Purpose of Review <p>7-Hydroxymitragynine (7-OH), a potent kratom alkaloid and semi-synthetic derivative, has recently emerged in the unregulated U.S. drug market. This review examines its pharmacology, clinical presentation, screening challenges, and treatment implications within the context of the ongoing opioid crisis.</p> Recent Findings <p>7-OH is a high-affinity partial agonist at the mu-opioid receptor with potency exceeding mitragynine and potentially comparable to other full opioid agonists. The increasing availability of concentrated, misbranded products has prompted regulatory warnings. Case reports document opioid-like withdrawal, tolerance, use disorder, hospitalizations, and fatalities. Standard urine immunoassays do not reliably detect 7-OH, complicating diagnosis. Emerging evidence supports buprenorphine-based treatment for withdrawal and extrapolated management of 7-OH use disorder.</p> Summary <p>7-OH should be conceptualized clinically as a potent, unregulated opioid. Proactive screening, DSM-5-TR–informed diagnosis, harm reduction counseling, and consideration of medications for opioid use disorder are warranted to mitigate growing public health risks.</p>