WARNINGDANGER OF DEATH
Most cases of fatal overdose occur when depressants like opioids are combined with other depressants such as alcohol, benzodiazepines or gabapentinoids. It is highly discouraged to combine these substances.
Acrylfentanyl
Acrylfentanyl is a synthetic opioid of the anilinopiperidine class and a structural analog of fentanyl that has been sold online as a designer drug.1 It is reported to be slightly more potent than fentanyl itself, with a longer duration of action. Very little reliable information exists regarding its safe use or dosage parameters. It is considered potentially neurotoxic and carcinogenic,1 and overdose carries significant risk of fatal respiratory depression.2
Dosage & Duration
Dosage
Extreme caution is advised when handling or consuming this substance.
Duration
Subjective Effects
The experience is that of a classic potent opioid: a warm, euphoric mood lift accompanied by pronounced relaxation, pain relief, and sedation, with little to no sensory alteration. As a fentanyl analog, its effect profile closely mirrors that of fentanyl itself, including a serious and potentially life-threatening degree of respiratory depression at higher doses.
Physical
The body feels heavy, relaxed, and free of pain. Typical opioid side effects accompany this, including itchiness, dry mouth, constipation, constricted pupils, and nausea, along with dose-dependent respiratory depression.
Sedation
Uncomfortable
Cognitive
The headspace is dominated by euphoria and an elevated, contented mood rather than any notable alteration of thought or perception.
Pharmacology
Pharmacodynamics
Acrylfentanyl is a highly potent opioid analgesic that acts at the μ-opioid receptor.3 In animal studies, it displaces naloxone with an IC50 of 1.4 nM, making it slightly more potent than fentanyl itself (1.6 nM).3 Because acrylamide derivatives are often used in drug discovery to produce covalent inhibitors that bind irreversibly to their targets, acrylfentanyl has been claimed to be naloxone-resistant.4 However, acute intoxication studies in mice have demonstrated that naloxone can displace acrylfentanyl from the opioid receptor.54
Pharmacokinetics
The metabolism of Acrylfentanyl has been documented. The observed biotransformations were N-dealkylation, monohydroxylation followed by glucuronidation, dihydroxylation followed by glucuronidation, dihydrodiol formation and dihydroxylation with methylation followed by amidehydrolysis.6
Dangerous
Highest riskThese combinations are considered extremely harmful and should always be avoided. Reactions to these drugs taken in combination are highly unpredictable and have a potential to cause death.
Unsafe
AvoidThere is considerable risk of physical harm when taking these combinations, they should be avoided where possible.
Caution
Use cautionThese combinations are not usually physically harmful, but may produce undesirable effects, such as physical discomfort or overstimulation. Extreme use may cause physical health issues. Synergistic effects may be unpredictable. Care should be taken when choosing to use this combination.
Tolerance
Opioids (full cross-tolerance expected with all μ-opioid receptor agonists)
Harm Potential
Addiction & Dependence
Psychological
HighClassified as habit-forming. As a potent fentanyl analog, it carries the high addiction potential characteristic of opioids.7
Toxicity
Acrylfentanyl has been linked to 20 deaths in Sweden and two deaths in Denmark in the summer of 2016. As a class, fentanyl analogs have killed hundreds of people throughout Europe and the former Soviet republics since the resurgence in use beginning in Estonia in the early 2000s.
Has been described as potentially neurotoxic.
Has been described as potentially carcinogenic.
History & Culture
Acrylfentanyl emerged as a novel psychoactive substance in the designer drug market during the mid-2010s as part of a broader wave of illicit fentanyl analogs.8 The compound is a structural analog of fentanyl, featuring an acryloyl group modification, and was…
Legality
International
Acryloylfentanyl is included in Schedule I of the 1961 Single Convention on Narcotic Drugs. UNODC records its international scheduling in 2018.
