Ephenidine - PsychonautWiki

Ephenidine

Not to be confused with Ephedrine.
Summary sheet: Ephenidine
Ephenidine
Ephenidine.svg
Chemical Nomenclature
Common names Ephenidine, NEDPA
Substitutive name Ephenidine
Systematic name N-Ethyl-1,2-diphenylethylamine
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.



⇣ Oral
Dosage
Threshold 30 mg
Light 30 - 70 mg
Common 70 - 100 mg
Strong 100 - 150 mg
Heavy 150 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


Ephenidine (also known as NEDPA and EPE) is a lesser-known novel dissociative substance of the diarylethylamine class. Ephenidine is an NMDA receptor antagonist[1] that is structurally related to diarylethylamines like diphenidine and methoxphenidine. Notable effects include sedation, hallucinations, anesthesia, and out-of-body states, referred to as "dissociative anesthesia".

Ephenidine and related diarylethylamines have been studied in humans as treatments for neurotoxic injuries.[2][3][4][5][6] Recreational use was not documented until the 2013 U.K. arylcyclohexylamine ban, when it was released on the online research chemical market.[7] It was marketed alongside diphenidine and methoxphenidine as a substitute for methoxetamine (MXE) despite users claiming markedly different effects.

Very little data exists about the pharmacological properties, metabolism, and toxicity of ephenidine, and it has an extremely limited history of human usage. The abuse of diarylethylamines has been linked to a number of fatal and non-fatal overdoses.[1] Many reports suggest that they may pose different risks than traditional dissociatives. 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.

Ephenidine has been described as a designer drug. Designer drugs are substances mimic the functional and structural features of commonly used illicit substances in order to circumvent government regulation.[8][9]

Chemistry

Ephenidine is a molecule of the diarylethylamine class. It contains a substituted phenethylamine skeleton with an additional phenyl ring bound to Rα. An ethyl chain is bound to the terminal amine RN of the phenethylamine. Ephenidine is structurally analogous to diphenidine and MXP, but is not a piperidine dissociative. Ephenidine shares a diphenylethylamine skeleton with diphenidine and MXP, but lacks a piperidine substitution.

Pharmacology

Further information: NMDA receptor antagonist

Ephenidine acts as an antagonist of the NMDA receptor (Ki = 66.4 nM).[10][11][12][13][14] The NMDA (N-methyl-D-aspartate) receptor is one of the major receptor subtypes for glutamate, the major excitatory neurotransmitter in the central nervous system (CNS). When NMDA channels are blocked, a loss of feeling (anesthesia), difficulty moving (immobilization), and at higher doses, the compound's equivalent of the “K-hole” results.

Ephenidine also possesses weaker affinity for the dopamine and norepinephrine transporters (379 nM and 841 nM, respectively) as well as σ1R (629 nM) and σ2R (722 nM) binding sites.[15]

Subjective effects

Ephenidine 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 and plugging 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
 

Auditory effects
 

Transpersonal effects
 

Experience reports

There are currently antecdotal reports which describe the effects of this compound within our experience index.

Additional experience reports can be found here:

Toxicity and harm potential

Further information: Research chemicals § Toxicity and harm potential, and Responsible use § Hallucinogens

The toxicity and long-term health effects of recreational ephenidine use do not seem to have been studied in any scientific context and the exact toxic dosage is unknown. This is because ephenidine has very little history of human usage.

Anecdotal reports from those who have tried ephenidine 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). Independent research should always be done to ensure that a combination of two or more substances is safe before consumption.

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

Tolerance and addiction potential

As with other NMDA receptor antagonists, the chronic use of ephenidine can be considered 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 the user suddenly stops their usage.

Tolerance to many of the effects of ephenidine 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). Ephenidine presents cross-tolerance with all dissociatives, meaning that after the consumption of ephenidine 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.

Legal status

 

This legality section is a stub.

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

Ephenidine is illegal in some countries as a structural isomer of the banned opioid drug lefetamine.[16][17]

  • Canada: As of March 2016, MT-45 and its analogues, one of which being ephenidine, are Schedule I controlled substances.[18] 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.
  • Germany: Ephenidine is a controlled substance under the NpSG (New Psychoactive Substances Act) as a derivative of 2-Phenylethylamine.[19]
  • Sweden: Following a suggestion by Sweden's public health agency that ephenidine be classified as a hazardous substance on June 2015, ephenidine became a scheduled substance as of August 2015.[20]
  • Switzerland: Ephenidine is a controlled substance specifically named under Verzeichnis E.[21]
  • Turkey: Ephenidine is a classed as drug and is illegal to possess, produce, supply, or import.[22]
  • United Kingdom: Ephenidine is illegal to produce, supply, or import in the U.K. under the Psychoactive Substance Act, which came into effect on May 26th, 2016.[23]
  • United States: Ephenidine could possibly be considered a positional isomer of SPA (lefetamine), which is a Schedule IV drug.[24] However, the isomer clauses within the legal text of the Schedules have rarely, if ever, been used for prosecution.

