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{{SummarySheet}}
{{SummarySheet}}
{{SubstanceBox/Diphenidine}}
{{SubstanceBox/Diphenidine}}
'''Diphenidine''' (also known as DPD, DND, 1,2-DEP, and DPH) is a lesser-known novel [[psychoactive class::dissociative]] substance of the [[chemical class::diarylethylamine]] class. It is structurally similar to [[methoxphenidine]] (MXP) and [[ephenidine]]. It is classified as an [[NMDA receptor antagonist]].<ref name="wallach">Wallach, J., Kang, H., Colestock, T., Morris, H., Bortolotto, Z. A., Collingridge, G. L., ... & Adejare, A. (2016). Pharmacological investigations of the dissociative ‘legal highs’ diphenidine, methoxphenidine and analogues. PLoS One, 11(6), e0157021. https://doi.org/10.1371/journal.pone.0157021</ref>
'''Diphenidine''' (also known as DPD, DND, 1,2-DEP, and DPH) is a lesser-known novel [[psychoactive class::dissociative]] substance of the [[chemical class::diarylethylamine]] class. It is structurally similar to [[methoxphenidine]] (MXP) and [[ephenidine]]. It is classified as an [[NMDA receptor antagonist]].<ref name="wallach">{{cite journal | vauthors=((Wallach, J.)), ((Kang, H.)), ((Colestock, T.)), ((Morris, H.)), ((Bortolotto, Z. A.)), ((Collingridge, G. L.)), ((Lodge, D.)), ((Halberstadt, A. L.)), ((Brandt, S. D.)), ((Adejare, A.)) | veditors=((Lee, J.)) | journal=PLOS ONE | title=Pharmacological Investigations of the Dissociative ‘Legal Highs’ Diphenidine, Methoxphenidine and Analogues | volume=11 | issue=6 | pages=e0157021 | date=17 June 2016 | url=https://dx.plos.org/10.1371/journal.pone.0157021 | issn=1932-6203 | doi=10.1371/journal.pone.0157021}}</ref>


The original synthesis of diphenidine was first reported in 1924.{{citation needed}} However, it was not selected for further development. Shortly after the 2013 UK [[arylcyclohexylamine]] ban, diphenidine and the related compound [[methoxphenidine]] became available on the grey market. In 2014, there were two cases of diphenidine being sold in combination with synthetic cannabinoids in Japanese herbal incense blends, one of which was implicated in a fatal overdose.
The original synthesis of diphenidine was first reported in 1924.{{citation needed}} However, it was not selected for further development. Shortly after the 2013 UK [[arylcyclohexylamine]] ban, diphenidine and the related compound [[methoxphenidine]] became available on the grey market. In 2014, there were two cases of diphenidine being sold in combination with synthetic cannabinoids in Japanese herbal incense blends, one of which was implicated in a fatal overdose.


[[Subjective effects]] include [[stimulation]], [[motor control loss]], [[pain relief]], [[internal hallucinations]], [[conceptual thinking]], [[euphoria]], and [[disconnective effects|dissociation]]. Dissociation is a complex mental state characterized by perceptual distortions and feelings of detachment from the environment and one's self. Anecdotal reports describe high doses of diphenidine producing "''bizarre somatosensory phenomena and transient anterograde amnesia''."<ref>From PCP to MXE: a comprehensive review of the non-medical use of dissociative drugs | http://onlinelibrary.wiley.com/doi/10.1002/dta.1620/abstract;jsessionid=C8EDD090D25084ED0088835B767DD0B9.f04t02</ref> The effects of diarylethylamines share similarities with [[arylcyclohexylamines]] like [[ketamine]] and [[phencyclidine]] ('''PCP'''), as well as [[dextromethorphan]] ('''DXM''').
[[Subjective effects]] include [[stimulation]], [[motor control loss]], [[pain relief]], [[internal hallucinations]], [[conceptual thinking]], [[euphoria]], and [[disconnective effects|dissociation]]. Dissociation is a complex mental state characterized by perceptual distortions and feelings of detachment from the environment and one's self. Anecdotal reports describe high doses of diphenidine producing "''bizarre somatosensory phenomena and transient anterograde amnesia''."<ref>{{cite journal | vauthors=((Morris, H.)), ((Wallach, J.)) | journal=Drug Testing and Analysis | title=From PCP to MXE: a comprehensive review of the non-medical use of dissociative drugs: PCP to MXE | volume=6 | issue=7–8 | pages=614–632 | date= July 2014 | url=https://onlinelibrary.wiley.com/doi/10.1002/dta.1620 | issn=19427603 | doi=10.1002/dta.1620}}</ref> The effects of diarylethylamines share similarities with [[arylcyclohexylamines]] like [[ketamine]] and [[phencyclidine]] ('''PCP'''), as well as [[dextromethorphan]] ('''DXM''').


