This is a laboratory reference. If you need help with active withdrawal, start with Withdrawal Help.
Researchers have reported more than 50 alkaloids across kratom specimens and chemical surveys. That count does not describe a fixed recipe. A validated 2022 assay found 12 or 13 of 14 targeted alkaloids in the commercial products it tested, with large differences in concentration between samples. The authors said the profiles suggested several plant chemotypes. Plant source and product processing can change the mixture.
The label minor alkaloid is imprecise. It can mean lower abundance, less research, or anything other than mitragynine. In the 2022 survey, the researchers classified paynantheine, speciociliatine, speciogynine, mitraciliatine, and isopaynantheine as major alkaloids, though their measured amounts varied by product. Other compounds appeared at lower levels or were harder to quantify.
Reading receptor data
Receptor papers measure different things. Combining those measurements into one “strength” ranking creates false certainty.
| Term | Meaning in a receptor study | Limit |
|---|---|---|
| Affinity (Kᵢ) | How well a compound displaced a labeled ligand from a receptor. A lower Kᵢ means stronger binding in that assay. | Binding alone does not show whether the compound activates or blocks the receptor. |
| Potency (EC₅₀ or IC₅₀) | The concentration that produced half of the measured effect. | Potency depends on the cell system, receptor density, signaling readout, and reference drug. |
| Efficacy (Emax) | The largest response measured relative to a reference agonist or antagonist. | A “partial” or “full” result can change with the assay and tissue. |
| Orthosteric agonist or antagonist | A compound binds at the receptor’s main ligand site and either activates it or blocks another agonist. | One signaling pathway may give a different classification from another. |
| Allosteric modulator | A compound changes the response to another ligand through a separate receptor site. | Modulation is not the same as activating the receptor on its own. |
Most results below come from engineered cells expressing human receptors, isolated animal tissue, or rodent experiments. They do not establish a human dose, a subjective effect, dependence liability, or a withdrawal syndrome.
The leaf and concentrated 7-OH are different mixtures
Leaf chemistry studies identify mitragynine alongside several related indole alkaloids, including paynantheine, speciogynine, speciociliatine, mitraciliatine, isopaynantheine, and corynantheidine. Kratom contains oxindole alkaloids such as mitraphylline and the corynoxines. The amount of each compound varies by plant and product.
Metabolism adds another layer. Human liver preparations convert mitragynine to 7-hydroxymitragynine (7-OH). In a controlled human tea study, the CYP3A inhibitor itraconazole lowered the ratio of 7-OH exposure to mitragynine exposure, supporting the same conversion in people. Researchers have studied 9-hydroxycorynantheidine, known as 9-O-desmethylmitragynine, as a metabolite and mitragynine analogue. Metabolism can raise exposure to an active product beyond the amount present in leaf. A cell response still needs pharmacokinetic evidence showing that the body reaches the tested concentration.
Concentrated 7-OH tablets need separate treatment. In one analysis of eight products labeled as kratom extracts, the researchers found 22 to 75 mg/g of 7-OH, low mitragynine, chromatograms that lacked other major leaf alkaloids, and unidentified peaks absent from authentic leaf. Those products did not reproduce the chemical mixture found in leaf. Researchers cannot infer a tablet’s ingredient list from leaf studies.
Opioid-receptor findings
A 2026 study tested a broad panel of kratom alkaloids under the same human μ-, κ-, and δ-opioid receptor methods. It paired radioligand binding with cAMP, β-arrestin-2, and GTPγS functional assays. The shared methods make comparisons within that paper more useful than numbers drawn from unrelated assays.
| Alkaloid | What the cited receptor studies found |
|---|---|
| Mitragynine | Reference compound. It had moderate μ-receptor affinity and acted as a partial μ-agonist in the 2026 cAMP assay. Liver-preparation and mouse studies found conversion to 7-OH; the mouse study linked that metabolite to mitragynine’s opioid-mediated analgesia. |
| Speciociliatine | Its human μ-receptor affinity exceeded mitragynine’s in the same 2026 assay (Kᵢ 49 vs. 238 nM), and it acted as a partial μ-agonist. This comparison says nothing about dose or exposure from leaf. |
| Paynantheine and speciogynine | Both produced weak, low-efficacy μ-agonist signals in the 2026 cAMP assay. A 2016 functional study reported μ-antagonism under its test conditions. Their classification depends on the assay and signaling readout. |
| Mitraciliatine and isopaynantheine | The 2026 cAMP and GTPγS assays found μ-antagonism plus κ-agonism. A 2021 BRET study classified mitraciliatine as a μ-partial agonist. The studies used different assay systems; researchers need to replicate the result. |
| Corynantheidine | An older isolated-tissue assay found μ-antagonism. A 2021 BRET study found partial agonism at the human μ-receptor (Emax about 37%) and μ-dependent antinociception after injection into the brains of mice. Calling it “the kratom opioid antagonist” hides that conflict. |
| 9-Hydroxycorynantheidine | An isolated guinea-pig ileum study found selective μ-receptor partial agonism. That experiment does not establish its effects after oral use in humans. |
| Corynoxine A, corynoxine B, and isospeciofoline | The 2026 panel found μ-agonism in its cAMP assay with little or no measurable β-arrestin-2 recruitment. These cell results do not establish a safety advantage. |
| Mitraphylline | The 2026 panel found no measurable orthosteric binding at human μ-, κ-, or δ-opioid receptors under its test conditions. |
The 2026 study found a different kind of signal from speciophylline (Uncarine D). It showed no measurable orthosteric binding or intrinsic agonism, yet it increased DAMGO binding and strengthened a submaximal met-enkephalin response at the human μ-receptor. The authors classified it as a positive allosteric modulator. Its functional potency was in the micromolar range, and no human study has shown that leaf use produces enough exposure for this effect.
