Grayanotoxins are a group of closely related
neurotoxin
Neurotoxins are toxins that are destructive to nerve tissue (causing neurotoxicity). Neurotoxins are an extensive class of exogenous chemical neurological insultsSpencer 2000 that can adversely affect function in both developing and mature ner ...
s named after ''
Leucothoe grayana'', a plant native to Japan originally named for 19th century American botanist
Asa Gray
Asa Gray (November 18, 1810 – January 30, 1888) is considered the most important American botanist of the 19th century. His ''Darwiniana'' was considered an important explanation of how religion and science were not necessarily mutually excl ...
.
Grayanotoxin I (grayanotaxane-3,5,6,10,14,16-hexol 14-acetate) is also known as andromedotoxin, acetylandromedol, rhodotoxin and asebotoxin. Grayanotoxins are produced by ''
Rhododendron
''Rhododendron'' (; from Ancient Greek ''rhódon'' "rose" and ''déndron'' "tree") is a very large genus of about 1,024 species of woody plants in the heath family (Ericaceae). They can be either evergreen or deciduous. Most species are nati ...
'' species and other plants in the family
Ericaceae
The Ericaceae are a family of flowering plants, commonly known as the heath or heather family, found most commonly in acidic and infertile growing conditions. The family is large, with c.4250 known species spread across 124 genera, making it th ...
.
Honey
Honey is a sweet and viscous substance made by several bees, the best-known of which are honey bees. Honey is made and stored to nourish bee colonies. Bees produce honey by gathering and then refining the sugary secretions of plants (primar ...
made from the
nectar
Nectar is a sugar-rich liquid produced by plants in glands called nectaries or nectarines, either within the flowers with which it attracts pollinating animals, or by extrafloral nectaries, which provide a nutrient source to animal mutualists ...
and so containing
pollen
Pollen is a powdery substance produced by seed plants. It consists of pollen grains (highly reduced microgametophytes), which produce male gametes (sperm cells). Pollen grains have a hard coat made of sporopollenin that protects the gametophyt ...
of these plants also contains grayanotoxins and is commonly referred to as mad honey.
Consumption of the plant or any of its secondary products, including mad honey, can cause a rare poisonous reaction called grayanotoxin poisoning, mad honey disease, honey intoxication, or rhododendron poisoning.
It is most frequently produced and consumed in regions of
Nepal
Nepal (; ne, नेपाल ), formerly the Federal Democratic Republic of Nepal ( ne,
सङ्घीय लोकतान्त्रिक गणतन्त्र नेपाल ), is a landlocked country in South Asia. It is mai ...
and
Turkey
Turkey ( tr, Türkiye ), officially the Republic of Türkiye ( tr, Türkiye Cumhuriyeti, links=no ), is a list of transcontinental countries, transcontinental country located mainly on the Anatolia, Anatolian Peninsula in Western Asia, with ...
as a recreational drug and traditional medicine.
Origin
![Rhododendron luteum2](https://upload.wikimedia.org/wikipedia/commons/f/fb/Rhododendron_luteum2.jpg)
Grayanotoxins are produced by plants in the family
Ericaceae
The Ericaceae are a family of flowering plants, commonly known as the heath or heather family, found most commonly in acidic and infertile growing conditions. The family is large, with c.4250 known species spread across 124 genera, making it th ...
, specifically members of the genera ''
Rhododendron
''Rhododendron'' (; from Ancient Greek ''rhódon'' "rose" and ''déndron'' "tree") is a very large genus of about 1,024 species of woody plants in the heath family (Ericaceae). They can be either evergreen or deciduous. Most species are nati ...
'', ''Pieris'', ''
Agarista'' and ''
Kalmia
''Kalmia'' is a genus of about ten species of evergreen shrubs from 0.2–5 m tall, in the family Ericaceae. They are native to North America (mainly in the eastern half of the continent) and Cuba. They grow in acidic soils, with different spec ...
