ABSTRACT

Introduction ............................................................................................................360 Brief History of the Secret Weapon in Honey ...................................................360 Rhododendron L. ............................................................................................... 361 Where Does the Poisoning Agent/Compound of Mad Honey Come From? ........ 362 Are There Any Other Nectar-Producing Plants Apart from Rhododendron Species? ............................................................................................................. 365 Is It True That the More Diverse the Bees, the More Diverse Mad Honeys Are Produced? ................................................................................................... 365

Structure of GTX ...................................................................................................366 Biosynthesis, Derivatives, Intermediates, and Toxicity of GTXs .....................366 Determination of GTXs..................................................................................... 367 Isolation of GTXs from Honey and Plant Parts ................................................ 367 Rhododendron Toxicity ..................................................................................... 369 Classic Works on Honey Poisoning in Europe and North America .................. 369

Modern Experimental Work ................................................................................... 370 Role of the Central Nervous System, Vagus Nerve, and Muscarinic Receptors in GTX Poisoning ............................................................................ 370 Effects of GTX at the Cellular Level ................................................................ 370 Effects on Renal and Hepatic Tissue and Glucose Metabolism ........................ 370 Clinical Course of GTX/Mad Honey Intoxication-A Cholinergic Toxidrome ......................................................................................................... 372 Toxic Dose and Duration of Illness ................................................................... 374 Treatment .......................................................................................................... 374 Mortality ............................................................................................................ 374 A Change in the Geographic Distribution of Human GTX/Mad Honey Poisoning ........................................................................................................... 374 Cultural Factors ................................................................................................. 375 Honey Production Techniques and the Stability of Mad Honey ....................... 375 Clinical Application .......................................................................................... 375

Conclusion ............................................................................................................. 375 Acknowledgment ................................................................................................... 376 References .............................................................................................................. 376

The use of mad honey as a “biological weapon” was rst described in 401 BC by the Athenian historian and army commander Xenophon (430-355 BC) (Gökçöl 1998; Gunduz et al. 2011). Xenophon fought the Makrons in what is now the Turkish province of Trabzon, and in his “Anabasis, The March of the Ten Thousand,” he describes in detail the effects on soldiers subjected to mad honey poisoning (Gökçöl 1998; Okmen 2004; Gunduz et al. 2011). These are the keys to the use of the terms “mad honey,” “hidden poison,” or “the rst biological weapon.”