Very little data exists about the pharmacological properties, metabolism, and toxicity of diphenidine in humans, and it has an extremely limited history of human usage. Some reports suggest that it may pose different toxicity risks than traditional dissociatives. It is also likely to have moderate to high abuse potential. As a result, it is highly advised to use [[harm reduction practices]] if using this substance.
Very little data exists about the pharmacological properties, metabolism, and toxicity of diphenidine in humans, and it has an extremely limited history of human usage. Some reports suggest that it may pose different toxicity risks than traditional dissociatives. It is also likely to have moderate to high abuse potential. As a result, it is highly advised to use [[harm reduction practices]] if using this substance.
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The synthesis of diphenidine was first reported in 1924. It employed a nitrile displacement reaction analogous to the one that would later be used to discover [[phencyclidine]] in 1956. Shortly after the 2013 UK ban on [[arylcyclohexylamines]], diphenidine and the related compound [[methoxphenidine]] became available on the grey market.
The synthesis of diphenidine was first reported in 1924. It employed a nitrile displacement reaction analogous to the one that would later be used to discover [[phencyclidine]] in 1956. Shortly after the 2013 UK ban on [[arylcyclohexylamines]], diphenidine and the related compound [[methoxphenidine]] became available on the grey market.


In 2014, there were two cases of diphenidine being sold in combination with synthetic [[cannabinoids]] in Japanese herbal incense blends. One herbal incense blend was found to contain diphenidine and [[5-fluoro-AB-PINACA]] at concentrations of 289 mg/g and 55.5 mg/g, respectively.<ref>http://link.springer.com/article/10.1007%2Fs11419-014-0240-y | http://worldwide.espacenet.com/publicationDetails/biblio?CC=EP&NR=0346791&KC=&FT=E&locale=en_EP</ref> Another product containing AB-CHMINACA, 5F-AMB, and diphenidine was implicated in a fatal overdose.<ref>Postmortem distribution of AB-CHMINACA, 5-fluoro-AMB, and diphenidine in body fluids and solid tissues in a fatal poisoning case: usefulness of adipose tissue for detection of the drugs in unchanged forms | http://link.springer.com/article/10.1007%2Fs11419-014-0245-6</ref>
In 2014, there were two cases of diphenidine being sold in combination with synthetic [[cannabinoids]] in Japanese herbal incense blends. One herbal incense blend was found to contain diphenidine and [[5-fluoro-AB-PINACA]] at concentrations of 289 mg/g and 55.5 mg/g, respectively.<ref>{{cite journal | vauthors=((Wurita, A.)), ((Hasegawa, K.)), ((Minakata, K.)), ((Watanabe, K.)), ((Suzuki, O.)) | journal=Forensic Toxicology | title=A large amount of new designer drug diphenidine coexisting with a synthetic cannabinoid 5-fluoro-AB-PINACA found in a dubious herbal product | volume=32 | issue=2 | pages=331–337 | date=1 August 2014 | url=https://doi.org/10.1007/s11419-014-0240-y | issn=1860-8973 | doi=10.1007/s11419-014-0240-y}}</ref> Another product containing AB-CHMINACA, 5F-AMB, and diphenidine was implicated in a fatal overdose.<ref>{{cite journal | vauthors=((Hasegawa, K.)), ((Wurita, A.)), ((Minakata, K.)), ((Gonmori, K.)), ((Nozawa, H.)), ((Yamagishi, I.)), ((Watanabe, K.)), ((Suzuki, O.)) | journal=Forensic Toxicology | title=Postmortem distribution of AB-CHMINACA, 5-fluoro-AMB, and diphenidine in body fluids and solid tissues in a fatal poisoning case: usefulness of adipose tissue for detection of the drugs in unchanged forms | volume=33 | issue=1 | pages=45–53 | date=1 January 2015 | url=https://doi.org/10.1007/s11419-014-0245-6 | issn=1860-8973 | doi=10.1007/s11419-014-0245-6}}</ref>


