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In 1946, it became the first prescription antihistamine approved by the U.S. Food and Drug Administration. It was approved for over-the-counter use in the 1980s.<ref name="Emanuel">{{cite journal | vauthors=((Emanuel, M. B.)) | journal=Clinical & Experimental Allergy | title=Histamine and the antiallergic antihistamines: a history of their discoveries: History of antiallergic antihistamines | volume=29 | pages=1–11 | date= July 1999 | url=http://doi.wiley.com/10.1046/j.1365-2222.1999.00004.x-i1 | issn=09547894 | doi=10.1046/j.1365-2222.1999.00004.x-i1}}</ref>
In 1946, it became the first prescription antihistamine approved by the U.S. Food and Drug Administration. It was approved for over-the-counter use in the 1980s.<ref name="Emanuel">{{cite journal | vauthors=((Emanuel, M. B.)) | journal=Clinical & Experimental Allergy | title=Histamine and the antiallergic antihistamines: a history of their discoveries: History of antiallergic antihistamines | volume=29 | pages=1–11 | date= July 1999 | url=http://doi.wiley.com/10.1046/j.1365-2222.1999.00004.x-i1 | issn=09547894 | doi=10.1046/j.1365-2222.1999.00004.x-i1}}</ref>
Today, it is typically used to treat allergies, but it may also be used for a number of conditions including itchiness, insomnia, motion sickness, nausea and the symptoms of Parkinson's disease.<ref>http://www.drugs.com/monograph/diphenhydramine-hydrochloride.html</ref>
Today, it is typically used to treat allergies, but it may also be used for several conditions, including itchiness, insomnia, motion sickness, nausea, and the symptoms of Parkinson's disease.<ref>http://www.drugs.com/monograph/diphenhydramine-hydrochloride.html</ref>
[[Subjective effects]] include [[sedation]], [[anxiety]], [[tactile hallucinations]], [[memory suppression]], [[thought disorganization]], [[Cognitive dysphoria|dysphoria]], and [[external hallucinations]]. Lower doses tend to produce a stoning, body-high effect while higher doses produce a state of [[delirium]] in which the user sees and hears fully-formed, extremely convincing [[hallucinations]]. Doses between these two points are uncomfortable and dysphoric.
[[Subjective effects]] include [[sedation]], [[anxiety]], [[tactile hallucinations]], [[memory suppression]], [[thought disorganization]], [[Cognitive dysphoria|dysphoria]], and [[external hallucinations]]. Lower doses tend to produce a stoning, body-high effect, while higher doses produce a state of [[delirium]] in which the user sees and hears fully-formed, compelling [[hallucinations]]. Doses between these two points are uncomfortable and dysphoric.
Notably, it is frequently reported to produce significant [[nausea]] and bodily discomfort ("body load"). Most people who try diphenhydramine do not report positive effects and do not wish to repeat the experience.
Notably, it is frequently reported to produce significant [[nausea]] and bodily discomfort ("body load"). Most people who try diphenhydramine do not report positive effects and do not wish to repeat the experience.
It is generally considered to have low abuse potential due to its dysphoric effects. The toxicity of recreational use is not well-studied. Anecdotal reports suggest that chronic use (i.e. high dose, repeated administration) may cause persisting hallucinations and impairments in cognition & memory. High doses have also been linked to seizures and cardiotoxicity.<ref>{{cite journal | vauthors=((Jang, D. H.)), ((Manini, A. F.)), ((Trueger, N. S.)), ((Duque, D.)), ((Nestor, N. B.)), ((Nelson, L. S.)), ((Hoffman, R. S.)) | journal=Clinical Toxicology | title=Status epilepticus and wide-complex tachycardia secondary to diphenhydramine overdose | volume=48 | issue=9 | pages=945–948 | date= November 2010 | url=http://www.tandfonline.com/doi/full/10.3109/15563650.2010.527850 | issn=1556-3650 | doi=10.3109/15563650.2010.527850}}</ref>
It is generally considered to have low abuse potential due to its dysphoric effects. The toxicity of recreational use is not well-studied. Anecdotal reports suggest that chronic use (i.e., high dose, repeated administration) may cause persisting hallucinations and impairments in cognition & memory. High doses have also been linked to seizures and cardiotoxicity.<ref>{{cite journal | vauthors=((Jang, D. H.)), ((Manini, A. F.)), ((Trueger, N. S.)), ((Duque, D.)), ((Nestor, N. B.)), ((Nelson, L. S.)), ((Hoffman, R. S.)) | journal=Clinical Toxicology | title=Status epilepticus and wide-complex tachycardia secondary to diphenhydramine overdose | volume=48 | issue=9 | pages=945–948 | date= November 2010 | url=http://www.tandfonline.com/doi/full/10.3109/15563650.2010.527850 | issn=1556-3650 | doi=10.3109/15563650.2010.527850}}</ref>
It is highly advised to use [[harm reduction practices]] if using this substance.
It is highly advised to use [[harm reduction practices]] if using this substance.
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Diphenhydramine was discovered in 1943 by George Rieveschl, a former professor at the University of Cincinnati.<ref>{{cite news | author=Hevesi D | url=https://www.nytimes.com/2007/09/29/business/29rieveschl.html?ref=health | title=George Rieveschl, 91, Allergy Reliever, Dies | newspaper=The New York Times | date=29 September 2007 | accessdate=14 October 2008 | deadurl=no | archive-url=https://web.archive.org/web/20111213132036/http://www.nytimes.com/2007/09/29/business/29rieveschl.html?ref=health | archivedate=13 December 2011 | df=dmy-all }}</ref><ref>{{cite web|url=http://www.ohiohistorycentral.org/w/Benadryl|title=Benadryl|date=|work=|publisher=Ohio History Central|accessdate=13 August 2015|deadurl=no|archive-url=https://web.archive.org/web/20150905130056/http://www.ohiohistorycentral.org/w/Benadryl|archivedate=5 September 2015|df=dmy-all}}</ref> In 1946, it became the first prescription antihistamine approved by the United States Food and Drug Administration (FDA).<ref name="BC">{{cite web |author=Ritchie J |url=http://www.bizjournals.com/cincinnati/stories/2007/09/24/daily52.html |title=UC prof, Benadryl inventor dies |date=24 September 2007 |work= |publisher=Business Courier of Cincinnati |accessdate=14 October 2008 |deadurl=no |archive-url=https://web.archive.org/web/20081224055505/http://www.bizjournals.com/cincinnati/stories/2007/09/24/daily52.html |archivedate=24 December 2008 |df=dmy-all }}</ref>
Diphenhydramine was discovered in 1943 by George Rieveschl, a former professor at the University of Cincinnati.<ref>{{cite news | author=Hevesi D | url=https://www.nytimes.com/2007/09/29/business/29rieveschl.html?ref=health | title=George Rieveschl, 91, Allergy Reliever, Dies | newspaper=The New York Times | date=29 September 2007 | accessdate=14 October 2008 | deadurl=no | archive-url=https://web.archive.org/web/20111213132036/http://www.nytimes.com/2007/09/29/business/29rieveschl.html?ref=health | archivedate=13 December 2011 | df=dmy-all }}</ref><ref>{{cite web|url=http://www.ohiohistorycentral.org/w/Benadryl|title=Benadryl|date=|work=|publisher=Ohio History Central|accessdate=13 August 2015|deadurl=no|archive-url=https://web.archive.org/web/20150905130056/http://www.ohiohistorycentral.org/w/Benadryl|archivedate=5 September 2015|df=dmy-all}}</ref> In 1946, it became the first prescription antihistamine approved by the United States Food and Drug Administration (FDA).<ref name="BC">{{cite web |author=Ritchie J |url=http://www.bizjournals.com/cincinnati/stories/2007/09/24/daily52.html |title=UC prof, Benadryl inventor dies |date=24 September 2007 |work= |publisher=Business Courier of Cincinnati |accessdate=14 October 2008 |deadurl=no |archive-url=https://web.archive.org/web/20081224055505/http://www.bizjournals.com/cincinnati/stories/2007/09/24/daily52.html |archivedate=24 December 2008 |df=dmy-all }}</ref>
In the 1960s diphenhydramine was found to inhibit reuptake of the [[neurotransmitter]] [[serotonin]].<ref name="Domino_1999" /> This discovery led to a search for viable [[antidepressant]]s with similar structures and fewer side effects, culminating in the invention of fluoxetine (Prozac), a [[selective serotonin reuptake inhibitor]] (SSRI).<ref name="Domino_1999">{{cite journal | vauthors = Domino EF | title = History of modern psychopharmacology: a personal view with an emphasis on antidepressants | journal = Psychosomatic Medicine | volume = 61 | issue = 5 | pages = 591–8 | year = 1999 | pmid = 10511010 | doi = 10.1097/00006842-199909000-00002 }}</ref><ref name="url_Adawi_Awdish">{{cite journal |vauthors=Awdishn RA, Whitmill M, Coba V, Killu K | title = Serotonin reuptake inhibition by diphenhydramine and concomitant linezolid use can result in serotonin syndrome | journal = Chest |date=October 2008 | volume = 134 | issue = 4 Meeting abstracts | url = http://journal.publications.chestnet.org/article.aspx?articleid=1094281 | doi = 10.1378/chest.134.4_MeetingAbstracts.c4002}}</ref>
In the 1960s, diphenhydramine was found to inhibit reuptake of the [[neurotransmitter]] [[serotonin]].<ref name="Domino_1999" /> This discovery led to a search for viable [[antidepressant]]s with similar structures and fewer side effects, culminating in the invention of fluoxetine (Prozac), a [[selective serotonin reuptake inhibitor]] (SSRI).<ref name="Domino_1999">{{cite journal | vauthors = Domino EF | title = History of modern psychopharmacology: a personal view with an emphasis on antidepressants | journal = Psychosomatic Medicine | volume = 61 | issue = 5 | pages = 591–8 | year = 1999 | pmid = 10511010 | doi = 10.1097/00006842-199909000-00002 }}</ref><ref name="url_Adawi_Awdish">{{cite journal |vauthors=Awdishn RA, Whitmill M, Coba V, Killu K | title = Serotonin reuptake inhibition by diphenhydramine and concomitant linezolid use can result in serotonin syndrome | journal = Chest |date=October 2008 | volume = 134 | issue = 4 Meeting abstracts | url = http://journal.publications.chestnet.org/article.aspx?articleid=1094281 | doi = 10.1378/chest.134.4_MeetingAbstracts.c4002}}</ref>
==Chemistry==
==Chemistry==
Diphenhydramine, or 2-(diphenylmethoxy)-N,N-dimethylethanamine, is an organic compound belonging to the ethanolamine class. The chemical structure of diphenhydramine consists of an ethylamine chain with two methyl groups bonded to the terminal nitrogen group R<sub>N</sub>. Additionally, this ethylamine chain is substituted at R<sub>2</sub> with a diphenylmethoxy group, forming an ether. The diphenylmethoxy group consists of two aromatic phenyl rings bonded to the carbon member of a methoxy group CH<sub>3</sub>O-.