''.
[ The genus ''Rhododendron'' alone encompasses over 750 species that grow around the world in parts of Europe, North America, Japan, Nepal and Turkey. They can grow at a variety of altitudes ranging from sea level to more than three kilometers above. While many of these species contain grayanotoxins, only a few contain significant levels. Species with high concentrations of grayanotoxins such as '' R. ponticum'', ''R. flavum'' and '' R. luteum'' are most commonly found in ]Nepal
Nepal (; ne, नेपाल ), formerly the Federal Democratic Republic of Nepal ( ne,
सङ्घीय लोकतान्त्रिक गणतन्त्र नेपाल ), is a landlocked country in South Asia. It is mai ...
and regions of Turkey
Turkey ( tr, Türkiye ), officially the Republic of Türkiye ( tr, Türkiye Cumhuriyeti, links=no ), is a list of transcontinental countries, transcontinental country located mainly on the Anatolia, Anatolian Peninsula in Western Asia, with ...
bordering the Black Sea
The Black Sea is a marginal mediterranean sea of the Atlantic Ocean lying between Europe and Asia, east of the Balkans, south of the East European Plain, west of the Caucasus, and north of Anatolia. It is bounded by Bulgaria, Georgia, Roma ...
.
Nearly all parts of grayanotoxin-producing rhododendrons contain the molecule, including the stem, leaves, flower, pollen
Pollen is a powdery substance produced by seed plants. It consists of pollen grains (highly reduced microgametophytes), which produce male gametes (sperm cells). Pollen grains have a hard coat made of sporopollenin that protects the gametophyt ...
and nectar
Nectar is a sugar-rich liquid produced by plants in glands called nectaries or nectarines, either within the flowers with which it attracts pollinating animals, or by extrafloral nectaries, which provide a nutrient source to animal mutualists ...
. Grayanotoxins can also be found in secondary plant products such as honey, labrador tea
Labrador tea is a common name for three closely related plant species in the genus ''Rhododendron'' as well as an herbal tea made from their leaves.
All three species are primarily wetland plants in the heath family. The herbal tea has been a ...
, cigarettes and herbal medicines.
Chemical structure
Grayanotoxins are low molecular weight
A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and bioch ...
hydrophobic
In chemistry, hydrophobicity is the physical property of a molecule that is seemingly repelled from a mass of water (known as a hydrophobe). In contrast, hydrophiles are attracted to water.
Hydrophobic molecules tend to be nonpolar and, th ...
compounds. They are structurally characterized as polyhydroxylated cyclic diterpene
Diterpenes are a class of chemical compounds composed of four isoprene units, often with the molecular formula C20H32. They are biosynthesized by plants, animals and fungi via the HMG-CoA reductase pathway, with geranylgeranyl pyrophosphate being ...
s. The base structure is a 5/7/6/5 ring system that does not contain nitrogen
Nitrogen is the chemical element with the symbol N and atomic number 7. Nitrogen is a nonmetal and the lightest member of group 15 of the periodic table, often called the pnictogens. It is a common element in the universe, estimated at se ...
. More than 25 grayanotoxin isoforms have been identified from ''Rhododendron'' species'','' but grayanotoxin I and III are thought to be the principal toxic isoforms. Different ''Rhododendron'' species contain multiple different grayanotoxin isoforms, contributing to differences in plant toxicity.
Mechanism of action
The toxicity of grayanotoxin is derived from its ability to interfere with voltage-gated sodium channels
Sodium channels are integral membrane proteins that form ion channels, conducting sodium ions (Na+) through a cell's membrane. They belong to the superfamily of cation channels and can be classified according to the trigger that opens the channel ...
located in the cell membrane
The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...
of neuron
A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...
s. The Na''v''1.''x'' channels consist of four homologous domains (I-IV), each containing six transmembrane alpha-helical
The alpha helix (α-helix) is a common motif in the secondary structure of proteins and is a right hand-helix conformation in which every backbone N−H group hydrogen bonds to the backbone C=O group of the amino acid located four residues e ...
segments (S1-S6). Grayanotoxin has a binding affinity
In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. The etymology stems from ''ligare'', which means 'to bind'. In protein-ligand binding, the ligand is usually a mol ...
