Substance Use Disorder Following Consumption of a Novel Synthetic 7-Hydroxymitragynine Product

Products containing semi-synthetic 7-hydroxymitragynine (7-OH), a potent mu-opioid receptor (MOR) agonist, have proliferated in the United States. In kratom leaf, trace amounts of 7-OH are formed by spontaneous oxidization of kratom's primary alkaloid, mitragynine. Hepatic and intestinal microsomes also convert mitragynine to 7-OH. Some products have sublingual and nasal administration routes that circumvent hepatic first-pass metabolism, increasing bioavailability and accelerating effect onset, features that increase risk. We report a patient who developed substance use disorder (SUD) related to a 7-OH sublingual film.

A 35-year-old man with supraventricular tachycardia and profound urinary retention described using "Hydroxie," a novel, semi-synthetic 7-OH product. He currently vaped cannabis and nicotine, and reported injection heroin addiction a decade prior. He used kratom 6 months before trying Hydroxie, which began 10 weeks before hospitalization. Within days of initiating use, he noticed tolerance; within 2 weeks, he was using one film every 1-2 hours. The patient met criteria for severe SUD related to Hydroxie and was inducted onto buprenorphine. Analysis confirmed 7-OH in the product and blood.

The MOR selectivity and brief duration of action of some 7-OH formulations support our observation that repeated use may lead to physical dependence. Standard laboratory testing can detect mitragynine but not 7-OH due to its relatively shorter half-life, an issue that may confuse semi-synthetic 7-OH use with kratom. Novel 7-OH products are not kratom. The potency of 7-OH places unwitting consumers who may believe they are using kratom, not a partial MOR agonist, at risk.