Diphenhydramine, or 2-(diphenylmethoxy)-N,N-dimethylethanamine, is an organic compound in the ethanolamine class. The chemical structure of diphenhydramine consists of an ethylamine chain with two methyl groups bonded to the terminal nitrogen group R<sub>N</sub>. This ethylamine chain is also substituted at R<sub>2</sub> with a diphenylmethoxy group, forming an ether. The diphenylmethoxy group consists of two aromatic phenyl rings bonded to the carbon member of a methoxy group CH<sub>3</sub>O-.
DPH is produced as a hydrochloride salt.
DPH is produced as a hydrochloride salt.
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Diphenhydramine is an [[agonist#agonists|inverse agonist]] of the peripheral histamine H<sub>1</sub> receptor and a central histamine H<sub>1</sub> receptor.{{citation needed}} The peripheral inverse agonism induces the allergy reducing effects.{{citation needed}} Like many first-generation antihistamines, it is also a competitive antagonist at [[acetylcholine|mACH receptors]].{{citation needed}}
Diphenhydramine is an [[agonist#agonists|inverse agonist]] of the peripheral histamine H<sub>1</sub> receptor and a central histamine H<sub>1</sub> receptor.{{citation needed}} The peripheral inverse agonism induces the allergy reducing effects.{{citation needed}} Like many first-generation antihistamines, it is also a competitive antagonist at [[acetylcholine|mACH receptors]].{{citation needed}}
Diphenhydramine is an [[acetylcholine]] [[receptor]] [[antagonist]]. Although the precise mechanism is not understood, the inhibition of the action of [[acetylcholine]] is thought to be primarily responsible for the delirium, sedation and intensely realistic hallucinations alongside the extremely uncomfortable and dysphoric physical side effects.
Diphenhydramine is an [[acetylcholine]] [[receptor]] [[antagonist]]. Although the precise mechanism is not understood, the inhibition of the action of [[acetylcholine]] is thought to be primarily responsible for the delirium, sedation, and intensely realistic hallucinations alongside the extremely uncomfortable and dysphoric physical side effects.
Diphenhydramine has been shown to block sodium channels and inhibit the reuptake of [[serotonin]].<ref name="Domino_1999" /> It also blocks voltage-gated potassium channels (VGKCs), meaning it has the potential to cause or lead to ''torsades de points'', a potentially dangerous cardiac condition that can lead to sudden cardiac death. <ref>{{cite journal | vauthors=((Khalifa, M.)), ((Drolet, B.)), ((Daleau, P.)), ((Lefez, C.)), ((Gilbert, M.)), ((Plante, S.)), ((O’Hara, G. E.)), ((Gleeton, O.)), ((Hamelin, B. A.)), ((Turgeon, J.)) | journal=The Journal of Pharmacology and Experimental Therapeutics | title=Block of potassium currents in guinea pig ventricular myocytes and lengthening of cardiac repolarization in man by the histamine H1 receptor antagonist diphenhydramine | volume=288 | issue=2 | pages=858–865 | date= February 1999 | issn=0022-3565}}</ref>
Diphenhydramine has been shown to block sodium channels and inhibit the reuptake of [[serotonin]].<ref name="Domino_1999" /> It also blocks voltage-gated potassium channels (VGKCs), meaning it has the potential to cause or lead to ''torsades de points'', a potentially dangerous cardiac condition that can lead to sudden cardiac death. <ref>{{cite journal | vauthors=((Khalifa, M.)), ((Drolet, B.)), ((Daleau, P.)), ((Lefez, C.)), ((Gilbert, M.)), ((Plante, S.)), ((O’Hara, G. E.)), ((Gleeton, O.)), ((Hamelin, B. A.)), ((Turgeon, J.)) | journal=The Journal of Pharmacology and Experimental Therapeutics | title=Block of potassium currents in guinea pig ventricular myocytes and lengthening of cardiac repolarization in man by the histamine H1 receptor antagonist diphenhydramine | volume=288 | issue=2 | pages=858–865 | date= February 1999 | issn=0022-3565}}</ref>
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==Subjective effects==
==Subjective effects==
According to user reports, diphenhydramine displays a non-linear dose-response, meaning the effects don't correspond directly with the dose. Doses under 300 mg are reported to produce restlessness, [[muscle relaxation]], and a [[spontaneous bodily sensations|body high]] while doses above 500 mg begin to produce a state of [[delirium]] in which the user sees and hears fully-formed, extremely convincing [[hallucinations]]. Doses in between these two extremes are said to be uncomfortable and dysphoric. [[Nausea]] and bodily discomfort ("body load") is reported almost universally.
According to user reports, diphenhydramine displays a non-linear dose response, meaning the effects don't correspond directly with the dose. Doses under 300 mg are reported to produce restlessness, [[muscle relaxation]], and a [[spontaneous bodily sensations|body high]]. In comparison, doses above 500 mg begin to produce a state of [[delirium]] in which the user sees and hears fully-formed, compelling [[hallucinations]]. Doses in between these two extremes are said to be uncomfortable and dysphoric. [[Nausea]] and bodily discomfort ("body load") are reported almost universally.
{{Preamble/SubjectiveEffects}}
{{Preamble/SubjectiveEffects}}
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|{{effects/physical|
|{{effects/physical|
*'''[[Effect::Sedation]]''' - Diphenhydramine produces considerable sedation and low doses are commonly used as a sleep aid. This sense of sedation is accompanied by a heavy body load which can become overwhelmingly uncomfortable. However, higher doses of diphenhydramine also have a stimulating quality that can make actual rest difficult.
*'''[[Effect::Sedation]]''' - Diphenhydramine produces considerable sedation, and low doses are commonly used as a sleep aid. This sense of sedation is accompanied by a heavy body load, which can become overwhelmingly uncomfortable. However, higher doses of diphenhydramine also have a stimulating quality that can make actual rest difficult.
*'''[[Effect::Spontaneous bodily sensations]]''' - Users commonly report all-encompassing, sharp and painful jolts of electricity that spontaneously manifest themselves uncontrollably in a similar rhythm to hiccups.
*'''[[Effect::Spontaneous bodily sensations]]''' - Users commonly report all-encompassing, sharp, and painful jolts of electricity that spontaneously manifest themselves uncontrollably in a similar rhythm to hiccups.
*'''[[Effect::Perception of bodily heaviness]]''' - One of the most apparent effects is having a massive body as if the gravity has been multiplied tenfold. This makes it extremely tough and uncomfortable to move.
*'''[[Effect::Perception of bodily heaviness]]''' - One of the most apparent effects is having a massive body as if gravity multiplied tenfold. This makes it extremely tough and uncomfortable to move.
*'''[[Effect::Restless leg syndrome]]''' - Restless legs are very prominent and arguably one of the most uncomfortable side effects of diphenhydramine. It can also last for days after the experience and can even be chronic when it is abused repeatedly.
*'''[[Effect::Restless leg syndrome]]''' - Restless legs are very prominent and arguably one of the most uncomfortable side effects of diphenhydramine. It can also last for days after the experience and can even be chronic when it is abused repeatedly.
*'''[[Effect::Tactile enhancement]]''' - This results in increased feelings of touch, pain, warmth and orgasms. It is usually only present at the peak and not during the come up or come down.
*'''[[Effect::Tactile enhancement]]''' - This results in increased feelings of touch, pain, warmth, and orgasms. It is usually only present at the peak, not during the come-up or down.
*'''[[Effect::Tactile suppression]]''' - Diphenhydramine produces feelings of numbness throughout the body. This is attributed to its ability to block sodium channels within the nerves.<ref name="Kim2000"/>
*'''[[Effect::Tactile suppression]]''' - Diphenhydramine produces feelings of numbness throughout the body. This is attributed to its ability to block sodium channels within the nerves.<ref name="Kim2000"/>
*'''[[Effect::Tactile hallucination]]''' - This is often a direct result of visual [[external hallucinations|hallucinations]] and they commonly feel and look as if insects are crawling on one's skin.
*'''[[Effect::Tactile hallucination]]''' - This is often a direct result of visual [[external hallucinations|hallucinations]], and they commonly feel and look as if insects are crawling on one's skin.
