Grayanotoxins in Mad Honey: Mechanisms of Toxicity, Clinical Management, and Therapeutic Implications

Mad honey, primarily derived from the nectar of Rhododendron species, has been used for centuries in traditional medicine due to benefits in managing hypertension, diabetes, and gastrointestinal disorders. However, its consumption carries health risks, including dizziness, hypotension, bradycardia, and, in severe cases, life-threatening cardiac complications. This review synthesizes research on the chemical composition and toxicological effects of mad honey, with a focus on grayanotoxins (GRAYs), key bioactive compounds responsible for its dual therapeutic and toxic effects. It examines regional variations in honey toxicity, particularly in endemic areas such as Nepal and Turkey, where traditional use persists. Additionally, the study explores the mechanisms of GRAY-induced toxicity, emphasizing its action on voltage-gated sodium channels (VGSCs), which leads to prolonged depolarization and autonomic dysfunction. Clinical case studies highlight the cardiovascular and neurological manifestations of mad honey poisoning, alongside current diagnostic management strategies, including atropine administration and supportive care. Despite its risks, emerging evidence suggests potential therapeutic applications, underscoring the need for standardized dosing, regulatory oversight, and public awareness. This study aims to inform healthcare professionals, researchers, and policymakers about the delicate balance between the medicinal benefits and hazards of mad honey, advocating for further research to optimize its safe use.