(IC50) of approximately 10 μM and binds the group II receptor site located on segment 6 of domains I and IV (IS6 and IVS6). Other toxins that bind to this region include the alkaloids veratridine
Veratridine is a steroidal alkaloid found in plants of the lily family, specifically the genera ''Veratrum'' and ''Schoenocaulon''. Upon absorption through the skin or mucous membranes, it acts as a neurotoxin by binding to and preventing the inac ...
, batrachotoxin
Batrachotoxin (BTX) is an extremely potent cardio- and neurotoxic steroidal alkaloid found in certain species of beetles, birds, and frogs. The name is from the Greek word grc, βάτραχος, bátrachos, frog, label=none. Structurally-related ...
and aconitine
Aconitine is an alkaloid toxin produced by various plant species belonging to the genus '' Aconitum'' (family Ranunculaceae), known also commonly by the names wolfsbane and monkshood. Monkshood is notorious for its toxic properties. Aconitine is ...
.
Experiments utilizing squid axonal membranes indicate that sodium channel binding likely occurs on the internal face of the neuron. Additionally, grayanotoxin only binds to the activated conformation of sodium channels. Normally, voltage gated sodium channels are activated (opened) only when the cell membrane potential
Membrane potential (also transmembrane potential or membrane voltage) is the difference in electric potential between the interior and the exterior of a biological cell. That is, there is a difference in the energy required for electric charges ...
reaches a specific threshold voltage. This activated conformation allows for an influx of sodium ions resulting in cell depolarization
In biology, depolarization or hypopolarization is a change within a cell, during which the cell undergoes a shift in electric charge distribution, resulting in less negative charge inside the cell compared to the outside. Depolarization is esse ...
, followed by the firing of an action potential
An action potential occurs when the membrane potential of a specific cell location rapidly rises and falls. This depolarization then causes adjacent locations to similarly depolarize. Action potentials occur in several types of animal cells, ...
. At the peak of the action potential, voltage-gated sodium channels are quickly inactivated and are only reset once the cell has repolarized to resting potential A relatively static membrane potential which is usually referred to as the ground value for trans-membrane voltage.
The relatively static membrane potential of quiescent cells is called the resting membrane potential (or resting voltage), as oppo ...
. When grayanotoxin is present, binding induces further conformational changes that prevent sodium channel inactivation and lead to a prolonged depolarization. Owing to its transient ability to activate channels and increase membrane permeability to sodium ions, grayanotoxin is classified as a reversible Na''v''1.''x'' agonist
An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...
.
Biological effects
Prolonged sodium channel activation and cell depolarization leads to overstimulation of the central nervous system
The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...
. Physical symptoms from grayanotoxin poisoning appear after a dose-dependent latent period of several minutes to approximately three hours. The most common clinical symptoms include various cardiovascular effects, nausea
Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...
and vomiting, and a change in consciousness. The cardiovascular effects may include hypotension
Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the dias ...
(low blood pressure) and various cardiac rhythm disorders such as sinus bradycardia
Sinus bradycardia is a sinus node dysfunction giving a heart rate that is lower than the normal 60–100 beats per minute (bpm) in humans. Bradycardia is generally defined to be a heart rate of under 60 bpm.
Signs and symptoms
The decreased hear ...
(slow regular heart rhythm), bradyarrhythmia
Bradycardia (also sinus bradycardia) is a slow resting heart rate, commonly under 60 beats per minute (BPM) as determined by an electrocardiogram. It is considered to be a normal heart rate during sleep, in young and healthy or elderly adults, a ...