*'''[[Effect::Nausea]]''' or '''[[Effect::Nausea suppression]]'''- Depending on the dose, diphenhydramine can both suppress and cause nausea. Low doses effectively suppress nausea, which is why it is marketed and sold as a motion sickness suppressant, while high doses cause it in significant amounts.
*'''[[Effect::Nausea]]''' or '''[[Effect::Nausea suppression]]'''- Depending on the dose, diphenhydramine can both suppress and cause nausea. Low doses effectively suppress nausea, which is why it is marketed and sold as a motion sickness suppressant, while high doses cause it in significant amounts.
*'''[[Effect::Abnormal heartbeat]]''' - Diphenhydramine is able to prolong the QT interval, potentially leading to torsades de pointes, an abnormal heart rhythm that can cause sudden cardiac death.<ref>{{cite journal | vauthors=((Thakur, A. C.)), ((Aslam, A. K.)), ((Aslam, A. F.)), ((Vasavada, B. C.)), ((Sacchi, T. J.)), ((Khan, I. A.)) | journal=International Journal of Cardiology | title=QT interval prolongation in diphenhydramine toxicity | volume=98 | issue=2 | pages=341–343 | date=15 February 2005 | url=https://www.sciencedirect.com/science/article/pii/S0167527304000786 | issn=0167-5273 | doi=10.1016/j.ijcard.2003.10.051}}</ref>
*'''[[Effect::Abnormal heartbeat]]''' - Diphenhydramine can prolong the QT interval, potentially leading to torsades de pointes, an abnormal heart rhythm that can cause sudden cardiac death.<ref>{{cite journal | vauthors=((Thakur, A. C.)), ((Aslam, A. K.)), ((Aslam, A. F.)), ((Vasavada, B. C.)), ((Sacchi, T. J.)), ((Khan, I. A.)) | journal=International Journal of Cardiology | title=QT interval prolongation in diphenhydramine toxicity | volume=98 | issue=2 | pages=341–343 | date=15 February 2005 | url=https://www.sciencedirect.com/science/article/pii/S0167527304000786 | issn=0167-5273 | doi=10.1016/j.ijcard.2003.10.051}}</ref>
*'''[[Effect::Cough suppression]]'''<ref>{{cite journal | vauthors=((Lilienfield, L. S.)), ((Rose, J. C.)), ((Princiotto, J. V.)) | journal=Clinical Pharmacology and Therapeutics | title=Antitussive activity of diphenhydramine in chronic cough | volume=19 | issue=4 | pages=421–425 | date= April 1976 | issn=0009-9236 | doi=10.1002/cpt1976194421}}</ref>
*'''[[Effect::Cough suppression]]'''<ref>{{cite journal | vauthors=((Lilienfield, L. S.)), ((Rose, J. C.)), ((Princiotto, J. V.)) | journal=Clinical Pharmacology and Therapeutics | title=Antitussive activity of diphenhydramine in chronic cough | volume=19 | issue=4 | pages=421–425 | date= April 1976 | issn=0009-9236 | doi=10.1002/cpt1976194421}}</ref>
*'''[[Effect::Dehydration]]'''{{citation needed}} - Diphenhydramine can be extremely dehydrating, which often leads to dry mouth and skin, chapped lips and nose bleeds. Users should drink plenty of water before and after an experience.
*'''[[Effect::Dehydration]]'''{{citation needed}} - Diphenhydramine can be extremely dehydrating, which often leads to dry mouth and skin, chapped lips, and nose bleeds. Users should drink plenty of water before and after an experience.
*'''[[Effect::Dry_mouth]]''' - Along with dehydration, diphenhydramine makes your mouth very dry. Water can temporarily remedy this, although it usually persists for the entirety of the trip.
*'''[[Effect::Dry mouth]]''' - Along with dehydration, diphenhydramine makes your mouth very dry. Water can temporarily remedy this, although it usually persists for the entirety of the trip.
*'''[[Effect::Dizziness]]'''
*'''[[Effect::Dizziness]]'''
*'''[[Effect::Frequent urination]]''' & '''[[Effect::Difficulty urinating]]''' - Diphenhydramine has the strange effect of making the user want to frequently urinate while making actual urination extremely difficult. This sensation is described as very uncomfortable.
*'''[[Effect::Frequent urination]]''' & '''[[Effect::Difficulty urinating]]''' - Diphenhydramine has the strange effect of making the user want to urinate while making actual urination extremely difficult frequently. This sensation is described as very uncomfortable.
*'''[[Effect::Gustatory hallucination]]''' - A foul metallic-like taste is present throughout the entire experience, which in combination with a dry mouth can be a very uncomfortable effect that can last for days after the experience. Eating or drinking flavored drinks will only make the taste go away temporarily. It can also appear as a sign of addiction, where it acts as a trigger for cravings.
*'''[[Effect::Gustatory hallucination]]''' - A foul metallic-like taste is present throughout the entire experience, combined with a dry mouth, which can be a very uncomfortable effect lasting for days after the experience. Eating or drinking flavored drinks will only make the taste go away temporarily. It can also appear as a sign of addiction, where it acts as a trigger for cravings.
*'''[[Effect::Hypotension]]'''<ref>{{cite journal |last1=Huynh |first1=David A. |last2=Abbas |first2=Malak |last3=Dabaja |first3=Ali |title=Diphenhydramine Toxicity |publisher=StatPearls |date=29 April 2023 |url=https://www.ncbi.nlm.nih.gov/books/NBK557578/ |OCLC=1021256616}}</ref>
*'''[[Effect::Hypotension]]'''<ref>{{cite journal |last1=Huynh |first1=David A. |last2=Abbas |first2=Malak |last3=Dabaja |first3=Ali |title=Diphenhydramine Toxicity |publisher=StatPearls |date=29 April 2023 |url=https://www.ncbi.nlm.nih.gov/books/NBK557578/ |OCLC=1021256616}}</ref>
*'''[[Effect::Increased heart rate]]'''<ref>{{cite journal |last1=Huynh |first1=David A. |last2=Abbas |first2=Malak |last3=Dabaja |first3=Ali |title=Diphenhydramine Toxicity |publisher=StatPearls |date=29 April 2023 |url=https://www.ncbi.nlm.nih.gov/books/NBK557578/ |OCLC=1021256616}}</ref>
*'''[[Effect::Increased heart rate]]'''<ref>{{cite journal |last1=Huynh |first1=David A. |last2=Abbas |first2=Malak |last3=Dabaja |first3=Ali |title=Diphenhydramine Toxicity |publisher=StatPearls |date=29 April 2023 |url=https://www.ncbi.nlm.nih.gov/books/NBK557578/ |OCLC=1021256616}}</ref>
*'''[[Effect::Increased bodily temperature]]'''
*'''[[Effect::Increased bodily temperature]]'''
*'''[[Effect::Temperature regulation suppression]]''' - This effect can lead the user to experience shivers, especially during the come up phase.
*'''[[Effect::Temperature regulation suppression]]''' - This effect can lead the user to experience shivers, especially during the come-up phase.
*'''[[Effect::Increased perspiration]]'''
*'''[[Effect::Increased perspiration]]'''
*'''[[Effect::Motor control loss]]'''
*'''[[Effect::Motor control loss]]'''
*'''[[Effect::Muscle cramps]]''' & '''[[Effect::Muscle spasms]]''' - Sudden muscle cramps and spasms can form unexpectedly. This is common at the beginning of the trip and usually passes quickly.
*'''[[Effect::Muscle cramps]]''' & '''[[Effect::Muscle spasms]]''' - Sudden muscle cramps and spasms can form unexpectedly. This is common at the beginning of the trip and usually passes quickly.
*'''[[Effect::Olfactory hallucination]]''' - It is common for users to smell a mild, thick and dull smell in the air that can easily be ignored most of the time. Some users also notice a smell enhancement{{citation needed}}
*'''[[Effect::Olfactory hallucination]]''' - It is common for users to smell a mild, thick, and dull smell in the air that can easily be ignored most of the time. Some users also notice a smell enhancement{{citation needed}}
*'''[[Effect::Physical fatigue]]'''
*'''[[Effect::Physical fatigue]]'''
*'''[[Effect::Pupil constriction]]''' ''or'' '''[[Effect::Pupil dilation]]''' - While it is known that diphenhydramine constricts pupils minimally<ref>{{cite journal | vauthors=((Hou, R. H.)), ((Scaife, J.)), ((Freeman, C.)), ((Langley, R. W.)), ((Szabadi, E.)), ((Bradshaw, C. M.)) | journal=British Journal of Clinical Pharmacology | title=Relationship between sedation and pupillary function: comparison of diazepam and diphenhydramine | volume=61 | issue=6 | pages=752–760 | date= June 2006 | url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1885114/ | issn=0306-5251 | doi=10.1111/j.1365-2125.2006.02632.x}}</ref>, many people also report that their pupils dilate, especially at high dosages when anti-cholinergic effects take place similar to substances like [[atropine]] or [[scopolamine]].
*'''[[Effect::Pupil constriction]]''' ''or'' '''[[Effect::Pupil dilation]]''' - While it is known that diphenhydramine constricts pupils minimally<ref>{{cite journal | vauthors=((Hou, R. H.)), ((Scaife, J.)), ((Freeman, C.)), ((Langley, R. W.)), ((Szabadi, E.)), ((Bradshaw, C. M.)) | journal=British Journal of Clinical Pharmacology | title=Relationship between sedation and pupillary function: comparison of diazepam and diphenhydramine | volume=61 | issue=6 | pages=752–760 | date= June 2006 | url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1885114/ | issn=0306-5251 | doi=10.1111/j.1365-2125.2006.02632.x}}</ref>, many people also report that their pupils dilate, especially at high dosages when anticholinergic effects take place similar to substances like [[atropine]] or [[scopolamine]].