===Names===
===Names===
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==Pharmacology==
==Pharmacology==
{{Further|NMDA receptor antagonist}}
{{Further|NMDA receptor antagonist}}
Diphenidine acts as an [[NMDA receptor antagonist]].<ref>NMDA receptor affinities of 1,2-diphenylethylamine and 1-(1,2-diphenylethyl)piperidine enantiomers and of related compounds (ScienceDirect) | http://www.sciencedirect.com/science/article/pii/S0968089609002624</ref><ref>Preparation and characterization of the ‘research chemical’ diphenidine, its pyrrolidine analogue, and their 2,2-diphenylethyl isomers | http://onlinelibrary.wiley.com/doi/10.1002/dta.1689/abstract</ref> NMDA receptors allow for electrical signals to pass between neurons in the brain and spinal column; for the signals to pass, the receptor must be open. Dissociatives close the NMDA receptors by blocking them. This disconnection of neurons leads to loss of feeling, difficulty moving, and eventually the famous “[[Visual_disconnection#Holes.2C_spaces_and_voids|hole]]”.
Diphenidine acts as an [[NMDA receptor antagonist]].<ref>{{cite journal | vauthors=((Berger, M. L.)), ((Schweifer, A.)), ((Rebernik, P.)), ((Hammerschmidt, F.)) | journal=Bioorganic & Medicinal Chemistry | title=NMDA receptor affinities of 1,2-diphenylethylamine and 1-(1,2-diphenylethyl)piperidine enantiomers and of related compounds | volume=17 | issue=9 | pages=3456–3462 | date=1 May 2009 | url=https://www.sciencedirect.com/science/article/pii/S0968089609002624 | issn=0968-0896 | doi=10.1016/j.bmc.2009.03.025}}</ref><ref>{{cite journal | vauthors=((Wallach, J.)), ((Kavanagh, P. V.)), ((McLaughlin, G.)), ((Morris, N.)), ((Power, J. D.)), ((Elliott, S. P.)), ((Mercier, M. S.)), ((Lodge, D.)), ((Morris, H.)), ((Dempster, N. M.)), ((Brandt, S. D.)) | journal=Drug Testing and Analysis | title=Preparation and characterization of the ‘research chemical’ diphenidine, its pyrrolidine analogue, and their 2,2-diphenylethyl isomers: Characterization of diphenylethylamines | volume=7 | issue=5 | pages=358–367 | date= May 2015 | url=https://onlinelibrary.wiley.com/doi/10.1002/dta.1689 | issn=19427603 | doi=10.1002/dta.1689}}</ref> NMDA receptors allow for electrical signals to pass between neurons in the brain and spinal column; for the signals to pass, the receptor must be open. Dissociatives close the NMDA receptors by blocking them. This disconnection of neurons leads to loss of feeling, difficulty moving, and eventually the famous “[[Visual_disconnection#Holes.2C_spaces_and_voids|hole]]”.


Although vendors of diphenidine have stated the compound acts as a [[dopamine]]-[[Reuptake Inhibitor|reuptake inhibitor]] and a [[serotonin]] [[reuptake inhibitor]] with [[Opioid receptors|µ-opioid]] affinity and typical [[Dissociatives#Subjective effects|dissociative]] effects, to date diphenidine has not been screened for affinity at the dopamine transporter. If this is indeed the case, however, it provides an explanation for its euphoric and often stimulating effects.
Although vendors of diphenidine have stated the compound acts as a [[dopamine]]-[[Reuptake Inhibitor|reuptake inhibitor]] and a [[serotonin]] [[reuptake inhibitor]] with [[Opioid receptors|µ-opioid]] affinity and typical [[Dissociatives#Subjective effects|dissociative]] effects, to date diphenidine has not been screened for affinity at the dopamine transporter. If this is indeed the case, however, it provides an explanation for its euphoric and often stimulating effects.


Diphenidine and related [[diarylethylamines]] have been studied in vitro as treatments for neurotoxic injury.<ref>1,2-diarylethylamines for treatment of neurotoxic injury | http://worldwide.espacenet.com/publicationDetails/biblio?CC=EP&NR=0346791&KC=&FT=E&locale=en_EP</ref> Diphenidine may be a stronger NMDA receptor antagonist for neurogenesis, neurological repair and neuroprotection than other more common NMDA receptor antagonistic dissociatives such as [[ketamine]], [[dextromethorphan]], [[PCP]] analogs, [[Iboga]] and [[methoxetamine]].
Diphenidine and related [[diarylethylamines]] have been studied in vitro as treatments for neurotoxic injury.<ref>{{Citation | vauthors=((Gray, N. M.)), ((Cheng, B. K.)) | title=1,2-diarylethylamines for treatment of neurotoxic injury | url=https://worldwide.espacenet.com/publicationDetails/biblio?CC=EP&NR=0346791&KC=&FT=E&locale=en_EP}}</ref> Diphenidine may be a stronger NMDA receptor antagonist for neurogenesis, neurological repair and neuroprotection than other more common NMDA receptor antagonistic dissociatives such as [[ketamine]], [[dextromethorphan]], [[PCP]] analogs, [[Iboga]] and [[methoxetamine]].


