Clicky

Medical & Clinical Research Journal

Medical & Clinical Research Journal — Peer-reviewed health analysis, supplement safety reviews, and clinical research summaries.

Does Kratom Bind to Opioid Receptors? Pharmacology Explained

By MedClinRes.org Clinical Research Team. Educational information only. Sources last checked October 3, 2026.

Short answer: yes, in laboratory studies. The U.S. Food and Drug Administration (FDA) states that mitragynine and 7-hydroxymitragynine (7-OH), two alkaloids in kratom, bind to the same brain receptors (mu opioid receptors) as opioid drugs such as codeine. The National Institute on Drug Abuse (NIDA) describes both as partially activating those receptors. They are not copies of morphine, though. 7-OH binds far more tightly than mitragynine, and some researchers think mitragynine's own receptor activity is weak and that much of its opioid-like effect comes after the body converts it to 7-OH.

What “binding” does and does not tell you

A compound that binds to a receptor sticks to it. Whether it then switches the receptor on, partly switches it on, or blocks it is a separate question called efficacy. How a compound behaves in a living person is a third question, and it depends on dose, metabolism, other drugs, and product purity. Most of the data below come from cells and animals, so they describe mechanisms, not what any individual will experience.

Receptor-activity comparison

The findings below are summarized from the studies named in each line. Numbers differ between laboratories because the assays differ, so treat them as ranges, not fixed values. A lower Ki means tighter binding. Efficacy percentages are measured against reference compounds chosen by each laboratory, so they are not strictly comparable across studies.

Mitragynine

  • Binding (in vitro): A 2016 study in cells with human receptors reported a mu opioid receptor Ki of about 0.233 µM (233 nM). A 2021 study in different cells reported about 7,709 nM, a gap of more than 30-fold between the two laboratories.
  • Activity (in vitro): The 2016 study found partial G-protein activation (maximum effect 34%) and no measurable beta-arrestin recruitment. The 2021 study found no significant agonism up to 100 µM.
  • Animal findings: In the 2021 rat study, mitragynine did not produce pain-blunting effects in a hot-plate test, though rats partly treated it like morphine in a drug-discrimination test. The 2016 authors also noted that mitragynine acted as an antagonist, not an agonist, at the mouse mu receptor, which complicates reading rodent data.
  • Human data: None of the sources reviewed here report human receptor-occupancy measurements for mitragynine.
  • Main limits: Conflicting in vitro results, species differences, and no direct human receptor data.

7-hydroxymitragynine (7-OH)

  • Binding (in vitro): Reported mu opioid receptor Ki of about 0.047 µM (47 nM) in 2016 and about 77.9 nM in 2021. The two laboratories roughly agree that 7-OH binds much more tightly than mitragynine.
  • Activity (in vitro): Partial agonist in both studies (maximum effect 47% in 2016 and 41.3% in 2021), with no measurable beta-arrestin recruitment in the 2016 study.
  • Animal findings: Produced pain-blunting effects in rats given by injection, with ED50 values of 11 and 16 mg/kg in two groups of trained rats. A 2019 mouse study concluded that 7-OH formed from mitragynine reaches brain levels high enough to account for mitragynine's pain-blunting effect in mice.
  • Human data: A small 2022 study of six healthy adults with prior kratom exposure, who drank a single 2 g kratom tea, measured 7-OH in blood at roughly 24 to 27 percent of mitragynine levels. It measured blood levels, not receptor binding.
  • Main limits: Injection doses in rats do not equal swallowed kratom products, the human study was tiny and single-dose, and FDA notes that 7-OH is a minor constituent (under 2 percent of total alkaloids) of natural kratom leaves.

Morphine (reference opioid)

  • Binding (in vitro): Ki of about 4.19 nM at the human mu opioid receptor in the 2021 study, much tighter than either kratom alkaloid in that same experiment.
  • Activity (in vitro): Full agonist (maximum effect 92.6%) in the same 2021 assay.
  • Main limits: Included only as a benchmark in one laboratory's experiment. These studies do not show that kratom is equivalent to, safer than, or weaker than morphine for a person.

Why 7-OH matters even when a product is mostly mitragynine

NIDA reports that the body converts mitragynine into 7-OH. A 2019 study found that this conversion happens in both mouse and human liver preparations, through liver enzymes of the CYP3A family, and its authors concluded that mitragynine itself does not directly engage opioid receptors at relevant doses in mice. That is one reason the cell-based binding numbers for mitragynine should not be read as a prediction of its effect in a person. How much this conversion matters in humans has not been settled by the sources reviewed here.

What this means for dependence and withdrawal

Because these compounds act on the mu opioid receptor, researchers take dependence seriously. NIDA states that people may experience mild to moderate withdrawal symptoms when they stop regular kratom use, that research is limited, and that the diagnostic manual DSM-5 has no specific kratom use disorder criteria. FDA lists physical dependence, withdrawal symptoms, and substance use disorder among its safety concerns. Human abuse-potential research remains limited, and FDA reports that it awarded a grant for a human abuse potential study in September 2024.

For context on recovery-related questions, see our related page, Kratom, Opioids, and Addiction Recovery: What Medical Research Says.

Safety points to know

  • FDA states that kratom is not lawfully marketed in the U.S. as a drug, dietary supplement, or food additive, and that it is concerned about liver toxicity, seizures, neonatal abstinence syndrome, and contamination such as Salmonella and heavy metals.
  • FDA says deaths associated with kratom have been rare and typically involved other substances, which makes kratom's role unclear. NIDA says nearly all reported cases involved other drugs or contaminants.
  • Product content varies, so a laboratory finding about a purified compound cannot be applied directly to a store-bought product.

Who should talk to a professional

  • Anyone using kratom regularly who wants to cut back or stop, especially if they notice withdrawal symptoms.
  • Anyone taking prescription medicines, opioid or otherwise, who should ask a pharmacist or clinician about possible interactions.
  • People who are pregnant or planning pregnancy, and anyone with liver, seizure, or mental health conditions.

For free, confidential treatment referral, the SAMHSA National Helpline is 1-800-662-4357. In a poisoning emergency, contact Poison Control at 1-800-222-1222 or call 911.

What you can do next

  1. Bring a list of everything you take, including kratom, to a pharmacist or clinician.
  2. Do not stop a prescribed medicine on your own because of anything you read here.
  3. Read the primary sources below, and treat any page, including this one, as a starting point and not as personal medical advice.

Glossary of pharmacology terms

  • Agonist: A compound that activates a receptor. A full agonist produces the largest response a system can give; a partial agonist produces a smaller maximum.
  • Antagonist: A compound that sits on a receptor and blocks other compounds from activating it.
  • Binding affinity (Ki): How tightly a compound attaches to a receptor. A smaller Ki means tighter binding.
  • Efficacy (Emax): How strongly a compound activates a receptor once bound, compared with a reference compound.
  • Beta-arrestin: A cell protein that some receptors recruit after activation. Researchers measure it as one of several signaling pathways.
  • CYP3A: A family of liver enzymes that can convert mitragynine to 7-OH.
  • In vitro: Done in cells or tissue samples, not in a living body.
  • ED50: The dose that produces a given effect in half of tested animals.
  • Mu opioid receptor: The main receptor through which morphine and many other opioids act.

Sources

This article is independent educational content from Med Clin Res and is not medical advice. It contains no product recommendations. See our Editorial Standards and Medical Disclaimer.