CASE FILES – Mad Honey

Toxicology Case Files from the Utah Poison Control Center

Teaching Points

• “Mad honey” is made by honeybees that forage on nectar containing large amounts of grayanotoxin produced by numerous Rhododendron species
• Common symptoms of mad honey ingestion include nausea, vomiting, delirium, hypotension, bradycardia, and rarely seizures
• Supportive treatment includes intravenous fluid administration and atropine
• Outcomes are generally good with no deaths in modern times

Case

A fifty-year-old female patient ingested mad honey obtained from India to treat gastrointestinal symptoms. She had previously used mad honey while living in Nepal without ill effect. Shortly after, the patient developed chest pain, lightheadedness, hallucinations, and low blood pressure per home monitor readings.

In the emergency department, the patient had a blood pressure of 90/60 with a heart rate in the 50s. She improved following atropine 0.5 mg IV x 2 doses and intravenous fluids. She was admitted for observation with no further episodes of bradycardia or hypotension and discharged the next day.

Mad Honey & Grayanotoxins

Mad honey and its ill effects have been recognized for centuries. Pompey’s army was decimated after being fed mad honey.¹ It is consumed in areas such as Turkey and Nepal as an alternative medicine.

Various plants in the Ericaceae family, including several in the genus Rhododendron, may contain grayanotoxins. Poisoning is most often associated with honey from Turkey. Grayanotoxin-producing species do grow in the United States, including the western azalea and mountain laurel.²

Grayanotoxin acts similarly to other botanical diterpenes such as aconitine (monkshood) and veratridine (false hellebore). It opens sodium channels and stabilizes them which leads to an initial depolarization and release of acetylcholine.³

Clinical effects of grayanotoxin poisoning include hypotension, bradycardia, and nausea/vomiting which are present in nearly all cases.⁴ True to its name, impaired consciousness may occur in about 67% of cases. Bradycardia may manifest as simple sinus bradycardia or even complete heart block.² Intravenous fluids and atropine are sufficient treatment in the vast majority of cases. No fatalities have been reported in the modern literature.

Toxic doses, of course, depend on the amount of grayanotoxin present in the honey, but significant effects are reported after doses of a tablespoon or less.⁵ Onset is generally rapid with resolution within 24 hours.

References

1. Leach DG. The history of rhododendron poisoning. Garden J 1967 ; 17 : 15 – 18
2. Gunduz A, Turedi S, Russell RM, Ayaz FA. Clinical review of grayanotoxin/mad honey poisoning past and present. Clin Toxicol (Phila). 2008 Jun;46(5):437-42. doi: 10.1080/15563650701666306. PMID: 18568799.
3. Maejima H, Kinoshita E, Seyama I, Yamaoka K. Distinct sites regulating grayanotoxin binding and unbinding to D4S6 of Na(v)1.4 sodium channel as revealed by improved estimation of toxin sensitivity. J Biol Chem. 2003 Mar 14;278(11):9464-71. doi: 10.1074/jbc.M212133200. Epub 2003 Jan 10. PMID: 12524436.
4. Yavuz H, Ozel A, Akkus I, Erkul I. Honey poisoning in Turkey. Lancet. 1991 Mar 30;337(8744):789-90. doi: 10.1016/0140-6736(91)91405-j. PMID: 1672407.
5. Yilmaz O, Eser M, Sahiner A, Altintop L, Yesildag O. Hypotension, bradycardia and syncope caused by honey poisoning. Resuscitation. 2006 Mar;68(3):405-8. doi: 10.1016/j.resuscitation.2005.07.014. Epub 2006 Feb 2. PMID: 16457936.