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Grayanotoxin

Original Wikipedia articleen.wikipedia.org/wiki/Grayanotoxin revision used (24 October 2026)

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Duration

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Mixing

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Backed by medical journals

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Other documented combinations

  • Dangerous Opioids - Grayanotoxins and opioids potentiate the sedation, hypotension, and decreased heart rate caused by each other, increasing the risk of sudden loss of consciousness or respiratory depression. PW
  • Unsafe Cholinergics - Because grayanotoxins potentiate the effects of acetylcholine, cholinergic substances such as nicotine, caffeine, and galantamine may carry an increased risk of cholinergic crisis. PW
  • Unsafe Depressants - Combining grayanotoxins with other depressants increase the risk of a sudden loss of consciousness. PW

Risks and toxicity

It is strongly recommended that one use harm reduction practices when using this substance. PW

Testing

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Effects

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Overview

Grayanotoxins are a group of closely related neurotoxins named after Leucothoe grayana, a plant native to Japan and named for 19th-century American botanist Asa Gray. Grayanotoxin I (grayanotoxane-3,5,6,10,14,16-hexol 14-acetate) is also known as andromedotoxin, acetylandromedol, rhodotoxin and asebotoxin. Grayanotoxins are produced by Rhododendron species and other plants in the family Ericaceae. Honey that contains grayanotoxins is commonly referred to as "mad honey".[1][2][3] WP

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 Turkey and Nepal as a recreational drug and traditional medicine.[3–6] WP

History

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Pharmacology

Mechanism of action

The toxicity of grayanotoxin is derived from its ability to interfere with voltage-gated sodium channels located in the cell membrane of neurons. The Naᵥ1.x channels consist of four homologous domains (I-IV), each containing six transmembrane alpha-helical segments (S1-S6). Grayanotoxin has a binding affinity (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, batrachotoxin and aconitine.[3][7] WP

Experiments using 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 reaches a specific threshold voltage. This activated conformation allows for an influx of sodium ions resulting in cell depolarization, followed by the firing of an action potential. 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. 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 Naᵥ1.x agonist.[7][8] WP

Chemistry

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Pop culture

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References

  1. Other Senning, Alexander. Elsevier's Dictionary of Chemoetymology. 2007
  2. Other The Merck Index. 1983
  3. Journal / agency Jansen SA, Kleerekooper I, Hofman ZL, Kappen IF, Stary-Weinzinger A, van der Heyden MA. Grayanotoxin poisoning: 'mad honey disease' and beyond. Cardiovascular Toxicology. September 2012. doi:10.1007/s12012-012-9162-2 · PMID 22528814 · PMC3404272
  4. Journal / agency Demircan A, Keleş A, Bildik F, Aygencel G, Doğan NO, Gómez HF. Mad honey sex: therapeutic misadventures from an ancient biological weapon. Annals of Emergency Medicine. December 2009. doi:10.1016/j.annemergmed.2009.06.010 · PMID 19683834
  5. Journal / agency Gunduz A, Şimşek P, Ayaz FA. Worldwide distribution and clinical characteristics of mad honey poisoning cases. Central European Journal of Public Health. March 2023. doi:10.21101/cejph.a7501 · PMID 37086424
  6. Journal / agency Sahin, Huseyin. Grayanotoxin-III Detection and Antioxidant Activity of Mad Honey. International Journal of Food Properties. 18 April 2015. doi:10.1080/10942912.2014.999866
  7. Other Sperelakis, Nicholas. Cell Physiology Source Book: Essentials of Membrane Biophysics. 2011
  8. Journal / agency Seyama I, Yamada K, Kato R, Masutani T, Hamada M. Grayanotoxin opens Na channels from inside the squid axonal membrane. Biophysical Journal. February 1988. doi:10.1016/s0006-3495(88)83088-1 · PMID 2449919 · PMC1330147

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