N-Ethylhexedrone

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Not to be confused with Hexedrone.
Summary sheet: N-Ethylhexedrone
N-Ethylhexedrone
N-ethyl-nor-hexedrone.svg
Chemical Nomenclature
Common names Hexen, Hex-en, NEH, Ethyl-Hexedrone
Substitutive name N-Ethylhexedrone, N-Ethyl-nor-hexedrone
Systematic name 2-(ethylamino)-1-phenylhexan-1-one
Class Membership
Psychoactive class Stimulant
Chemical class Cathinone
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 1 mg
Light 2 - 5 mg
Common 5 - 10 mg
Strong 10 - 20 mg
Heavy 20 mg +
Duration
Total 1 - 4 hours
Onset 2 - 10 minutes
Peak 10 - 30 minutes
Offset 15 - 30 minutes
After effects 2 - 4 hours




⇣ Insufflated
Dosage
Threshold 5 mg
Light 15 - 30 mg
Common 30 - 40 mg
Strong 40 - 50 mg
Heavy 50 mg +
Duration
Total 2 - 5 hours
Onset 2 - 8 minutes
Peak 30 - 90 minutes
Offset 1 - 4 hours
After effects 1 - 8 hours






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
Alcohol
MXE
Dissociatives
MDMA
Stimulants
DXM
25x-NBOMe
25x-NBOH
Tramadol
MAOIs


N-Ethylhexedrone (also known as NEH, ethyl-hex, hex-en and hexen)[1] is a lesser-known novel stimulant substance of the cathinone class. N-Ethylhexedrone is a derivative of hexedrone and is part of a diverse group of compounds called the substituted cathinones. Little is known about its pharmacology, although it likely acts by increasing levels of norepinephrine and dopamine in the brain.

N-Ethylhexedrone was first synthesized by Boehringer Ingelheim in 1964.[1] It appears to have emerged on the online research chemical market in late 2015.[2] It is an example of a novel psychoactive substance specifically chosen to mimic the features of prohibited substances and bypass drug laws. It is one of a number of substances collectively referred to as "bath salts".[3]

User reports characterize N-ethylhexedrone as having euphoric stimulant effects comparable to those of crack-cocaine and α-PVP-type compounds, particularly when they insufflated or vaporized. Like other substituted cathinones, N-ethylhexedrone has gained notoriety for its association with compulsive redosing and addictive behaviors when abused.

Very little is known about the pharmacology, metabolism, and toxicity of N-ethylhexedrone. Due to this, it is highly advised to use harm reduction practices if using this substance.

History and culture

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This History and culture section is a stub.

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

N-Ethylhexedrone was patented by the German pharmaceutical company Boehringer Ingelheim in 1964 as a potential anorexigenic agent. The patent describes its synthesis together with other derivatives of aminoketone.[1]

The substance spread remarkably quickly in the NPS market in different European countries.[1] It was first identified in a sample from the Belgian Customs laboratory which was received at the JRC on November 2015. In January 2016, it was identified at the JRC in a sample provided by French Customs. Subsequently, in February 2016, the EMCDDA received notifications of the identification of this substance from other countries, such as Sweden, The Netherlands, France, Belgium and Slovenia.[4]

In 2017 it was the most frequent seized cathinone in the EU, Norway and Turkey.[5] In 2018, it was the most commonly identified cathinone after pentylone in Drug Enforcement Administration seizures.[3]

Chemistry

N-Ethylhexedrone is a derivative of hexedrone, in which the methyl group attached to the nitrogen atom is substituted by an ethyl group. It is structurally similar to pentedrone, and also α-pyrrolidinohexiophenone (A-PHP), from which it differs by the substitution of a pyrrolidine group with an N-ethyl group.[1]

The compound is a molecule of the cathinone chemical class. The term "substituted cathinone" refers to a broad array of substances based on cathinone, the principally active constituent of the khat plant. Cathinone is principally constituted of a amphetamine core (a phenethylamine core with an alkyl group attached to the alpha carbon) and an oxygen group attached to the beta carbon. Cathinones are also known as the beta-ketone (βk) (double-bonded oxygen to the β-carbon) analogs of amphetamines. Notably, the cathinone backbone can be modified in three different places to create hundreds of possible compounds, which include substituents on the aromatic ring (R2-R5), the alpha carbon (Rα), or the amine group (RN1, RN2).[6]

Relative to cathinone, N-ethylhexedrone consists of two added substitutions. At the Rα position, a n-Butyl substitution forms a hexan chain. The second substitution is an ethyl group, that's attached to the amine group at RN2, thus forming N-ethyl.