==Subjective effects==
==Subjective effects==
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*'''[[Effect::Dizziness]]''' - Although uncommon, some people report dizziness under the influence of diphenidine.
*'''[[Effect::Dizziness]]''' - Although uncommon, some people report dizziness under the influence of diphenidine.
*'''[[Effect::Nausea]]''' - It's worth noting that high dose diphenidine trips can sometimes result in nausea and vomiting at the peak of the trip. For most people, this is surprisingly not as unpleasant as they would initially expect due to the accompanying detachment from the physical senses.
*'''[[Effect::Nausea]]''' - It's worth noting that high dose diphenidine trips can sometimes result in nausea and vomiting at the peak of the trip. For most people, this is surprisingly not as unpleasant as they would initially expect due to the accompanying detachment from the physical senses.
*'''[[Effect::Orgasm suppression]]''' - Orgasm enhancement can also be present, even at higher doses. This effect varies from person to person.
*'''[[Effect::Orgasm suppression]]''' & '''[[Effect::Orgasm enhancement]]''' - Orgasm enhancement can sometimes also be present, even at higher doses, although this effect is not reliable.


}}
}}
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{{toxicity}}
{{toxicity}}
{{further|Research chemicals#Toxicity and harm potential|Responsible use #Hallucinogens}}
{{further|Research chemicals#Toxicity and harm potential|Responsible use #Hallucinogens}}
The toxicity and long-term health effects of recreational diphenidine use do not seem to have been studied in any scientific context and the [[Toxicity::exact toxic dosage is unknown]]. This is because diphenidine has very little history of human usage.  
The toxicity and long-term health effects of recreational diphenidine use do not appear to have been studied in any scientific context and the [[Toxicity::exact toxic dosage is unknown]]. This is because diphenidine has very little history of human usage.  


Anecdotal evidence from those who have tried diphenidine suggest that there do not seem to be any negative health effects attributed to simply trying this drug at low to moderate doses by itself and using it sparingly (but nothing can be completely guaranteed). [https://www.google.com/ Independent research] should always be done to ensure that a combination of two or more substances is safe before consumption.  
Some anecdotal reports suggest diphenidine may increase the risk of [[mania]] and [[psychosis]]. This is common with many dissociatives, particularly with those that provide stimulation such as [[PCP]].
 
It has been reported that regular use can lead to increased blood pressure and rapid heart rate.


It is strongly recommended that one use [[responsible drug use|harm reduction practices]] when using this substance.
It is strongly recommended that one use [[responsible drug use|harm reduction practices]] when using this substance.
There is some anecdotal evidence that when not used responsibly, diphenidine may have an elevated risk of inducing [[mania]]. This is common with many dissociatives, particularly with those that provide stimulation such as [[PCP]].


===Dependence and abuse potential===
===Dependence and abuse potential===
As with other NMDA receptor antagonists, the chronic use of diphenidine can be considered [[Addiction potential::moderately addictive with a high potential for abuse]] and is capable of causing psychological dependence among certain users. When addiction has developed, cravings and [[withdrawal effects]] may occur if a person suddenly stops their usage.
As with other NMDA receptor antagonists, the chronic use of diphenidine can be considered [[Addiction potential::moderately addictive with a high potential for abuse]]. It is likely capable of causing psychological dependence among certain users. When addiction has developed, cravings and [[withdrawal effects]] may occur if one suddenly stops their usage.


