Kratom leaf contains multiple alkaloids; the two that matter clinically are mitragynine and 7-hydroxymitragynine (7-OH). 7-OH binds the mu-opioid receptor more tightly than mitragynine and drives the opioid-like risk of concentrated 7-OH products. This page covers the receptor pharmacology of both alkaloids and why concentrated 7-OH is clinically different from plain kratom leaf.
This page is optional reading. You do not need to understand pharmacology to succeed in treatment.
This is a science page, not a treatment plan. Use your personalized plan from your provider for any medication instructions.
What is kratom?
Kratom is the leaf of Mitragyna speciosa, a tropical tree in the coffee family (Rubiaceae). The leaves contain more than 40 alkaloids. The two most clinically discussed are mitragynine and 7-hydroxymitragynine (7-OH). Kratom leaf, extracts, and concentrated 7-OH products are not all the same — product type, dose, concentration, frequency, and co-use with other substances all matter.
→ Read more: What is kratom? A clinical overview.
What is 7-hydroxymitragynine (7-OH)?
7-hydroxymitragynine (7-OH) is a potent indole alkaloid derived from the Mitragyna speciosa (kratom) tree. It occurs naturally in kratom leaf in very small amounts — often less than 0.05% of the leaf's dry weight (FDA's 7-OH scientific assessment). When kratom is consumed, the human body also produces a small amount of 7-OH endogenously via CYP3A4-mediated oxidation of mitragynine (Kruegel et al., ACS Cent. Sci. 2019).
In mice, plasma 7-OH appears at roughly 1/15 of mitragynine concentration after oral mitragynine dosing (Kruegel et al. 2019). Although 7-OH is a small fraction of mitragynine exposure, it is much more potent at the mu-opioid receptor and is believed to account for much of kratom's opioid-like effects.
Recently, 7-OH has been synthetically produced and isolated, and is now commonly sold in smoke shops — most often as chewable tablets, gummies, dissolvables, or "shots." Because these products deliver 7-OH at amounts far beyond what occurs naturally in plain kratom leaf, they have earned the nickname "gas station opioid." FDA describes 7-OH as having potent mu-opioid agonist properties and significant misuse liability.
How does 7-OH interact with opioid receptors?
7-OH acts as a partial agonist at mu (µ)-opioid receptors and as an antagonist at delta (δ) and kappa (κ) opioid receptors. The WHO 44th ECDD pre-review describes both mitragynine and 7-OH as partial mu-opioid receptor agonists, with 7-OH binding 5–23 times more strongly to the mu-receptor than mitragynine.
- µ (mu)-opioid receptor: partial agonist. Where 7-OH produces analgesic, sedative, and euphoric effects.
- δ (delta)-opioid receptor: antagonist. The δ-receptor is normally linked to mood effects and tolerance. Blocking it may theoretically blunt some antidepressant or euphoric effects and slow tolerance development.
- κ (kappa)-opioid receptor: antagonist. The κ-receptor is normally associated with dysphoria, anxiety, and hallucinations. Blocking it may reduce those unpleasant effects, which paradoxically may increase 7-OH's misuse liability by removing the natural "brake" on opioid reinforcement.
Notably, although 7-OH binds the mu-receptor more strongly than mitragynine does, morphine has greater mu-receptor affinity than 7-OH (8–10× higher per WHO summary), and 7-OH's higher functional potency comes from a combination of binding, intrinsic activity, and signaling efficiency rather than affinity alone.
What is biased agonism — and why does it matter for 7-OH?
After binding the mu-opioid receptor, 7-OH preferentially activates the G-protein signaling pathway while only weakly triggering the β-arrestin-2 pathway. Because β-arrestin-2 signaling is linked to several classic opioid adverse effects — respiratory depression, constipation, and tolerance — some studies suggest 7-OH may produce fewer of these effects at analgesic doses, with a relative ceiling on respiratory depression compared to full agonists like morphine.
How do affinity, occupancy, efficacy, and potency fit together?
Four pharmacology concepts are often confused but mean different things. A useful analogy: imagine a room full of seats (the receptors). A molecule has to reach the room, find a seat, stay in the seat, and then turn on the receptor. Each of those steps is governed by a different property.
1. Affinity — the grip
Affinity describes how strongly a molecule binds to a receptor. A high-affinity molecule is more likely to attach and stay attached. 7-OH has demonstrated high affinity for mu-opioid receptors in multiple binding studies (FDA; Hiranita et al., JPET 2021).
One important nuance: 7-OH has substantially greater receptor affinity than mitragynine, but per the WHO pre-review, morphine has greater affinity than 7-OH in summarized studies. Affinity comparisons depend on the assay and should be stated carefully.
