|Summary sheet: Ethylmorphine|
|Common names||Ethylmorphine, Codethyline, Dionine|
|Systematic name||7,8-didehydro-4,5-α-epoxy- 3-ethoxy-17-methylmorphinan-6-α-ol|
|Routes of Administration|
Ethylmorphine, also known as codethyline and dionine, is a semi-synthetic morphinan opioid first created by Merck in 1884 and used as a weaker alternative to morphine. Today, it is most commonly used as an antitussive which is available in cough syrup preparations like Cocillana, Cosylan, Solvipect comp. (in combination with guaifenesin) and Lepheton (in combination with ephedrine), or in tablet form sold as Tussipax (in combination with codeine). Cough syrup preparations commonly include a mild laxative to counter the constipation which is a common side effect of opioids.
Ethylmorphine is also used in ophthalmic preparations as dionine to treat inflammations of the eye. In 1904, an ethylmorphine preparation was described as "a new ocular analgesic."
Ethylmorphine, or 3-ethylmorphine, is an opioid of the morphinan class. Ethylmorphine and other molecules of this class contain a polycyclic core of three benzene rings fused in a zig-zag pattern called phenanthrene. A fourth nitrogen containing ring is fused to the phenanthrene at R9 and R13 with the nitrogen member looking at R17 of the combined structure. This structure is called morphinan.
Ethylmorphine, along with other morphinans, contains an ether bridge between two of its rings, connecting R4 and R5 through an oxygen group. It contains a hydroxy group (OH-) bound at R6 and a methyl group located on the nitrogen atom at R17. On the same ring containing the hydroxy group, ethylmorphine contains a double bond which is shared with codeine and morphine.
Ethylmorphine is closely related to morphine; both contain an oxygen group at R3, but this oxygen group in ethylphenidate is substituted by an ethyl group (making an ethoxy group). Ethylmorphine differs from the naturally occurring codeine (3-methylmorphine) only in having an ethoxy group in place of the methoxy group (they are homologous). It is also analogous to the other morphinans such as dihydrocodeine, heroin, hydrocodone, and oxycodone.
The active metabolites of ethylmorphine, notably morphine, exert their effects by binding to and activating the μ-opioid receptor. This occurs because opioids structurally mimic endogenous endorphins which are naturally found within the body and also work upon the μ-opioid receptor set. The way in which opioids structurally mimic these natural endorphins results in their euphoria, pain relief and anxiolytic effects. This is because endorphins are responsible for reducing pain, causing sleepiness, and feelings of pleasure. They can be released in response to pain, strenuous exercise, orgasm, or general excitement.
Ethylmorphine has been described as less potent than morphine but slightly more potent than codeine.
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 ☠.
The general head space of ethylmorphine is described by many as one of intense euphoria, relaxation, anxiety suppression and pain relief.
- Pain relief
- Euphoria - This particular substance can be considered as less intense in its physical euphoria when compared with that of morphine or diacetylmorphine (heroin).
- Respiratory depression
- Cough suppression
- Difficulty urinating
- Stomach cramps
- Pupil constriction
- Decreased libido
- Appetite suppression
- Orgasm suppression
- Euphoria - Like codeine, this particular substance can be considered as less intense in its cognitive euphoria when compared with that of morphine or diacetylmorphine (heroin) due to the upper limit of how much can be converted into its active form through metabolism. It is still, however, capable of extreme intensity and overwhelming bliss at heavier dosages with a low tolerance. The sensation itself can be described as powerful and overwhelming feeling of emotional bliss, contentment, and happiness.
- Anxiety suppression
- Compulsive redosing
- Dream potentiation
There are currently no anecdotal reports which describe the effects of this compound within our experience index. Additional experience reports can be found here:
Toxicity and harm potential
Ethylmorphine has a low toxicity relative to dose. However, despite its relatively low toxicity for an opioid, at least one death has been attributed to oral consumption of ethylmorphine alone, without the presence of other depressants. As with all opioids, long-term effects can vary but can include diminished libido, apathy and memory loss. It is also potentially lethal when mixed with depressants like alcohol or benzodiazepines.
It is strongly recommended that one use harm reduction practices when using this drug.
Tolerance and addiction potential
As with other opioids, the chronic use of ethylmorphine can be ethylmorphine very addictive with a high potential for abuse and is capable of causing psychological dependence among certain users. When addiction has developed, cravings and withdrawal symptoms may occur if a person suddenly stops their usage.
Tolerance to many of the effects of ethylmorphine develops with prolonged and repeated use. The rate at which this occurs develops at different rates for different effects, with tolerance to the constipation-inducing effects developing particularly slowly for instance. 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). Ethylmorphine presents cross-tolerance with all other opioids, meaning that after the consumption of ethylmorphine all opioids will have a reduced effect.
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.
- Alcohol - Both substances potentiate the ataxia and sedation caused by the other and can lead to unexpected loss of consciousness at high doses. Place affected patients in the recovery position to prevent vomit aspiration from excess. Memory blackouts are likely
- Amphetamines - Stimulants increase respiration rate which allows for a higher dose of opiates than would otherwise be used. If the stimulant wears off first then the opiate may overcome the user and cause respiratory arrest.
- Benzodiazepines - Central nervous system and/or respiratory-depressant effects may be additively or synergistically present. The two substances potentiate each other strongly and unpredictably, very rapidly leading to unconsciousness. While unconscious, vomit aspiration is a risk if not placed in the recovery position blackouts/memory loss likely.
- Cocaine - Stimulants increase respiration rate, which allows for a higher dose of opiates than would otherwise be used. If the stimulant wears off first then the opiate may overcome the patient and cause respiratory arrest.
