Talk:Grayanotoxin
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| Summary sheet: Grayanotoxin |
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| Chemical Nomenclature | |||||||||||||||||||||||
| Common names | Mad Honey | ||||||||||||||||||||||
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| Psychoactive class | Depressant | ||||||||||||||||||||||
| Chemical class | Diterpene | ||||||||||||||||||||||
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History and culture
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This History and culture section is a stub. As a result, it may contain incomplete or wrong information. You can help by expanding it. |
Grayanotoxins are an active constituent of a variety of plants with a history of medicinal and recreational use, including species of rhododendron and monotropa uniflora [1]. Most commonly, grayanotoxins are consumed in the form of mad honey, which is contaminated with grayanotoxins from bees that pollinate rhododendron flowers [2]. Mad honey is reportedly used as an aphrodisiac, painkiller, treatment for hypertension, and as a recreational drug, particularly in Nepal and the Black Sea region of Turkey [2]. Historically, mad honey has been added to alcoholic drinks to increase their potency [3].
The Gurung people of Nepal are especially known to harvest mad honey for its supposed hallucinogenic properties [4].
Chemistry
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This chemistry section is incomplete. You can help by adding to it. |
Pharmacology
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This pharmacology section is incomplete. You can help by adding to it. |
Grayanotoxins are a group of toxic diterpenes found in the ericacaeae family of plants [5]. More than 25 grayanotoxin isoforms have been isolated from rhododendron, though grayanotoxin I and grayanotoxin III are considered to be the most responsible for the toxic pharmacological effects of grayanotoxin-containing plants.[6] Grayanotoxin I, as well as grayanotoxin III, act as agonists of voltage-gated sodium channels.[7][8] Through this mechanism, grayanotoxins increase the release of neurotransmitters in the central nervous system such as GABA [8], glutamate [8], and acetylcholine [9].
Additionally, grayanotoxin III may act as an antagonist of central glutamate receptors, further contributing to CNS depressant effects [10]. Reports of grayanotoxin intoxication include symptoms of the cholinergic toxidrome such as decreased heart rate, hypotension, and an altered mental status [5].
Subjective effects
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This subjective effects section is a stub. As such, it is still in progress and may contain incomplete or wrong information. You can help by expanding or correcting it. |
Disclaimer: The effects listed below cite the Subjective Effect Index (SEI), an open research literature based on anecdotal user reports and the personal analyses of PsychonautWiki contributors. As a result, they should be viewed with a healthy degree of skepticism.
It is also worth noting that these effects will not necessarily occur in a predictable or reliable manner, although higher doses are more liable to induce the full spectrum of effects. Likewise, adverse effects become increasingly likely with higher doses and may include addiction, severe injury, or death ☠.
Physical effects 
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- Sedation
- Muscle relaxation [11]
- Mouth numbing [12] - This effect occurs along with paresthesia, or a tingling sensation, especially in the extremities.
- Physical euphoria - This effect manifests as a warm tingling sensation, particularly in the face and extremities, along with a sense of bodily numbness.
- Physical fatigue
- Decreased heart rate - This effect is dose-dependent, potentially fatal, and occurs along with decreased blood pressure [5].
- Decreased blood pressure
- Pain relief [13]
- Nausea - This effect may occur as a result of both decreased blood pressure and the local irritant effect of grayanotoxins. In higher doses, grayanotoxins may cause vomiting [5].
- Increased perspiration
- Headache [14]
- Increased salivation
- Diarrhea [5] - Grayanotoxin-containing plants have been historically used as laxatives.
- Motor control loss [15]
- Temperature regulation suppression - This may manifest as hypothermia.
- Dizziness - This effect may occur along with vertigo [5].
- Appetite suppression [16]
- Increased libido - Mad honey is sometimes used as an alternative treatment for sexual dysfunction [5].
Visual effects 
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Suppressions
Distortions
- Drifting - This effect is qualitatively similar to that of other cholinergic substances, and is likely a result of the effects of grayanotoxins on sodium channels.
- Visual haze [19]
- Brightness alteration [20] - Grayanotoxin may make colors appear darker.
Hallucinatory states
- External hallucination - Deliriant-like hallucinations have been reported after high-dose ingestion of grayanotoxins, this is rarely reported and is unlikely to occur at common doses. [21]
- Internal hallucination
Cognitive effects 
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- Cognitive fatigue [22]
- Confusion
- Irritability [23]
- Sleepiness - At sufficient doses, grayanotoxins may cause sedation and even a sudden loss of consciousness [24].
- Cognitive euphoria - This effect manifests as a sense of relaxation [25]
- Cognitive dysphoria [26]
- Anxiety suppression - Grayanotoxin-containing plants, such as monotropa uniflora, have been historically used for their anxiolytic effects [27].
Auditory effects 
Experience reports
There are currently 0 experience reports which describe the effects of this substance in our experience index.
Additional experience reports can be found here:
Toxicity and harm potential
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This toxicity and harm potential section is a stub. As a result, it may contain incomplete or even dangerously wrong information! You can help by expanding upon or correcting it. |
It is strongly recommended that one use harm reduction practices when using this substance.
