Siti R. Yusof et al. (2018). Rate And Extent Of Mitragynine And 7‐Hydroxymitragynine Blood–Brain Barrier Transport And Their Intra‐Brain Distribution: The Missing Link In Pharmacodynamic Studies. Addiction Biology, 24, 935 - 945. https://doi.org/10.1111/adb.12661.

Title: BBB Transport and Brain Distribution of Kratom Alkaloids

Research Scope and Objectives

The latest research paper delves into the intricate world of mitragynine and 7-hydroxymitragynine, the active compounds found in the plant Mitragyna speciosa, commonly known as kratom. Kratom, with its reported potential in managing chronic pain and aiding in opioid withdrawal, has sparked interest, especially amidst the opioid crisis. This study aimed to uncover the mystery surrounding the blood-brain barrier (BBB) transport of mitragynine and 7-hydroxymitragynine, shedding light on their interaction with the efflux transporter P-glycoprotein (P-gp) and their distribution within the brain. The researchers utilized in vitro models to study the rate of BBB permeation of the compounds and their interaction with P-gp. Interestingly, mitragynine exhibited higher permeability than 7-hydroxymitragynine, indicating a potential for better transport across the BBB. Both compounds were found to inhibit P-gp and were subject to efflux by this transporter.

In Vivo Observations in Rats

In vivo studies in rats revealed that less than 10% of unbound mitragynine and 7-hydroxymitragynine in plasma were able to cross the BBB. However, the intra-brain distribution of the compounds differed significantly, with mitragynine showing an 18-fold higher brain tissue uptake compared to 7-hydroxymitragynine. Mitragynine also displayed a moderate capacity to accumulate inside brain parenchymal cells, while 7-hydroxymitragynine had restricted cellular barrier transport.

Insights and Implications of Findings

The findings from this comprehensive investigation provide essential insights into the pharmacokinetics of mitragynine and 7-hydroxymitragynine, crucial for designing and interpreting future experiments aimed at establishing exposure-response relationships. Understanding how these compounds interact with the BBB and intra-brain distribution could pave the way for more effective and targeted treatments for pain management and opioid withdrawal. The study's detailed methodologies and results offer a significant contribution to the field, unlocking a missing link in the pharmacodynamic studies of these plant-derived compounds.