See also

External links

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
  • Wink, Carina S. D., et al. “Lefetamine‐Derived Designer Drugs N‐Ethyl‐1,2‐Diphenylethylamine (NEDPA) and N‐Iso‐Propyl‐1,2‐Diphenylethylamine (NPDPA): Metabolism and Detectability in Rat Urine Using GC‐MS, LC‐MSn and LC‐HR‐MS/MS.” Drug Testing and Analysis, John Wiley & Sons, Ltd, 3 Mar. 2014, https://onlinelibrary.wiley.com/doi/abs/10.1002/dta.1621.
  • “Toxicokinetics of Lefetamine and Derived Diphenylethylamine Designer Drugs-Contribution of Human Cytochrome P450 Isozymes to Their Main Phase I Metabolic Steps.” Toxicology Letters, Elsevier, 11 Aug. 2015, https://www.sciencedirect.com/science/article/pii/S0378427415300333.
  • “Ephenidine: A New Psychoactive Agent with Ketamine-like NMDA Receptor Antagonist Properties.” Neuropharmacology, Pergamon, 9 Aug. 2016, https://www.sciencedirect.com/science/article/pii/S0028390816303392.
  • Eiden, Céline, et al. “Ephenidine, Diphenidine, and Methoxphenidine Complications Reported to the French Addictovigilance Network.” Fundamental & Clinical Pharmacology, John Wiley & Sons, Ltd (10.1111), 23 July 2018, https://onlinelibrary.wiley.com/doi/abs/10.1111/fcp.12395.