*'''[[Effect::Rapid breathing]]'''
*'''[[Effect::Rapid breathing]]'''
*'''[[Effect::Skin flushing]]''' - Flushed skin occurs mostly around the eyes, but can also be seen all over the body.
*'''[[Effect::Skin flushing]]''' - Flushed skin occurs mostly around the eyes but can also be seen all over the body.
*'''[[Effect::Temporary erectile dysfunction]]'''
*'''[[Effect::Temporary erectile dysfunction]]'''
*'''[[Effect::Itchiness]]''' - This effect happens in high doses, however, it reduces itchiness in lower doses due to [[histamine]] antagonism..
*'''[[Effect::Itchiness]]''' - This effect happens in high doses. However, it reduces itchiness in lower doses due to [[histamine]] antagonism.
*'''[[Effect::Teeth grinding]]''' - Some users report jaw clenching.{{citation needed}}
*'''[[Effect::Teeth grinding]]''' - Some users report jaw clenching.{{citation needed}}
*'''[[Effect::Appetite suppression]]''' - Possibly due to the bronchodilation that makes swallowing uncomfortable,{{citation needed}} DPH is able to make eating uncomfortable as well. This could make a user force themselves to eat, or to stop eating entirely despite hunger before the effects kick in.{{citation needed}}
*'''[[Effect::Appetite suppression]]''' - Possibly due to the bronchodilation that makes swallowing uncomfortable,{{citation needed}} DPH is able to make eating uncomfortable as well. This could make a user force themselves to eat, or to stop eating entirely despite hunger before the effects kick in.{{citation needed}}
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{{effects/visual|
{{effects/visual|
While diphenhydramine produces visual hallucinations, it does not enhance visual stimuli in the manner of [[psychedelics]]. Instead, it tends to degrade and decrease visual acuity and processing that results in increased hallucinations and degraded vision. This becomes more apparent in darker areas than in well-lit ones.
While diphenhydramine produces visual hallucinations, it does not enhance visual stimuli in the manner of [[psychedelics]]. Instead, it tends to degrade and decrease visual acuity and processing, which results in increased hallucinations and degraded vision. This becomes more apparent in darker areas than in well-lit ones.
====Suppression====
====Suppression====
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====Distortions====
====Distortions====
*'''[[Effect::Drifting]]''' ''([[Visual drifting#Melting|melting]], [[Visual drifting#Breathing|breathing]], [[Visual drifting#Morphing|morphing]] and [[Visual drifting#Flowing|flowing]])'' - Compared to hallucinogens, this effect can be described as intricate in complexity, jittery and flexible in motion, static in their permanence, realistic in believability, and interactive in plasticity. It is also very faint.
*'''[[Effect::Drifting]]''' ''([[Visual drifting#Melting|melting]], [[Visual drifting#Breathing|breathing]], [[Visual drifting#Morphing|morphing]] and [[Visual drifting#Flowing|flowing]])'' - Compared to hallucinogens, this effect can be described as intricate in complexity, jittery and flexible in motion, static in their permanence, realistic in believability, and interactive in plasticity. It is also very faint.
*'''[[Effect::Object alteration]]''' - The textures seen are described as transparent whirling lines and swirls which move at changing speeds and jitter uncontrollably. They only appear slightly above surfaces, walls and ceilings and can not be felt.
*'''[[Effect::Object alteration]]''' - The textures seen are described as transparent whirling lines and swirls that move at changing speeds and jitter uncontrollably. They only appear slightly above surfaces, walls, and ceilings and can not be felt.
*'''[[Effect::Brightness alteration]]''' - Diphenhydramine can cause one's vision to decrease in brightness and become dark and gloomy.
*'''[[Effect::Brightness alteration]]''' - Diphenhydramine can cause one's vision to decrease in brightness and become dark and gloomy.
*'''[[Effect::Visual haze]]'''
*'''[[Effect::Visual haze]]'''
====Hallucinatory states====
====Hallucinatory states====
*'''[[Effect::External hallucination]]''' (''[[effect::autonomous entities]]''; ''[[effect::settings, sceneries, and landscapes]]''; ''[[effect::perspective hallucinations]]'' and ''[[effect::scenarios and plots]]'') - Relative to other [[hallucinogens]], this effect occurs more frequently at moderate to heavy doses and is the defining feature of the experience. It can be comprehensively described through its [[Visual_effects:_Internal_hallucinations#Variations|variations]] as delirious in believability, controllable or autonomous in controllability and solid in style. The most common themes for these hallucinations include those of both everyday occurrences such as smoking phantom cigarettes, talking to people who are not there, seeing and feeling insects and immersion in sinister or nightmarish experiences.
*'''[[Effect::External hallucination]]''' (''[[effect::autonomous entities]]''; ''[[effect::settings, sceneries, and landscapes]]''; ''[[effect::perspective hallucinations]]'' and ''[[effect::scenarios and plots]]'') - Relative to other [[hallucinogens]], this effect occurs more frequently at moderate to heavy doses and is the defining feature of the experience. It can be comprehensively described through its [[Visual_effects:_Internal_hallucinations#Variations|variations]] as delirious in believability, controllable, or autonomous in controllability and solid in style. The most common themes for these hallucinations include those of everyday occurrences such as smoking phantom cigarettes, talking to people who are not there, seeing and feeling insects, and immersion in sinister or nightmarish experiences.
*'''[[Effect::Internal hallucination]]''' (''[[effect::autonomous entities]]''; ''[[effect::settings, sceneries, and landscapes]]''; ''[[effect::perspective hallucinations]]'' and ''[[effect::scenarios and plots]]'') - Relative to other [[hallucinogens]], this effect occurs briefly and spontaneously at moderate doses but becomes progressively extended in its occurrence and duration proportional to dosage before eventually becoming all-encompassing. It can be comprehensively described through its [[Visual_effects:_Internal_hallucinations#Variations|variations]] as delirious in believability, interactive in style, equal in new experiences and memory replays in content, autonomous in controllability and solid in style. [[Internal hallucinations]] may occur at lighter dosages than needed to cause [[external hallucinations]] and [[delirium]].
*'''[[Effect::Internal hallucination]]''' (''[[effect::autonomous entities]]''; ''[[effect::settings, sceneries, and landscapes]]''; ''[[effect::perspective hallucinations]]'' and ''[[effect::scenarios and plots]]'') - Relative to other [[hallucinogens]], this effect occurs briefly and spontaneously at moderate doses but becomes progressively extended in its occurrence and duration proportional to dosage before eventually becoming all-encompassing. It can be comprehensively described through its [[Visual_effects:_Internal_hallucinations#Variations|variations]] as delirious in believability, interactive in style, equal in new experiences and memory replays in content, autonomous in controllability, and solid in style. [[Internal hallucinations]] may occur at lighter dosages than needed to cause [[external hallucinations]] and [[delirium]].
*'''[[Effect::Peripheral information misinterpretation]]'''
*'''[[Effect::Peripheral information misinterpretation]]'''
*'''[[Effect::Shadow people]]'''
*'''[[Effect::Shadow people]]'''
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|{{effects/cognitive|
|{{effects/cognitive|
The head space of diphenhydramine is described by many as generally negative and dysphoric, often consisting of extreme paranoia and feelings of impending doom. It is extremely confusing and disorienting and often results in a complete inability to communicate or understand normal language.
The headspace of diphenhydramine is described by many as generally negative and dysphoric, often consisting of extreme paranoia and feelings of impending doom. It is highly confusing and disorienting and usually results in a complete inability to communicate or understand standard language.
*'''[[Effect::Analysis suppression]]''' - At higher dosages, a person could experience a complete halt of external information processing, which can make the user unable to perform simple tasks or make decisions.
*'''[[Effect::Analysis suppression]]''' - At higher dosages, a person could experience a complete halt of external information processing, which can make the user unable to perform simple tasks or make decisions.
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*'''[[Effect::Sleepiness]]''' - Diphenhydramine is reported to be extremely tiring. Low doses are often used and sold as a sleep aid.
*'''[[Effect::Sleepiness]]''' - Diphenhydramine is reported to be extremely tiring. Low doses are often used and sold as a sleep aid.
*'''[[Effect::Wakefulness]]''' - Even though diphenhydramine is primarily a [[depressant]] and causes sleepiness, it has stimulant effects on the body, which can also keep the user awake. This effect predominates sleepiness at higher dosages.
*'''[[Effect::Wakefulness]]''' - Even though diphenhydramine is primarily a [[depressant]] and causes sleepiness, it has stimulant effects on the body, which can also keep the user awake. This effect predominates sleepiness at higher dosages.
*'''[[Effect::Cognitive dysphoria|Dysphoria]]''' - The levels of dysphoria experienced, however, vary between people with a very small percentage of users reporting that they do not seem to experience them at all.
*'''[[Effect::Cognitive dysphoria|Dysphoria]]''' - The levels of dysphoria experienced, however, vary between people, with a tiny percentage of users reporting that they do not seem to experience them at all.
*'''[[Effect::Cognitive fatigue]]'''
*'''[[Effect::Cognitive fatigue]]'''
*'''[[Effect::Confusion]]''' - Diphenhydramine causes significant confusion which can result in a complete inability to understand others' intentions, emotions, humor and even simple sentences.
*'''[[Effect::Confusion]]''' - Diphenhydramine causes significant confusion, resulting in a complete inability to understand others' intentions, emotions, humor, and even simple sentences.
*'''[[Effect::Creativity suppression]]'''
*'''[[Effect::Creativity suppression]]'''
*'''[[Effect::Decreased libido]]''' - Interestingly, one's sex drive seems to have diminished, although sex and masturbation are considered more enjoyable in a unique way and often come with powerful orgasms.