Tolerance to many of the effects of diphenidine [[Time to full tolerance::develops with prolonged and repeated use]]. This results in users having to administer increasingly large doses to achieve the same effects. After that, it takes about [[Time to half tolerance::3 - 7 days]] for the tolerance to be reduced to half and [[Time to zero tolerance::1 - 2 weeks]] to be back at baseline (in the absence of further consumption). Diphenidine presents cross-tolerance with [[Cross-tolerance::all [[dissociative]]s]], meaning that after the consumption of diphenidine all [[dissociative]]s will have a reduced effect.
Tolerance to many of the effects of diphenidine [[Time to full tolerance::develops with prolonged and repeated use]]. This results in users having to administer increasingly large doses to achieve the same effects. After that, it takes about [[Time to half tolerance::3 - 7 days]] for the tolerance to be reduced to half and [[Time to zero tolerance::1 - 2 weeks]] to be back at baseline (in the absence of further consumption). Diphenidine presents cross-tolerance with [[Cross-tolerance::all [[dissociative]]s]], meaning that after the consumption of diphenidine all [[dissociative]]s will have a reduced effect.
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Diphenidine is currently a legal grey area drug worldwide and is easily accessible  through the use of online [[research chemical]] vendors. However, this does not guarantee anyone to be immune from legal prosecution should they be found in possession of this substance as the legality is likely to vary from country to country.
Diphenidine is currently a legal grey area drug worldwide and is easily accessible  through the use of online [[research chemical]] vendors. However, this does not guarantee anyone to be immune from legal prosecution should they be found in possession of this substance as the legality is likely to vary from country to country.


*'''Canada:''' As of March 2016, MT-45 and its analogues, one of which being Diphenidine, are Schedule I controlled substances.<ref>Regulations Amending the Food and Drug Regulations (Parts G and J — Lefetamine, AH-7921, MT-45 and W-18) | http://www.gazette.gc.ca/rp-pr/p2/2016/2016-06-01/html/sor-dors106-eng.php</ref> Possession without legal authority can result in maximum 7 years imprisonment. Only those with a law enforcement agency, person with an exemption permit or institutions with Minister's authorization may possess the drug.
*'''Canada:''' As of March 2016, MT-45 and its analogues, one of which being Diphenidine, are Schedule I controlled substances.<ref>{{Citation | vauthors=((Government of Canada, P. W. and G. S. C.)) | year=2016 | title=Canada Gazette – Regulations Amending the Food and Drug Regulations (Parts G and J — Lefetamine, AH-7921, MT-45 and W-18) | url=https://gazette.gc.ca/rp-pr/p2/2016/2016-06-01/html/sor-dors106-eng.html}}</ref> Possession without legal authority can result in maximum 7 years imprisonment. Only those with a law enforcement agency, person with an exemption permit or institutions with Minister's authorization may possess the drug.
*'''Switzerland:''' Diphenidine is a controlled substance specifically named under Verzeichnis E.<ref>{{cite web|url=https://www.admin.ch/opc/de/classified-compilation/20101220/index.html|title=Verordnung des EDI über die Verzeichnisse der Betäubungsmittel, psychotropen Stoffe, Vorläuferstoffe und Hilfschemikalien|publisher=Bundeskanzlei [Federal Chancellery of Switzerland]|access-date=January 1, 2020|language=de}}</ref>
*'''Switzerland:''' Diphenidine is a controlled substance specifically named under Verzeichnis E.<ref>{{cite web|url=https://www.admin.ch/opc/de/classified-compilation/20101220/index.html|title=Verordnung des EDI über die Verzeichnisse der Betäubungsmittel, psychotropen Stoffe, Vorläuferstoffe und Hilfschemikalien|publisher=Bundeskanzlei [Federal Chancellery of Switzerland]|access-date=January 1, 2020|language=de}}</ref>
*'''Turkey:''' Diphenidine is a classed as drug and is illegal to possess, produce, supply, or import.<ref name="Bakanlar Kurulu Kararı - Karar Sayısı : 2016/9712">https://resmigazete.gov.tr/eskiler/2017/01/20170112-8.pdf</ref>
*'''Turkey:''' Diphenidine is a classed as drug and is illegal to possess, produce, supply, or import.<ref name="Bakanlar Kurulu Kararı - Karar Sayısı : 2016/9712">https://resmigazete.gov.tr/eskiler/2017/01/20170112-8.pdf</ref>
*'''United Kingdom:''' It is illegal to produce, supply, or import this drug under the Psychoactive Substance Act, which came into effect on May 26th, 2016.<ref>Psychoactive Substances Act 2016 (Legislation.gov.uk) | http://www.legislation.gov.uk/ukpga/2016/2/contents/enacted</ref>
*'''United Kingdom:''' It is illegal to produce, supply, or import this drug under the Psychoactive Substance Act, which came into effect on May 26th, 2016.<ref>{{Citation | title=Psychoactive Substances Act 2016 | url=https://www.legislation.gov.uk/ukpga/2016/2/contents/enacted}}</ref>
*'''United States:''' Diphenidine is a schedule II substance and is illegal without a prescription.<ref>https://www.unodc.org/LSS/Substance/Details/7ee627dd-c3ed-42d2-b84f-81edef0d6466</ref>


