How to read receptor data
- Affinity — how strongly a molecule binds
- Potency — concentration for a defined assay effect
- Efficacy — response size relative to a reference agonist
- Clinical relevance — whether human exposure reaches the needed tissue concentration long enough to matter
Mu-opioid receptor (dominant pathway)
7-OH is a high-potency human MOR agonist. In a 2026 systematic human-receptor study it bound hMOR with nanomolar affinity and produced cAMP signaling with high measured efficacy in that system; earlier lower-reserve assays described lower maximal efficacy.
Defensible synthesis: 7-OH is a high-potency MOR agonist with strongly G-protein-biased and assay-dependent intrinsic efficacy. It behaves as a partial agonist in some systems and approaches full functional efficacy in others. That is more accurate than unqualified “full” or “weak partial.”
Signaling bias is not proven human safety
Preferential G-protein signaling with little β-arrestin-2 recruitment in some assays is mechanistically interesting. It does not justify claims that 7-OH cannot cause respiratory depression, tolerance, or dependence. Rat work has shown naloxone-reversible ventilatory depression.
Kappa and delta
Secondary KOR activity appears in some functional systems; contribution to human intoxication, dysphoria, analgesia, or withdrawal is not quantified. 7-OH also shows reproducible DOR activity in newer human cAMP work at lower potency; clinical contribution remains unknown. There is no accepted “gamma opioid receptor” for 7-OH or kratom.
Nonopioid pathways (mainly botanical)
Best-supported nonopioid pathway in botanical kratom is 5-HT1A activation by metabolites of minor alkaloids—not proof that purified 7-OH is a serotonergic antidepressant. Mitragynine shows low-potency α1A agonism and α2A antagonism in contemporary human-receptor experiments; neither 7-OH nor 9-hydroxycorynantheidine supports the claim that major metabolites directly activate α2 receptors.
What not to put on an “activated receptors” diagram
- Functionally activated at plausible potency: MOR; KOR/DOR in selected compounds/assays; 5-HT1A for two O-desmethyl metabolites; α1A for mitragynine
- Binds or modulates without established activation: several serotonin/dopamine targets, α2A antagonism, hERG/channel effects, CYP enzymes, speciophylline MOR allosteric modulation
- Unsupported as principal mechanism: CB1-mediated analgesia, direct α2 agonism by mitragynine, “gamma opioid receptor”
Deep references
- Appendix D — receptor target catalogue
- Pharmacology & testing combined reference
- Full longform resource (modules 03–04 and receptor tables)
- Chemistry & testing summary