*'''[[Effect::Decreased libido]]''' - Interestingly, one's sex drive seems to have diminished, although sex and masturbation are considered more enjoyable in a unique way and often come with powerful orgasms.
*'''[[Effect::Delirium]]''' - Delirium may be experienced with extremely high doses which may necessitate hospitalization.
*'''[[Effect::Delirium]]''' - Delirium may be experienced with extremely high doses, which may necessitate hospitalization.
*'''[[Effect::Delusion]]'''
*'''[[Effect::Delusion]]'''
*'''[[Effect::Depression]]'''
*'''[[Effect::Depression]]'''
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*'''[[Effect::Feelings of impending doom]]'''
*'''[[Effect::Feelings of impending doom]]'''
*'''[[Effect::Focus suppression]]'''
*'''[[Effect::Focus suppression]]'''
*'''[[Effect::Glossolalia]]'''
*'''[[Effect::Increased music appreciation]]'''
*'''[[Effect::Increased music appreciation]]'''
*'''[[Effect::Language suppression]]'''
*'''[[Effect::Language suppression]]'''
*'''[[Effect::Memory suppression]]''' - Memory suppression on diphenhydramine is extremely strong. Short-term memory loss is affected in a manner similar to [[cannabis]].
*'''[[Effect::Memory suppression]]''' - Memory suppression on diphenhydramine is extremely strong. Short-term memory loss is affected like [[cannabis]].
**'''[[Effect::Amnesia]]''' - At higher dosages, diphenhydramine can cause a complete halt of external information processing, which can make the user unable to perform simple tasks or make decisions.
**'''[[Effect::Amnesia]]''' - At higher dosages, diphenhydramine can cause a complete halt of external information processing, making the user unable to perform simple tasks or make decisions.
*'''[[Effect::Motivation suppression]]''' - Diphenhydramine can cause a complete loss of motivation to do almost anything. This is often accompanied by [[depression]] and can make the user extremely bored and restless.
*'''[[Effect::Motivation suppression]]''' - Diphenhydramine can cause a complete loss of motivation to do almost anything. This is often accompanied by [[depression]] and can make the user extremely bored and restless.
*'''[[Effect::Psychosis]]'''
*'''[[Effect::Psychosis]]'''
*'''[[Effect::Thought deceleration]]'''
*'''[[Effect::Thought deceleration]]'''
*'''[[Effect::Thought disorganization]]'''
*'''[[Effect::Thought disorganization]]'''
*'''[[Effect::Time distortion]]''' - Although not extreme, time dilation is definitely felt and can be overwhelming if the user is having a difficult trip.
*'''[[Effect::Time distortion]]''' - Although not extreme, time dilation is felt and can be overwhelming if the user is having a difficult trip.
Diphenhydramine is available in several different forms over the counter and online.
Diphenhydramine is available in several forms, both over the counter and online.
*'''Pills''' are available over the counter and online. Well-known brands include Benadryl, Benylin, Dramamine, Nytol, Sominex, Vivinox and ZzzQuil. Rarely, some of these products may contain other medicines, including [[DXM|dextromethorphan]], guaifenesin, and acetaminophen. Care should be taken when using these products to ensure that there is not an overdose on other medicines in these DPH-containing products.
*'''Pills''' are available over the counter and online. Well-known brands include Benadryl, Benylin, Dramamine, Nytol, Sominex, Vivinox, and ZzzQuil. Rarely, some of these products may contain other medicines, including [[DXM|dextromethorphan]], guaifenesin, and acetaminophen. Care should be taken when using these products to ensure that there is not an overdose of other medicines in these DPH-containing products.
*'''Liquid''' is available over the counter and online. Diphenhydramine in liquid form can be taken orally or injected. Well-known brands include Benadryl and ZzzQuil. Rarely, some of these products may contain other medicines, including [[DXM|dextromethorphan]], guaifenesin, and acetaminophen. Care should be taken when using these products to ensure that there is not an overdose on other medicines in DPH-containing products.
*'''Liquid''' is available over the counter and online. Diphenhydramine in liquid form can be taken orally or injected. Well-known brands include Benadryl and ZzzQuil. Rarely, some of these products may contain other medicines, including [[DXM|dextromethorphan]], guaifenesin, and acetaminophen. Care should be taken when using these products to ensure no overdose of other medicines in DPH-containing products.
*'''Powder''' is available online. Diphenhydramine in powdered form can be taken orally as well as via injection. Any other routes of administration other than oral are not recommended because diphenhydramine burns and dehydrates skin tissue, which leads to extremely painful burns and bleeding.
*'''Powder''' is available online. Diphenhydramine in powdered form can be taken orally or via injection. Any other routes of administration are not recommended because diphenhydramine burns and dehydrates skin tissue, leading to extremely painful burns and bleeding.
'''Dimenhydrinate''' ('''DMH''') is a combination drug of Diphenhydramine and [[8-Chlorotheophylline]]<ref>{{cite journal |last1=Putra |first1=Okky Dwichandra |last2=Yoshida |first2=Tomomi |last3=Umeda |first3=Daiki |last4=Higashi |first4=Kenjirou |last5=Uekusa |first5=Hidehiro |last6=Yonemochi |first6=Etsuo |title=Crystal Structure Determination of Dimenhydrinate after More than 60 Years: Solving Salt–Cocrystal Ambiguity via Solid-State Characterizations and Solubility Study |journal=Crystal Growth & Design |date=29 July 2016 |volume=16 |issue=9 |pages=5223–5229 |doi=10.1021/acs.cgd.6b00771}}</ref>, marketed as '''Draminate''', '''Dramamine''', and '''Gravol''' among others, it is used to treat [[nausea]].
'''Dimenhydrinate''' ('''DMH''') is a combination drug of diphenhydramine and [[8-Chlorotheophylline]]<ref>{{cite journal |last1=Putra |first1=Okky Dwichandra |last2=Yoshida |first2=Tomomi |last3=Umeda |first3=Daiki |last4=Higashi |first4=Kenjirou |last5=Uekusa |first5=Hidehiro |last6=Yonemochi |first6=Etsuo |title=Crystal Structure Determination of Dimenhydrinate after More than 60 Years: Solving Salt–Cocrystal Ambiguity via Solid-State Characterizations and Solubility Study |journal=Crystal Growth & Design |date=29 July 2016 |volume=16 |issue=9 |pages=5223–5229 |doi=10.1021/acs.cgd.6b00771}}</ref>, marketed as '''Draminate''', '''Dramamine''', and '''Gravol''' among others, it is used to treat [[nausea]].
It is most commonly available as tablets, although it is also available in liquid form and as a [[Routes_of_administration#Rectal|suppository]]. In practice, dimenhydrinate is half as potent as pure diphenhydramine, by weight, dimenhydrinate is between 53% to 55.5% diphenhydramine.<ref>{{cite web | title = Dimenhydrinate injection, solution |url= http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=bc71539e-1a33-4709-8a24-c2894e8dbc1c |website=Daily Med |publisher=U.S. National Library of Medicine |access-date=19 July 2014 |archive-url=https://web.archive.org/web/20141013094705/http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bc71539e-1a33-4709-8a24-c2894e8dbc1c |archive-date=13 October 2014}}</ref> The addition of the caffeine-like stimulant 8-Chlorotheophylline is reported to increase the dangerous cardiovascular effects diphenhydramine already has alone. This stimulant effect is also reported to make the trip more restless and dysphoric, with the added negative of being too wakeful to sleep the trip away.
It is most commonly available as tablets, although it is also available in liquid form and as a [[Routes_of_administration#Rectal|suppository]]. In practice, dimenhydrinate is half as potent as pure diphenhydramine. By weight, dimenhydrinate is between 53% to 55.5% diphenhydramine.<ref>{{cite web | title = Dimenhydrinate injection, solution |url= http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=bc71539e-1a33-4709-8a24-c2894e8dbc1c |website=Daily Med |publisher=U.S. National Library of Medicine |access-date=19 July 2014 |archive-url=https://web.archive.org/web/20141013094705/http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bc71539e-1a33-4709-8a24-c2894e8dbc1c |archive-date=13 October 2014}}</ref> The addition of the caffeine-like stimulant 8-Chlorotheophylline is reported to increase the dangerous cardiovascular effects diphenhydramine already has alone. This stimulant effect is also reported to make the trip more restless and dysphoric, with the added negative of being too wakeful to sleep the trip away.
==Toxicity and harm potential==
==Toxicity and harm potential==
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The toxicity and long-term health effects of recreational diphenhydramine use have not been studied extensively.
The toxicity and long-term health effects of recreational diphenhydramine use have not been studied extensively.
Diphenhydramine can be extremely unpredictable and the mechanism by which it produces hallucinations has the potential to result in serious injury, hospitalization or death. Additionally, diphenhydramine puts users in a state where they have little control over their actions. Diphenhydramine can provoke bizarre and nonsensical behavior which may put the user at risk.
Diphenhydramine can be highly unpredictable, and the mechanism by which it produces hallucinations has the potential to result in serious injury, hospitalization, or death. Additionally, diphenhydramine puts users in a state where they have little control over their actions. Diphenhydramine can provoke bizarre and nonsensical behavior, which may put the user at risk.
Anecdotal reports suggest that regular use of diphenhydramine can have serious effects on one's kidney and bladder with the potential to result in issues similar to that of [[ketamine]] cystitis.
Anecdotal reports suggest that regular use of diphenhydramine can have profound effects on one's kidney and bladder with the potential to result in issues similar to that of [[ketamine]] cystitis.