Pharmacology

Very little data exists on the human pharmacokinetics and pharmacodynamics of N-ethylhexedrone and other substituted cathinones. Like amphetamines, synthetic cathinones exert their stimulating and sympathomimetic effects via increasing synaptic concentration of catecholamines such as dopamine, serotonin and norepinephrine. These molecules are able to inhibit monoamine reuptake transporters producing a decreased clearance of the neurotransmitters from the synapse. Furthermore, they may cause release of biogenic amines from intracellular stores.[7] It appears that N-ethylhexedrone has high preference for the dopamine transporter.[1]

Based on the structure and assuming that N-ethylhexedrone is metabolized similarly to other cathinones, this compound is likely metabolized through N-dealkylation and/or reduction of the carbonyl group followed by N-dealkylation.[1]

Synthetic cathinones are generally less able than amphetamines to cross the blood–brain barrier because the beta-keto group causes an increase in polarity. Unlike other synthetic cathinones, pyrrolidine derivatives have a higher ability to cross the blood–brain barrier because the pyrrolidine ring confers a low polarity to these molecules. The studies on the metabolism of synthetic cathinones have shown that they are N-demethylated, the keto group is reduced to hydroxyl and ring alkyl groups are oxidised.[8]

Subjective effects

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 This subjective effects section is a stub.

As such, it is still in progress and may contain incomplete or wrong information.

You can help by expanding or correcting it.

User reports suggests that N-ethylhexedrone has more side effects compared to other stimulants like mephedrone or NEP. This can lead to excessive redosing, sobriety delusions and toxicity, which can eventually lead to highly uncomfortable experiences. The effects of vaporized N-ethylhexedrone are reported to be much stronger and more euphoric with less side effects than when insufflated or taken orally, but extreme care should be taken with this route of administration due to the degree it promotes compulsive and reckless use.

Another commonly noted property of N-ethylhexedrone is its tendency to produce a powerful initial rush which fades away and cannot be brought back by redosing, only increasing the negative physical and mental side effects.

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

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


Physical effects
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Cognitive effects
User.svg

Auditory effects
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After effects
Aftereffects (3).svg

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

Further information: Research chemicals § Toxicity and harm potential

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

Early anecdotal reports from those who have tried N-ethylhexedrone suggests that there do not seem to be any negative health effects attributed to simply trying it at low to moderate doses by itself and using it in a sparing and controlled fashion (but nothing can be completely guaranteed).

Some users have reported N-ethylhexedrone to be caustic to the nasal membrane when it is insufflated.[citation needed]

A toxicology screening indicated that measured with yeast and SH-SY5Y cells, N-Ethylhexedrone seems to be the most toxic among the five cathionones tested.[9]

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

Tolerance and addiction potential

As with other stimulants, the chronic use of N-ethylhexedrone can be considered moderately addictive with a high potential for abuse and seems to be readily liable of causing psychological dependence among certain users. When addiction has developed, cravings and withdrawal effects may occur if a person suddenly stops their usage.

Tolerance to many of the effects of N-ethylhexedrone 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 total absence of further consumption). N-Ethylhexedrone presents cross-tolerance with all noradrenergic and dopaminergic stimulants, meaning that after the consumption of N-ethylhexedrone all stimulants will have a reduced effect.