==See also==
==See also==

Latest revision as of 10:57, 30 May 2024

Not to be confused with Diphenhydramine (also known as "DPH").
Summary sheet: Diphenidine
Diphenidine
Chemical Nomenclature
Common names Diphenidine
Systematic name (±)-1-(1,2-Diphenylethyl)piperidine
Class Membership
Psychoactive class Dissociative
Chemical class Diarylethylamine
Routes of Administration

WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section.


Smoked
Dosage
Threshold ??"??" is not a number. mg
Light ??"??" is not a number. - 20 mg
Common 20 - 40 mg
Strong 40 - 55 mg
Heavy > 55 mg
Duration
Total 1 - 3 hours
Onset 30 - 90 seconds
Peak 0.5 - 2 hours
Offset 20 - 40 minutes
After effects 2 - 5 hours
Oral
Dosage
Threshold 30 mg
Light 40 - 65 mg
Common 65 - 100 mg
Strong 100 - 130 mg
Heavy > 130 mg
Duration
Total 2 - 5 hours
Onset 15 - 30 minutes
After effects 4 - 24 hours




Rectal
Dosage
Threshold 5 mg
Light 10 - 20 mg
Common 20 - 40 mg
Strong 40 - 80 mg
Heavy 80 mg +
Duration
Total 5 - 7 hours
Onset 10 - 30 minutes





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.

Interactions
Stimulants
Depressants

Diphenidine (also known as DPD, DND, 1,2-DEP, and DPH) is a lesser-known novel dissociative substance of the diarylethylamine class. It is structurally similar to methoxphenidine (MXP) and ephenidine. It is classified as an NMDA receptor antagonist.[1]

The original synthesis of diphenidine was first reported in 1924.[citation needed] However, it was not selected for further development. Shortly after the 2013 UK arylcyclohexylamine ban, diphenidine and the related compound methoxphenidine became available on the grey market. In 2014, there were two cases of diphenidine being sold in combination with synthetic cannabinoids in Japanese herbal incense blends, one of which was implicated in a fatal overdose.

Subjective effects include stimulation, motor control loss, pain relief, internal hallucinations, conceptual thinking, euphoria, and dissociation. Dissociation is a complex mental state characterized by perceptual distortions and feelings of detachment from the environment and one's self. Anecdotal reports describe high doses of diphenidine producing "bizarre somatosensory phenomena and transient anterograde amnesia."[2] The effects of diarylethylamines share similarities with arylcyclohexylamines like ketamine and phencyclidine (PCP), as well as dextromethorphan (DXM).

Very little data exists about the pharmacological properties, metabolism, and toxicity of diphenidine in humans, and it has an extremely limited history of human usage. Some reports suggest that it may pose different toxicity risks than traditional dissociatives. It is also likely to have moderate to high abuse potential. As a result, it is highly advised to use harm reduction practices if using this substance.

History and culture

This History and culture section is a stub.

As a result, it may contain incomplete or wrong information. You can help by expanding it.

The synthesis of diphenidine was first reported in 1924. It employed a nitrile displacement reaction analogous to the one that would later be used to discover phencyclidine in 1956. Shortly after the 2013 UK ban on arylcyclohexylamines, diphenidine and the related compound methoxphenidine became available on the grey market.

In 2014, there were two cases of diphenidine being sold in combination with synthetic cannabinoids in Japanese herbal incense blends. One herbal incense blend was found to contain diphenidine and 5-fluoro-AB-PINACA at concentrations of 289 mg/g and 55.5 mg/g, respectively.[3] Another product containing AB-CHMINACA, 5F-AMB, and diphenidine was implicated in a fatal overdose.[4]

Names

Diphenidine is sometimes referred to as "DPH" in scientific studies despite this name already being in use and widely accepted as meaning diphenhydramine, an unrelated substance.

Chemistry

Generic structure of a piperdine molecule.

Diphenidine is a molecule of the diarylethylamine class. The basic skeleton of diphenidine is a phenethylamine with a substituted Rα in phenyl ring. At the terminals of the piperidine ring, an amino group is attached through phenethylamine chain. Hence, diphenidine belongs to the piperidine dissociative class of compounds. Diphenidine is structurally analogous to MXP, lacking a 2-methoxy substitution on one of its phenyl rings.

