Fentanyl

From PsychonautWiki
Jump to: navigation, search
Dialog-warning.svg.png

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.[1]

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


Fentanyl
Fentanyl.svg
Chemical Nomenclature
Common names Fentanyl, fentanil, Sublimaze, Actiq, Durogesic, Duragesic, Fentora, Matrifen, Haldid, Onsolis, Instanyl, Abstral, Lazanda
Systematic name N-(1-(2-Phenylethyl)-4-piperidinyl)-N-phenylpropanamide
Class Membership
Psychoactive class Opioid
Chemical class Piperidine
Routes of Administration

WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section.





Sublingual
Dosage
Bioavailability 50%[citation needed]
Threshold 5 - 10 μg
Light 10 - 25 μg
Common 25 - 50 μg
Strong 50 - 75 μg
Heavy 75 μg +
Duration
Total 1 - 4 hours
Onset 15 - 30 minutes
Insufflated
Dosage
Bioavailability 89%[citation needed]
Threshold 5 - 10 μg
Light 10 - 25 μg
Common 25 - 50 μg
Strong 50 - 75 μg
Heavy 75 μg +
Duration
Total 1 - 4 hours
Onset 15 - 30 minutes


Transdermal
Dosage
Bioavailability 92%[citation needed]
Threshold 5 - 12 μg
Light 12 - 25 μg
Common 25 - 50 μg
Strong 50 - 100 μg
Heavy 100 μg +
Duration
Total 48 - 72 hours
Onset 2 - 4 hours




DISCLAIMER: PW's dosage information is gathered from users and resources for educational purposes only. It is not a recommendation and should be verified with other sources for accuracy.

Fentanyl (also known as Fentanil and by the brand names Sublimaze,[2] Actiq, Durogesic, Duragesic, Fentora, Matrifen, Haldid, Onsolis,[3] Instanyl,[4] Abstral,[5] Lazanda[6] among others[7]) is a potent synthetic opioid of the piperidine chemical class that is known to produce analgesia with a rapid onset and short duration of action relative to other opioids (e.g. morphine or heroin) when administered.[8]

Fentanyl 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[9][10] and roughly 80 to 100 times more potent than morphine.[citation needed]

The subjective effects of fentanyl are similar to those of heroin, with the exception that many users report a noticeably less euphoric "high" that is associated with substances in the opioid class along with stronger respiratory depression, sedation and pain relief.

A wide range of pharmaceutical fentanyl preparations are available, including transdermal skin patches, lollipops, buccal tablets or patches, nasal sprays, and inhalers.[11] 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.[12]

History

Fentanyl was first synthesized by Paul Janssen in 1960[13] following the medical inception of pethidine several years earlier. Janssen developed fentanyl by assaying analogues of the structurally related substance pethidine for opioid activity.[14] 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[15] with several new delivery methods now available, including a sublingual spray for cancer patients.[16][17] In 2013, 1700 kilograms were used globally.[18]

Chemistry

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.

Pharmacology

The recreational effects of this compound 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.

Subjective effects

The effects listed below are based upon the subjective effects index and personal experiences of PsychonautWiki contributors. These effects should be taken with a grain of salt and will rarely (if ever) occur all at once, but heavier 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.

Physical effects
Child.svg

Cognitive effects
User.svg

Visual effects
Eye.svg

Experience reports

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

Fentanyl by New Hampshire state police forensic lab - This image serves as a portrayal of lethal doses for heroin and fentanyl.

Non-medical use of fentanyl by individuals without opiate tolerance can be very dangerous and has resulted in numerous deaths.[19][20] 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 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.[21] 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.[22]

Dangerous interactions

Although many substances are safe on their own, they can become dangerous and even life-threatening when combined with other substances. The list below contains some common potentially dangerous combinations, but may not include all of them. Certain combinations may be safe in low doses of each but still, increase the potential risk of death. Independent research should always be done to ensure that a combination of two or more substances is safe before consumption.

  • Depressants (1,4-Butanediol, 2m2b, alcohol, barbiturates, benzodiazepines, GHB/GBL, methaqualone) - This combination can result in dangerous or even fatal levels of respiratory depression. These substances potentiate the muscle relaxation, sedation and amnesia caused by one another and can lead to unexpected loss of consciousness at high doses. There is also an increased risk of vomiting during unconsciousness and death from the resulting suffocation. If this occurs, users should attempt to fall asleep in the recovery position or have a friend move them into it.
  • Dissociatives - This combination can result in an increased risk of vomiting during unconsciousness and death from the resulting suffocation. If this occurs, users should attempt to fall asleep in the recovery position or have a friend move them into it.
  • Stimulants - It is dangerous to combine fentanyl, a depressant, with stimulants due to the risk of excessive intoxication. Stimulants decrease the sedative effect of fentanyl, which is the main factor most people consider when determining their level of intoxication. Once the stimulant wears off, the effects of fentanyl will be significantly increased, leading to intensified disinhibition as well as other effects. If combined, one should strictly limit themselves to taking a certain amount of fentanyl.

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.

Legal status

  • 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).[citation needed]

See also

External links

References

  1. Risks of Combining Depressants (Tripsit) | https://tripsit.me/combining-depressants/
  2. 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
  3. Improving Onsolosis | http://www.onsolis.com/
  4. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Summary_for_the_public/human/000959/WC500033142.pdf
  5. 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
  6. Lazanda (Fentanyl) Nasal Spray CII | https://web.archive.org/web/20170216184309/https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022569s005lbl.pdf
  7. Drugs.com, Fentanyl | http://www.drugs.com/international/fentanyl.html
  8. http://aspi.wisc.edu/wpi/focus/spring96.htm
  9. FENTANYL : Incapacitating Agent | http://www.cdc.gov/niosh/ershdb/EmergencyResponseCard_29750022.html
  10. Mutschler, Ernst; Schäfer-Korting, Monika (2001). Arzneimittelwirkungen (in German) (8 ed.). Stuttgart: Wissenschaftliche Verlagsgesellschaft. p. 286. ISBN 3-8047-1763-2.
  11. Drugs.com Fentanyl Fact Sheet https://www.drugs.com/dosage/fentanyl.html
  12. 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
  13. The history and development of the fentanyl series (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/1517629
  14. A personal perspective on Dr. Paul Janssen (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/15771410
  15. FENTANYL AND ANALOGUES | http://livertox.nih.gov/FentanylAndAnalogues.htm
  16. Subsys (fentanyl sublingual spray) | http://www.centerwatch.com/drug-information/fda-approved-drugs/drug/1179/subsys-fentanyl-sublingual-spray
  17. Long-term Safety and Efficacy Study of Fentanyl Sublingual Spray for the Treatment of Breakthrough Cancer Pain | https://clinicaltrials.gov/ct2/show/NCT00538863
  18. Narcotic Drugs Report 2014, UN | https://www.incb.org/documents/Narcotic-Drugs/Technical-Publications/2014/Narcotic_Drugs_Report_2014.pdf
  19. DEA: Deaths from fentanyl-laced heroin surging | http://www.usatoday.com/story/news/2015/03/18/surge-in-overdose-deaths-from-fentanyl/24957967/
  20. Prince died of accidental overdose of opioid fentanyl, medical examiner says - http://www.cnn.com/2016/06/02/health/prince-death-opioid-overdose/
  21. Why Heroin Relapse Often Ends In Death - Lauren F Friedman (Business Insider) | http://www.businessinsider.com.au/philip-seymour-hoffman-overdose-2014-2
  22. 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
  23. 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