Psychosis

Main article: Stimulant psychosis

Abuse of compounds within the stimulant class at high dosages for prolonged periods of time can potentially result in a stimulant psychosis that may present with a variety of symptoms (e.g., anxiety and paranoia, hallucinations, or delusions).[10] A review on treatment for (dextro)amphetamine, and methamphetamine abuse-induced psychosis states that about 5–15% of users fail to recover completely.[10][11] The same review asserts that, based upon at least one trial, antipsychotic medications effectively resolve the symptoms of acute amphetamine psychosis.[10]

Dangerous interactions

Warning: Many psychoactive substances that are reasonably safe to use on their own can suddenly become dangerous or even life-threatening when combined with certain other substances. The following lists 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.

  • 25x-NBOMe & 25x-NBOH - 25x compounds are highly stimulating and physically straining. Combinations with N-Ethylhexedrone should be strictly avoided due to the risk of excessive stimulation and heart strain. This can result in increased blood pressure, vasoconstriction, panic attacks, thought loops, seizures, and heart failure in extreme cases.
  • Alcohol - Combining alcohol with stimulants can be dangerous due to the risk of accidental over-intoxication. Stimulants mask alcohol's depressant effects, which is what most people use to assess their degree of intoxication. Once the stimulant wears off, the depressant effects will be left unopposed, which can result in blackouts and severe respiratory depression. If mixing, the user should strictly limit themselves to only drinking a certain amount of alcohol per hour.
  • DXM - Combinations with DXM should be avoided due to its inhibiting effects on serotonin and norepinephrine reuptake. There is an increased risk of panic attacks and hypertensive crisis, or serotonin syndrome with serotonin releasers (MDMA, methylone, mephedrone, etc.). Monitor blood pressure carefully and avoid strenuous physical activity.
  • MDMA - Any neurotoxic effects of MDMA are likely to be increased when other stimulants are present. There is also a risk of excessive blood pressure and heart strain (cardiotoxicity).
  • MXE - Some reports suggest combinations with MXE may dangerously increase blood pressure and increase the risk of mania and psychosis.
  • Dissociatives - Both classes carry a risk of delusions, mania and psychosis, and these risk may be multiplied when combined.
  • Stimulants - N-Ethylhexedrone may be dangerous to combine with other stimulants like cocaine as they can increase one's heart rate and blood pressure to dangerous levels.
  • Tramadol - Tramadol is known to lower the seizure threshold[12] and combinations with stimulants may further increase this risk.

Legal status

Internationally, N-ethylhexedrone was added to the UN Convention on Psychotropic Substances as a Schedule II controlled substance in March 2020.[14][15]

  • Brazil: Possession, production and sale is illegal as it is listed on Portaria SVS/MS nº 344 since June 5, 2017.[16]
  • Canada: N-Ethylhexedrone is a Schedule I controlled substance.[1]
  • Germany: N-Ethylhexedrone is controlled under the NpSG[17] (New Psychoactive Substances Act) as of November 26, 2016.[18] Production and import with the aim to place it on the market, administration to another person, placing it on the market and trading is punishable. Possession is illegal but not punishable.[19][20] The legislator considers it possible that orders of N-ethylhexedrone are punishable as an incitement to place it on the market.[21]
  • Hungary: N-Ethylhexedrone is controlled as a new psychoactive substance.[1]
  • Ireland: N-Ethylhexedrone is controlled under SI 173/2017 under Schedule 1, paragraph 1(b) (page 35) as the substance is structurally derived from 2-amino-1-phenyl-1-propanone and is I the 3-position of the propanone side-chain with an alkyl substituent in this case, an ethyl group (subparagraph iii).[22]
  • Japan: N-Ethylhexedrone is a controlled substance.[23]
  • Sweden: N-Ethylhexedrone was classified as a potentially dangerous substance in Sweden on June 21, 2016, and is thus a controlled substance but neither narcotics-classified or fully outlawed.[24]
  • Switzerland: N-Ethylhexedrone can be considered a controlled substance as a defined derivative of Cathinone under Verzeichnis E point 1. It is legal when used for scientific or industrial use.[25]
  • United Kingdom: N-Ethylhexedrone is a Class B drug in the United Kingdom as a result of the cathinone catch-all clause.[26]
  • United States: N-Ethylhexedrone was placed in Schedule I by a DEA temporary scheduling order effective July 2019; the order was set to expire in July 2021, but on July 16, 2021 it was extended until July 2022.[27]

