Morphine and several mitragynine-derived compounds can activate the µ-opioid receptor (MOR). Morphine uses a different molecular scaffold. Receptor results cannot equate their doses, duration, dependence risk, or withdrawal course.
This page separates four measurements that researchers and product claims often collapse into one:
- Compound identity
- MOR binding affinity in a named assay
- Receptor signaling after binding
- Effects after a dose reaches a living organism
Researchers have more molecular and cell-assay data than controlled human comparisons. No binding value on this page is a human dose conversion or a predictor of withdrawal severity.
The compounds in scope
| Compound | Relationship | Evidence |
|---|---|---|
| Morphine | A morphinan alkaloid from a different structural family | Researchers use it as a reference MOR agonist and assay control. Its scaffold differs from the compounds in the mitragynine series. |
| Mitragynine | The most abundant alkaloid in kratom leaf | Parent scaffold for the other mitragynine compounds on this page. See Kratom Leaf. |
| 7-Hydroxymitragynine (7-OH) | Oxidation at C-7 of the mitragynine scaffold | CYP3A enzymes form 7-OH from mitragynine in human liver preparations. Mouse work found that formed 7-OH contributed to mitragynine antinociception. That does not establish the same contribution to every human effect. |
| 7-Acetoxymitragynine | The C-7 acetate ester of 7-OH | A 2002 synthesis and isolated-tissue study found low maximal inhibition in guinea-pig ileum. Its hydrolysis, pharmacokinetics, and human activity remain unreported in the cited literature. |
| MGM-15 | 1,2-dihydro-7-hydroxymitragynine; reduction of the N(1)-C(2) bond in 7-OH | A semi-synthetic µ/δ ligand studied in receptor systems and mice. A 2025 study confirmed MGM-15 in MGM-labeled tablets bought from a commercial source. Researchers have not published controlled human pharmacology. |
| MGM-16 | The fluorinated analog of MGM-15 | A semi-synthetic µ/δ agonist studied in receptor systems and mouse pain models. Researchers have not published human pharmacology. |
| Mitragynine pseudoindoxyl | A spiro-pseudoindoxyl rearrangement product in the mitragynine series | A potent MOR ligand in mouse-receptor assays. 7-OH converted to pseudoindoxyl in human plasma in vitro; that experiment did not establish the extent of this conversion in people. |
The Chemical Structures appendix shows the skeletal formulas.
MGM-15 identity and product labels
MGM-15 has a defined chemical identity: 1,2-dihydro-7-hydroxymitragynine. DHM is an ambiguous abbreviation that can appear on products without specifying which bond was reduced. A CFSRE forensic monograph identified MGM-15 in some drug materials represented as DHM, so the two names do overlap in the market. MIT-A is a marketing label, not a stable chemical name in the peer-reviewed literature.
A 2025 analysis identified MGM-15 in tablets sold with MGM labeling. That result verifies the tablets tested in that study; it does not verify every product sold under MGM, DHM, or MIT-A branding. Product identity requires compound-specific laboratory analysis. A 2026 product survey found frequent differences between labels and measured contents across tablets, films, and liquid shots.
Four measurements that answer different questions
| Measurement | What it measures | What it does not show |
|---|---|---|
| Kᵢ, binding affinity | The concentration-dependent displacement of a radioligand at equilibrium. Lower Kᵢ means tighter binding within that assay. | Residence time, signaling strength, dose, duration, or clinical potency. |
| EC₅₀, functional potency | The concentration that produces half of a compound’s maximum response in a stated functional assay. | Binding affinity or the size of that maximum response. |
| Emax, efficacy | The largest response measured in that assay, with the result often normalized to a reference agonist. | A universal property independent of receptor density, cell type, pathway, and reference drug. |
| ED₅₀, organism-level potency | The dose that produces half of a defined endpoint in a particular animal model and route. | Human dose equivalence or receptor affinity. |
Exposure adds another layer. Dose, absorption, route, protein binding, distribution, metabolism, and clearance determine how much active compound reaches a receptor and for how long.
MOR binding affinity, compared within assays
There is no defensible universal ranking made by pasting Kᵢ values from different laboratories into one list. Species, receptor construct, membrane preparation, radioligand, and analysis method can all shift the result. The tables below preserve the comparisons from each experiment.