Assay design explains some disagreement. Receptor species, cell type, receptor reserve, signaling pathway, and route of administration can change the measured response. An agonist label belongs to a stated experiment.
Serotonin findings
Paynantheine and speciogynine bound with high affinity to human 5-HT₁ₐ and 5-HT₂ᵦ receptors in a 2021 study. Neither parent alkaloid activated those receptors in the study’s cell assays. Their 9-O-desmethyl metabolites activated 5-HT₁ₐ signaling and reduced basal 5-HT₂ᵦ signaling.
The same researchers gave paynantheine and speciogynine to rats by injection. Both produced antinociception, and a selective 5-HT₁ₐ antagonist shifted the dose-response curves. That result supports a serotonin-dependent effect in that rat model. It does not show that either parent compound acts as a human antidepressant, or that stopping it causes an SSRI-like discontinuation syndrome.
No controlled human study has linked these alkaloids to brain zaps, mood changes, or a distinct serotonergic phase of kratom withdrawal.
Adrenergic findings
A 2020 binding screen found that corynantheidine had high affinity for the human α₁D adrenergic receptor (Kᵢ about 42 nM). The study measured binding, not whether corynantheidine activates or blocks α₁D signaling. Describing that result as “strong adrenergic activity” skips the missing functional experiment.
Mitragynine produced different adrenergic results across assay types. A 2025 study found low-potency partial agonism at one human α₁A signaling pathway and competitive antagonism at human α₂A receptors in cell-based tests. A 2024 study had found no significant α₂A activation in a GTPγS assay, yet mitragynine produced an α₂-agonist-like drug-discrimination effect in rats. The 2025 researchers tested more signaling pathways and found no evidence that mitragynine, 7-OH, or 9-hydroxycorynantheidine activated α₂ receptors. The rat result remains unexplained and does not establish α₂ agonism in humans.
Researchers can use binding screens to choose follow-up experiments. Binding alone does not establish that minor alkaloids drive the sweating, restlessness, blood-pressure changes, or anxiety of withdrawal.
Limits for 7-OH withdrawal
Controlled human withdrawal studies have not isolated individual minor alkaloids. Receptor studies cannot identify the minor alkaloids, metabolites, or synthesis byproducts in a specific concentrated product, or establish whether exposure reached a concentration that could affect serotonin or adrenergic signaling. A residual symptom during buprenorphine treatment could come from incomplete opioid coverage, another substance, sleep loss, dehydration, or a medical condition. Receptor data cannot choose among them.
Buprenorphine acts at opioid receptors. A symptom that remains after taking it does not identify a non-opioid mechanism. The receptor literature offers testable hypotheses, not an individual diagnosis.
Research limits. Do not use receptor affinities or cell assay potency to calculate doses, combine products, or self-treat withdrawal. Mixing 7-OH or other opioids with alcohol, benzodiazepines, gabapentinoids, or other depressants calls for medical supervision. For treatment help, call SAMHSA at 1-800-662-4357 or use FindTreatment.gov.
Sources
- Hemby et al., Frontiers in Pharmacology 2026, uniform human opioid-receptor binding, functional selectivity, and allosteric testing across indole and oxindole alkaloids
- Manwill et al., Planta Medica 2022, validated quantitation of 14 alkaloids in plants and commercial products
- León et al., Journal of Medicinal Chemistry 2021, serotonin-receptor binding, functional assays, metabolism, and rat antinociception
- Obeng et al., Journal of Medicinal Chemistry 2020, opioid and adrenergic binding plus functional testing of selected indole alkaloids
- Chakraborty et al., ACS Chemical Neuroscience 2021, human-receptor BRET assays and mouse experiments on minor indole and oxindole alkaloids
- Kruegel et al., Journal of the American Chemical Society 2016, human opioid-receptor signaling assays of mitragynine, paynantheine, speciogynine, and speciociliatine
- Obeng et al., European Journal of Pharmacology 2024, α₂-receptor testing in human-cell assays and rat drug-discrimination experiments
- Chen et al., ACS Chemical Neuroscience 2025, mitragynine and metabolite testing at α-adrenergic receptors
- Matsumoto et al., Life Sciences 2006, 9-hydroxycorynantheidine in isolated guinea-pig ileum
- Kruegel et al., ACS Central Science 2019, conversion of mitragynine to 7-OH in liver preparations and mice
- Mongar et al., ACS Pharmacology & Translational Science 2024, human pharmacokinetics of mitragynine and 7-OH formed through metabolism after kratom tea
- Brown et al., Journal of AOAC International 2026, analysis of eight commercial products labeled as 7-OH kratom extracts
Related pages
- Chemical Structures shows the skeletal formulas for selected alkaloids, metabolites, and derivatives.
- Kratom Leaf covers leaf composition and use in plain language.
- Morphine vs. Mitragyna Alkaloids compares selected structures and opioid-receptor measurements.
- 7-OH covers concentrated 7-OH products and their withdrawal profile.