See also

External links

References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 1.16 1.17 1.18 1.19 1.20 1.21 1.22 1.23 Critical Review Report: N-Ethylhexedrone (PDF). Expert Committee on Drug Dependence (ECDD). Forty-second Meeting. World Health Organisation (WHO). October 2019. 
  2. ↑ "N-Ethylhexedrone". Google Trends. Retrieved October 16, 2020. 
  3. ↑ 3.0 3.1 Eshleman, A. J.; Nagarajan, S.; Wolfrum, K. M.; Reed, J. F.; Swanson, T. L.; Nilsen, A.; Janowsky, A. (2019). "Structure-activity relationships of bath salt components: substituted cathinones and benzofurans at biogenic amine transporters". Psychopharmacology. 236 (3): 939–952. doi:10.1007/s00213-018-5059-5. eISSN 1432-2072. ISSN 0033-3158. OCLC 2409222. PMC 6500773 Freely accessible. PMID 30397775. 
  4. ↑ Guillou, C.; Reniero, F.; Vicente, J. L.; Holland, M.; Kolar, K.; Chassaigne, H.; Tirendi, S.; Schepers, H. (2018). "Collaboration of the Joint Research Centre and European Customs Laboratories for the Identification of New Psychoactive Substances". Current Pharmaceutical Biotechnology. 19 (2): 91–98. doi:10.2174/1389201019666180523122717. ISSN 1389-2010. OCLC 1085815223. PMC 6110040 Freely accessible. PMID 29792142. 
  5. ↑ "EU Drug Markets Report 2019" (PDF). European Monitoring Centre for Drugs and Drug Addiction (EMCDDA); Europol. 2019. p. 185. doi:10.2810/796253 Freely accessible. ISBN 978-92-9497-459-4. 
  6. ↑ Liu, C.; Jia, W.; Li, T.; Hua, Z.; Qian, Z. (2017). "Identification and analytical characterization of nine synthetic cathinone derivatives N-ethylhexedrone, 4-Cl-pentedrone, 4-Cl-α-EAPP, propylone, N-ethylnorpentylone, 6-MeO-bk-MDMA, α-PiHP, 4-Cl-α-PHP, and 4-F-α-PHP". Drug Testing and Analysis. 9 (8): 1162–1171. doi:10.1002/dta.2136. eISSN 1942-7611. ISSN 1942-7603. OCLC 231680670. PMID 27863142. 
  7. ↑ Cozzi, N. V.; Sievert, M. K.; Shulgin, A. T.; Jacob 3rd, P.; Ruoho, A. E. (1999). "Inhibition of plasma membrane monoamine transporters by β-ketoamphetamines". European Journal of Pharmacology. 381 (1): 63–69. doi:10.1016/s0014-2999(99)00538-5. eISSN 1879-0712. ISSN 0014-2999. OCLC 01568459. PMID 10528135. 
  8. ↑ Meyer, M. R.; Maurer, H. H. (2010). "Metabolism of Designer Drugs of Abuse: An Updated Review". Current Drug Metabolism. 11 (5): 468–482. doi:10.2174/138920010791526042. eISSN 1875-5453. ISSN 1389-2002. OCLC 55201006. PMID 20540700. 
  9. ↑ https://www.who.int/medicines/access/controlled-substances/Final_N-ethylhexedrone.pdf?ua=1
  10. ↑ 10.0 10.1 10.2 Shoptaw, S.; Kao, U.; Ling, W. (2009). "Treatment for amphetamine psychosis". Cochrane Database of Systematic Reviews (1). doi:10.1002/14651858.CD003026.pub3 Freely accessible. eISSN 1469-493X. ISSN 2044-4702. OCLC 99039924. PMC 7004251 Freely accessible. PMID 19160215. CD003026. 
  11. ↑ Frederick G. Hofmann (1983). A Handbook on Drug and Alcohol Abuse: The Biomedical Aspects (2nd ed.). New York: Oxford University Press. p. 329. ISBN 9780195030570. OCLC 899099215. 
