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However, its consumption carries health risks, including dizziness, hypotension, bradycardia, and, in severe cases, life\u2010threatening 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\u2010induced toxicity, emphasizing its action on voltage\u2010gated 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.\n                  <\/jats:p>","DOI":"10.1002\/jat.4855","type":"journal-article","created":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T06:50:07Z","timestamp":1752130207000},"page":"2240-2256","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Grayanotoxins in Mad Honey: Mechanisms of Toxicity, Clinical Management, and Therapeutic Implications"],"prefix":"10.1002","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6267-193X","authenticated-orcid":false,"given":"Mahendra","family":"Aryal","sequence":"first","affiliation":[{"name":"Department of Chemistry Tribhuvan University, Tri\u2010Chandra Campus  Kathmandu Nepal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,9]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.34257\/GJMRKVOL21IS5PG33"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3126\/bibechana.v22i1.74118"},{"issue":"2","key":"e_1_2_10_4_1","first-page":"82","article-title":"Determination of Grayanotoxin I and Grayanotoxin III in Mad Honey From Nepal Using Liquid Chromatography\u2010Tandem Mass Spectrometry","volume":"35","author":"Ahn S. 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