Cumulative diphenhydramine use has been tentatively linked to an increased risk of developing dementia.<ref>{{cite journal | vauthors=((Gray, S. L.)), ((Anderson, M. L.)), ((Dublin, S.)), ((Hanlon, J. T.)), ((Hubbard, R.)), ((Walker, R.)), ((Yu, O.)), ((Crane, P. K.)), ((Larson, E. B.)) | journal=JAMA internal medicine | title=Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study | volume=175 | issue=3 | pages=401–407 | date= March 2015 | issn=2168-6114 | doi=10.1001/jamainternmed.2014.7663}}</ref>
Cumulative diphenhydramine use has been tentatively linked to an increased risk of developing dementia.<ref>{{cite journal | vauthors=((Gray, S. L.)), ((Anderson, M. L.)), ((Dublin, S.)), ((Hanlon, J. T.)), ((Hubbard, R.)), ((Walker, R.)), ((Yu, O.)), ((Crane, P. K.)), ((Larson, E. B.)) | journal=JAMA internal medicine | title=Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study | volume=175 | issue=3 | pages=401–407 | date= March 2015 | issn=2168-6114 | doi=10.1001/jamainternmed.2014.7663}}</ref>
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===Overdose===
===Overdose===
The overdose threshold for diphenhydramine is commonly held to be around 1000 milligrams; however, sensitive individuals, or individuals taking other drugs alongside it can overdose with less. The main effects of an overdose are similar to those of heavy doses. Effects include [[delirium]], [[psychosis]], [[anxiety]], [[confusion]], [[hypotension]], dryness, [[difficulty urinating|urinary retention]], [[dizziness]], [[pupil dilation|dilated pupils]] and [[increased heart rate]]. Some of the more serious side effects at these doses include an even higher risk of [[seizures]], and dangerous cardiovascular effects such as arrhythmia ([[abnormal heartbeat]]).<ref>{{cite journal |last1=Huynh |first1=David A. |last2=Abbas |first2=Malak |last3=Dabaja |first3=Ali |title=Diphenhydramine Toxicity |publisher=StatPearls |date=29 April 2023 |url=https://www.ncbi.nlm.nih.gov/books/NBK557578/ |OCLC=1021256616}}</ref>
The overdose threshold for diphenhydramine is commonly held to be around 1000 milligrams; however, sensitive individuals or individuals taking other drugs alongside it can overdose with less. The main effects of an overdose are similar to those of heavy doses. Effects include [[delirium]], [[psychosis]], [[anxiety]], [[confusion]], [[hypotension]], dryness, [[difficulty urinating|urinary retention]], [[dizziness]], [[pupil dilation|dilated pupils]] and [[increased heart rate]]. Some of the more serious side effects at these doses include an even higher risk of [[seizures]] and dangerous cardiovascular effects such as arrhythmia ([[abnormal heartbeat]]).<ref>{{cite journal |last1=Huynh |first1=David A. |last2=Abbas |first2=Malak |last3=Dabaja |first3=Ali |title=Diphenhydramine Toxicity |publisher=StatPearls |date=29 April 2023 |url=https://www.ncbi.nlm.nih.gov/books/NBK557578/ |OCLC=1021256616}}</ref>
The user may be completely unable to distinguish reality from hallucinations. For this reason there is a significant risk of the user responding to a delusional environment and injuring themselves or others, as well as the possibility of engaging in too much physical activity which can further strain the heart or cause [[rhabdomyolysis]].<ref>{{cite journal | vauthors=((Emadian, S. M.)), ((Caravati, E. M.)), ((Herr, R. D.)) | journal=The American Journal of Emergency Medicine | title=Rhabdomyolysis: a rare adverse effect of diphenhydramine overdose | volume=14 | issue=6 | pages=574–576 | date= October 1996 | issn=0735-6757 | doi=10.1016/S0735-6757(96)90103-5}}</ref> Individuals experiencing delusions should, if possible, not be agitated. The first lines of treatment for overdose should be [[benzodiazepines]], although medical attention should always be sought.
The user may be completely unable to distinguish reality from hallucinations. For this reason, there is a significant risk of the user responding to a delusional environment and injuring themselves or others, as well as the possibility of engaging in too much physical activity which can further strain the heart or cause [[rhabdomyolysis]].<ref>{{cite journal | vauthors=((Emadian, S. M.)), ((Caravati, E. M.)), ((Herr, R. D.)) | journal=The American Journal of Emergency Medicine | title=Rhabdomyolysis: a rare adverse effect of diphenhydramine overdose | volume=14 | issue=6 | pages=574–576 | date= October 1996 | issn=0735-6757 | doi=10.1016/S0735-6757(96)90103-5}}</ref> Individuals experiencing delusions should, if possible, not be agitated. The first line of treatment for overdose should be [[benzodiazepines]], although medical attention should always be sought.
Diphenhydramine can become [[Toxicity::fatal at amounts close to or exceeding 2 grams]].{{citation needed}} This can result in death, especially when combined with most [[stimulant]]s, [[depressant]]s and [[MAOI]]s.
Diphenhydramine can become [[Toxicity::fatal at amounts close to or exceeding 2 grams]].{{citation needed}} This can result in death, especially when combined with most [[stimulant]]s, [[depressant]]s and [[MAOI]]s.
===Psychosis===
===Psychosis===
Some anecdotal reports suggest that diphenhydramine causes [[psychosis]] and [[delirium]] at a significantly higher rate than other [[hallucinogens]] (i.e. [[psychedelics]] and [[dissociatives]]).{{citation needed}} There are a large number of experience reports online which describe states of psychotic delirium, amnesia, and other serious consequences after abusing the substance. In many cases, it has resulted in hospitalization and death.{{citation needed}}
Some anecdotal reports suggest that diphenhydramine causes [[psychosis]] and [[delirium]] at a significantly higher rate than other [[hallucinogens]] (i.e. [[psychedelics]] and [[dissociative]]). {{citation needed}} There are a large number of experience reports online that describe states of psychotic delirium, amnesia, and other serious consequences after abusing the substance. In many cases, it has resulted in hospitalization and death.{{citation needed}}
The recreational use of diphenhydramine is generally not advised. If deciding to use this substance, one should use extreme caution and [[responsible drug use|harm reduction practices]], such as having a sober [[trip sitter]].
The recreational use of diphenhydramine is generally not advised. If deciding to use this substance, one should use extreme caution and [[responsible drug use|harm reduction practices]], such as having a sober [[trip sitter]].
===Dependence and abuse potential===
===Dependence and abuse potential===
Diphenhydramine [[Addiction potential::produces dependence with chronic use]]. In comparison to other [[hallucinogens]], DPH has been reported to have significantly less abuse potential than other hallucinogens. This is simply because the vast majority of people who try it do not wish to repeat the experience.
Diphenhydramine [[Addiction potential::produces dependence with chronic use]]. In comparison to other [[hallucinogens]], DPH has been reported to have significantly less abuse potential than other hallucinogens. Most people who try it do not wish to repeat the experience.
Tolerance to many of the effects of DPH develops [[Time to full tolerance::with repeated use]]. This results in users having to administer increasingly large doses to achieve the same effects. After that, it takes about [[Time to zero tolerance::1 - 2 weeks]] for tolerance to return to baseline (in the absence of further consumption). DPH presents cross-tolerance with [[Cross-tolerance::all [[deliriant]]s]], meaning that after the consumption of DPH, all [[deliriant]]s will have a reduced effect.
Tolerance to many of the effects of DPH develops [[Time to full tolerance::with repeated use]]. Users have to administer increasingly large doses to achieve the impact. After that, it takes about [[Time to zero tolerance::1 - 2 weeks]] for tolerance to return to baseline (in the absence of further consumption). DPH presents cross-tolerance with [[Cross-tolerance::all [[deliriant]]s]], meaning that after the consumption of DPH, all [[deliriant]]s will have a reduced effect.
===Dangerous interactions===
===Dangerous interactions===
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==Legal status==
==Legal status==
Diphenhydramine is available either over the counter or by prescription in most countries. However, some countries require the purchaser to be over 16, 18 or 21.
Diphenhydramine is available either over the counter or by prescription in most countries. However, some countries require the purchaser to be over 16, 18, or 21.
*'''Zambia:''' Diphenhydramine is illegal to possess and sell in Zambia; foreigners have been detained for possession.<ref>{{cite web |url=https://www.parliament.gov.zm/sites/default/files/documents/acts/Pharmacy%20and%20Poisons%20Act.pdf |title=The Pharmacy and Poisons Act |publisher=Ministry of Legal Affairs, Government of the Republic of Zambia}}</ref>
*'''Zambia:''' Diphenhydramine is illegal to possess and sell in Zambia; foreigners have been detained for possession.<ref>{{cite web |url=https://www.parliament.gov.zm/sites/default/files/documents/acts/Pharmacy%20and%20Poisons%20Act.pdf |title=The Pharmacy and Poisons Act |publisher=Ministry of Legal Affairs, Government of the Republic of Zambia}}</ref>
*'''United States:''' Diphenhydramine is widely available over-the-counter in the United States. It is an approved drug and is legal to buy, possess, and ingest without a license or prescription.<ref>{{Citation | title=Erowid Diphenhydramine (Benadryl) Vault : Legal Status | url=https://erowid.org/pharms/diphenhydramine/diphenhydramine_law.shtml}}</ref>
*'''United States:''' Diphenhydramine is widely available over-the-counter in the United States. It is an approved drug and is legal to buy, possess, and ingest without a license or prescription.<ref>{{Citation | title=Erowid Diphenhydramine (Benadryl) Vault : Legal Status | url=https://erowid.org/pharms/diphenhydramine/diphenhydramine_law.shtml}}</ref>
*'''Poland:''' Diphenhydramine is not a controlled substance under Polish law, but is only available over the counter in medicine that contains paracetamol.<nowiki><ref></nowiki>[https://www.lekinfo24.pl/opis-leku/l,diphenhydramine-difenhydramina,dp,doustna,mnid,584.html]
*'''Poland:''' Diphenhydramine is not a controlled substance under Polish law, it can only be bought by individuals over the age of 18 and is found only in sleep medication.<ref>{{Citation | title= Leki zawierające difenhydramine| url=https://www.lekinfo24.pl/opis-leku/l,diphenhydramine-difenhydramina,dp,doustna,mnid,584.html}}</ref>
==See also==
==See also==
Latest revision as of 14:12, 2 July 2025
Diphenhydramine use is associated with highly uncomfortable and/or dangerous experiences.