  12. ↑ Talaie, H.; Panahandeh, R.; Fayaznouri, M. R.; Asadi, Z.; Abdollahi, M. (2009). "Dose-independent occurrence of seizure with tramadol". Journal of Medical Toxicology. 5 (2): 63–67. doi:10.1007/BF03161089. eISSN 1937-6995. ISSN 1556-9039. OCLC 163567183. 
  13. ↑ Gillman, P. K. (2005). "Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity". British Journal of Anaesthesia. 95 (4): 434–441. doi:10.1093/bja/aei210 Freely accessible. eISSN 1471-6771. ISSN 0007-0912. OCLC 01537271. PMID 16051647. 
  14. ↑ "WHO: World Health Organization recommends 12 NPS for scheduling". December 2019. Retrieved October 16, 2020. 
  15. ↑ "CND accepts all WHO recommendations on the control of several psychoactive substances from the 42nd ECDD meeting". World Health Organization (WHO). March 18, 2020. Retrieved October 16, 2020. 
  16. ↑ "RESOLUÇÃO-RDC No- 159, DE 2 DE JUNHO DE 2017". Diário Official da União (in Portuguese). Governo Federal do Brasil [Federal Government of Brazil] (published June 5, 2017). May 23, 2017. p. 103. ISSN 1677-7042. N°106. Archived from the original on January 16, 2020. 
  17. ↑ "Anlage NpSG" (in German). Bundesamt für Justiz [Federal Office of Justice]. Retrieved December 10, 2019. 
  18. ↑ "Gesetz zur Bekämpfung der Verbreitung neuer psychoaktiver Stoffe" (PDF). Bundesgesetzblatt Jahrgang 2016 Teil I Nr. 55 (in German). Bundesanzeiger Verlag (published November 25, 2016). November 21, 2016. pp. 2615–2622. ISSN 0341-1095. OCLC 1004462279. 
  19. ↑ "§ 4 NpSG" (in German). Bundesamt für Justiz [Federal Office of Justice]. Retrieved December 10, 2019. 
  20. ↑ "§ 3 NpSG" (in German). Bundesamt für Justiz [Federal Office of Justice]. Retrieved December 10, 2019. 
  21. ↑ "Gesetzentwurf der Bundesregierung: Entwurf eines Gesetzes zur Bekämpfung der Verbreitung neuer psychoaktiver Stoffe" (PDF) (in German). Deutscher Bundestag. May 30, 2016. p. 20. Drucksache 18/8579. 
  22. ↑ "Information Note-COM (2019) 631 Final" (PDF). Controlled Drugs and Pharmacy Legislation Unit. January 13, 2020. 
  23. ↑ "指定薬物一覧" (PDF) (in Japanese). 厚生労働省 [Ministry of Health, Labour and Welfare (MHLW)]. Retrieved December 27, 2019. 
  24. ↑ "31 nya ämnen kan klassas som narkotika eller hälsofarlig vara" (in Swedish). Folkhälsomyndigheten [Public Health Agency of Sweden]. June 21, 2016. Retrieved October 17, 2020. 
  25. ↑ "Verordnung des EDI über die Verzeichnisse der Betäubungsmittel, psychotropen Stoffe, Vorläuferstoffe und Hilfschemikalien" (in German). Bundeskanzlei [Federal Chancellery of Switzerland]. Retrieved January 1, 2020. 
  26. ↑ "Part II: Class B Drugs". "Misuse of Drugs Act 1971". UK Government. Retrieved October 18, 2020. 
  27. ↑ "Temporary Placement of N-Ethylhexedrone, α-PHP, 4–MEAP, MPHP, PV8, and 4-Chloro-α-PVP in Schedule I". Federal Register. Vol. 84 (138). Drug Enforcement Administration (DEA). July 18, 2019. pp. 34291–34297. Retrieved October 18, 2020. 
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