Human cloned receptors in one 2026 assay
Hemby et al. 2026 used the same radioligand-binding method in CHO-K1 cells expressing human opioid receptors.
| Compound | hMOR Kᵢ, nM | Interpretation within this experiment |
|---|---|---|
| Morphine | 1.50 ± 0.04 | Tightest of these three |
| 7-OH | 15.1 ± 3.7 | About 16-fold tighter than mitragynine and about 10-fold weaker than morphine |
| Mitragynine | 238 ± 28 | Weakest of these three |
Mouse cloned receptors in one 2016 assay
Váradi et al. 2016 used CHO cells expressing cloned mouse opioid receptors and a different radioligand.
| Compound | mMOR-1 Kᵢ, nM | Interpretation within this experiment |
|---|---|---|
| Mitragynine pseudoindoxyl | 0.75 ± 0.18 | Tightest of these four |
| Morphine | 4.6 ± 1.8 | Reference |
| 7-OH | 37 ± 4 | About sixfold tighter than mitragynine |
| Mitragynine | 230 ± 47 | Weakest of these four |
Brain-membrane binding in one 2014 assay
Matsumoto et al. 2014 measured MOR binding in guinea-pig brain membranes. This assay included MGM-15 and MGM-16 but not 7-OH or pseudoindoxyl in the reported comparison.
| Compound | MOR Kᵢ, nM | DOR Kᵢ, nM |
|---|---|---|
| MGM-16 | 2.1 ± 0.028 | 7.0 ± 0.23 |
| Morphine | 2.7 ± 0.24 | 40 ± 6.0 |
| MGM-15 | 6.4 ± 0.30 | 16 ± 1.0 |
Within this experiment, morphine had a lower MOR Kᵢ than MGM-15. MGM-16 had a lower MOR Kᵢ than morphine. Both MGM compounds also bound DOR, which is why the paper described them as µ/δ ligands.
Do not compare 0.75 nM from the mouse-clone table with 1.50 nM from the human-clone table. Those values came from different systems. They support within-study comparisons, not a single league table across all compounds.
Binding does not settle agonist efficacy
Functional assays ask what the receptor system does after a compound binds. The answer can change with the pathway and experimental system.
| Study and system | Mitragynine at MOR | 7-OH at MOR |
|---|---|---|
| Kruegel et al. 2016, G-protein BRET at human MOR | EC₅₀ 339 ± 178 nM; Emax 34% of DAMGO | EC₅₀ 34.5 ± 4.5 nM; Emax 47% of DAMGO |
| Obeng et al. 2021, [³⁵S]GTPγS at human MOR | No detectable agonist response under the reported conditions; the researchers measured antagonist behavior | Emax 41.3%; partial agonism under the reported conditions |
| Hemby et al. 2026, inhibition of cAMP at human MOR | EC₅₀ 396.0 ± 22.6 nM; Emax 69.4% of DAMGO | Table 2 reports EC₅₀ 9.7 ± 0.8 nM; Emax 97.6% of DAMGO |
The Hemby paper’s narrative gives different 7-OH cAMP point estimates from its Table 2: 13.6 nM and 85.9%. This page reproduces the table values. The paper does not explain the discrepancy.
Either set places 7-OH near the reference agonist’s maximum in that cAMP system, unlike the lower maxima in the BRET and [³⁵S]GTPγS systems.
The same limitation applies to the semi-synthetic compounds. In the 2014 [³⁵S]GTPγS assay, MGM-15 produced 72 ± 4.7% of the MOR reference maximum (EC₅₀ 250 ± 61 nM), while MGM-16 produced 94 ± 1.8% (EC₅₀ 18 ± 0.055 nM). Váradi et al. reported pseudoindoxyl at 84 ± 5% in a mouse-MOR [³⁵S]GTPγS assay. A label such as “partial agonist” or “full agonist” must therefore name the assay and reference. It is not a permanent ranking of the molecules.
β-arrestin results do not prove respiratory safety
Kruegel et al. did not detect β-arrestin-2 recruitment by mitragynine or 7-OH at hMOR in their assay. Hemby et al. also found no detectable hMOR β-arrestin-2 recruitment for either compound under its conditions. These are cell-signaling results, not clinical safety outcomes.
A three-laboratory replication found morphine and fentanyl respiratory depression unchanged in β-arrestin-2 knockout mice (Kliewer et al. 2020). Failure to recruit β-arrestin in one cell assay cannot establish a human respiratory ceiling or rule out overdose risk.
