This substance is extraordinarily potent (i.e. active in the microgram range), to the point that the pure powder can result in a fatal overdose if spilled on one's skin. For this reason, it should never be eyeballed. Fentanyl can also be fatal when combined with depressants such as opiates, benzodiazepines, barbiturates, gabapentinoids, thienodiazepines or other GABAergic substances.
It is strongly encouraged to wear gloves while handling, use volumetric dosing combined with a milligram scale, and to not consume either moderate or heavy dosages of other depressants in combination with this drug.
|Summary sheet: Fentanyl|
|Common names||Fentanyl, fentanil, Sublimaze, Actiq, Durogesic, Duragesic, Fentora, Matrifen, Haldid, Onsolis, Instanyl, Abstral, Lazanda|
|Routes of Administration|
|Selective serotonin re-uptake inhibitors|
|Serotonin-norepinephrine reuptake inhibitors|
Fentanyl (also known as Fentanil and by the brand names Sublimaze, Actiq, Durogesic, Duragesic, Fentora, Matrifen, Haldid, Onsolis, Instanyl, Abstral, Lazanda among others) is a potent opioid substance of the piperidine class. It is a strong agonist at the μ-opioid receptors and approximately 40 to 50 times more potent than pharmaceutical grade (i.e. 100% pure) heroin and roughly 80 to 100 times more potent than morphine.
A wide range of pharmaceutical fentanyl preparations are available, including transdermal skin patches, lollipops, buccal tablets or patches, nasal sprays, and inhalers. On the street, it is typically encountered in powder form, where it is often cut into or sold as heroin and other drugs, which has resulted in numerous accidental overdoses and fatalities. In 2016, fentanyl and analogues were the most common cause of overdose deaths in the United States at more than 20,000, about half of all opioid-related deaths.
Subjective effects are similar to those of heroin and includes pain relief (analgesia), sedation, respiratory depression, and euphoria. However, it has a rapid onset and short duration of action relative to other opioids, which can lead to compulsive redosing. Additionally, many users report noticeably less euphoria with fentanyl and its analogs. As a result, it is generally considered to have low recreational value.
Fentanyl is a highly dangerous substance due its addictiveness and the difficulty with which it can be safely dosed, a result of its incredible potency. Users are advised to be aware of the extreme risk they are placing themselves in if they choose to use fentanyl. Users are also advised to test all of their opioids (and substances in general) for fentanyl and other adulterants using reagent testing kits.
- 1 History and culture
- 2 Chemistry
- 3 Pharmacology
- 4 Subjective effects
- 5 Toxicity and harm potential
- 6 Legal status
- 7 See also
- 8 External links
- 9 References
History and culture
Fentanyl was first synthesized by Paul Janssen in 1960 following the medical inception of pethidine several years earlier. Janssen developed fentanyl by assaying analogues of the structurally related substance pethidine for opioid activity. The widespread use of fentanyl triggered the production of fentanyl citrate which entered the clinical practice as a general anesthetic under the trade name Sublimaze in the 1960s. Following this, many other fentanyl analogues were developed and introduced into medical practice, including sufentanil, alfentanil, remifentanil, and carfentanil.
In the mid-1990s, fentanyl was first introduced for widespread palliative use with the clinical introduction of the Duragesic patch. It was followed in the next decade by the introduction of the first quick-acting prescription formulations of fentanyl for personal use, the Actiq lollipop and Fentora buccal through the delivery method of estradiol Mylan transdermal patches. As of 2012, fentanyl was the most widely used synthetic opioid in clinical practice with several new delivery methods now available, including a sublingual spray for cancer patients. In 2013, 1700 kilograms were used globally.
Fentanyl is a member of the phenylpiperidine class of synthetic opioids. Its structure features a piperidine ring bound at its nitrogen constituent RN to a phenyl ring through an ethyl chain. The opposite carbon of the piperidine ring is bonded to the nitrogen member of a propanamide group, a three carbon chain with a nitrogen constituent adjacent to a carbon bonded to a ketone oxygen. This propanamide group is also substituted with an additional phenyl ring at RN.
The recreational effects of fentanyl occur 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.
Fentanyl's strong potency compared to that of morphine is mainly due to its high lipophilicity (the ability of a chemical compound to dissolve in fats, oils, and lipids). Because of this, it can more easily penetrate the central nervous system in comparison to other opioids.
Disclaimer: The effects listed below are cited from the subjective effect index, which is based on anecdotal reports and the personal experiences of PsychonautWiki contributors. As a result, they should be treated with a healthy degree of skepticism. It is worth noting that these effects will rarely (if ever) occur all at once, although higher doses will increase the chances of inducing a full range of effects. Likewise, adverse effects become much more likely on higher doses and may include serious injury or death.
- Sedation - Fentanyl can be described as much more sedating then other opiates. Even at moderate dosages, fentanyl can result in overwhelming feelings of sedation and tiredness that is considerably more sedating than that of heroin and oxycodone.
- Pain relief - In comparison to other opiates, fentanyl can be described as a strong analgesic, providing relief even at non-recreational doses.