2. Occupancy — how many seats are filled
Occupancy is how many receptors are occupied at a given exposure. It depends on dose, absorption, blood level, receptor affinity, metabolism, and how quickly the substance leaves the body. Because 7-OH is potent and binds the mu-opioid receptor, concentrated products may produce a large opioid-like effect from relatively small amounts. Exact human receptor occupancy depends on exposure and has not been established as a simple public number.
3. Efficacy — the key turn
After a molecule binds, efficacy describes how strongly it activates the receptor. Some studies describe mitragynine and 7-OH as partial agonists at the mu-opioid receptor (WHO ECDD), with 7-OH having greater receptor activation than mitragynine. Functional assays do not all agree — some find partial agonist activity, others find full agonist-like behavior. FDA summarizes 7-OH as producing mu-opioid agonist effects without committing to a single classification.
4. Potency — the punch
Potency means the amount needed to produce a given effect. FDA reports that in one functional assay (Takayama et al. 2002, guinea pig ileum bioassay), 7-OH was approximately 13-fold more potent than morphine and 46-fold more potent than mitragynine. FDA also reports preclinical data showing 7-OH produced respiratory depression with more than 3-fold greater potency than morphine.
These numbers should not be used as patient dosing conversions. Potency depends on the assay, the endpoint, the route of administration, and the species. The clinical point is that concentrated 7-OH products can deliver strong opioid-like effects at small amounts.
5. Pharmacokinetics — how it moves through the body
Kratom pharmacokinetics are still being characterized. The WHO pre-review cites a small human study (Trakulsrichai et al. 2015, n=10 daily kratom users) reporting a mitragynine terminal half-life of ~23 ± 16 hours. Human data on oral bioavailability of mitragynine and 7-OH remain limited.
Because kratom and 7-OH products vary widely, and because human PK data are limited, induction timing and start plans should be individualized by your provider — not based on a simple universal rule.
Pharmacology at a glance
| Concept | Scientific term | Simple analogy | Why it matters for 7-OH |
|---|---|---|---|
| Affinity | Binding affinity / Ki | The grip | 7-OH binds mu-opioid receptors with substantially greater affinity than mitragynine; morphine has greater affinity than 7-OH per WHO. |
| Occupancy | Fractional receptor occupancy | Musical chairs | The more receptor "seats" occupied at a given exposure, the larger the opioid-like signal. Exact human occupancy is not a simple public number. |
| Efficacy | Intrinsic activity | The key turn | 7-OH produces mu-opioid agonist effects; studies differ on partial vs full agonist-like behavior depending on the assay. |
| Potency | EC50 / dose-response | The punch | 7-OH produces strong effects at small amounts (FDA: ~13× morphine, 46× mitragynine in Takayama 2002 guinea-pig ileum assay). |
| Pharmacokinetics | Absorption, metabolism, half-life | How fast it gets in, how long it stays | Mitragynine half-life ~23 ± 16 h in a small daily-user study (Trakulsrichai 2015). Human PK data limited; start plans must be individualized. |
Think of opioid receptors like seats in a room.
A substance has to reach the room, find a seat, stay there, and turn on the receptor.
Concentrated 7-OH products are concerning because 7-OH binds mu-opioid receptors and produces strong opioid-like effects at small amounts.
That does not mean every kratom product is the same. Plain kratom leaf, kratom extracts, and concentrated 7-OH products can have very different risk profiles.
The practical point is simple: concentrated 7-OH can act much more like an opioid than people expect. That is why dependence can escalate quickly and withdrawal can feel intense.
- U.S. Food and Drug Administration — FDA and Kratom (including 7-OH scientific assessment).
- U.S. Food and Drug Administration — Products Containing 7-OH Can Cause Serious Harm.
- World Health Organization — 44th ECDD Pre-Review of Kratom (Mitragyna speciosa) and Its Alkaloids.
- Kruegel AC, Uprety R, Grinnell SG, et al. 7-Hydroxymitragynine Is an Active Metabolite of Mitragynine and a Key Mediator of Its Analgesic Effects. ACS Central Science 2019.
- Hiranita T, et al. Mitragynine and 7-Hydroxymitragynine: Discrimination, Reinforcement, and Antinociception. JPET 2021.
- Trakulsrichai S, et al. Pharmacokinetics of mitragynine in man. Drug Des Devel Ther 2015.
- Gillis A, Sreenivasan V, Christie MJ. Intrinsic Efficacy of Opioid Ligands and Its Importance for Apparent Bias, Operational Analysis, and Therapeutic Window. Trends Pharmacol. Sci. 2020.
- Blue Ridge Poison Center, UVA Health. ToxTalks: 7-hydroxymitragynine — The newest smoke shop craze. August 2025.
Last reviewed: May 2026 · Reviewed by: MyStreetHealth Medical Team
