Grayanotoxin: Difference between revisions

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{{decree|type=notice|message=This article is in the 'Talk' namespace because it is an unfinished draft. This section is used to host drafts for unpublished articles as well as discussions for published ones. If you'd like to use this area to discuss this draft, please do so in the 'Discussion' section at the very bottom of the page. This notice will be removed once this draft has been approved for publication by an administrator.}}

~~{{headerpanel|{{Approval}}}}~~

~~For tips on how to properly format a substance article, please refer to this document: [[Content Style Guide - Substance]]~~

==History and culture==

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The Gurung people of Nepal are especially known to harvest mad honey for its supposed hallucinogenic properties <ref>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.</ref>.

==Chemistry==

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*'''[[Effect::[[Decreased blood pressure]]]]'''

*'''[[Effect::[[Pain relief]]]] <ref>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.</ref>'''

*'''[[Effect::[[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 <ref name=":0">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.</ref>.

*'''[[Effect::[[Increased perspiration]]]]'''

*'''[[Effect::[[Headache]]]]''' <ref>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.</ref>

*'''[[Effect::[[Increased salivation]]]]'''

*'''[[Effect::[[Diarrhea]]]]''' <ref name=":0">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.</ref> - Grayanotoxin-containing plants have been historically used as laxatives.

*'''[[Effect::[[Motor control loss]]]]''' <ref>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.</ref>

*'''[[Effect::[[Temperature regulation suppression]]]]''' - This may manifest as hypothermia.

*'''[[Effect::[[Temperature regulation suppression]]]]''' - This may manifest as [[Temperature regulation suppression|hypothermia]].

*'''[[Effect::[[Dizziness]]]]''' - This effect may occur along with vertigo <ref name=":0">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.</ref>.

*'''[[Effect::[[Appetite suppression]]]]''' <ref>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.</ref>

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}}

{{effects/visual|

~~If applicable, a brief paragraph summary of the substance's visual effects may be included here.~~

~~You may select visual effects to add below [[Subjective effect index#Visual effects|here]].~~

====Suppressions====

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====Distortions====

*'''[[Effect::[[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.

*'''[[Effect::[[Drifting]]]]''' - This effect is qualitatively similar to that of other [[Cholinergics|cholinergic substances]], and is likely a result of the effects of grayanotoxins on sodium channels.

*'''[[Effect::[[Visual haze]]]]''' <ref>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.</ref>

*'''[[Effect::[[Brightness alteration]]]]''' <ref>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.</ref> - Grayanotoxin may make colors appear darker.

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====Hallucinatory states====

*'''[[Effect::[[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. <ref>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.</ref>

*'''[[Effect::[[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. <ref>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.</ref>

*'''[[Effect::[[Internal hallucination]]]]'''

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|{{effects/cognitive|

~~If applicable, a brief paragraph summary of the substance's cognitive effects may be included here.~~

~~You may select from a list of cognitive effects to add below [[Subjective effect index#Cognitive effects|here]].~~

*'''[[Effect::Cognitive ~~effect1~~]]'''

*'''[[Effect::[[Cognitive fatigue]]]]''' <ref>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.</ref>

*'''[[Effect::Cognitive ~~effect2~~]]'''

*'''[[Effect::[[Confusion]]]]'''

*'''[[Effect::Cognitive ~~effect3~~]]'''

*'''[[Effect::[[Irritability]]]]''' <ref>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.</ref>

*'''[[Effect::[[Sleepiness]]]]''' - At sufficient doses, grayanotoxins may cause [[sedation]] and even a sudden loss of consciousness <ref>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.</ref>.

*'''[[Effect::[[Cognitive euphoria]]]]''' - This effect manifests as a sense of relaxation <ref>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.</ref>

*'''[[Effect::[[Cognitive dysphoria]]]]''' <ref>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.</ref>

*'''[[Effect::[[Anxiety suppression]]]]''' - Grayanotoxin-containing plants, such as monotropa uniflora, have been historically used for their anxiolytic effects <ref>Wickes Felter, Harvey; Uri Lloyd, John (1898). King's American dispensatory (19th 3rd rev ed.). Ohio Valley Co. p. 1277.</ref>.

}}

{{effects/auditory|

~~If applicable, a brief paragraph summary of the substance's auditory effects may be included here.~~

~~You may select from a list of auditory effects to add below~~ [[~~Subjective effect index#~~Auditory ~~effects|here~~]].

*'''[[Effect::[[Auditory acuity suppression]]]]''' <ref>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</ref>

*'''[[Effect::Auditory effect1]]'''

*'''[[Effect::Auditory effect2]]'''

}}

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===Lethal dosage===

===Tolerance and addiction potential===

===Dangerous interactions===

*'''[[UnsafeInteraction::Cholinergics]]''' - Because grayanotoxins potentiate the effects of [[acetylcholine]], cholinergic substances such as [[nicotine]], [[caffeine]], and [[galantamine]] may carry an increased risk of [[cholinergic crisis]].

*'''[[UnsafeInteraction::Depressants]]''' - Combining grayanotoxins with other [[depressants]] increase the risk of a sudden loss of consciousness.

