7-Hydroxymitragynine

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

Synthesis

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

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. 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.

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.

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. This action was publicized to not be targeting Mitragyna speciosa itself. 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.

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. 7-hydroxymitragynine has been described as a "prototypical" compound to develop a new generation of opioids with an improved safety profile.

References

References

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