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WARNINGDANGER OF DEATH
High doses alone or ordinary doses in combination with other depressants can fatally stop breathing.
Fentanyl
N-(1-Phenethylpiperidin-4-yl)-N-phenylpropanamide
Fent, Fenty, Fetty, Apache, China Girl
Fentanyl is a synthetic opioid1 of the anilidopiperidine class first synthesized by Paul Janssen in 19602 and approved for medical use in the United States in 19682. It is approximately 50 to 100 times more potent than morphine1 and is used clinically for breakthrough cancer pain and intraoperative analgesia2. Fentanyl is widely encountered as an adulterant in illicit drug supplies, particularly heroin, though also as an adulterant in other substances like cocaine and methamphetamine1, where its extreme potency has contributed to numerous accidental overdoses and fatalities1.
Dosage & Duration
Dosage
Doses are population estimates that vary widely between individuals.
Threshold~5 µg
Light5-25 µg
Moderate25-50 µg
Strong50-75 µg
Heavy75+ µg
Bioavailability
~64%
Due to the compound's extreme potency, accurate measurement is critical and the margin for error is very narrow. The risk of fatal overdose is high, particularly from respiratory depression. Individuals without opioid tolerance should use substantially lower starting amounts.
Duration
Onset5-15 minutes
Total1-4 hours
Subjective Effects
Legacy content. A statistically backed ontology from Mindstate Design Labs is coming soon.
Effects vary widely by individual, dose, and context.
Physical
Cognitive
Pharmacology
Pharmacodynamics
Fentanyl activates the μ-opioid, δ-opioid and κ-opioid receptors, though with considerably lower affinity and relatively modest functional contribution at the latter two sites.8 μ-opioid receptor activation triggers G-protein-coupled signaling that inhibits neuronal activity through decreased cAMP production and altered ion conductance.9 Its exceptionally high lipid solubility enables rapid penetration of the central nervous system and may play part in its potency.10
Pharmacokinetics
Fentanyl undergoes extensive first-pass metabolism when taken orally, predominantly via CYP3A4-catalyzed N-dealkylation to norfentanyl, which accounts for approximately 99% of its biotransformation.1112 Minor pathways include amide hydrolysis and alkyl hydroxylation.12 All known metabolites are pharmacologically inactive.13 Fentanyl is 80 to 85% bound to plasma proteins and fentanyl does not bind to plasma cells, mostly binding to α-1-acid glycoprotein but also attaches to albumin and lipoproteins.1314 with a terminal half-life of approximately 7 hours.1315 Within 72 hours, roughly 75% of a dose is excreted in urine (less than 7% unchanged) and 9% in feces.16 Formulation-specific plasma timing is not subjective effect duration. LAZANDA nasal spray has a median Tmax of 15 to 21 minutes after a single dose,4 and SUBSYS sublingual spray has a median Tmax of 0.67 to 1.25 hours.5 Transdermal-system concentrations generally level off between 12 and 24 hours for the remainder of the 72-hour application period.7
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
Tolerance timelines are rules of thumb, not exact schedules, and vary widely between individuals and use patterns.
Full Tolerance
Ongoing repeated fentanyl exposure can reduce responsiveness to many of its effects. This does not occur at the same speed for every effect; constipation-related tolerance tends to build particularly slowly compared with opioid effects such as euphoria and analgesia.
Baseline Reset
1-2 weeks
Half Tolerance
3-7 days
Cross Tolerance
All other opioids
Harm Potential
Addiction & Dependence
Psychological
Extremely HighFentanyl is considered extremely addictive with a high potential for abuse.1718
Physical
Extremely HighPhysical dependence develops with regular use.17 Withdrawal symptoms are severe and include diarrhea, nausea, sleep disorders, photophobia, autonomic hyperactivity runny nose, yawning and goosebumps.19
Toxicity
Respiratory System
The primary acute danger is respiratory depression, which at overdose levels can cause anoxia, respiratory arrest, and death; this risk is substantially heightened in opioid-naive individuals and when combined with other CNS depressants.citation needed Wooden chest syndrome, a sudden rigidity of abdominal muscles and diaphragm causing complete respiratory failure, can occur with high doses.