Pharmacology

Further information: NMDA receptor antagonist

Diphenidine acts as an NMDA receptor antagonist.[5][6] NMDA receptors allow for electrical signals to pass between neurons in the brain and spinal column; for the signals to pass, the receptor must be open. Dissociatives close the NMDA receptors by blocking them. This disconnection of neurons leads to loss of feeling, difficulty moving, and eventually the famous “hole”.

Although vendors of diphenidine have stated the compound acts as a dopamine-reuptake inhibitor and a serotonin reuptake inhibitor with µ-opioid affinity and typical dissociative effects, to date diphenidine has not been screened for affinity at the dopamine transporter. If this is indeed the case, however, it provides an explanation for its euphoric and often stimulating effects.

Diphenidine and related diarylethylamines have been studied in vitro as treatments for neurotoxic injury.[7] Diphenidine may be a stronger NMDA receptor antagonist for neurogenesis, neurological repair and neuroprotection than other more common NMDA receptor antagonistic dissociatives such as ketamine, dextromethorphan, PCP analogs, Iboga and methoxetamine.

Subjective effects

The general head space of diphenidine is often described as euphoric and clear-headed in comparison to that of ketamine and reminiscent of ephenidine at lower dosages. Moderate or higher dosages can sometimes unwillingly turn very confusing and dysphoric without any apparent cause.

Diphenidine is reported to have a much more rapid onset and lower half-life when vaporized or smoked. When consumed this way, it is a suspected to be carcinogenic when excess heat is used. Some user reports have concluded that vaporization requires as low as 20% of what would be a common oral dose for that person.

Disclaimer: The effects listed below cite the Subjective Effect Index (SEI), an open research literature based on anecdotal user reports and the personal analyses of PsychonautWiki contributors. As a result, they should be viewed with a healthy degree of skepticism.

It is also worth noting that these effects will not necessarily occur in a predictable or reliable manner, although higher doses are more liable to induce the full spectrum of effects. Likewise, adverse effects become increasingly likely with higher doses and may include addiction, severe injury, or death ☠.

Physical effects

Visual effects

Cognitive effects

Disconnective effects

Experience reports

Anecdotal reports which describe the effects of this compound within our experience index include:

Additional experience reports can be found here:

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 diphenidine use do not appear to have been studied in any scientific context and the exact toxic dosage is unknown. This is because diphenidine has very little history of human usage.

Some anecdotal reports suggest diphenidine may increase the risk of mania and psychosis. This is common with many dissociatives, particularly with those that provide stimulation such as PCP.

It has been reported that regular use can lead to increased blood pressure and rapid heart rate.

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

Dependence and abuse potential

As with other NMDA receptor antagonists, the chronic use of diphenidine can be considered moderately addictive with a high potential for abuse. It is likely capable of causing psychological dependence among certain users. When addiction has developed, cravings and withdrawal effects may occur if one suddenly stops their usage.

Tolerance to many of the effects of diphenidine develops with prolonged and repeated use. This results in users having to administer increasingly large doses to achieve the same effects. After that, it takes about 3 - 7 days for the tolerance to be reduced to half and 1 - 2 weeks to be back at baseline (in the absence of further consumption). Diphenidine presents cross-tolerance with [[Cross-tolerance::all dissociatives]], meaning that after the consumption of diphenidine all dissociatives 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 - Both stimulants and dissociatives carry the risk of adverse psychological reactions like anxiety, mania, delusions and psychosis and these risks are exacerbated when the two substances are combined.
  • Depressants - Because both depress the respiratory system, this combination can result in an increased risk of suddenly falling unconscious, vomiting and choking to death from the resulting suffocation. If nausea or vomiting occurs, users should attempt to fall asleep in the recovery position or have a friend move them into it.

Diphenidine is currently a legal grey area drug worldwide and is easily accessible through the use of online research chemical vendors. However, this does not guarantee anyone to be immune from legal prosecution should they be found in possession of this substance as the legality is likely to vary from country to country.