References

  1. ↑ 1.0 1.1 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. ↑ Nancy M. Gray; Brian K. Cheng (6 April 1994). "Patent EP 0346791 - 1,2-diarylethylamines for treatment of neurotoxic injury". G.D. Searle, LLC – via SureChEMBL. 
  3. ↑ Michael L. Berger; Anna Schweifer; Patrick Rebernik; Friedrich Hammerschmidt (May 2009). "NMDA receptor affinities of 1,2-diphenylethylamine and 1-(1,2-diphenylethyl)piperidine enantiomers and of related compounds". Bioorganic & Medicinal Chemistry. 17 (1): 3456–3462. doi:10.1016/j.bmc.2009.03.025. PMID 19345586. 
  4. ↑ Jason Wallach; Pierce V. Kavanagh; Gavin McLaughlin; Noreen Morris; John D. Power; Simon P. Elliott; Marion S. Mercier; David Lodge; Hamilton Morris; Nicola M. Dempster; Simon D. Brandt (May 2015). "Preparation and characterization of the 'research chemical' diphenidine, its pyrrolidine analogue, and their 2,2-diphenylethyl isomers". Drug Testing and Analysis. 7 (5): 358–367. doi:10.1002/dta.1689. PMID 25044512. 
  5. ↑ Thurkauf, Andrew; Monn, James; Mattson, Marienna V.; Jacobson, Arthur E.; Rice, Kenner C. (1989). "Structural and conformational aspects of the binding of aryl-alkyl amines to the phencyclidine binding site" (PDF). NIDA research monograph. 95: 51–56. ISSN 1046-9516. PMID 2561843. 
  6. ↑ Goodson, L. H.; Wiegand, C. J. W.; Splitter, Janet S. (November 1946). "Analgesics. I. N-Alkylated-1,2-diphenylethylamines Prepared by the Leuckart Reaction". Journal of the American Chemical Society. 68 (11): 2174–2175. doi:10.1021/ja01215a018. PMID 21002222. 
  7. ↑ McLaughlin, G., Morris, N., Kavanagh, P. V., Power, J. D., O’Brien, J., Talbot, B., Elliott, S. P., Wallach, J., Hoang, K., Morris, H., Brandt, S. D. (January 2016). "Test purchase, synthesis, and characterization of 2-methoxydiphenidine (MXP) and differentiation from its meta - and para -substituted isomers: Characterization of 2-, 3- and 4-methoxydiphenidine isomers". Drug Testing and Analysis. 8 (1): 98–109. doi:10.1002/dta.1800. ISSN 1942-7603. 
  8. ↑ Morris, H., Wallach, J. (August 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. doi:10.1002/dta.1620. ISSN 1942-7611. 
  9. ↑ Van Hout, M. C., Hearne, E. (March 2015). ""Word of mouse": indigenous harm reduction and online consumerism of the synthetic compound methoxphenidine". Journal of Psychoactive Drugs. 47 (1): 30–41. doi:10.1080/02791072.2014.974002. ISSN 0279-1072. 
  10. ↑ Nancy M. Gray; Brian K. Cheng (6 April 1994). "Patent EP 0346791 - 1,2-diarylethylamines for treatment of neurotoxic injury". G.D. Searle, LLC – via SureChEMBL. 
  11. ↑ Michael L. Berger; Anna Schweifer; Patrick Rebernik; Friedrich Hammerschmidt (May 2009). "NMDA receptor affinities of 1,2-diphenylethylamine and 1-(1,2-diphenylethyl)piperidine enantiomers and of related compounds". Bioorganic & Medicinal Chemistry. 17 (1): 3456–3462. doi:10.1016/j.bmc.2009.03.025. PMID 19345586. 
  12. ↑ Jason Wallach; Pierce V. Kavanagh; Gavin McLaughlin; Noreen Morris; John D. Power; Simon P. Elliott; Marion S. Mercier; David Lodge; Hamilton Morris; Nicola M. Dempster; Simon D. Brandt (May 2015). "Preparation and characterization of the 'research chemical' diphenidine, its pyrrolidine analogue, and their 2,2-diphenylethyl isomers". Drug Testing and Analysis. 7 (5): 358–367. doi:10.1002/dta.1689. PMID 25044512. 
  13. ↑ Thurkauf, Andrew; Monn, James; Mattson, Marienna V.; Jacobson, Arthur E.; Rice, Kenner C. (1989). "Structural and conformational aspects of the binding of aryl-alkyl amines to the phencyclidine binding site" (PDF). NIDA research monograph. 95: 51–56. ISSN 1046-9516. PMID 2561843. 
  14. ↑ Goodson, L. H.; Wiegand, C. J. W.; Splitter, Janet S. (November 1946). "Analgesics. I. N-Alkylated-1,2-diphenylethylamines Prepared by the Leuckart Reaction". Journal of the American Chemical Society. 68 (11): 2174–2175. doi:10.1021/ja01215a018. PMID 21002222. 
  15. ↑ Kang, Heather; Park, Pojeong; Bortolotto, Zuner A.; Brandt, Simon D.; Colestock, Tristan; Wallach, Jason; Collingridge, Graham L.; Lodge, David (2016). "Ephenidine: A new psychoactive agent with ketamine-like NMDA receptor antagonist properties". Neuropharmacology. 112 (Pt A): 144–149. doi:10.1016/j.neuropharm.2016.08.004. PMC 5084681  . PMID 27520396. 
  16. ↑ Wink, C. S. D., Meyer, G. M. J., Wissenbach, D. K., Jacobsen-Bauer, A., Meyer, M. R., Maurer, H. H. (October 2014). "Lefetamine-derived designer drugs N-ethyl-1,2-diphenylethylamine (NEDPA) and N-iso-propyl-1,2-diphenylethylamine (NPDPA): metabolism and detectability in rat urine using GC-MS, LC-MSn and LC-HR-MS/MS". Drug Testing and Analysis. 6 (10): 1038–1048. doi:10.1002/dta.1621. ISSN 1942-7611. 
  17. ↑ Wink, C. S. D., Meyer, G. M. J., Meyer, M. R., Maurer, H. H. (4 November 2015). "Toxicokinetics of lefetamine and derived diphenylethylamine designer drugs-Contribution of human cytochrome P450 isozymes to their main phase I metabolic steps". Toxicology Letters. 238 (3): 39–44. doi:10.1016/j.toxlet.2015.08.012. ISSN 1879-3169. 
  18. ↑ 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) 
  19. ↑ "Neue-psychoaktive-Stoffe-Gesetz (NpSG)" [New Psychoactive Substances Act (NpSG)] (PDF) (in German). Bundesamt für Justiz [Federal Office of Justice]. November 21, 2016. Retrieved August 14, 2020. 
  20. ↑ Nyhetsarkiv — Folkhälsomyndigheten 
  21. ↑ "Verordnung des EDI über die Verzeichnisse der Betäubungsmittel, psychotropen Stoffe, Vorläuferstoffe und Hilfschemikalien" (in German). Bundeskanzlei [Federal Chancellery of Switzerland]. Retrieved January 1, 2020. 
  22. ↑ https://resmigazete.gov.tr/eskiler/2017/01/20170112-8.pdf
  23. ↑ Psychoactive Substances Act 2016 
  24. ↑ DEA website | http://www.deadiversion.usdoj.gov/21cfr/cfr/1308/1308_14.htm
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