Featured Poison

Grayanotoxins: Of Rhododendrons and Mad Honey

Rhododendron by Justin Brower

Rhododendron by Justin Brower

I grew up in the Puget Sound area of northwest Washington surrounded by rhododendron.  Lots of rhododendron.  It is the state flower after all.  The rhododendron in Washington have large evergreen leaves, bloom in nearly every color, and can grow to be quite large (~8 feet around).  I’d bet that nearly every home within a square mile around our house had a rhododendron or two, or three.  We had four.  Three in the front and one in the back.  The one in the back was my favorite, it was the deepest, darkest purple color you could imagine.  It was majestic.

Rhododendrons belong to the genus Rhododendron, and consists of about 1000 species.  The species most prevalent in Washington is Rhododendron macrophyllum, the so called Pacific rhododendron.  Now that I’m in the kinda-South I’m surrounded by another Rhododendron.  This time it’s the species colloquially known as azalea.  I don’t like azaleas.  They have impressive, massive blooms, but they only last a week, then they look like crap the rest of the year.  We had about a dozen around our house when we bought it, but I dug them up with a pick axe.  The photo to the left is a “real” rhododenron, to me at least, and is the last one standing at our place.  Survival of the prettiest.

While the rhododendron in the United States is easy to control and a desired ornamental, a species prevalent in Europe and southern Asia, Rhododendron ponticum, is not.  Unlike most varieties in the States, R. ponticum propagates itself with suckers and abundant seed formation.  It is deemed an invasive species and a problem for the British Isles because it crowds out native flora.  Sounds a lot like blackberry bushes in Washington.

GrayonotoxinsAside from being pretty, it is also poisonous.  My parents never told me this, and I’m sure I’ve eaten a flower or thirty in my wee lad days.  I guess they just didn’t love me enough.  Sniff.  Enough with the fake wallowing.  I was probably safe.  Probably.

Not all Rhododenron are created equal, and have varying concentrations of grayanotoxins, a group of cyclic diterpenes, depending upon species, location, and time of year.  The figure on the right illustrates the most common of the 60 or so grayanotoxins that have been identified.  Grayanotoxins exert their toxicity by binding to sodium ion channels on cell membranes and preventing them from closing quickly, like aconitine.  The result is a state of depolarization in which sodium ions are freely flowing into the cells, and calcium influx is on the rise.  The increase in calcium stimulates the release of acetylcholine, and as my faithful readers remember from the case of King Joffrey and the tales of physostigmine, an increase of acetylcholine can cause a cholinergic syndrome remembered by SLUDGE: Salivation, Lacrimation, Urination, Defecation, GI upset, and Emesis.

Clinical symptoms include increased sweating, salivation and nausea.  What is not typically seen (or perhaps at all) is lacrimation and urination, so while not a classical cholinergic syndrome, ER docs and toxicologists will recognize the symptoms (1).  Perhaps the more important symptoms are the cardiac related events.  During a toxic episode patients may experience bradycardia (low heart rate) and hypotension (low blood pressure), which explains the multiple reports of fainting.  Fortunately, fatal grayanotoxin poisoning is extremely rare, and cardiac issues are usually resolved within 24 hours with the aid of atropine (2).

So I guess I wasn’t in any mortal danger – you’re off the hook, Dad – but that doesn’t mean that poisonings don’t occur.  The young and the old are always most susceptible, and the amount and species ingested is important as well.  But the primary source of grayanotoxin poisoning comes from what is known as “mad honey.”  This is honey that is made from bees that have collected nectar from grayanotoxin containing plants, primarily Rhododendron.  “Mad honey” seems to be most prevalent in Turkey, in the Black Sea region, where locals can distinguish it from “good” honey because of its bitter taste (3).

A popular legend involves a battle between Roman general Pompey facing off against the forces of King Mithridates of Pontus, in the Trabzon area of Turkey in 67 B.C.  King Mithridates knew of the “mad honey” in that region, which is on the Black Sea, or course, but General Pompey did not.  His men dived right into the beehives, became intoxicated and ill, and were promptly slaughtered by Mithridates’ men.  An ancient biological weapon!  If only we’d left it at that.

You would think that known toxicity and plenty of legend and lore would keep people away from “mad honey,” but no.  Some seem to view it as a traditional medicine and use it to treat a variety of ailments, such as arthritis and diabetes, and risk being poisoned of course.  A surprising, or not, reason for intentionally purchasing “mad honey” is for sexual dysfunction and increasing sexual performance (4).  One report (4), lists the average age of men using “mad honey” to be 55, with some as old as 80.  For some reason I doubt the “mad honey” label urges you to ask your doctor if you’re healthy enough for sexual activity.

Whether or not this works, I don’t know, I’ll get back to you later.  Brownchickenbrowncow.  But in the meantime, don’t eat the rhododenron.  And stay away from beehives, you don’t know where they’ve been.

*** [Homepage featured image of Rhododendron by Justin Brower] ***

1. Gunduz, Abdulkadir, Suleyman Turedi, Robert M. Russell, and Faik Ahmet Ayaz. “Clinical Review of Grayanotoxin/mad Honey Poisoning past and Present.”Clinical Toxicology 46.5 (2008): 437-42.
2. Okuyan, Ertugrul, Ahmet Uslu, and Mustafa Ozan Levent. “Cardiac Effects of ‘mad Honey’: A Case Series.” Clinical Toxicology 48.6 (2010): 528-32.
3. Koca, Ilkay, and Ahmet F. Koca. “Poisoning by Mad Honey: A Brief Review.”Food and Chemical Toxicology 45.8 (2007): 1315-318.
4. Demircan, Ahmet, Ayfer Keleş, Fikret Bildik, Gülbin Aygencel, N. Özgür Doğan, and Hernán F. Gómez. “Mad Honey Sex: Therapeutic Misadventures From an Ancient Biological Weapon.” Annals of Emergency Medicine 54.6 (2009): 824-29.

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