- Physical euphoria - Fentanyl can be considered as less intense in its physical euphoria when compared with that of morphine or diacetylmorphine (heroin). The sensation itself can be described as strong feelings of intense physical comfort, warmth and bliss which spread throughout the body.
- Itchiness - Unlike other opioids, fentanyl presents very little itch response due to little to no amounts of released histamines.
- Respiratory depression - In comparison to other opiates, fentanyl displays this effect at lower doses relative to euphoria then other opiates, and even at low doses results in the sensation that the breath is slowed down mildly to moderately, but does not cause noticeable impairment. At high doses and overdoses, opioid-induced respiratory depression can result in a shortness of breath, abnormal breathing patterns, semi-consciousness, or unconsciousness. Severe overdoses can result in a coma or death without immediate medical attention.
- Cough suppression
- Decreased libido
- Difficulty urinating
- Pupil constriction
- Increased perspiration
- Decreased blood pressure
- Appetite suppression
- Orgasm suppression
- Cognitive euphoria - Fentanyl can be considered less intense in its cognitive euphoria when compared with that of morphine or 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
- Double vision - At high doses, the eyes un-focus and re-focus uncontrollably. This creates a blurred effect and double vision that is present no matter where one focuses their eyes.
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
Non-medical use of fentanyl by individuals without opiate tolerance can be very dangerous and has resulted in numerous deaths. It is potentially fatal at heavy dosages and even those with opiate tolerances are at high risk for overdoses. Once the fentanyl is in the user's system, it is extremely difficult to stop its course because of the nature of absorption. Because of the extremely high strength of pure fentanyl powder, it is very difficult to dilute appropriately, and often the resulting mixture may be far too strong and, therefore, very dangerous. It is also potentially lethal when mixed with depressants like alcohol or benzodiazepines.
Like most opioids, pure fentanyl at appropriate dosages does not cause many long-term complications other than dependence and constipation. Outside of the extremely powerful addiction and physical dependence, the harmful or toxic aspects of opioid usage are exclusively associated with not taking the necessary precautions in regards to its administration, overdosing and using impure products.
It is important to consider that particular care must be taken with fentanyl due to its extreme potency and ability to be absorbed through the skin. This means that simply unintentionally spilling a very small amount of fentanyl on one's skin could result in a fatal overdose.
Heavy dosages of fentanyl can result in respiratory depression, leading onto fatal or dangerous levels of anoxia (oxygen deprivation). This occurs because the breathing reflex is suppressed by agonism of µ-opioid receptors proportional to the dosage consumed.
Fentanyl can also cause nausea and vomiting; a significant number of deaths attributed to opioid overdose are caused by aspiration of vomit by an unconscious victim. This is when an unconscious or semi-conscious user who is lying on their back vomits into their mouth and unknowingly suffocates. It can be prevented by ensuring that one is lying on their side with their head tilted downwards so that the airways cannot be blocked in the event of vomiting while unconscious (also known as the recovery position). In the case of an overdose, it is advised to administer a dose of naloxone intravenously or intramuscularly to counteract the effects of the substance.
It is strongly recommended that one use harm reduction practices when using this substance.
Tolerance and addiction potential
As with other opioids, the chronic use of fentanyl can be considered extremely addictive with a high potential for abuse and is capable of causing psychological and physical 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 fentanyl 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). Fentanyl presents cross-tolerance with all other opioids, meaning that after the consumption of fentanyl all opioids will have a reduced effect.
The risk of fatal opioid overdoses rise sharply after a period of cessation and relapse, largely because of reduced tolerance. To account for this lack of tolerance, it is safer to only dose a fraction of one's usual dosage if relapsing. It has also been found that the environment one is in can play a role in opioid tolerance. In one scientific study, rats with the same history of heroin administration were significantly more likely to die after receiving their dose in an environment not associated with the substance in contrast to a familiar environment.
Although many psychoactive substances are reasonably safe to use on their own, they can quickly become dangerous or even life-threatening when taken with other substances. The following lists some known dangerous combinations, but cannot be guaranteed to include all of them. Independent research should always be conducted to ensure that a combination of two or more substances is safe to consume. Some interactions listed 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 - CNS depression, difficult breathing, heart issues, hepatoxic, just very unsafe combination all around. 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 and fatal 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 - This combination can potentiate the effects of the opioid
- 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 likely.
- PCP - PCP can reduce opioid tolerance, increasing the risk of overdose.
- Tramadol - Concomitant use of tramadol increases the seizure risk in patients taking other opioids. These agents are often individually epileptogenic and may have additive effects on seizure threshold during coadministration. Central nervous system- and/or respiratory-depressant effects may be additively or synergistically present
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 syrian rue, banisteriopsis caapi, 2C-T-7, αMT, phenelzine, selegiline, and moclobemide
- Serotonin releasers such as MDMA, 4-FA, methamphetamine, methylone and αMT
- Selective serotonin re-uptake inhibitors (SSRIs)
- Serotonin-norepinephrine reuptake inhibitors (SNRIs) such as tramadol and DXM
- Austria: Fentanyl is legal for medical use under the AMG (Arzneimittelgesetz Österreich) and illegal when sold or possessed without a prescription under the SMG (Suchtmittelgesetz Österreich).