- DXM - Generally considered to be toxic. CNS depression, difficulty breathing, heart issues, and liver toxicity have been observed. Additionally if one takes DXM, their tolerance of opiates goes down slightly, thus causing additional synergistic effects.
- GHB/GBL - The two substances potentiate each other strongly and unpredictably, very rapidly leading to unconsciousness. While unconscious, vomit aspiration is a risk if not placed in the recovery position
- Ketamine - Both substances bring a risk of vomiting and unconsciousness. If the user falls unconscious while under the influence there is a severe risk of vomit aspiration if they are not placed in the recovery position.
- MAOIs - Coadministration of monoamine oxidase inhibitors (MAOIs) with certain opioids has been associated with rare reports of severe adverse reactions. There appear to be two types of interaction, an excitatory and a depressive one. Symptoms of the excitatory reaction may include agitation, headache, diaphoresis, hyperpyrexia, flushing, shivering, myoclonus, rigidity, tremor, diarrhea, hypertension, tachycardia, seizures, and coma. Death has occurred in some cases.
- MXE - MXE can potentiate the effects of opioids but also increases the risk of respiratory depression and organ toxicity.
- Nitrous - Both substances potentiate the ataxia and sedation caused by the other and can lead to unexpected loss of consciousness at high doses. While unconscious, vomit aspiration is a risk if not placed in the recovery position. Memory blackouts are common.
- PCP - PCP may reduce opioid tolerance, increasing the risk of overdose.
- Tramadol - Increased risk of seizures. Tramadol itself is known to induce seizures and it may have additive effects on seizure threshold with other opioids. Central nervous system- and/or respiratory-depressant effects may be additively or synergistically present.
- Grapefruit - While grapefruit is not psychoactive, it may affect the metabolism of certain opioids. Tramadol, oxycodone, and fentanyl are all primarily metabolized by the enzyme CYP3A4, which is potently inhibited by grapefruit juice. This may cause the drug to take longer to clear from the body. it may increase toxicity with repeated doses. Methadone may also be affected. Codeine and hydrocodone are metabolized by CYP2D6. People who are on medicines that inhibit CYP2D6, or that lack the enzyme due to a genetic mutation will not respond to codeine as it can not be metabolized into its active product: morphine.
Internationally, Ethylmorphine is listed in the Single Convention on Narcotic Drugs in Schedule III.
- France: Tussipax tablets containing 10 mg of ethylmorphine and 10 mg of codeine are sold over the counter.
- Germany: Ethylmorphine is controlled under BtMG Anlage II, making it illegal to manufacture, import, possess, sell, or transfer it without a license. There is an exception for preparations containing up to 2.5% or up to 100mg ethylmorphine per unit, which can be prescribed on a narcotic prescription form.
- Norway: Cosylan and Solvipect comp. cough syrups containing ethylmorphine hydrochloride 1.7mg/mL and 2.5mg/mL, respectively, are regulated in prescription Class B. They are commonly prescribed for dry cough.
- Russia: Ethylmorphine is a Schedule II controlled substance.
- Sweden: Cocillana-Etyfin cough syrup containing ethylmorphine 2.5mg/mL is sold as a prescription drug. The same goes for Lepheton, a combination containing 0.82 mg/mL ethylmorphine hydrochloride and 2.05 mg/mL ephedrine.
- Switzerland: Ethylmorphine is a controlled substance specifically named under Verzeichnis A. Medicinal use is permitted. Some preparations containing ethylmorphine are included in Verzechnis C, while certain ones are excluded.
- United Kingdom: Ethylmorphine is a Class B controlled substance under the Misuse of Drugs Act. This is the same class as codeine, but unlike codeine, there exist no legal preparations of ethylmorphine.
- United States: No preparations containing ethylmorphine are on the market in the US. Pure ethylmorphine is listed in Schedule II and combination products containing no more than ethylmorphine 3mg/mL (or 15 mg per dosage unit together with a non-narcotic active ingredient) are listed in Schedule III. Preparations containing no more than ethylmorphine 1mg/mL or 1mg/g are listed in schedule V. This is similar to codeine, but unlike codeine, ethylmorphine is not available for medical purposes in the United States.
In general, ethylmorphine and codeine, owing to their structural and pharmacological similarity, are treated similarly by law in most countries.
- Risks of Combining Depressants - TripSit
- Hinshelwood, J. (30 April 1904). "Dionine: A New Ocular Analgesic". Br Med J. 1 (2261): 1009–1010. doi:10.1136/bmj.1.2261.1009-a. ISSN 0007-1447.
- Ethylmorphine , CasNO.76-58-4
- Kintz, P., Jamey, C., Mangin, P. (1 March 1994). "Ethylmorphine concentrations in human samples in an overdose case". Archives of Toxicology. 68 (3): 210–211. doi:10.1007/s002040050057. ISSN 1432-0738.
- Ershad, M., Cruz, M. D., Mostafa, A., Mckeever, R., Vearrier, D., Greenberg, M. I. (March 2020). "Opioid Toxidrome Following Grapefruit Juice Consumption in the Setting of Methadone Maintenance". Journal of Addiction Medicine. 14 (2): 172–174. doi:10.1097/ADM.0000000000000535. ISSN 1932-0620.
- Single Convention on Narcotic Drugs, 2022
- Anlage II BtMG - Einzelnorm
- Постановление Правительства РФ от 01.10.2012 N 1002 (ред. от 09.08.2019)
- Cocillana-Etyfin - FASS Allmänhet
- Lepheton® - FASS Allmänhet
- "Verordnung des EDI über die Verzeichnisse der Betäubungsmittel, psychotropen Stoffe, Vorläuferstoffe und Hilfschemikalien" (in German). Bundeskanzlei [Federal Chancellery of Switzerland]. Retrieved January 1, 2020.
- Misuse of Drugs Act 1971