Cardiovascular
Acute cardiovascular effects including vasodilation occur during intoxication; this is generally not associated with long-term cardiac damage at appropriate doses and do not significantly affect cardiac contractility at regular doses.citation needed
Gastrointestinal
Constipation is one of the few long-term complications associated with appropriate fentanyl use; tolerance to this effect develops particularly slowly compared to other opioid effects.citation needed
Psychosis Risk
Hallucinations, delirium (including narcotic delirium), and confusion have been reported as adverse effects.1520 Post-acute withdrawal may include psychosis in extreme cases. These effects are relatively uncommon during typical use and are more associated with high doses, overdose, or withdrawal states.
Seizure Risk
Seizures are documented as a severe withdrawal symptom following chronic use and abrupt discontinuation, rather than as a direct effect of fentanyl intoxication.20 Withdrawal should be conducted gradually under medical supervision to minimize seizure risk.
History & Culture
Discovery and Synthesis
Fentanyl was first synthesized in 1959 by Belgian scientist Paul Janssen at Janssen Pharmaceutica, his relatively newly established pharmaceutical company.citation needed The compound was developed through systematic screening of chemical analogues of pethidine (marketed as Demerol) for enhanced…
Legality
International
Fentanyl is a narcotic drug in Schedule I of the 1961 Single Convention as amended. It is not listed as a psychotropic substance in the 1971 Convention schedules and is not a listed precursor chemical in the 1988 Convention Tables I or II.
By Country
Illegal4
FinlandIllegalFentanyl is listed in Annex I to Government Decree 543/2008 on substances, preparations and plants regarded as narcotics. Under Finland's Narcotics Act, narcotics may not be produced, imported, exported, transported, transited, distributed, traded, possessed, or used except as permitted for medical, scientific, or other statutory purposes.
New ZealandIllegalMisuse of Drugs Act 197548
Fentanyl is listed as a Class A controlled drug in Schedule 1 of the Misuse of Drugs Act 1975. The Act makes the unauthorised import, export, production, manufacture, supply, administration, sale, and possession of a Class A controlled drug an offence.
PhilippinesIllegalFentanyl is a dangerous drug under the Comprehensive Dangerous Drugs Act of 2002 because the Act incorporates the schedules annexed to the 1961 Single Convention on Narcotic Drugs, whose Schedule I lists fentanyl. Unauthorized importation, sale, delivery, manufacture, possession, and use of dangerous drugs are criminal offences; the Act preserves authorized medical use by licensed practitioners.
SingaporeIllegalMisuse of Drugs Act 197364
Fentanyl is listed as a Class A controlled drug in the First Schedule to Singapore's Misuse of Drugs Act 1973. The Act treats unauthorised possession, trafficking, manufacture, and import or export of controlled drugs as offences, subject to its statutory authorisations. The Class A entry also covers fentanyl compounds structurally derived from N-(1-Methyl-4-piperidyl)-N-phenyl formamide and salts of substances within that entry.
Controlled / restricted1
SpainRestrictedFentanilo is a Lista I narcotic drug under the Single Convention framework applied in Spain by Ley 17/1967. Article 2(1) of that law treats substances in Convention Lists I and II as estupefacientes, while the AEMPS states that Lista I substances are subject to rigorous control and require an official narcotics prescription for dispensing. Authorised industrial, therapeutic, scientific and teaching uses remain permitted; this is not a blanket prohibition.
Prescription19
United StatesPrescription only21 CFR 1308.12(c), Schedule II74
Controlled under the Controlled Substances Act as a Schedule II opiate.7576 FDA approved for medical use since 1968. Illegal to sell without a DEA license and illegal to possess without a valid prescription. Certain formulations such as Abstral require distributors to implement FDA-approved risk evaluation and mitigation strategy (REMS) programs.
ArgentinaPrescription onlyFentanilo is listed in Lista I of Resolución 2622/88, which updates the controlled-narcotic lists under Ley 17.818. It is a medicinal substance used in human medicine and is prescribed for severe acute or chronic pain; non-medical use is illegal. The list also controls the substance's possible isomers, esters, ethers, and salts under the terms stated in the annex.
