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

Background: 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. Case Presentation: 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 C max (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. Discussion: 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.