*'''[[DangerousInteraction::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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-{{decree|type=notice|message=This article is in the 'Talk' namespace because it is an unfinished draft. This section is used to host drafts for unpublished articles as well as discussions for published ones. If you'd like to use this area to discuss this draft, please do so in the 'Discussion' section at the very bottom of the page. This notice will be removed once this draft has been approved for publication by an administrator.}}
-{{headerpanel|{{Approval}}}}
 {{SummarySheet}}
 {{talk:SubstanceBox/Grayanotoxin}}
-<!-- Please ensure that any new substance articles are first published in the 'Talk' namespace. For example, a new article on substance XYZ should have the title "Talk: XYZ" instead of "XYZ". Once the submitted article has been reviewed and determined to meet the guidelines and standards, it will be published by a staff member. -->
-For tips on how to properly format a substance article, please refer to this document: [[Content Style Guide - Substance]]
 ==History and culture==
@@ Line 14: / Line 7: @@
 The Gurung people of Nepal are especially known to harvest mad honey for its supposed hallucinogenic properties <ref>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.</ref>.
 ==Chemistry==
@@ Line 41: / Line 32: @@
 *'''[[Effect::[[Decreased blood pressure]]]]'''
 *'''[[Effect::[[Pain relief]]]] <ref>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.</ref>'''
 *'''[[Effect::[[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 <ref name=":0">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.</ref>.
+*'''[[Effect::[[Increased perspiration]]]]'''
+*'''[[Effect::[[Headache]]]]''' <ref>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.</ref>
 *'''[[Effect::[[Increased salivation]]]]'''
 *'''[[Effect::[[Diarrhea]]]]''' <ref name=":0">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.</ref> - Grayanotoxin-containing plants have been historically used as laxatives.
 *'''[[Effect::[[Motor control loss]]]]''' <ref>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.</ref>
-*'''[[Effect::[[Temperature regulation suppression]]]]''' - This may manifest as hypothermia.
+*'''[[Effect::[[Temperature regulation suppression]]]]''' - This may manifest as [[Temperature regulation suppression|hypothermia]].
 *'''[[Effect::[[Dizziness]]]]''' - This effect may occur along with vertigo <ref name=":0">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.</ref>.
 *'''[[Effect::[[Appetite suppression]]]]''' <ref>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.</ref>
@@ Line 52: / Line 45: @@
 }}
 {{effects/visual|
-If applicable, a brief paragraph summary of the substance's visual effects may be included here.
-You may select visual effects to add below [[Subjective effect index#Visual effects|here]].
 ====Suppressions====
@@ Line 63: / Line 53: @@
 ====Distortions====
-*'''[[Effect::[[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.
+*'''[[Effect::[[Drifting]]]]''' - This effect is qualitatively similar to that of other [[Cholinergics|cholinergic substances]], and is likely a result of the effects of grayanotoxins on sodium channels.
 *'''[[Effect::[[Visual haze]]]]''' <ref>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.</ref>
 *'''[[Effect::[[Brightness alteration]]]]''' <ref>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.</ref> - Grayanotoxin may make colors appear darker.
@@ Line 70: / Line 60: @@
 ====Hallucinatory states====
-*'''[[Effect::[[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. <ref>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.</ref>
+*'''[[Effect::[[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. <ref>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.</ref>
 *'''[[Effect::[[Internal hallucination]]]]'''
@@ Line 76: / Line 66: @@
 |{{effects/cognitive|
-If applicable, a brief paragraph summary of the substance's cognitive effects may be included here.
-You may select from a list of cognitive effects to add below [[Subjective effect index#Cognitive effects|here]].
-*'''[[Effect::Cognitive effect1]]'''
+*'''[[Effect::[[Cognitive fatigue]]]]''' <ref>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.</ref>
-*'''[[Effect::Cognitive effect2]]'''
+*'''[[Effect::[[Confusion]]]]'''
-*'''[[Effect::Cognitive effect3]]'''
+*'''[[Effect::[[Irritability]]]]''' <ref>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.</ref>
+*'''[[Effect::[[Sleepiness]]]]''' - At sufficient doses, grayanotoxins may cause [[sedation]] and even a sudden loss of consciousness <ref>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.</ref>.
+*'''[[Effect::[[Cognitive euphoria]]]]''' - This effect manifests as a sense of relaxation <ref>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.</ref>
+*'''[[Effect::[[Cognitive dysphoria]]]]''' <ref>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.</ref>
+*'''[[Effect::[[Anxiety suppression]]]]''' - Grayanotoxin-containing plants, such as monotropa uniflora, have been historically used for their anxiolytic effects <ref>Wickes Felter, Harvey; Uri Lloyd, John (1898). King's American dispensatory (19th 3rd rev ed.). Ohio Valley Co. p. 1277.</ref>.
 }}
 {{effects/auditory|
-If applicable, a brief paragraph summary of the substance's auditory effects may be included here.
-You may select from a list of auditory effects to add below [[Subjective effect index#Auditory effects|here]].
+*'''[[Effect::[[Auditory acuity suppression]]]]''' <ref>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</ref>
-*'''[[Effect::Auditory effect1]]'''
-*'''[[Effect::Auditory effect2]]'''
 }}
@@ Line 107: / Line 95: @@
 ===Lethal dosage===
 ===Tolerance and addiction potential===
 ===Dangerous interactions===
 {{DangerousInteractions}}
 {{DangerousInteractions/Intro}}
+*'''[[UnsafeInteraction::Cholinergics]]''' - Because grayanotoxins potentiate the effects of [[acetylcholine]], cholinergic substances such as [[nicotine]], [[caffeine]], and [[galantamine]] may carry an increased risk of [[cholinergic crisis]].
+*'''[[UnsafeInteraction::Depressants]]''' - Combining grayanotoxins with other [[depressants]] increase the risk of a sudden loss of consciousness.
+*'''[[DangerousInteraction::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==