Lethal dosage
Tolerance and addiction potential
Dangerous interactions
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This dangerous interactions section is a stub. As such, it may contain incomplete or invalid information. You can help by expanding upon or correcting it. |
Warning: Many psychoactive substances that are reasonably safe to use on their own can suddenly become dangerous and even life-threatening when combined with certain other substances. The following list provides some known dangerous interactions (although it is not guaranteed to include all of them).
Always conduct independent research (e.g. Google, DuckDuckGo, PubMed) to ensure that a combination of two or more substances is safe to consume. Some of the listed interactions have been sourced from TripSit.
- Cholinergics - Because grayanotoxins potentiate the effects of acetylcholine, cholinergic substances such as nicotine, caffeine, and galantamine may carry an increased risk of cholinergic crisis.
- Depressants - Combining grayanotoxins with other depressants increase the risk of a sudden loss of consciousness.
- 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.
Legal status
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This legality section is a stub. As such, it may contain incomplete or wrong information. You can help by expanding it. |
See also
External links
(List along order below)
Literature
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References
- ↑ "Monotropa uniflora Indian Pipe". Plants for a Future. Retrieved 2022-08-13.
- ↑ 2.0 2.1 Ullah S, Khan SU, Saleh TA, Fahad S. Mad honey: uses, intoxicating/poisoning effects, diagnosis, and treatment. RSC Adv. 2018 May 22;8(33):18635-18646. doi: 10.1039/c8ra01924j. PMID: 35541133; PMCID: PMC9080652
- ↑ "Grayanotoxins". Foodborne Pathogenic Microorganisms and Natural Toxins Handbook. US FDA. 2012. Retrieved August 7, 2015.
- ↑ Shrestha TM, Nepal G, Shing YK, Shrestha L. Cardiovascular, psychiatric, and neurological phenomena seen in mad honey disease: A clinical case report. Clin Case Rep. 2018 Oct 22;6(12):2355-2357. doi: 10.1002/ccr3.1889. PMID: 30564328; PMCID: PMC6293183.
- ↑ 5.0 5.1 5.2 5.3 5.4 5.5 5.6 Gunduz A, Turedi S, Russell RM, Ayaz FA. Clinical review of grayanotoxin/mad honey poisoning past and present. Clin Toxicol (Phila). 2008 Jun;46(5):437-42. doi: 10.1080/15563650701666306. PMID: 18568799.
- ↑ Jansen SA, Kleerekooper I, Hofman ZL, Kappen IF, Stary-Weinzinger A, van der Heyden MA. Grayanotoxin poisoning: 'mad honey disease' and beyond. Cardiovasc Toxicol. 2012 Sep;12(3):208-15. doi: 10.1007/s12012-012-9162-2. PMID: 22528814; PMCID: PMC3404272.
- ↑ Yuki T, Yamaoka K, Yakehiro M, Seyama I. State-dependent action of grayanotoxin I on Na(+) channels in frog ventricular myocytes. J Physiol. 2001 Aug 1;534(Pt 3):777-90. doi: 10.1111/j.1469-7793.2001.00777.x. PMID: 11483708; PMCID: PMC2278746.
- ↑ 8.0 8.1 8.2 Kim SE, Shin MC, Akaike N, Kim CJ. Presynaptic effects of grayanotoxin III on excitatory and inhibitory nerve terminals in rat ventromedial hypothalamic neurons. Neurotoxicology. 2010 Mar;31(2):230-8. doi: 10.1016/j.neuro.2009.12.006. Epub 2009 Dec 28. PMID: 20038438.
- ↑ Pischon H, Petrick A, Müller M, Köster N, Pietsch J, Mundhenk L. Grayanotoxin I Intoxication in Pet Pigs. Veterinary Pathology. 2018;55(6):896-899. doi:10.1177/0300985818789482
- ↑ Ohgaki T, Uchida S, Meguri H, Ogita K, Yoneda Y. Preventive action of quisqualic acid against grayanotoxin-induced suppression of locomotor activity in mice. Neuropharmacology. 1988 Oct;27(10):1045-53. doi: 10.1016/0028-3908(88)90066-4. PMID: 3070432.
- ↑ Ohgaki T, Meguri H, Ogita K, Yoneda Y. Tetrodotoxin-insensitive central depression by grayanotoxin-III in mice. Brain Res. 1987 Nov 10;425(2):364-8. doi: 10.1016/0006-8993(87)90521-x. PMID: 2448007.
- ↑ Shrestha TM, Nepal G, Shing YK, Shrestha L. Cardiovascular, psychiatric, and neurological phenomena seen in mad honey disease: A clinical case report. Clin Case Rep. 2018 Oct 22;6(12):2355- 2357. doi: 10.1002/ccr3.1889. PMID: 30564328; PMCID: PMC6293183.
- ↑ Gunduz A, Eraydin I, Turkmen S, Kalkan OF, Turedi S, Eryigit U, Ayar A. Analgesic effects of mad honey (grayanotoxin) in mice models of acute pain and painful diabetic neuropathy. Hum Exp Toxicol. 2014 Feb;33(2):130-5. doi: 10.1177/0960327113482693. Epub 2013 Apr 12. PMID: 23584354.
