptors while antagonizing δ- and κ-opioid receptors; unlike traditional opioids, it appears not to recruit the β-arrestin pathway, which may influence its side effect profile.
Recreational use has increased in the United States, often in concentrated retail products. 7-OH occurs only in very small amounts in natural kratom leaves (<2% of total alkaloids), so most commercial material is produced semisynthetically through oxidation of mitragynine. In animal studies, the compound has shown strong analgesic potency (reported up to ~13× that of morphine) and produces opioid-like tolerance and withdrawal. Reports to poison control have risen substantially, and in 2025 the U.S. Food and Drug Administration recommended that it be scheduled; it is not approved for any medical or dietary supplement use.
It is being studied as a potential template for developing opioids with improved safety profiles.[7]
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.[8][9] Both 7-OH-MIT and mitragynine do not appear to activate the β-arrestin pathway, distinguishing it from traditional opiate and opioid chemicals.[8] 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.[10] 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.[11] Another study found the binding affinity of 7-OH-MIT to be MOR 13.5 nM, DOR 155 nM, and KOR 123 nM.[11] 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.[12]
Synthesis
In natural kratom leaves, 7-hydroxymitragynine is only present in small amounts, comprising less than 2% of overall alkaloid content.[13] 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.[14] 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.[13]
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.[15]
Legal status
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.[16][17] This action was publicized to not be targeting Mitragyna speciosa itself.[18] 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.[19]
Research
A study on 7-hydroxymitragynine's safety was unable to identify an LD50 orally due to a lack of deaths occurring. In a later part of the same study they found both mitragynine and 7-hydroxymitragynine to be able to cause respiratory depression when given intravenously. This same study also showed seizures in many of the surviving mice from the mitragynine group.[20] 7-Hydroxymitragynine has been described as a "prototypical" compound to develop a new generation of opioids with an improved safety profile.[7]