Deliriants are highly unpredictable and may result in erratic behaviors, self-injury, hospitalization, or death. It should be noted that most individuals do not choose to repeat the experience due to its unpleasant nature.
WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section.
DISCLAIMER: PW's dosage information is gathered from users and resources for educational purposes only. It is not a recommendation and should be verified with other sources for accuracy.
Diphenhydramine (also known as DPH, Dimedrol, Benadryl, and many others) is a deliriant substance of the ethanolamine class.
It is a first-generation H1antihistamine that is widely used as a generic, over-the-counter medication to treat allergies.
When exceeding approved doses, diphenhydramine produces powerful deliriant effects.
Diphenhydramine was first synthesized in 1943.
In 1946, it became the first prescription antihistamine approved by the U.S. Food and Drug Administration. It was approved for over-the-counter use in the 1980s.[1]
Today, it is typically used to treat allergies, but it may also be used for several conditions, including itchiness, insomnia, motion sickness, nausea, and the symptoms of Parkinson's disease.[2]
Notably, it is frequently reported to produce significant nausea and bodily discomfort ("body load"). Most people who try diphenhydramine do not report positive effects and do not wish to repeat the experience.
It is generally considered to have low abuse potential due to its dysphoric effects. The toxicity of recreational use is not well-studied. Anecdotal reports suggest that chronic use (i.e., high dose, repeated administration) may cause persisting hallucinations and impairments in cognition & memory. High doses have also been linked to seizures and cardiotoxicity.[3]
Diphenhydramine was discovered in 1943 by George Rieveschl, a former professor at the University of Cincinnati.[4][5] In 1946, it became the first prescription antihistamine approved by the United States Food and Drug Administration (FDA).[6]
Diphenhydramine, or 2-(diphenylmethoxy)-N,N-dimethylethanamine, is an organic compound in the ethanolamine class. The chemical structure of diphenhydramine consists of an ethylamine chain with two methyl groups bonded to the terminal nitrogen group RN. This ethylamine chain is also substituted at R2 with a diphenylmethoxy group, forming an ether. The diphenylmethoxy group consists of two aromatic phenyl rings bonded to the carbon member of a methoxy group CH3O-.
DPH is produced as a hydrochloride salt.
Pharmacology
Diphenhydramine is an inverse agonist of the peripheral histamine H1 receptor and a central histamine H1 receptor.[citation needed] The peripheral inverse agonism induces the allergy reducing effects.[citation needed] Like many first-generation antihistamines, it is also a competitive antagonist at mACH receptors.[citation needed]
Diphenhydramine is an acetylcholinereceptorantagonist. Although the precise mechanism is not understood, the inhibition of the action of acetylcholine is thought to be primarily responsible for the delirium, sedation, and intensely realistic hallucinations alongside the extremely uncomfortable and dysphoric physical side effects.
Diphenhydramine has been shown to block sodium channels and inhibit the reuptake of serotonin.[7] It also blocks voltage-gated potassium channels (VGKCs), meaning it has the potential to cause or lead to torsades de points, a potentially dangerous cardiac condition that can lead to sudden cardiac death. [9]
The receptor binding affinities are listed as follows:[10][7]
Receptor Site
Binding Affinity (nM, Lower = Stronger)
H1
9.6-16
H2
missing data
H3
>10,000
H4
>10,000
M1
80-100
M2
120-490
M3
84-229
M4
53-112
M5
30-260
SERT
≥3,800
Subjective effects
According to user reports, diphenhydramine displays a non-linear dose response, meaning the effects don't correspond directly with the dose. Doses under 300 mg are reported to produce restlessness, muscle relaxation, and a body high. In comparison, doses above 500 mg begin to produce a state of delirium in which the user sees and hears fully-formed, compelling hallucinations. Doses in between these two extremes are said to be uncomfortable and dysphoric. Nausea and bodily discomfort ("body load") are reported almost universally.
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 PsychonautWikicontributors. 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
Sedation - Diphenhydramine produces considerable sedation, and low doses are commonly used as a sleep aid. This sense of sedation is accompanied by a heavy body load, which can become overwhelmingly uncomfortable. However, higher doses of diphenhydramine also have a stimulating quality that can make actual rest difficult.
Spontaneous bodily sensations - Users commonly report all-encompassing, sharp, and painful jolts of electricity that spontaneously manifest themselves uncontrollably in a similar rhythm to hiccups.
Perception of bodily heaviness - One of the most apparent effects is having a massive body as if gravity multiplied tenfold. This makes it extremely tough and uncomfortable to move.
Restless leg syndrome - Restless legs are very prominent and arguably one of the most uncomfortable side effects of diphenhydramine. It can also last for days after the experience and can even be chronic when it is abused repeatedly.
Tactile enhancement - This results in increased feelings of touch, pain, warmth, and orgasms. It is usually only present at the peak, not during the come-up or down.
Tactile suppression - Diphenhydramine produces feelings of numbness throughout the body. This is attributed to its ability to block sodium channels within the nerves.[10]
Tactile hallucination - This is often a direct result of visual hallucinations, and they commonly feel and look as if insects are crawling on one's skin.
Nausea or Nausea suppression- Depending on the dose, diphenhydramine can both suppress and cause nausea. Low doses effectively suppress nausea, which is why it is marketed and sold as a motion sickness suppressant, while high doses cause it in significant amounts.
Abnormal heartbeat - Diphenhydramine can prolong the QT interval, potentially leading to torsades de pointes, an abnormal heart rhythm that can cause sudden cardiac death.[11]
Dehydration[citation needed] - Diphenhydramine can be extremely dehydrating, which often leads to dry mouth and skin, chapped lips, and nose bleeds. Users should drink plenty of water before and after an experience.
Dry mouth - Along with dehydration, diphenhydramine makes your mouth very dry. Water can temporarily remedy this, although it usually persists for the entirety of the trip.
Frequent urination & Difficulty urinating - Diphenhydramine has the strange effect of making the user want to urinate while making actual urination extremely difficult frequently. This sensation is described as very uncomfortable.
Gustatory hallucination - A foul metallic-like taste is present throughout the entire experience, combined with a dry mouth, which can be a very uncomfortable effect lasting for days after the experience. Eating or drinking flavored drinks will only make the taste go away temporarily. It can also appear as a sign of addiction, where it acts as a trigger for cravings.
Muscle cramps & Muscle spasms - Sudden muscle cramps and spasms can form unexpectedly. This is common at the beginning of the trip and usually passes quickly.
Olfactory hallucination - It is common for users to smell a mild, thick, and dull smell in the air that can easily be ignored most of the time. Some users also notice a smell enhancement[citation needed]
Pupil constrictionorPupil dilation - While it is known that diphenhydramine constricts pupils minimally[15], many people also report that their pupils dilate, especially at high dosages when anticholinergic effects take place similar to substances like atropine or scopolamine.
Appetite suppression - Possibly due to the bronchodilation that makes swallowing uncomfortable,[citation needed] DPH is able to make eating uncomfortable as well. This could make a user force themselves to eat, or to stop eating entirely despite hunger before the effects kick in.[citation needed]
Visual effects
While diphenhydramine produces visual hallucinations, it does not enhance visual stimuli in the manner of psychedelics. Instead, it tends to degrade and decrease visual acuity and processing, which results in increased hallucinations and degraded vision. This becomes more apparent in darker areas than in well-lit ones.
Suppression
Double vision- This effect is commonly present at moderate to high doses.
Visual acuity suppression - This effect can result in blurry vision to the point of blindness. It sometimes can last for days after the experience itself.
Distortions
Drifting(melting, breathing, morphing and flowing) - Compared to hallucinogens, this effect can be described as intricate in complexity, jittery and flexible in motion, static in their permanence, realistic in believability, and interactive in plasticity. It is also very faint.
Object alteration - The textures seen are described as transparent whirling lines and swirls that move at changing speeds and jitter uncontrollably. They only appear slightly above surfaces, walls, and ceilings and can not be felt.
Brightness alteration - Diphenhydramine can cause one's vision to decrease in brightness and become dark and gloomy.
External hallucination (autonomous entities; settings, sceneries, and landscapes; perspective hallucinations and scenarios and plots) - Relative to other hallucinogens, this effect occurs more frequently at moderate to heavy doses and is the defining feature of the experience. It can be comprehensively described through its variations as delirious in believability, controllable, or autonomous in controllability and solid in style. The most common themes for these hallucinations include those of everyday occurrences such as smoking phantom cigarettes, talking to people who are not there, seeing and feeling insects, and immersion in sinister or nightmarish experiences.
The headspace of diphenhydramine is described by many as generally negative and dysphoric, often consisting of extreme paranoia and feelings of impending doom. It is highly confusing and disorienting and usually results in a complete inability to communicate or understand standard language.
