Complicating Factors Surrounding Concurrent Use of Kratom and a Novel 7-hydroxymitragynine Product Among a Participant Enrolled in a Kratom Clinical Trial.

Abstract

7-Hydroxymitragynine (7-OH) is a highly selective mu opioid receptor agonist with binding affinity greater than morphine. Although trace amounts of 7-OH are found in kratom, it is formed by metabolism in humans after kratom ingestion. Novel semi-synthetic 7-OH products are manufactured by mono-oxidation of kratom's primary alkaloid, mitragynine. Formulations include sublingual tablets, powders, and liquid shots. We report a case of a study participant with self-reported 7-OH use. A 23-year-old man using kratom for 3 years was enrolled into a clinical trial evaluating kratom pharmacokinetics, behavioral pharmacology, and withdrawal. He typically used 1.5-2g of kratom whole-leaf powder 6 times/day. Following scheduled kratom product self-administration during the study, several outcomes were atypical, including blunted subjective kratom effects. He reported recent initiation of a "new kratom product" ("Opia") identified as semi-synthetic 7-OH; he was using 20 mg 3 times/day for 4 days before study admission. Mitragynine (29.7 ng/mL) plasma concentration peaked at 1.5 hours post kratom self-administration, while 7-OH Cmax (11.7 ng/mL) occurred before self-administration, confirming prior ingestion of 7-OH. The participant reported withdrawal symptoms and requested early discharge from the study, but refused the study protocol kratom "rescue dose," stating he preferred to take his "stronger" product. Clinicians must obtain detailed self-reports from patients who report any kratom use. As 7-OH products are misleadingly marketed as kratom, and as both long-time kratom consumers and kratom-naive individuals may experiment with these novel products, improved assessment methods are urgently needed in the absence of real-time confirmatory testing.