(slow irregular heart rhythm) and partial or complete atrioventricular block
Atrioventricular block (AV block) is a type of heart block that occurs when the electrical signal traveling from the atria, or the upper chambers of the heart, to ventricles, or the lower chambers of the heart, is impaired. Normally, the sinoatr ...
.
Other early-onset symptoms may include diplopia
Diplopia is the simultaneous perception of two images of a single object that may be displaced horizontally or vertically in relation to each other. Also called double vision, it is a loss of visual focus under regular conditions, and is often v ...
and blurred vision, dizziness, hypersalivation
Hypersalivation, or ptyalism, also known as sialorrhea or hypersialosis is the excessive production of saliva. It has also been defined as increased amount of saliva in the mouth, which may also be caused by decreased clearance of saliva.Medscape ...
, perspiration, weakness and paresthesia
Paresthesia is an abnormal sensation of the skin (tingling, pricking, chilling, burning, numbness) with no apparent physical cause. Paresthesia may be transient or chronic, and may have any of dozens of possible underlying causes. Paresthesias ar ...
in the extremities and around the mouth. In higher doses, symptoms can include loss of coordination, severe and progressive muscular weakness, electrocardiographic
Electrocardiography is the process of producing an electrocardiogram (ECG or EKG), a recording of the heart's electrical activity. It is an electrogram of the heart which is a graph of voltage versus time of the electrical activity of the hear ...
changes of bundle branch block
A bundle branch block is a defect in one the bundle branches in the electrical conduction system of the heart.
Anatomy and physiology
The heart's electrical activity begins in the sinoatrial node (the heart's natural pacemaker), which is situat ...
and/or ST-segment elevations as seen in ischemic myocardial threat, and nodal rhythm or Wolff-Parkinson-White syndrome.
The primary mediator of this grayanotoxin pathophysiology
Pathophysiology ( physiopathology) – a convergence of pathology with physiology – is the study of the disordered physiological processes that cause, result from, or are otherwise associated with a disease or injury. Pathology is the ...
is the paired vagus nerve
The vagus nerve, also known as the tenth cranial nerve, cranial nerve X, or simply CN X, is a cranial nerve that interfaces with the parasympathetic control of the heart, lungs, and digestive tract. It comprises two nerves—the left and right ...
(tenth cranial nerve). The vagus nerve is a major component of the parasympathetic nervous system
The parasympathetic nervous system (PSNS) is one of the three divisions of the autonomic nervous system, the others being the sympathetic nervous system and the enteric nervous system. The enteric nervous system is sometimes considered part of ...
(a branch of the autonomic nervous system
The autonomic nervous system (ANS), formerly referred to as the vegetative nervous system, is a division of the peripheral nervous system that supplies viscera, internal organs, smooth muscle and glands. The autonomic nervous system is a control ...
) and innervates various organs including the lungs, stomach, kidney and heart
The heart is a muscular organ in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as carbon dioxide t ...
. In one study, experimental administration of grayanotoxin to bilaterally vagotomized rats failed to induce bradycardia
Bradycardia (also sinus bradycardia) is a slow resting heart rate, commonly under 60 beats per minute (BPM) as determined by an electrocardiogram. It is considered to be a normal heart rate during sleep, in young and healthy or elderly adults, a ...
, a common symptom of grayanotoxin poisoning, supporting the role of vagal stimulation. Vagal stimulation of the myocardium
Cardiac muscle (also called heart muscle, myocardium, cardiomyocytes and cardiac myocytes) is one of three types of vertebrate muscle tissues, with the other two being skeletal muscle and smooth muscle. It is an involuntary, striated muscle that ...
, specifically, is mediated by M2-subtype muscarinic acetylcholine receptor
Muscarinic acetylcholine receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled receptor complexes in the cell membranes of certain neurons and other cells. They play several roles, including acting as the main end-rece ...
s (mAChR). In severe cases of grayanotoxin poisoning, atropine
Atropine is a tropane alkaloid and anticholinergic medication used to treat certain types of nerve agent and pesticide poisonings as well as some types of slow heart rate, and to decrease saliva production during surgery. It is typically given i ...