AustraliaPrescription onlyTherapeutic Goods (Poisons Standard—October 2025) Instrument 2025, Schedule 826
Classified as a Schedule 8 controlled drug, meaning it is available for legitimate medical use under strict prescription controls.27 Additionally designated as a border controlled substance under Criminal Code Act 9.1.314, with further restrictions imposed by individual states and territories. Unauthorized possession, production, or supply is prohibited.
BelgiumPrescription onlyRoyal Decree of 6 September 2017 regulating narcotic and psychotropic substances (consolidated Justel text)3031
Fentanyl is controlled in Annex I of Belgium’s Royal Decree of 6 September 2017, which incorporates the 1961 Convention Yellow List. The decree requires prior authorization for dealing in listed products and limits that authorization to medical or scientific purposes. A pharmacist may dispense an Annex I medicine to the public only on a lawfully obtained, signed, and dated medical prescription; that prescription must state the prescriber’s address, dose, number of units, dosage, and, where applicable, treatment duration.
BrazilPrescription onlyFentanyl (fentanila) is listed in Lista A1 of Portaria SVS/MS nº 344/1998 as a narcotic subject to Notificação de Receita A. Dispensing a medicine containing a Lista A1 substance requires that prescription notification, and the pharmacy or drugstore may dispense it only when the notification and prescription are properly completed. Activities involving the controlled substance or medicines containing it require special authorization under the regulation.
CanadaPrescription onlyControlled Drugs and Substances Act, Schedule I, item 1634
Controlled under Schedule I of the Controlled Drugs and Substances Act.35 Medical use requires prescription. In some jurisdictions such as Ontario, patients prescribed fentanyl patches must return used patches to pharmacies before receiving prescription refills as a diversion prevention measure.
Czech RepublicPrescription onlyFentanyl is listed in Annex 1 of the Government Regulation’s controlled-substances schedules. The Act classifies substances in Annexes 1–7 as controlled narcotic or psychotropic substances. A person acquires a controlled medicinal preparation for personal use only on a prescription or through a health-care provider. Annex 1 medicinal products are prescribed and dispensed only on an e-prescription marked ‘vysoce návyková látka’ or, exceptionally, a blue-stripe paper prescription.
IrelandPrescription onlyFentanyl is listed in Schedule 2 of the Misuse of Drugs Regulations 2017, which have applied since 4 May 2017. Unauthorised production, supply, importation and exportation of a controlled drug are prohibited, and unauthorised possession is an offence. Schedule 2 fentanyl may be possessed for medical, dental or veterinary administration under a practitioner's directions and supplied by authorised practitioners and pharmacists.
MexicoPrescription onlyLey General de Salud45
Fentanyl is classified as an estupefaciente in Article 234 of Mexico's Ley General de Salud. Acts involving estupefacientes are subject to the law's health-control regime, and medical prescriptions for them must use special prescription forms issued to authorized professionals.
PolandPrescription onlyRozporządzenie Ministra Zdrowia z dnia 17 sierpnia 2018 r. w sprawie wykazu substancji psychotropowych, środków odurzających oraz nowych substancji psychoaktywnych (Dz.U. 2018 poz. 1591), załącznik nr 25152
Fentanyl is listed in Group I-N of the Polish Minister of Health's controlled-narcotics schedule, which entered into force on 21 August 2018. Group I-N narcotics may be used only for medical, industrial, or research purposes. Medicinal preparations containing narcotics are dispensed by pharmacies only on a specially marked prescription or requisition, and unauthorized possession is punishable by imprisonment of up to three years.