By Country
References
Source Pages
Citations
- Gasperini S, Bilel S, Cocchi V, Marti M, Lenzi M, & Hrelia P. (2022). The Genotoxicity of Acrylfentanyl, Ocfentanyl and Furanylfentanyl Raises the Concern of Long-Term Consequences. https://doi.org/10.3390/ijms23221440612
- Acryloylfentanyl to be placed under control across the EU. (2017). https://www.euda.europa.eu/news/2017/8/acryloylfentanyl-under-control-accross-eu_en1
- Bruce E. Maryanoff, Eric J. Simon, Theresa Gioannini, & H. Gorissen. (August 1982). Potential affinity labels for the opiate receptor based on fentanyl and related compounds. Journal of Medicinal Chemistry, 25(8), 913–919. https://doi.org/10.1021/jm00350a00612
- Michael G. Feasel, Theodore S. Moran, Boyle C. Cheng, & Saadyah Averick. (2024). Are carfentanil and acrylfentanyl naloxone resistant?. 15, 1359851. https://doi.org/10.3389/fpsyt.2024.135985112
- Sabrine Bilel, Joaquim Azevedo Neto, Raffaella Arfè, Micaela Tirri, Rosa Maria Gaudio, Anna Fantinati, Tatiana Bernardi, Federica Boccuto, Beatrice Marchetti, Giorgia Corli, Giovanni Serpelloni, Fabio De-Giorgio, Davide Malfacini, Claudio Trapella, Girolamo Calo’, & Matteo Marti. (May 2022). In vitro and in vivo pharmaco-dynamic study of the novel fentanyl derivatives: Acrylfentanyl, Ocfentanyl and Furanylfentanyl. Neuropharmacology, 209. https://doi.org/10.1016/j.neuropharm.2022.1090201
- Shimpei Watanabe, Svante Vikingsson, Markus Roman, Henrik Green, Robert Kronstrand, & Ariane Wohlfarth. (2017). In Vitro and In Vivo Metabolite Identification Studies for the New Synthetic Opioids Acetylfentanyl, Acrylfentanyl, Furanylfentanyl, and 4-Fluoro-Isobutyrylfentanyl. https://doi.org/10.1208/s12248-017-0070-z1
- Wilde M, Pichini S, Pacifici R, Tagliabracci A, Busardò FP, Auwärter V, & Solimini R. (2019). Metabolic Pathways and Potencies of New Fentanyl Analogs. https://doi.org/10.3389/fphar.2019.002381
- Report on the risk assessment of N-(1-phenethylpiperidin-4-yl)-N-phenylacrylamide (acryloylfentanyl) in the framework of the Council Decision on new psychoactive substances. European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) (2017). https://www.drugsandalcohol.ie/28294/1/EMCDDA_Acrloylfentanyl.pdf123
- Torben Breindahl, Andreas Kimergård, Mette Findal Andreasen, & Daniel Sejer Pedersen. (March 2017). Identification of a new psychoactive substance in seized material: the synthetic opioid N-phenyl-N-[1-(2-phenethyl)piperidin-4-yl]prop-2-enamide (Acrylfentanyl). Drug Testing and Analysis, 9(3), 415–422. https://doi.org/10.1002/dta.20461
- Controlled Drugs and Substances Act, Schedule I. laws-lois.justice.gc.ca (n.d.). https://laws-lois.justice.gc.ca/eng/acts/C-38.8/FullText.html1
- Betäubungsmittelgesetz, Anlage I. gesetze-im-internet.de (n.d.). https://www.gesetze-im-internet.de/btmg_1981/BJNR106810981.html1
- Ley General de Salud. diputados.gob.mx (n.d.). https://www.diputados.gob.mx/LeyesBiblio/pdf/LGS.pdf1
- Opiumwet. wetten.overheid.nl (n.d.). https://wetten.overheid.nl/BWBR0001941/1
- First Schedule, Misuse of Drugs Act 1973. sso.agc.gov.sg (n.d.). https://sso.agc.gov.sg/Act/MDA1973?ProvIds=Sc1-1
- First Schedule, Misuse of Drugs Act 1973. sso.agc.gov.sg (n.d.). https://sso.agc.gov.sg/Act/MDA1973?ProvIds=pr5-1
- Förordning (1992:1554) om kontroll av narkotika. riksdagen.se (n.d.). https://www.riksdagen.se/sv/dokument-och-lagar/dokument/svensk-forfattningssamling/forordning-19921554-om-kontroll-av-narkotika_sfs-1992-1554/1
- Misuse of Drugs Act 1971 and Misuse of Drugs Regulations 2001. gov.uk (n.d.). https://www.gov.uk/government/publications/controlled-drugs-list--2/list-of-most-commonly-encountered-drugs-currently-controlled-under-the-misuse-of-drugs-legislation1
- Schedules of Controlled Substances: Placement of Furanyl Fentanyl, 4-Fluoroisobutyryl Fentanyl, Acryl Fentanyl, Tetrahydrofuranyl Fentanyl, and Ocfentanil in Schedule I. federalregister.gov (2018-11-29). https://www.federalregister.gov/documents/2018/11/29/2018-26045/schedules-of-controlled-substances-placement-of-furanyl-fentanyl-4-fluoroisobutyryl-fentanyl-acryl12
- Controlled Substance Schedules. DEA Diversion Control Division, U.S. Department of Justice (n.d.). https://www.deadiversion.usdoj.gov/schedules/schedules.html1
Further Reading
Guerrieri et al. 2017 - Acrylfentanyl: Another new psychoactive drug with fatal consequences- Helander et al. 2018 - Intoxications involving acrylfentanyl in Sweden
Reddit r/researchchemicals - PSA: Acrylfentanyl user reports on naloxone resistance (2017)
UNODC: Early Warning Advisory - Analytical Report on Acrylfentanyl (2017)- Watanabe et al. 2017 - Acrylfentanyl: metabolism, potency and forensic cases
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