grayanotoxin

Grayanotoxins are a group of closely related diterpene toxins produced by certain Rhododendron species, notably Rhododendron ponticum, and by plants in the Ericaceae family. They occur in the nectar and pollen and can accumulate in honey produced by bees foraging on these flowers. When consumed, grayanotoxins are responsible for mad honey poisoning, a form of intoxication widely reported in the Middle East, the Caucasus, and parts of Asia.

Mechanism of action involves binding to voltage-gated sodium channels in nerve and cardiac tissue, specifically at site 5 on the alpha subunit. The toxins prevent normal inactivation of the channel, stabilizing it in an open state and leading to prolonged depolarization and increased neuronal and cardiac excitability. This disruption of autonomic balance can cause bradycardia, hypotension, and, in severe cases, atrioventricular block.

Clinical features typically begin 30 minutes to 2 hours after ingestion and include nausea, vomiting, dizziness, weakness, sweating, hypersalivation, and malaise; cardiovascular symptoms such as hypotension and bradycardia are common, with syncope or confusion possible. Severe poisoning may involve ataxia, dyspnea, seizures, or coma.

Treatment is supportive, focusing on airway and circulation. Monitor vital signs; administer intravenous fluids as needed. Atropine can be used to treat bradycardia, and severe cases may require cardiac pacing. Activated charcoal may be considered if ingestion was recent. There is no specific antidote for grayanotoxin poisoning.

Mad honey intoxication has historical and regional associations with honey derived from rhododendron nectar. Toxin content varies with plant species, season, and geography, and avoidance is advised in areas where grayanotoxin-containing honey is produced.