RussiaPrescription onlyGovernment Resolution No. 681 of 30 June 1998 (current consolidated heading: edition 11 June 2025, amendments effective 27 July 2025), List II; Federal Law No. 3-FZ of 8 January 1998, Article 31; Ministry of Health Order No. 1094n of 24 November 2021 (prescribing and prescription forms, effective through 1 March 2028); Ministry of Health Order No. 100n of 7 March 2025, Annex 2 (dispensing rules, effective 1 September 2025 through 1 September 2031); Government Resolution No. 1002 of 1 October 2012 (criminal-law quantity thresholds, edition 11 June 2025); Criminal Code Articles 228 and 228.1 (edition 4 August 2026).5354555657585960616263
Only Russian-registered medicinal products may be used medically; the current dispensing rule additionally requires a licensed entity authorized for narcotics circulation and the specified prescription/medical-organization route. Fentanyl patches are List II transdermal systems and therefore use the form 148-1/у-88 exception under Order 1094n; other List II fentanyl forms follow the special 107/у-НП/e-prescription route, subject to the product's registered form and rules. Criminal quantity thresholds are the fentanyl-specific 0.002 g / 0.01 g / 2 g values, while fentanyl-N-oxide and other derivatives require their own exact legal entry.
SwitzerlandPrescription onlyBetäubungsmittelverzeichnisverordnung des EDI (BetmVV-EDI), Verzeichnis a68
Specifically named in Verzeichnis A (List A) of controlled substances. Medicinal use is permitted with appropriate authorization, but non-medical possession and supply are prohibited.
TurkeyRed prescription onlyDesignated as a 'red prescription' substance, the most restricted prescription category in Turkey.69 Illegal to sell or possess without a valid prescription from an authorized physician.
UkrainePrescription onlyCabinet of Ministers of Ukraine Resolution No. 770 of 6 May 2000, On Approval of the List of Narcotic Drugs, Psychotropic Substances and Precursors7071
Fentanyl is listed in Table II, List No. 1 of Ukraine's List of Narcotic Drugs, Psychotropic Substances and Precursors, whose circulation is restricted. Narcotic medicines are dispensed through licensed pharmacies on a prescription issued by a treating physician.
References
Source Pages
Citations
- Fentanyl. Centers for Disease Control and Prevention (2025-06-09). https://www.cdc.gov/overdose-prevention/about/fentanyl.html1234
- Theodore H. Stanley. (2014). The Fentanyl Story. The Journal of Pain, 15(12), 1215-1226. https://doi.org/10.1016/j.jpain.2014.08.010123
- PsychonautWiki. psychonautwiki.org (n.d.). https://psychonautwiki.org/wiki/Fentanyl/Summary123
- LAZANDA (fentanyl) nasal spray, US prescribing information. dailymed.nlm.nih.gov (n.d.). https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=73f38bde-2132-2b5a-e053-2a91aa0a6efb12
- SUBSYS (fentanyl sublingual spray), US prescribing information. dailymed.nlm.nih.gov (n.d.). https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=18a413e9-11e0-4a8f-86c0-d33b37b7b771123
- TripSit Wiki. wiki.tripsit.me (n.d.). https://wiki.tripsit.me/wiki/Fentanyl1
- Fentanyl Transdermal System, US prescribing information. dailymed.nlm.nih.gov (n.d.). https://dailymed.nlm.nih.gov/dailymed/downloadpdffile.cfm?setId=b12fc2d1-555b-4a44-87f6-a2421324b2de12
- Donna A. Volpe, Grainne A. McMahon Tobin, R. Daniel Mellon, Aspandiar G. Katki, Robert J. Parker, Thomas Colatsky, Timothy J. Kropp, & S. Leigh Verbois. (2011). Uniform assessment and ranking of opioid Mu receptor binding constants for selected opioid drugs. https://doi.org/10.1016/j.yrtph.2010.12.00712
- Dhaliwal A, Gupta M. Physiology, Opioid Receptor. (n.d.). https://www.ncbi.nlm.nih.gov/books/NBK546642/1
- Eamonn Kelly, Katy Sutcliffe, Damiana Cavallo, Nokomis Ramos‐Gonzalez, Norah Alhosan, & Graeme Henderson. (2021). The anomalous pharmacology of fentanyl. https://doi.org/10.1111/bph.155731
Further Reading
Article Status
Step 1 · Automated synthesisAn autonomous workflow built by Josie Kins compiled this article's foundation from information published across the web.
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A first pass manual review and edit of article prose and copy has been performed by subject-matter expert Lyrea. This does not guarantee factual accuracy. An additional human review for each of this article's citations is yet to be performed.
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Lyrea · Added a source: Fentanyl-Induced Chest Wall Rigidity
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