- Australia: Fentanyl is placed under Schedule 8, meaning that it is available for medical use, but possession, production or supply of it is illegal without authority. 
- Canada: Fentanyl is a Schedule I drug in Canada's Controlled Drugs and Substance Act.
- Germany: Fentanyl is a controlled substance under Anlage III of the BtMG. It can only be prescribed on a narcotic prescription form.
- Netherlands: Fentanyl is a List I substance of the Opium Law.
- Russia: Fentanyl is a Schedule II controlled substance.
- United Kingdom: Fentanyl is a controlled Class A drug under the Misuse of Drugs Act 1971.
- United States: Fentanyl is a Schedule II controlled substance per the Controlled Substance Act. Distributors of Abstral are required to implement an FDA-approved risk evaluation and mitigation strategy (REMS) program. Health insurers have begun to require precertification and/or quantity limits for Actiq prescriptions.
- Risks of Combining Depressants (Tripsit) | https://tripsit.me/combining-depressants/
- SUBLIMAZE Injection | https://web.archive.org/web/20170702004717/http://www.janssen.com/australia/sites/www_janssen_com_australia/files/prod_files/live/sublimaze_pi.pdf
- Improving Onsolosis | http://www.onsolis.com/
- European public assessment report (EPAR) for Instanyl | http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Summary_for_the_public/human/000959/WC500033142.pdf
- Lazanda (Fentanyl) Nasal Spray CII | https://web.archive.org/web/20170216184309/https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022569s005lbl.pdf
- Drugs.com, Fentanyl | http://www.drugs.com/international/fentanyl.html
- FENTANYL : Incapacitating Agent | http://www.cdc.gov/niosh/ershdb/EmergencyResponseCard_29750022.html
- Mutschler, Ernst; Schäfer-Korting, Monika (2001). Arzneimittelwirkungen (in German) (8 ed.). Stuttgart: Wissenschaftliche Verlagsgesellschaft. p. 286. ISBN 3-8047-1763-2.
- Drugs.com Fentanyl Fact Sheet https://www.drugs.com/dosage/fentanyl.html
- SAMHSA "Fact Sheet: Fentanyl-Laced Heroin and Cocaine" https://www.samhsa.gov/sites/default/files/programs_campaigns/medication_assisted/dear_colleague_letters/2013-colleague-letter-fentanyl-analogues.pdf
- "Nearly half of opioid-related overdose deaths involve fentanyl". National Institute on Drug Abuse. 2018-05-01. Archived from the original on 2018-06-14. Retrieved 2018-06-14.
- Hedegaard, H; Bastian, BA; Trinidad, JP; Spencer, M; Warner, M (December 2018). "Drugs Most Frequently Involved in Drug Overdose Deaths: United States, 2011-2016". National Vital Statistics Reports : From the Centers for Disease Control and Prevention, National Center for Health Statistics, National Vital Statistics System. 67 (9): 1–14. PMID 30707673.
- The history and development of the fentanyl series (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/1517629
- A personal perspective on Dr. Paul Janssen (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/15771410
- FENTANYL AND ANALOGUES | http://livertox.nih.gov/FentanylAndAnalogues.htm
- Subsys (fentanyl sublingual spray) | http://www.centerwatch.com/drug-information/fda-approved-drugs/drug/1179/subsys-fentanyl-sublingual-spray
- Long-term Safety and Efficacy Study of Fentanyl Sublingual Spray for the Treatment of Breakthrough Cancer Pain | https://clinicaltrials.gov/ct2/show/NCT00538863
- Narcotic Drugs Report 2014, UN | https://www.incb.org/documents/Narcotic-Drugs/Technical-Publications/2014/Narcotic_Drugs_Report_2014.pdf
- DEA: Deaths from fentanyl-laced heroin surging | http://www.usatoday.com/story/news/2015/03/18/surge-in-overdose-deaths-from-fentanyl/24957967/
- Prince died of accidental overdose of opioid fentanyl, medical examiner says - http://www.cnn.com/2016/06/02/health/prince-death-opioid-overdose/
- Why Heroin Relapse Often Ends In Death - Lauren F Friedman (Business Insider) | http://www.businessinsider.com.au/philip-seymour-hoffman-overdose-2014-2
- Siegel, S., Hinson, R., Krank, M., & McCully, J. (1982). Heroin “overdose” death: contribution of drug-associated environmental cues. Science, 216(4544), 436–437. https://doi.org/10.1126/science.7200260
- Gillman, P. K. (2005). Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity. British Journal of Anaesthesia, 95(4), 434-441. https://doi.org/10.1093/bja/aei210
- Canada's Controlled Drugs and Substances Act | https://laws.justice.gc.ca/eng/acts/C-38.8/page-12.html#h-34
- Постановление Правительства РФ от 01.10.2012 N 1002 (ред. от 09.08.2019) | https://www.consultant.ru/cons/cgi/online.cgi?req=doc&base=LAW&n=331879&dst=100294&date=03.12.2019
- Misuse of Drugs Act 1971 | http://www.legislation.gov.uk/ukpga/1971/38/schedule/2