N-Ethylhexedrone
| Summary sheet: N-Ethylhexedrone |
| N-Ethylhexedrone | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| 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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Alcohol | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DXM | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| MXE | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| MDMA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Stimulants | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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), a research literature based on anecdotal reports and the personal experiences of PsychonautWiki contributors. As a result, they should be regarded with a healthy degree of skepticism. It is 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 much more likely with higher doses and may include addiction, serious injury, or death.
Physical effects 
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- Stimulation[1] - N-Ethylhexedrone is reported to be be moderately to extremely stimulating and energetic.
- Spontaneous bodily sensations - As with related cathininones, it is commonly reported that medium to high doses of N-ethylhexedrone can produce a pleasurable "body high" characterized by pleasant tingling sensations, which are stronger than that of amphetamine but weaker than a-PVP.
- Tactile enhancement and Tactile suppression - Reports suggest that at moderate to high dosages, N-ethylhexedrone is slightly anesthetic which is reminiscent to cocaine.
- Pain relief
- Mouth numbing - N-Ethylhexedrone presents a moderate local anesthetic effect.
- Vasoconstriction[1] - A number of reports indicate, N-ethylhexedrone can be considered slightly vasoconstrictive.
- Increased bodily temperature[1]
- Increased blood pressure[1]
- Increased heart rate[1]
- Abnormal heartbeat[1]
- Increased perspiration[1]
- Appetite suppression[1]
- Stamina enhancement
- Nausea - Mild to moderate nausea can occur at moderate to heavy dosages.
- Body odor alteration - This happens at a less consistent rate than with methamphetamine.
- Dehydration[1]
- Dry mouth[1]
- Temporary erectile dysfunction - This effect seems to be more apparent when compared to similar substances such as NEP.
- Muscle contractions[1]
- Teeth grinding[1] - This component can be considered to be less intense when compared with that of MDMA and more similar to the teeth-grinding that can result from general cathinone use like a-PHP or NEP.
Cognitive effects 
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The headspace of N-ethylhexedrone is typically described as extreme mental stimulation accompanied by a powerful sense of euphoria.
- Thought acceleration
- Disinhibition
- Euphoria[1] - This effect is usually not as powerful as with amphetamine or mephedrone.
- Analysis enhancement - This effect is mostly present in lower doses and is considered weak compared to other stimulant compounds. At high doses, it becomes overshadowed by euphoric stimulation.
- Immersion enhancement
- Focus enhancement - This component is most effective at low doses as anything higher will usually impair concentration due to the accompanying euphoria.
- Motivation enhancement
- Time compression
- Ego inflation
- Increased music appreciation
- Compulsive redosing - This is perhaps the most well-known aspect of this substance. This can result in unwanted binges of sometimes excessive amounts and a higher risk of addiction.
- Paranoia[1]
Auditory effects 
- Auditory effects are usually present at extremely high dosages, or when taken in a dangerously sleep deprived state.
After effects 
- N-Ethylhexedrone's comedown is usually described as more slow and less dysphoric than the same effect found within MDMA or methamphetamine but harsher than that of NEP. The effects which occur during the offset of a stimulant experience generally feel negative and uncomfortable in comparison to the effects which occurred during its peak. This is often referred to as a "comedown" and occurs because of neurotransmitter depletion. Its effects commonly include:
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
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]
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
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).[9] A review on treatment for (dextro)amphetamine, and methamphetamine abuse-induced psychosis states that about 5–15% of users fail to recover completely.[9][10] The same review asserts that, based upon at least one trial, antipsychotic medications effectively resolve the symptoms of acute amphetamine psychosis.[9]
Dangerous interactions
Although many psychoactive substances are reasonably safe to use on their own, they can suddenly become dangerous or even life-threatening when combined with other substances. The following list includes some known dangerous combinations (although it is not guaranteed to include all of them). Independent research (e.g. Google, DuckDuckGo) should always be conducted 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 - Members of the 25x family are highly stimulating and physically straining. Combinations with stimulants should be avoided due to the risk of excessive stimulation. This can result in panic attacks, thought loops, seizures, increased blood pressure, vasoconstriction, and heart failure in extreme cases.
- Alcohol - Alcohol can be dangerous to combine with stimulants due to the risk of accidental over-intoxication. Stimulants mask the sedative effects of alcohol, which is the main factor people use to assess their degree of intoxication. Once the stimulant wears off, the depressant effects of alcohol are left unopposed, which can result in blackouts and respiratory depression. If combined, one should strictly limit themselves to only drinking a certain amount of alcohol per hour.
