From Kratom to Semi‐Synthetic Opioids: The Rise and Risks of MGM‐15

Kratom ( Mitragyna speciosa ), a plant native to Southeast Asia, has long been used for its stimulant and analgesic properties. 7‐Hydroxymitragynine (7‐HMG) is a potent and selective opioid agonist in vitro and demonstrates a potent opioid effect in living subjects, reversible by naloxone. It has been semi‐synthesized into products that are readily available in retail and virtual shops. It is known that 7‐HMG has earned the nickname “legal morphine,” and has gained popularity among users seeking pain relief and/or a “high” comparable with prescription opioids. Medicinal chemistry efforts have led to synthetic 7‐HMG derivatives such as MGM‐15, where stereospecific saturation of the imine N(1)–C(2) double bond increases opioid receptor affinity and activity. Despite its higher in vitro opioid potency, MGM‐15 is currently sold in the US for human consumption as a “research chemical” in tablet form, even though there is an absence of this being studied in humans and obviously no FDA approval. In this study, we analyzed commercially available MGM‐labeled tablets using UPLC–MS/MS and subsequently evaluated the binding affinities of purified MGM‐15 across multiple opioid receptors. Tablets contained an average of 10.9 ± 0.2 mg (10.7 to 11.2 mg) of MGM‐15, with no naturally occurring kratom alkaloids or illicit substances detected. MGM‐15 shows greater hMOR and hDOR binding affinities than 7‐HMG, indicating the potential for higher opioid effects and risks, emphasizing the urgent need for more research to advise regulation and hopefully prevent misuse and harm.