Pharmacokinetic-Pharmacodynamic Modeling of the Antinociceptive Effect of Mitragynine, the Most Abundant Kratom Alkaloid in Mice

Mitragyna speciosa Korth, commonly known as kratom, is a tree native to Southeast Asia. Kratom leaves and its brewed tea have been consumed traditionally as a folk remedy and drink for social gatherings in Malaysia and Thailand. It is self-prescribed for mood elevation, pain relief, and/or mitigation of opioid withdrawal symptoms. Mitragynine is the most abundant kratom alkaloid (~40% of total alkaloidal content) and is considered to be responsible for the therapeutic activity of kratom. Mitragynine is a partial agonist at µ-opioid and a competitive antagonist at alpha1A receptor. It has shown promising activity to reduce heroin self-administration without tolerance or cross-tolerance to morphine. During this rapid-fire session, we will discuss the phytochemistry, pharmacokinetics, and PK-PD model for the translational development of mitragynine as a treatment for opioid use disorder.