The classical opioids (morphine, codeine) and the kratom-derived alkaloids (mitragynine, 7-OH, MGM-15, pseudoindoxyl) hit the same receptor, but their structures, binding affinities, and what happens when you modify them in a lab are different in ways that matter for how dependence develops and how withdrawal behaves.
This page lines them up: structure family, key modification, µ-opioid receptor binding affinity, and what each modification does. It’s the molecular-level counterpart to the lay overviews in the Compounds section.
The compounds compared
Six compounds, five structurally related to mitragynine plus morphine as a reference from a different alkaloid family.
| Compound | Structural family | Notes |
|---|---|---|
| Morphine | Phenanthrene (poppy-derived) | Reference opioid. Not structurally related to mitragynine. |
| Mitragynine | Indole alkaloid (kratom leaf) | Parent compound. The other five on this page are all modifications of this molecule. See Kratom Leaf for the lay overview and the alkaloid-content profile. |
| 7-Hydroxymitragynine (7-OH) | Mitragynine + –OH at C-7 | The active metabolite of mitragynine in the body. Concentrated as a standalone product. See 7-OH. |
| 7-Acetoxymitragynine | 7-OH with the C-7 hydroxyl converted to an acetate ester | A prodrug, hydrolyzes back to 7-OH in the body. |
| Dihydro-7-hydroxymitragynine (MGM-15) | 7-OH with the indolenine C=N bond saturated (+H₂) | High-affinity semi-synthetic; one of the most potent kratom-derived compounds in widely-circulating products. Also sold as MIT-A and (mislabeled) DHM — see the note below. See MGM-15. Further modification (notably the 9-fluoro analog MGM-16) produces compounds more potent still in the published literature, though MGM-16 itself is not documented in any US consumer product as of this writing. |
| Pseudoindoxyl mitragynine | Mitragynine after oxidative rearrangement of the indole core to an indoxyl | See pseudo. |
Chemical structures for all six are on the Chemical Structures appendix.
A note on DHM and MIT-A
Products sold under the labels “DHM” or “MIT-A” have been characterized as MGM-15, not as a distinct compound. Dihydro- mitragynine (saturation of the side-chain C=C bond on mitragynine) is chemically possible in a lab but isn’t documented in characterized commercial products. References elsewhere on the site or on labels that say “DHM” or “MIT-A” are pointing at the same molecule covered by MGM-15.
Structural modifications and µ-opioid binding
Each modification in the table below is a single-step change from either mitragynine or 7-OH. The two modifications with the largest published affinity effects are hydroxylation at C-7 (mitragynine → 7-OH, the metabolite that mediates most of mitragynine’s opioid activity in vivo) and the oxidative indole-to-indoxyl rearrangement that produces pseudoindoxyl, which carries the highest µ-opioid affinity of the kratom-derived compounds on this page.
| Modification | Starts from | Produces | What it does |
|---|---|---|---|
| Hydroxylation at C-7 | Mitragynine | 7-Hydroxymitragynine | Adds a hydrogen-bond donor; large µ-opioid affinity jump |
| Reduction (+H₂) of indolenine C=N | 7-Hydroxymitragynine | Dihydro-7-hydroxymitragynine (MGM-15) | Flexible indoline; tightest receptor fit of the kratom-derived compounds |
| Acetylation of 7-OH | 7-Hydroxymitragynine | 7-Acetoxymitragynine | Ester caps the 7-OH; prodrug hydrolyzes back to 7-OH in vivo |
| Oxidative rearrangement (indole → indoxyl) | Mitragynine | Pseudoindoxyl mitragynine | Carbonyl H-bond acceptor; planar indoxyl core; moderate-to-high affinity |
Affinity is not activity (read this before the table)
Receptor binding affinity (Kᵢ) gets cited as if it’s the whole pharmacology story. It isn’t. Three independent things drive what a compound actually does:
- Affinity is how tightly the molecule sticks to the receptor. A low Kᵢ means it binds at low concentrations and stays bound; a high Kᵢ means weaker binding. The Kᵢ values in the table below are all µ-opioid affinities.
- Activity (also called intrinsic activity or efficacy) is
what the receptor does once the molecule is bound. Three
patterns:
- Full agonists activate the receptor maximally. Morphine, fentanyl, and oxycodone behave this way at µ.
- Partial agonists activate the receptor at less than the maximum, no matter how much you take. This is the ceiling effect. Buprenorphine is the textbook example: very high µ-affinity (~0.2 nM, tighter than morphine), but its maximum receptor activation sits well below morphine’s. That’s why bupe can be safer in overdose despite binding so tightly. All of the kratom-derived compounds on this page — mitragynine, 7-OH, MGM-15, pseudoindoxyl — are partial µ agonists in the published receptor-pharmacology work. Their differences in effect come from differing affinity (how much receptor occupancy they get at a given dose) and differing partial- activity ceilings (how much activation that occupancy produces), not from one being a full agonist and another being partial.
