Ephylone

Synthetic cathinones were first synthesized in the late 1920s, starting with methcathinone and mephedrone. However, they did not find medical use due to their side effects. In the early 2000s, synthetic cathinones began to be sold in "head" shops and online as designer drugs, also known as research chemicals and "legal highs".^[3] Their quasi-legality and ability to substitute for traditional stimulants like cocaine or amphetamine made them popular in certain demographics. Due to a history of being falsely marketed as bath salt products, they are referred in the media as "bath salts."

The synthesis of ephylone was first described in a patent filed by Boehringer Ingelheim in 1969. It was described alongside the synthesis of other novel central nervous system stimulants including pentylone, butylone and dibutylone. However, its pharmacological properties were not tested and it was never marketed.

The emergence of ephylone on the recreational drug market was reported in drug seizures for the first time in 2016. According to 2017 DEA reports, ephylone was the number one reported synthetic cathinone accounting for 55%, 50% and 38% of cases reported for the first three quarters of 2017, respectively.^[2]

Reports about the availability and effects of ephylone began to appear in forums such as bluelight.org or drugs-forum.com by mid-2015. A 2018 report issued by the drug testing organization Energy Control found evidence indicating increasing use of ephylone as a counterfeit or adulterant for MDMA.^[4]

Ephylone, or N-ethylpentylone, is a synthetic substance belonging to a group known as substituted cathinones. Substituted cathinones are derivatives of the naturally occurring substance cathinone, which is one of the psychoactive principles in khat (Catha edullis). Cathinone is composed of a phenethylamine core with an alkyl group attached to the alpha carbon, and a ketone group attached to the beta carbon.

Ephylone is a structural analog of pentylone. Pentylone's chemical structure consists of a cathinone core substituted with a methylenedioxy ring at R3 and R4 of the phenyl ring, a propyl group at the alpha carbon, and a methyl group at the amino group. Ephylone has an identical structure with the exception of an N-ethyl alkyl substituting for the N-methyl moiety.

Very little data exists on the human pharmacokinetics and pharmacodynamics of ethylone 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.^[5]

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.^[6]

Compared to other stimulant-entactogens, ephylone is reported to be more stimulating than entactogenic. Entactogenic feelings are said to be weak compared to substances like MDMA, 6-APB or methylone. Ephylone is also described as less euphoric and satisfying than traditional entactogens. Reports suggest that the physical side effects increase disproportionately to the desirable effects, which may promote compulsive redosing.

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 ☠.

Experience reports

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

Additional experience reports can be found here:

• Erowid Experience Vaults: Ephylone

Ephylone is a research chemical with a very short history of human usage. Very little is known about its long-term health effects and the exact toxic dosage is unknown.

Numerous reports of hospitalizations and overdose deaths indicate that ephylone is extremely toxic at very high dosages.^[7] The DEA claimed approximately 151 ephylone-related deaths occurred in the U.S. between 2014 and 2018.^[8] Higher dosages of ephylone have been linked to serotonin syndrome, rhabdomyolysis, kidney injury, acidemia and other life-threatening symptoms.^[2]

It is strongly advised to use harm reduction practices if using this substance.

Dependence and abuse potential

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

Tolerance to many of the effects of ephylone develops with prolonged and repeated use. This results in users having to administer increasingly large doses to achieve the same effects.

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 - Combining ephylone with other stimulants may result in dangerous increases in blood pressure and heart rate.
• 25x-NBOMe & 25x-NBOH - 25x compounds are highly stimulating and physically straining. Combinations with Ephylone 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 - Ephylone 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^[9] and combinations with stimulants may further increase this risk.

Serotonin syndrome risk

Combinations with the following substances can cause dangerously high serotonin levels. Serotonin syndrome requires immediate medical attention and can be fatal if left untreated.

• MAOIs - Such as banisteriopsis caapi, syrian rue, phenelzine, selegiline, and moclobemide.^[10]
• Serotonin releasers - Such as MDMA, 4-FA, methamphetamine, methylone and αMT.
• SSRIs - Such as citalopram and sertraline
• SNRIs - Such as tramadol and venlafaxine
• 5-HTP

Ephylone is currently unscheduled in most parts of the world.

• Brazil: On September 7, 2018, all Cathinone analogues are controlled substances considered illegal to possess, use and distribute. This was made possible due to a blanket ban law appended to Portaria SVS/MS nº 344.^[11]
• Germany: Ephylone is controlled under Anlage II BtMG (Narcotics Act, Schedule II)^[12] as of December 21, 2019.^[13] It is illegal to manufacture, possess, import, export, buy, sell, procure or dispense it without a license.^[14]
• Switzerland: Ephylone 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.^[15]
• United States: On July 13, 2018, the DEA issued a temporary scheduling order to place ephylone in schedule I of the Controlled Substances Act (CSA).^[8] This makes the production, sale, and possession of ephylone illegal.

• Responsible use
• Entactogens
• Stimulants
• Cathinones
• Methylone
• MDPV

• Ephylone (Wikipedia)
• Ephylone (Isomer Design)

• Prosser, J. M., & Nelson, L. S. (2012). The toxicology of bath salts: a review of synthetic cathinones. Journal of Medical Toxicology, 8(1), 33-42. https://doi.org/0.1007/s13181-011-0193-z.
• Wood, M. R., Bernal, I., & Lalancette, R. A. (2017). The hydrochloride hydrates of pentylone and dibutylone and the hydrochloride salt of ephylone: the structures of three novel designer cathinones. Structural Chemistry, 28(5), 1369-1376. http://dx.doi.org/10.1007/s11224-017-0951-x
• Krotulski, A. J., Papsun, D. M., De Martinis, B. S., Mohr, A. L., & Logan, B. K. (2018). N-Ethyl Pentylone (Ephylone) Intoxications: Quantitative Confirmation and Metabolite Identification in Authentic Human Biological Specimens. Journal of Analytical Toxicology. https://doi.org/10.1093/jat/bky025