Kratom living monograph
μ-opioid receptors, 7-OH formation, CYP3A, and uncertain adrenergic evidence.
Pharmacology
The effect profile arises from multiple alkaloids and metabolites. Cellular and animal findings can explain possible mechanisms but do not replace clinical efficacy or safety evidence.
Mitragynine and especially 7-hydroxymitragynine show opioid-receptor activity. Preclinical studies describe signalling that differs from classic full agonists; this must not be interpreted as absence of breathing or dependence risk.
Journal of the American Chemical Society, 2016ACS Central Science, 2019WHO Expert Committee on Drug Dependence, 2021Preclinical work and a small human study support CYP3A-mediated conversion of mitragynine to 7-OH as a contributor to effects. The extent can vary with product, metabolism, and interactions.
ACS Central Science, 2019ACS Pharmacology & Translational Science, 2024Animal studies showed alpha-2-like functional effects, while newer receptor studies do not support a simple alpha-2 agonist explanation and report antagonist or alpha-1A partial-agonist activity. “Alpha-2 agonist” is therefore not an established clinical shorthand.
European Journal of Pharmacology, 2024ACS Chemical Neuroscience, 2025Kratom alkaloids use several metabolic pathways. Small human studies show a clinical interaction signal at intestinal CYP3A; laboratory findings alone cannot predict every medication interaction.
Clinical Pharmacology & Therapeutics, 2023ACS Pharmacology & Translational Science, 2024Mechanisms depend on product and alkaloid composition. Findings for an isolated molecule must not be transferred uncritically to leaf, extracts, or mixed products.
Trust
Each source is tied to a claim domain. “Reviewed” means editorial source review—not individual medical clearance.
Pharmaceutics · 2022
Contributes: Analysed 2 g leaf product; human PK for multiple alkaloids.
Limit: Only six healthy participants and one low exposure; not generalisable to extracts.
Clinical Pharmacology & Therapeutics · 2023
Contributes: Controlled study in twelve people; modest midazolam/intestinal-CYP3A signal.
Limit: Low tea exposure and small healthy sample; not generalisable to high exposure, extracts, or every medicine.
ACS Pharmacology & Translational Science · 2024
Contributes: Small clinical study supports CYP3A-mediated formation of 7-OH in humans.
Limit: Specific tea/inhibitor protocol; not a complete explanation of subjective effects.
Journal of the American Chemical Society · 2016
Contributes: Receptor and signalling data for Mitragyna alkaloids.
Limit: Predominantly preclinical; cellular signalling is not a clinical safety guarantee.
ACS Central Science · 2019
Contributes: Preclinical data on 7-OH formation, potency, and opioid activity.
Limit: Animal, cellular, and ex-vivo evidence; not a direct clinical dosing basis.
European Journal of Pharmacology · 2024
Contributes: In-vitro and animal data on adrenergic hypotheses.
Limit: No clinical confirmation; functional animal findings without simple in-vitro receptor activation.
Contributes: Newer in-vitro findings challenge a simple alpha-2 agonist classification.
Limit: Receptor assay without clinical exposure or outcome assessment.