Metabolism changes which molecule reaches the receptor
Kruegel et al. 2019 showed CYP3A-mediated conversion of mitragynine to 7-OH in mouse and human liver preparations. In mice, generated 7-OH reached brain concentrations that could account for much of mitragynine’s MOR-mediated antinociception. The experiment did not show that 7-OH mediates every effect of mitragynine in people.
Kamble et al. 2020 found conversion of 7-OH to mitragynine pseudoindoxyl in human plasma in vitro. The rate was much lower in the tested nonhuman plasma. Human in-vivo formation and exposure were not measured by that experiment.
Researchers have not published comparable human pharmacokinetic data for MGM-15, MGM-16, or 7-acetoxymitragynine. An acetate ester’s susceptibility to hydrolysis does not show that 7-acetoxymitragynine acts as a 7-OH prodrug in people.
Limits of mouse potency figures
Matsumoto et al. measured thermal antinociception in a mouse tail-flick test. MGM-16’s reported ED₅₀ was about 71 times lower than morphine’s after subcutaneous dosing and about 240 times lower after oral dosing. Those ratios describe one endpoint, species, timing protocol, and route. They do not mean that MGM-16 is “240 times stronger” in people, and they do not provide a safe human dose.
The same paper found different receptor results for MGM-15 and MGM-16, which shows why the compound names should not be treated as one category. MGM-16 adds a fluorine substitution to MGM-15 and had higher MOR/DOR affinity and functional potency in those assays.
Supported conclusions and open questions
The evidence supports these conclusions:
- Matched human-MOR assays give 7-OH greater affinity and lower functional EC₅₀ values than mitragynine.
- The matched 2026 assay gives morphine about tenfold greater hMOR affinity than 7-OH.
- Pseudoindoxyl had subnanomolar affinity in one cloned mouse-MOR assay, but that number cannot be inserted into a human-receptor ranking.
- MGM-15 and MGM-16 bind both MOR and DOR in the published assays. MGM-16 was more potent than MGM-15 in the 2014 receptor and mouse studies.
- Agonist efficacy depends on the signaling assay. “Partial” is not a stand-alone claim without the assay, receptor system, and reference agonist.
The evidence does not establish:
- receptor-binding values as human dose conversions;
- a clinical potency ranking across morphine, 7-OH, MGM-15, MGM-16, and pseudoindoxyl;
- comparative human respiratory safety from β-arrestin assays;
- comparative rates of tolerance, dependence, or withdrawal from molecular structure alone;
- the contents of a product from a DHM, MIT-A, or MGM label alone; or
- human pharmacokinetics for MGM-15, MGM-16, or 7-acetoxymitragynine.
Research limits. This page explains molecular and preclinical evidence. It cannot tell you what to take or how to taper. For practical coming-off options, see Withdrawal Help and involve a clinician when you can.
Primary sources
- Hemby et al., Frontiers in Pharmacology 2026, matched human opioid-receptor binding and functional assays
- Váradi et al., Journal of Medicinal Chemistry 2016, pseudoindoxyl binding, signaling, and mouse antinociception
- Matsumoto et al., Journal of Pharmacology and Experimental Therapeutics 2014, MGM-15 and MGM-16 binding, signaling, and mouse antinociception
- Kruegel et al., Journal of the American Chemical Society 2016, human-receptor signaling by mitragynine and 7-OH
- Obeng et al., Journal of Pharmacology and Experimental Therapeutics 2021, matched binding and functional comparison of mitragynine, 7-OH, and reference opioids
- Kruegel et al., ACS Central Science 2019, conversion of mitragynine to 7-OH
- Kamble et al., ACS Pharmacology & Translational Science 2020, conversion of 7-OH to pseudoindoxyl in plasma in vitro
- Takayama et al., Journal of Medicinal Chemistry 2002, synthesis and isolated-tissue testing of 7-OH derivatives including 7-acetoxymitragynine
- Gour et al., Drug Testing and Analysis 2025, MGM-15 analysis in commercial tablets and human-receptor binding
- Gour et al., Drug Testing and Analysis 2026, label-content comparisons across semisynthetic kratom-derived products
- Kliewer et al., British Journal of Pharmacology 2020, multi-laboratory β-arrestin-2 knockout replication
Related pages
- Kratom minor alkaloids: receptor evidence beyond mitragynine
- Chemical Structures appendix: skeletal formulas for the compounds discussed here
- Compounds: practical overviews for 7-OH, MGM-15, MGM-16, pseudoindoxyl, and kratom leaf