(a non-specific "mAChR antagonist" or Muscarinic antagonist
A muscarinic receptor antagonist (MRA) is a type of anticholinergic agent that blocks the activity of the muscarinic acetylcholine receptor. The muscarinic receptor is a protein involved in the transmission of signals through certain parts of the ...
) can be used to treat bradycardia and other heart rhythm malfunctions. In addition to correcting rhythm disorders, administration of fluids and vasopressors
An antihypotensive agent, also known as a vasopressor agent or simply vasopressor, or pressor, is any substance, whether endogenous or a medication
A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or sim ...
can also help treat hypotension and mitigate other symptoms.
Patients exposed to low doses of grayanotoxin typically recover within a few hours. In more severe cases, symptoms may persist for 24 hours or longer and may require medical treatment (as described above). Despite the risk from cardiac problems, grayanotoxin poisoning is rarely fatal in humans.
Animal poisoning
In contrast to humans, grayanotoxin poisoning can be lethal for other animals. Nectar
Nectar is a sugar-rich liquid produced by plants in glands called nectaries or nectarines, either within the flowers with which it attracts pollinating animals, or by extrafloral nectaries, which provide a nutrient source to animal mutualists ...
containing grayanotoxin can kill honeybees, though some seem to have resistance to it and can produce honey from the nectar (see below). According to a team of researchers from the UK and Ireland, worker bumblebee
A bumblebee (or bumble bee, bumble-bee, or humble-bee) is any of over 250 species in the genus ''Bombus'', part of Apidae, one of the bee families. This genus is the only extant group in the tribe Bombini, though a few extinct related gener ...
s are not harmed and may be preferable as pollinators because they transfer more pollen. Consequently, it may be advantageous for plants to produce grayanotoxin in order to be pollinated by bumblebees.
Mad honey intoxication
Bees that collect pollen
Pollen is a powdery substance produced by seed plants. It consists of pollen grains (highly reduced microgametophytes), which produce male gametes (sperm cells). Pollen grains have a hard coat made of sporopollenin that protects the gametophyt ...
and nectar from grayanotoxin-containing plants often produce honey
Honey is a sweet and viscous substance made by several bees, the best-known of which are honey bees. Honey is made and stored to nourish bee colonies. Bees produce honey by gathering and then refining the sugary secretions of plants (primar ...
that also contains grayanotoxins. This so-called "mad honey" is the most common cause of grayanotoxin poisoning in humans. Small-scale producers of mad honey typically harvest honey from a small area or single hive
A hive may refer to a beehive, an enclosed structure in which some honey bee species live and raise their young.
Hive or hives may also refer to:
Arts
* ''Hive'' (game), an abstract-strategy board game published in 2001
* "Hive" (song), a 201 ...
in order to produce a final product containing a significant concentration of grayanotoxin. In contrast, large-scale honey production often mixes honey gathered from different locations, diluting the concentration of any contaminated honey.
Mad honey is deliberately produced in some regions of the world, most notably Nepal
Nepal (; ne, नेपाल ), formerly the Federal Democratic Republic of Nepal ( ne,
सङ्घीय लोकतान्त्रिक गणतन्त्र नेपाल ), is a landlocked country in South Asia. It is mai ...
and the Black Sea
The Black Sea is a marginal mediterranean sea of the Atlantic Ocean lying between Europe and Asia, east of the Balkans, south of the East European Plain, west of the Caucasus, and north of Anatolia. It is bounded by Bulgaria, Georgia, Roma ...
region of Turkey
Turkey ( tr, Türkiye ), officially the Republic of Türkiye ( tr, Türkiye Cumhuriyeti, links=no ), is a list of transcontinental countries, transcontinental country located mainly on the Anatolia, Anatolian Peninsula in Western Asia, with ...
