Mad honey poisoning in Nepal: ecology, epidemiology, and clinical spectrum of grayanotoxin intoxication (2009-2026).

Wild honey from the Himalayan cliff bee Apis laboriosa, commonly known as mad honey, has been consumed across Nepal's mid-Himalayan belt for centuries for its perceived medicinal and psychoactive properties, yet its capacity to cause grayanotoxin poisoning has never been systematically documented. The bee forages on Rhododendron species whose nectar contains grayanotoxins, which become concentrated in the honey it produces. We reviewed 27 publications describing approximately 68 cases of grayanotoxin poisoning spanning five decades, situating the clinical epidemiology within the ecological framework of the Rhododendron-Apis laboriosa-human toxin pathway. Most cases originate in Gandaki Province, with Bagmati and Koshi Provinces increasingly represented. Middle-aged men account for roughly 72% of patients, predominantly self-treating hypertension or sexual dysfunction, and poisonings cluster sharply in spring when Rhododendron bloom and honey harvest coincide. Bradycardia and hypotension occur in nearly every case; a smaller subset develops neurological or psychiatric symptoms, and no fatalities have been recorded. Diagnosis remains entirely clinical, as grayanotoxin assay capacity is absent across all Nepali hospitals. Mad honey is increasingly traded online to consumers in North America, Europe, and East Asia who lack the dosing knowledge of traditional Himalayan communities, while A. laboriosa populations continue to decline from overharvesting and habitat loss. A thorough understanding of this toxin pathway is essential for evidence-based risk communication, trade regulation, and conservation of a critical high-altitude pollinator.