- DXM - Combinations with DXM should be handled with extreme care due to DXM's effects on serotonin and norepinephrine reuptake. This can lead to panic attacks, hypertensive crisis, or serotonin syndrome with stimulants that increase levels of serotonin (MDMA, methylone, mephedrone, etc.). Monitor blood pressure carefully and avoid strenuous physical activity.
- MDMA - The neurotoxic effects of MDMA may be increased when combined with other stimulants. There is also a risk of excessive heart strain.
- MXE - Combinations with MXE may dangerously elevate blood pressure and increase the risk of psychosis.
- Stimulants - N-Ethylhexedrone can be potentially dangerous in combination with other stimulants like cocaine as they can increase one's heart rate and blood pressure to dangerous levels.
- Tramadol - Tramadol lowers the seizure threshold.[11] Combinations with stimulants may further increase this risk.
- MAOIs - This combination may increase the amount of neurotransmitters such as dopamine to dangerous or even fatal levels. Examples include syrian rue, banisteriopsis caapi, and some antidepressants.[12]
Legal status
Internationally, N-ethylhexedrone was added to the UN Convention on Psychotropic Substances as a Schedule II controlled substance in March 2020.[13][14]
- Brazil: Possession, production and sale is illegal as it is listed on Portaria SVS/MS nº 344 since June 5, 2017.[15]
- Canada: N-Ethylhexedrone is a Schedule I controlled substance.[1]
- Germany: N-Ethylhexedrone is controlled under the NpSG[16] (New Psychoactive Substances Act) as of November 26, 2016.[17] 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.[18][19] The legislator considers it possible that orders of N-ethylhexedrone are punishable as an incitement to place it on the market.[20]
- 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).[21]
- Japan: N-Ethylhexedrone is a controlled substance.[22]
- 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.[23]
- 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.[24]
- United Kingdom: N-Ethylhexedrone is a Class B drug in the United Kingdom as a result of the cathinone catch-all clause.[25]
- United States: N-Ethylhexedrone was placed in Schedule I by a DEA temporary scheduling order effective July 2019; the order will expire in July 2021 unless extended or made permanent.[26]
See also
External links
References
- ↑ 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.
- ↑ "N-Ethylhexedrone". Google Trends. Retrieved October 16, 2020.
- ↑ 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
. PMID 30397775.
- ↑ 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 . PMID 29792142.
- ↑ "EU Drug Markets Report 2019" (PDF). European Monitoring Centre for Drugs and Drug Addiction (EMCDDA); Europol. 2019. p. 185. doi:10.2810/796253 . ISBN 978-92-9497-459-4.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 9.0 9.1 9.2 Shoptaw, S.; Kao, U.; Ling, W. (2009). "Treatment for amphetamine psychosis". Cochrane Database of Systematic Reviews (1). doi:10.1002/14651858.CD003026.pub3 . eISSN 1469-493X. ISSN 2044-4702. OCLC 99039924. PMC 7004251 . PMID 19160215. CD003026.
- ↑ 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.
- ↑ 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.
- ↑ 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 . eISSN 1471-6771. ISSN 0007-0912. OCLC 01537271. PMID 16051647.
- ↑ "WHO: World Health Organization recommends 12 NPS for scheduling". December 2019. Retrieved October 16, 2020.
- ↑ "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.
- ↑ "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.
- ↑ "Anlage NpSG" (in German). Bundesamt für Justiz [Federal Office of Justice]. Retrieved December 10, 2019.
- ↑ "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.
- ↑ "§ 4 NpSG" (in German). Bundesamt für Justiz [Federal Office of Justice]. Retrieved December 10, 2019.
- ↑ "§ 3 NpSG" (in German). Bundesamt für Justiz [Federal Office of Justice]. Retrieved December 10, 2019.
- ↑ "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.
- ↑ "Information Note-COM (2019) 631 Final" (PDF). Controlled Drugs and Pharmacy Legislation Unit. January 13, 2020.
- ↑ "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.
- ↑ "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.
- ↑ "Verordnung des EDI über die Verzeichnisse der Betäubungsmittel, psychotropen Stoffe, Vorläuferstoffe und Hilfschemikalien" (in German). Bundeskanzlei [Federal Chancellery of Switzerland]. Retrieved January 1, 2020.
- ↑ "Part II: Class B Drugs". "Misuse of Drugs Act 1971". UK Government. Retrieved October 18, 2020.
- ↑ "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.