. In Nepal, this type of honey is used by the Gurung people
Gurung (exonym; ) or Tamu (endonym; Gurung: ) are an ethnic group indigenous to the hills and mountains of Gandaki Province of Nepal. Gurung people predominantly live around the Annapurna region in Manang, Mustang, Dolpo, Kaski, Lamjung, Gorkha, ...
for both its hallucinogenic properties and supposed medicinal benefits. In Turkey, mad honey known as ''deli bal'' is also used as a recreational drug and traditional medicine. It is most commonly made from the nectar of ''Rhododendron luteum
''Rhododendron luteum'', the yellow azalea or honeysuckle azalea, is a species of flowering plant in the heath family Ericaceae, native to southeastern Europe and southwest Asia. In Europe, it occurs from southern Poland and Austria south throu ...
'' and ''Rhododendron ponticum
''Rhododendron ponticum'', called common rhododendron or pontic rhododendron, is a species of ''Rhododendron'' native to the Iberian Peninsula in southwest Europe and the Caucasus region in northern West Asia.
Description
''R. ponticum'' is a d ...
'' in the Caucasus
The Caucasus () or Caucasia (), is a region between the Black Sea and the Caspian Sea, mainly comprising Armenia, Azerbaijan, Georgia, and parts of Southern Russia. The Caucasus Mountains, including the Greater Caucasus range, have historically ...
region''.'' In the eighteenth century, this honey was exported to Europe to add to alcoholic drinks to give them extra potency. In modern times, it is consumed locally and exported to North America, Europe and Asia.
In addition to various ''Rhododendron'' species, mad honey can also be made from several other grayanotoxin-containing plants. Honey produced from the nectar of ''Andromeda polifolia
''Andromeda polifolia'', common name bog-rosemary, is a species of flowering plant in the heath family Ericaceae, native to northern parts of the Northern Hemisphere. It is the only member of the genus ''Andromeda'', and is only found in bogs in ...
'' contains high enough levels of grayanotoxin to cause full body paralysis
Paralysis (also known as plegia) is a loss of motor function in one or more muscles. Paralysis can also be accompanied by a loss of feeling (sensory loss) in the affected area if there is sensory damage. In the United States, roughly 1 in 50 ...
and potentially fatal breathing difficulties
Shortness of breath (SOB), also medically known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathe well enough. The American Thoracic Society defines it as "a subjective experience of breathing di ...
due to diaphragm
Diaphragm may refer to:
Anatomy
* Thoracic diaphragm, a thin sheet of muscle between the thorax and the abdomen
* Pelvic diaphragm or pelvic floor, a pelvic structure
* Urogenital diaphragm or triangular ligament, a pelvic structure
Other
* Diap ...
paralysis. Honey obtained from spoonwood Spoonwood is a common name for two plants:
*''Kalmia latifolia'', a North American plant known as mountain laurel and numerous other names emphasizing its poisonous nature, such as lambkill, kill-kid, and calf-kill.
*''Trichilia havanensis
''Tri ...
and allied species such as sheep-laurel can also cause illness. The honey from ''Lestrimelitta limao
''Lestrimelitta limao'' is a neotropical eusocial bee species found in Brazil and Panama and is part of the Apidae family. It is a species of stingless bees that practices obligate nest robbing. They have never been spotted foraging from flowers ...
'' also produces this paralyzing effect seen in the honey of ''A. polifolia'' and is also toxic to humans.
Although mad honey is used in traditional medicine
Traditional medicine (also known as indigenous medicine or folk medicine) comprises medical aspects of traditional knowledge that developed over generations within the folk beliefs of various societies, including indigenous peoples, before the ...
in Turkey, the majority of grayanotoxin poisoning cases occur in middle-aged males who use the honey for perceived sexual enhancement.