  • Canada: As of March 2016, MT-45 and its analogues, one of which being Diphenidine, are Schedule I controlled substances.[8] Possession without legal authority can result in maximum 7 years imprisonment. Only those with a law enforcement agency, person with an exemption permit or institutions with Minister's authorization may possess the drug.
  • Switzerland: Diphenidine is a controlled substance specifically named under Verzeichnis E.[9]
  • Turkey: Diphenidine is a classed as drug and is illegal to possess, produce, supply, or import.[10]
  • United Kingdom: It is illegal to produce, supply, or import this drug under the Psychoactive Substance Act, which came into effect on May 26th, 2016.[11]
  • United States: Diphenidine is a schedule II substance and is illegal without a prescription.[12]

See also

Community

Literature

  • Wallach, J., Kang, H., Colestock, T., Morris, H., Bortolotto, Z. A., Collingridge, G. L., ... & Adejare, A. (2016). Pharmacological investigations of the dissociative ‘legal highs’ diphenidine, methoxphenidine and analogues. PLoS One, 11(6), e0157021. https://doi.org/10.1371/journal.pone.0157021
  • Morris, H., & Wallach, J. (2014). From PCP to MXE: A comprehensive review of the non-medical use of dissociative drugs. Drug Testing and Analysis, 6(7–8), 614–632. https://doi.org/10.1002/dta.1620

References

  1. Wallach, J., Kang, H., Colestock, T., Morris, H., Bortolotto, Z. A., Collingridge, G. L., Lodge, D., Halberstadt, A. L., Brandt, S. D., Adejare, A. (17 June 2016). Lee, J., ed. "Pharmacological Investigations of the Dissociative 'Legal Highs' Diphenidine, Methoxphenidine and Analogues". PLOS ONE. 11 (6): e0157021. doi:10.1371/journal.pone.0157021. ISSN 1932-6203. 
  2. Morris, H., Wallach, J. (July 2014). "From PCP to MXE: a comprehensive review of the non-medical use of dissociative drugs: PCP to MXE". Drug Testing and Analysis. 6 (7–8): 614–632. doi:10.1002/dta.1620. ISSN 1942-7603. 
  3. Wurita, A., Hasegawa, K., Minakata, K., Watanabe, K., Suzuki, O. (1 August 2014). "A large amount of new designer drug diphenidine coexisting with a synthetic cannabinoid 5-fluoro-AB-PINACA found in a dubious herbal product". Forensic Toxicology. 32 (2): 331–337. doi:10.1007/s11419-014-0240-y. ISSN 1860-8973. 
  4. Hasegawa, K., Wurita, A., Minakata, K., Gonmori, K., Nozawa, H., Yamagishi, I., Watanabe, K., Suzuki, O. (1 January 2015). "Postmortem distribution of AB-CHMINACA, 5-fluoro-AMB, and diphenidine in body fluids and solid tissues in a fatal poisoning case: usefulness of adipose tissue for detection of the drugs in unchanged forms". Forensic Toxicology. 33 (1): 45–53. doi:10.1007/s11419-014-0245-6. ISSN 1860-8973. 
  5. Berger, M. L., Schweifer, A., Rebernik, P., Hammerschmidt, F. (1 May 2009). "NMDA receptor affinities of 1,2-diphenylethylamine and 1-(1,2-diphenylethyl)piperidine enantiomers and of related compounds". Bioorganic & Medicinal Chemistry. 17 (9): 3456–3462. doi:10.1016/j.bmc.2009.03.025. ISSN 0968-0896. 
  6. Wallach, J., Kavanagh, P. V., McLaughlin, G., Morris, N., Power, J. D., Elliott, S. P., Mercier, M. S., Lodge, D., Morris, H., Dempster, N. M., Brandt, S. D. (May 2015). "Preparation and characterization of the 'research chemical' diphenidine, its pyrrolidine analogue, and their 2,2-diphenylethyl isomers: Characterization of diphenylethylamines". Drug Testing and Analysis. 7 (5): 358–367. doi:10.1002/dta.1689. ISSN 1942-7603. 
  7. Gray, N. M., Cheng, B. K., 1,2-diarylethylamines for treatment of neurotoxic injury 
  8. Government of Canada, P. W. and G. S. C. (2016), Canada Gazette – Regulations Amending the Food and Drug Regulations (Parts G and J — Lefetamine, AH-7921, MT-45 and W-18) 
  9. "Verordnung des EDI über die Verzeichnisse der Betäubungsmittel, psychotropen Stoffe, Vorläuferstoffe und Hilfschemikalien" (in Deutsch). Bundeskanzlei [Federal Chancellery of Switzerland]. Retrieved January 1, 2020. 
  10. https://resmigazete.gov.tr/eskiler/2017/01/20170112-8.pdf
  11. Psychoactive Substances Act 2016 
  12. https://www.unodc.org/LSS/Substance/Details/7ee627dd-c3ed-42d2-b84f-81edef0d6466