Human Mitragynine and 7-Hydroxymitragynine Pharmacokinetics after Single and Multiple Daily Doses of Oral Encapsulated Dried Kratom Leaf Powder

Authors

Marilyn A. Huestis, Thomas Jefferson UniversityFollow
Martin A. Brett
John Bothmer
Ramsey Atallah

Document Type

Article

Publication Date

2-23-2024

Comments

This article is the author's final published version in Molecules, Volume 29, Issue 5, March 2024, Article number 984.

The published version is available at https://doi.org/10.3390/molecules29050984.

Copyright © 2024 by the authors

Abstract

Kratom leaves, consumed by millions worldwide as tea or ground leaf powder, contain multiple alkaloids, with mitragynine being the most abundant and responsible for most effects. Mitragynine is a partial µ-opioid receptor agonist and competitive antagonist at κ- and δ-opioid receptors; however, unlike morphine, it does not activate the β-arrestin-2 respiratory depression pathway. Due to few human mitragynine data, the largest randomized, between-subject, double-blind, placebo-controlled, dose-escalation study of 500–4000 mg dried kratom leaf powder (6.65–53.2 mg mitragynine) was conducted. LC-MS/MS mitragynine and 7-hydroxymitragynine plasma concentrations were obtained after single and 15 daily doses. Mitragynine and 7-hydroxymitragynine C_max increased dose proportionally, and AUC was slightly more than dose proportional. The median mitragynine T_max was 1.0–1.3 h after single and 1.0–1.7 h after multiple doses; for 7-hydroxymitragynine T_max, it was 1.2–1.8 h and 1.3–2.0 h. Steady-state mitragynine concentrations were reached in 8–9 days and 7-hydroxymitragynine within 7 days. The highest mean mitragynine T_1/2 was 43.4 h after one and 67.9 h after multiple doses, and, for 7-hydroxymitragynine, it was 4.7 and 24.7 h. The mean 7-hydroxy-mitragynine/mitragynine concentration ratios were 0.20–0.31 after a single dose and decreased (0.15–0.21) after multiple doses. These mitragynine and 7-hydroxymitragynine data provide guidance for future clinical kratom dosing studies and an interpretation of clinical and forensic mitragynine and 7-hydroxymitragynine concentrations.

Recommended Citation

Huestis, Marilyn A.; Brett, Martin A.; Bothmer, John; and Atallah, Ramsey, "Human Mitragynine and 7-Hydroxymitragynine Pharmacokinetics after Single and Multiple Daily Doses of Oral Encapsulated Dried Kratom Leaf Powder" (2024). Institute of Emerging Health Professions Faculty Papers. Paper 27.
https://jdc.jefferson.edu/iehpfp/27

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.

Language

English