Historical use
The intoxicating effects of mad honey have been known for thousands of years. There have been many famous episodes of human inebriation caused by its consumption. Xenophon
Xenophon of Athens (; grc, wikt:Ξενοφῶν, Ξενοφῶν ; – probably 355 or 354 BC) was a Greek military leader, philosopher, and historian, born in Athens. At the age of 30, Xenophon was elected commander of one of the biggest Anci ...
, Aristotle
Aristotle (; grc-gre, Ἀριστοτέλης ''Aristotélēs'', ; 384–322 BC) was a Greek philosopher and polymath during the Classical period in Ancient Greece. Taught by Plato, he was the founder of the Peripatetic school of phil ...
, Strabo
Strabo''Strabo'' (meaning "squinty", as in strabismus) was a term employed by the Romans for anyone whose eyes were distorted or deformed. The father of Pompey was called "Pompeius Strabo". A native of Sicily so clear-sighted that he could see ...
, Pliny the Elder
Gaius Plinius Secundus (AD 23/2479), called Pliny the Elder (), was a Roman author, naturalist and natural philosopher, and naval and army commander of the early Roman Empire, and a friend of the emperor Vespasian. He wrote the encyclopedic '' ...
and Columella
Lucius Junius Moderatus Columella (; Arabic: , 4 – ) was a prominent writer on agriculture in the Roman Empire.
His ' in twelve volumes has been completely preserved and forms an important source on Roman agriculture, together with the wo ...
all document the results of eating this "maddening" honey, believed to be from the pollen and nectar of ''Rhododendron luteum
''Rhododendron luteum'', the yellow azalea or honeysuckle azalea, is a species of flowering plant in the heath family Ericaceae, native to southeastern Europe and southwest Asia. In Europe, it occurs from southern Poland and Austria south throu ...
'' and ''Rhododendron ponticum
''Rhododendron ponticum'', called common rhododendron or pontic rhododendron, is a species of ''Rhododendron'' native to the Iberian Peninsula in southwest Europe and the Caucasus region in northern West Asia.
Description
''R. ponticum'' is a d ...
''. According to Xenophon's ''Anabasis'', an invading Greek army was accidentally poisoned by harvesting and eating the local Asia Minor honey, but they all made a quick recovery without any fatalities. Having heard of this incident, and realizing that foreign invaders would be ignorant of the dangers of the local honey, King Mithridates later used the honey as a deliberate poison when Pompey
Gnaeus Pompeius Magnus (; 29 September 106 BC – 28 September 48 BC), known in English as Pompey or Pompey the Great, was a leading Roman general and statesman. He played a significant role in the transformation of ...
's army attacked the Heptakometes in Asia Minor in 69 BC. The Roman soldiers became delirious and nauseated after being tricked into eating the toxic honey, at which point Mithridates's army attacked.
Popular culture
Mad honey disease is an element of the 2009 movie ''Sherlock Holmes
Sherlock Holmes () is a fictional detective created by British author Arthur Conan Doyle. Referring to himself as a " consulting detective" in the stories, Holmes is known for his proficiency with observation, deduction, forensic science and ...
''.
See also
*''Incilius alvarius
The Colorado River toad (''Incilius alvarius''), formerly known as the Sonoran Desert toad, is found in northern Mexico and the southwestern United States. It exudes toxins from glands within its skin that have psychoactive properties.
Descri ...
''
*''Sarpa salpa
''Sarpa salpa'', known commonly as the dreamfish, salema, salema porgy, cow bream or goldline, is a species of sea bream, recognisable by the golden stripes that run down the length of its body, and which can cause ichthyoallyeinotoxism when ea ...
''
*Potassium channel
Potassium channels are the most widely distributed type of ion channel found in virtually all organisms. They form potassium-selective pores that span cell membranes. Potassium channels are found in most cell types and control a wide variety of cel ...
References
{{commons category, Grayanotoxins
Beekeeping
Neurotoxins
Ion channel toxins
Diterpenes
Cyclopentanes
Sodium channel openers
Plant toxins