Assessing the Pharmacokinetics and Drug Interaction Liability of Kratom, an Opioid-like Natural Product

This healthy-volunteer crossover study evaluates whether a well-characterized kratom product (2 g oral tea) alters the pharmacokinetics of validated probe drugs for CYP3A4 (midazolam) and CYP2D6 (dextromethorphan).

Arm 1 administers kratom alone; Arm 2a gives the probe cocktail alone; Arm 2b gives kratom plus the probe cocktail, with a 7-day washout between relevant arms. Primary analyses will assess midazolam pharmacokinetics; secondary analyses include dextromethorphan and kratom constituent PK to inform PBPK modelling.