- Antagonists bind without activating, and block agonists. Naloxone (Narcan) is the canonical µ antagonist; naltrexone is longer-acting.
- Exposure is how much of the molecule actually reaches the receptor, which depends on dose, pharmacokinetics (half-life, absorption), and route of administration.
The combination is what matters in real life. A low-Kᵢ partial agonist (buprenorphine, mitragynine) can produce less effect than a moderate-Kᵢ full agonist (morphine). A “very high affinity” compound dosed at micrograms produces very different real-world receptor occupancy than a “moderate affinity” compound dosed at milligrams.
The table below shows column 1: affinity. It does not show columns 2 or 3. Read it as “how tightly each compound binds µ,” then come back here when interpreting what that means for effect at typical doses.
µ-opioid receptor binding affinity ranking
Compounds ranked by reported µ-opioid receptor binding affinity (Kᵢ, in nanomolar, lower = tighter binding). Values vary by species, methodology, and laboratory; ranges below reflect the range across published studies rather than a single canonical value.
| Compound | Kᵢ (µ-opioid) | Source |
|---|---|---|
| Pseudoindoxyl mitragynine (pseudo) | ≈ 0.8 nM | Varadi et al. 2016 (MOR-1) |
| Morphine | ≈ 1 nM | reference (classical literature) |
| Dihydro-7-hydroxymitragynine (MGM-15) | 6.4 nM | Matsumoto et al. 2014 (guinea pig brain, [³H]DAMGO displacement) |
| 7-Hydroxymitragynine | ≈ 7–47 nM | Obeng et al. 2020 (hMOR, ~7 nM); Matsumoto et al. 2004 (guinea pig brain, 37–47 nM) |
| Mitragynine | ≈ 160–240 nM | Obeng et al. 2020 (hMOR, 161 nM); older guinea pig brain assays report 80–230 nM. Kruegel et al. 2019 reports functional EC₅₀ 339 nM at hMOR, not Kᵢ. |
| 7-Acetoxymitragynine | Not formally established | hydrolyzes to 7-OH in vivo |
Potency rankings vary by what’s measured. Receptor binding studies, isolated-tissue analgesia, behavioral models, and human reports don’t always order the same way. The table above reflects receptor-binding affinity specifically. See Affinity is not activity above for what affinity does and doesn’t tell you.
Implications for the kratom synthetic landscape
Every compound on this page except morphine is a one- or two-step modification of mitragynine. The dominant chemistry pattern of the kratom synthetic market is: start with mitragynine; add an –OH at C-7 (or convert to its ester); optionally further modify to extend the duration or shift the receptor profile; sell the result. MGM-15 (the dihydro reduction of 7-OH) is a µ/δ dual agonist (Matsumoto et al. 2014 report MOR Kᵢ 6.4 nM, DOR Kᵢ 16 nM) and is reported as longer-acting in community use, though human plasma PK isn’t formally published; pseudoindoxyl (the indoxyl rearrangement) carries the highest µ-affinity of any kratom-derived compound characterized so far. Both sit on top of the mitragynine → 7-OH step.
This is part of why the concentrated synthetic products are qualitatively different from leaf kratom in dependence formation speed and withdrawal severity. The mitragynine in leaf reaches the µ receptor in the body primarily through its conversion to 7-OH; concentrated 7-OH delivers the active compound directly, at doses the leaf can’t produce. The clinical and lay implications are on the Compounds section pages; this page is the structural-pharmacology counterpart.
A note on this list’s scope. The six compounds above aren’t the ceiling of what’s chemically possible from the mitragynine scaffold, they’re the ones with characterized µ-opioid affinity data and clinical exposure. More aggressively modified analogs exist (the 9-fluoro analog MGM-16 is the most-discussed example, reported at approximately 240× the potency of morphine orally and ~71× subcutaneously in mouse tail-flick antinociception assays per Matsumoto et al. 2014). They aren’t ranked here because the receptor-binding literature for them is thinner. Don’t read this table as the complete spectrum; read it as the slice with reliable data.
Reference, not advice. This is structural pharmacology. It won’t tell you what to take or how to taper, those decisions belong with a clinician familiar with your situation. For coming-off paths see Withdrawal Help.
Sources
- León et al., J Med Chem 2021 , receptor pharmacology of mitragynine alkaloids
- Obeng et al., J Med Chem 2020 , receptor profile of mitragynine derivatives
- Mitragynine pharmacology review (Mitragyna speciosa, Wikipedia summary with primary refs)
- Chemical Structures (appendix) , 2D skeletal-formula diagrams
Where to read next
- Minor Alkaloids: the six better-studied alkaloids beyond mitragynine and their activity across µ-opioid, serotonergic, and adrenergic systems
- Chemical Structures (Appendix) , visual structures for everything on this page
- Compounds: the clinical / lay overviews per compound: 7-OH, MGM-15 (which covers what’s sold as MIT-A and DHM), pseudo, kratom leaf