Analysis suppression - At higher dosages, a person could experience a complete halt of external information processing, which can make the user unable to perform simple tasks or make decisions.
Anxiety & Paranoia - Anxiety and paranoia are more commonly reported on diphenhydramine than almost any other substance. However, there is a threshold dose (around 500mg) where it begins to disappear.
Sleepiness - Diphenhydramine is reported to be extremely tiring. Low doses are often used and sold as a sleep aid.
Wakefulness - Even though diphenhydramine is primarily a depressant and causes sleepiness, it has stimulant effects on the body, which can also keep the user awake. This effect predominates sleepiness at higher dosages.
Dysphoria - The levels of dysphoria experienced, however, vary between people, with a tiny percentage of users reporting that they do not seem to experience them at all.
Confusion - Diphenhydramine causes significant confusion, resulting in a complete inability to understand others' intentions, emotions, humor, and even simple sentences.
Decreased libido - Interestingly, one's sex drive seems to have diminished, although sex and masturbation are considered more enjoyable in a unique way and often come with powerful orgasms.
Delirium - Delirium may be experienced with extremely high doses, which may necessitate hospitalization.
Disinhibition - Disinhibition on diphenhydramine is different from substances like alcohol, as it may not even be present in certain situations and is heavily influenced by anxiety and paranoia.
Dream potentiation - Diphenhydramine is extremely effective at potentiating dreams. This can result in not just increased intensity but a change in dream content, leading to dreams that are both vivid and extremely bizarre.
Memory suppression - Memory suppression on diphenhydramine is extremely strong. Short-term memory loss is affected like cannabis.
Amnesia - At higher dosages, diphenhydramine can cause a complete halt of external information processing, making the user unable to perform simple tasks or make decisions.
Motivation suppression - Diphenhydramine can cause a complete loss of motivation to do almost anything. This is often accompanied by depression and can make the user extremely bored and restless.
There are currently 15 experience reports describing the effects of this substance in our experience index. You can also submit your own experience report using the same link.
Diphenhydramine is available in several forms, both over the counter and online.
Pills are available over the counter and online. Well-known brands include Benadryl, Benylin, Dramamine, Nytol, Sominex, Vivinox, and ZzzQuil. Rarely, some of these products may contain other medicines, including dextromethorphan, guaifenesin, and acetaminophen. Care should be taken when using these products to ensure that there is not an overdose of other medicines in these DPH-containing products.
Liquid is available over the counter and online. Diphenhydramine in liquid form can be taken orally or injected. Well-known brands include Benadryl and ZzzQuil. Rarely, some of these products may contain other medicines, including dextromethorphan, guaifenesin, and acetaminophen. Care should be taken when using these products to ensure no overdose of other medicines in DPH-containing products.
Powder is available online. Diphenhydramine in powdered form can be taken orally or via injection. Any other routes of administration are not recommended because diphenhydramine burns and dehydrates skin tissue, leading to extremely painful burns and bleeding.
Dimenhydrinate
Dimenhydrinate
Dimenhydrinate (DMH) is a combination drug of diphenhydramine and 8-Chlorotheophylline[16], marketed as Draminate, Dramamine, and Gravol among others, it is used to treat nausea.
It is most commonly available as tablets, although it is also available in liquid form and as a suppository. In practice, dimenhydrinate is half as potent as pure diphenhydramine. By weight, dimenhydrinate is between 53% to 55.5% diphenhydramine.[17] The addition of the caffeine-like stimulant 8-Chlorotheophylline is reported to increase the dangerous cardiovascular effects diphenhydramine already has alone. This stimulant effect is also reported to make the trip more restless and dysphoric, with the added negative of being too wakeful to sleep the trip away.
Toxicity and harm potential
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. Note: Always conduct independent research and use harm reduction practices if using this substance.
The toxicity and long-term health effects of recreational diphenhydramine use have not been studied extensively.
Diphenhydramine can be highly unpredictable, and the mechanism by which it produces hallucinations has the potential to result in serious injury, hospitalization, or death. Additionally, diphenhydramine puts users in a state where they have little control over their actions. Diphenhydramine can provoke bizarre and nonsensical behavior, which may put the user at risk.
Anecdotal reports suggest that regular use of diphenhydramine can have profound effects on one's kidney and bladder with the potential to result in issues similar to that of ketamine cystitis.
Cumulative diphenhydramine use has been tentatively linked to an increased risk of developing dementia.[18]
The overdose threshold for diphenhydramine is commonly held to be around 1000 milligrams; however, sensitive individuals or individuals taking other drugs alongside it can overdose with less. The main effects of an overdose are similar to those of heavy doses. Effects include delirium, psychosis, anxiety, confusion, hypotension, dryness, urinary retention, dizziness, dilated pupils and increased heart rate. Some of the more serious side effects at these doses include an even higher risk of seizures and dangerous cardiovascular effects such as arrhythmia (abnormal heartbeat).[19]
The user may be completely unable to distinguish reality from hallucinations. For this reason, there is a significant risk of the user responding to a delusional environment and injuring themselves or others, as well as the possibility of engaging in too much physical activity which can further strain the heart or cause rhabdomyolysis.[20] Individuals experiencing delusions should, if possible, not be agitated. The first line of treatment for overdose should be benzodiazepines, although medical attention should always be sought.
Diphenhydramine can become fatal at amounts close to or exceeding 2 grams.[citation needed] This can result in death, especially when combined with most stimulants, depressants and MAOIs.
Psychosis
Some anecdotal reports suggest that diphenhydramine causes psychosis and delirium at a significantly higher rate than other hallucinogens (i.e. psychedelics and dissociative). [citation needed] There are a large number of experience reports online that describe states of psychotic delirium, amnesia, and other serious consequences after abusing the substance. In many cases, it has resulted in hospitalization and death.[citation needed]
The recreational use of diphenhydramine is generally not advised. If deciding to use this substance, one should use extreme caution and harm reduction practices, such as having a sober trip sitter.
Dependence and abuse potential
Diphenhydramine produces dependence with chronic use. In comparison to other hallucinogens, DPH has been reported to have significantly less abuse potential than other hallucinogens. Most people who try it do not wish to repeat the experience.
Tolerance to many of the effects of DPH develops with repeated use. Users have to administer increasingly large doses to achieve the impact. After that, it takes about 1 - 2 weeks for tolerance to return to baseline (in the absence of further consumption). DPH presents cross-tolerance with [[Cross-tolerance::all deliriants]], meaning that after the consumption of DPH, all deliriants will have a reduced effect.
Dangerous interactions
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.
Stimulants - Due to diphenhydramine's excitatory cardiac effect, combining it with stimulants poses a risk of an abnormal heart rhythm, severe tachycardia, or a heart attack as well as other cardiovascular events.
Benzodiazepines - Benzodiazepines can suppress the visual effects of diphenhydramine. However, this combination can produce a dangerous amount of sedation and respiratory depression.[citation needed]
Anticholinergics - Due to diphenhydramine's excitatory cardiac effect, combining it with other anticholinergics poses a risk of an abnormal heart rhythm, severe tachycardia, or a heart attack as well as other cardiovascular events (inhibition of acetylcholine causes increased heart rate).
Legal status
Diphenhydramine is available either over the counter or by prescription in most countries. However, some countries require the purchaser to be over 16, 18, or 21.
Zambia: Diphenhydramine is illegal to possess and sell in Zambia; foreigners have been detained for possession.[22]
United States: Diphenhydramine is widely available over-the-counter in the United States. It is an approved drug and is legal to buy, possess, and ingest without a license or prescription.[23]
Poland: Diphenhydramine is not a controlled substance under Polish law, it can only be bought by individuals over the age of 18 and is found only in sleep medication.[24]
↑"Benadryl". Ohio History Central. Archived from the original on 5 September 2015. Retrieved 13 August 2015.
↑Ritchie J (24 September 2007). "UC prof, Benadryl inventor dies". Business Courier of Cincinnati. Archived from the original on 24 December 2008. Retrieved 14 October 2008.
↑Khalifa, M., Drolet, B., Daleau, P., Lefez, C., Gilbert, M., Plante, S., O’Hara, G. E., Gleeton, O., Hamelin, B. A., Turgeon, J. (February 1999). "Block of potassium currents in guinea pig ventricular myocytes and lengthening of cardiac repolarization in man by the histamine H1 receptor antagonist diphenhydramine". The Journal of Pharmacology and Experimental Therapeutics. 288 (2): 858–865. ISSN0022-3565.
↑ 10.010.1Kim, Y. S., Shin, Y. K., Lee, C., Song, J. (27 October 2000). "Block of sodium currents in rat dorsal root ganglion neurons by diphenhydramine". Brain Research. 881 (2): 190–198. doi:10.1016/s0006-8993(00)02860-2. ISSN0006-8993.
↑Lilienfield, L. S., Rose, J. C., Princiotto, J. V. (April 1976). "Antitussive activity of diphenhydramine in chronic cough". Clinical Pharmacology and Therapeutics. 19 (4): 421–425. doi:10.1002/cpt1976194421. ISSN0009-9236.
↑Gray, S. L., Anderson, M. L., Dublin, S., Hanlon, J. T., Hubbard, R., Walker, R., Yu, O., Crane, P. K., Larson, E. B. (March 2015). "Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study". JAMA internal medicine. 175 (3): 401–407. doi:10.1001/jamainternmed.2014.7663. ISSN2168-6114.
↑Emadian, S. M., Caravati, E. M., Herr, R. D. (October 1996). "Rhabdomyolysis: a rare adverse effect of diphenhydramine overdose". The American Journal of Emergency Medicine. 14 (6): 574–576. doi:10.1016/S0735-6757(96)90103-5. ISSN0735-6757.
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