- ↑ Ullah S, Khan SU, Saleh TA, Fahad S. Mad honey: uses, intoxicating/poisoning effects, diagnosis, and treatment. RSC Adv. 2018 May 22;8(33):18635-18646. doi: 10.1039/c8ra01924j. PMID: 35541133; PMCID: PMC9080652.
- ↑ Ohgaki T, Uchida S, Meguri H, Ogita K, Yoneda Y. Preventive action of quisqualic acid against grayanotoxin-induced suppression of locomotor activity in mice. Neuropharmacology. 1988 Oct;27(10):1045-53. doi: 10.1016/0028-3908(88)90066-4. PMID: 3070432.
- ↑ Jansen SA, Kleerekooper I, Hofman ZL, Kappen IF, Stary-Weinzinger A, van der Heyden MA. Grayanotoxin poisoning: 'mad honey disease' and beyond. Cardiovasc Toxicol. 2012 Sep;12(3):208-15. doi: 10.1007/s12012-012-9162-2. PMID: 22528814; PMCID: PMC3404272.
- ↑ Jansen SA, Kleerekooper I, Hofman ZL, Kappen IF, Stary-Weinzinger A, van der Heyden MA. Grayanotoxin poisoning: 'mad honey disease' and beyond. Cardiovasc Toxicol. 2012 Sep;12(3):208-15. doi: 10.1007/s12012-012-9162-2. PMID: 22528814; PMCID: PMC3404272.
- ↑ Setareh-Shenas S, Kaplin S, Bania TC, Kornberg R. A Rare Case of Mad Honey Disease: A Reversible Cause of Complete Heart Block. JACC Case Rep. 2019 Nov 13;1(4):579-582. doi: 10.1016/j.jaccas.2019.09.015. PMID: 34316883; PMCID: PMC8288791.
- ↑ Roy, Saurav & Biswas, Soumya & Ghosh, Saikat & Roy, Pragyan. (2019). The Himalayan hallucinogenic honey and its future prospects and proposed uses. 10.13140/RG.2.2.29254.63041.
- ↑ Setareh-Shenas S, Kaplin S, Bania TC, Kornberg R. A Rare Case of Mad Honey Disease: A Reversible Cause of Complete Heart Block. JACC Case Rep. 2019 Nov 13;1(4):579-582. doi: 10.1016/j.jaccas.2019.09.015. PMID: 34316883; PMCID: PMC8288791.
- ↑ Shrestha TM, Nepal G, Shing YK, Shrestha L. Cardiovascular, psychiatric, and neurological phenomena seen in mad honey disease: A clinical case report. Clin Case Rep. 2018 Oct 22;6(12):2355-2357. doi: 10.1002/ccr3.1889. PMID: 30564328; PMCID: PMC6293183.
- ↑ Jansen SA, Kleerekooper I, Hofman ZL, Kappen IF, Stary-Weinzinger A, van der Heyden MA. Grayanotoxin poisoning: 'mad honey disease' and beyond. Cardiovasc Toxicol. 2012 Sep;12(3):208-15. doi: 10.1007/s12012-012-9162-2. PMID: 22528814; PMCID: PMC3404272.
- ↑ Ullah S, Khan SU, Saleh TA, Fahad S. Mad honey: uses, intoxicating/poisoning effects, diagnosis, and treatment. RSC Adv. 2018 May 22;8(33):18635-18646. doi: 10.1039/c8ra01924j. PMID: 35541133; PMCID: PMC9080652.
- ↑ Jansen SA, Kleerekooper I, Hofman ZL, Kappen IF, Stary-Weinzinger A, van der Heyden MA. Grayanotoxin poisoning: 'mad honey disease' and beyond. Cardiovasc Toxicol. 2012 Sep;12(3):208-15. doi: 10.1007/s12012-012-9162-2. PMID: 22528814; PMCID: PMC3404272.
- ↑ Shrestha TM, Nepal G, Shing YK, Shrestha L. Cardiovascular, psychiatric, and neurological phenomena seen in mad honey disease: A clinical case report. Clin Case Rep. 2018 Oct 22;6(12):2355-2357. doi: 10.1002/ccr3.1889. PMID: 30564328; PMCID: PMC6293183.
- ↑ Ullah S, Khan SU, Saleh TA, Fahad S. Mad honey: uses, intoxicating/poisoning effects, diagnosis, and treatment. RSC Adv. 2018 May 22;8(33):18635-18646. doi: 10.1039/c8ra01924j. PMID: 35541133; PMCID: PMC9080652.
- ↑ Wickes Felter, Harvey; Uri Lloyd, John (1898). King's American dispensatory (19th 3rd rev ed.). Ohio Valley Co. p. 1277.
- ↑ Demircan A, Keles A, Bildik F, Aygelcel G, Dogan NO, Gomez HF. Mad honey sex: Therapeutic misadventures from an ancient biological weapon. An Emerg Med 2009; 54: 824-9