Fentanyl

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This substance is extraordinarily potent (i.e. active in the microgram range). For this reason, it should be handled with extreme care and 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

{{#arraydefine: InhaledDosage | Threshold;, Light;, Common;, Strong;, Heavy; }} {{#arraydefine: InhaledDuration | Total;, Onset;, Come up;, Peak;, Offset;, After effects; }} {{#arraydefine: SmokedDosage | Threshold;, Light;, Common;, Strong;, Heavy; }} {{#arraydefine: SmokedDuration | Total;, Onset;, Come up;, Peak;, Offset;, After effects; }} {{#arraydefine: OralDosage | Threshold;, Light;, Common;, Strong;, Heavy; }} {{#arraydefine: OralDuration | Total;, Onset;, Come up;, Peak;, Offset;, After effects; }} {{#arraydefine: SublingualDosage | Threshold;Sublingual threshold dose::5 - 10 Sublingual dose units::μg, Light;Sublingual min light dose::10 - Sublingual max light dose::25 μg, Common;Sublingual min common dose::25 - Sublingual max common dose::50 μg, Strong;Sublingual min strong dose::50 - Sublingual max strong dose::75 μg, Heavy;Sublingual heavy dose::75 μg + }} {{#arraydefine: SublingualDuration | Total;Sublingual min total time::1 - Sublingual max total time::4Sublingual total time units::hours, Onset;Sublingual min onset time::15 - Sublingual max onset time::30Sublingual onset time units::minutes, Come up;, Peak;, Offset;, After effects; }} {{#arraydefine: BuccalDosage | Threshold;, Light;, Common;, Strong;, Heavy; }} {{#arraydefine: BuccalDuration | Total;, Onset;, Come up;, Peak;, Offset;, After effects; }} {{#arraydefine: InsufflatedDosage | Threshold;Insufflated threshold dose::5 - 10 Insufflated dose units::μg, Light;Insufflated min light dose::10 - Insufflated max light dose::25 μg, Common;Insufflated min common dose::25 - Insufflated max common dose::50 μg, Strong;Insufflated min strong dose::50 - Insufflated max strong dose::75 μg, Heavy;Sublingual heavy dose::75 μg + }} {{#arraydefine: InsufflatedDuration | Total;Insufflated min total time::1 - Insufflated max total time::4Insufflated total time units::hours, Onset;Insufflated min onset time::15 - Insufflated max onset time::30Insufflated onset time units::minutes, Come up;, Peak;, Offset;, After effects; }} {{#arraydefine: RectalDosage | Threshold;, Light;, Common;, Strong;, Heavy; }} {{#arraydefine: RectalDuration | Total;, Onset;, Come up;, Peak;, Offset;, After effects; }} {{#arraydefine: TransdermalDosage | Threshold;Transdermal threshold dose::5 - 12 Transdermal dose units::μg, Light;Transdermal min light dose::12 - Transdermal max light dose::25 μg, Common;Transdermal min common dose::25 - Transdermal max common dose::50 μg, Strong;Transdermal min strong dose::50 - Transdermal max strong dose::100 μg, Heavy;Transdermal heavy dose::100 μg + }} {{#arraydefine: TransdermalDuration | Total;Transdermal min total time::48 - Transdermal max total time::72Transdermal total time units::hours, Onset;Transdermal min onset time::2 - Transdermal max onset time::4Transdermal onset time units::hours, Come up;, Peak;, Offset;, After effects; }} {{#arraydefine: SubcutaneousDosage | Threshold;, Light;, Common;, Strong;, Heavy; }} {{#arraydefine: SubcutaneousDuration | Total;, Onset;, Come up;, Peak;, Offset;, After effects; }} {{#arraydefine: IntramuscularDosage | Threshold;, Light;, Common;, Strong;, Heavy; }} {{#arraydefine: IntramuscularDuration | Total;, Onset;, Come up;, Peak;, Offset;, After effects; }} {{#arraydefine: IntravenousDosage | Threshold;, Light;, Common;, Strong;, Heavy; }} {{#arraydefine: IntravenousDuration | Total;, Onset;, Come up;, Peak;, Offset;, After effects; }} {{#arraydefine: uncertaininteractions | {{#ask:Fentanyl |?UncertainInteraction |headers=hide |format=list |mainlabel=- |link=none }} }} {{#arraydefine: unsafeinteractions | {{#ask:Fentanyl |?UnsafeInteraction |headers=hide |format=list |mainlabel=- |link=none }} }} {{#arraydefine: dangerousinteractions | {{#ask:Fentanyl |?DangerousInteraction |headers=hide |format=list |mainlabel=- |link=none }} }} {{#arrayprint:uncertaininteractions||@@@@| }} {{#arrayprint:unsafeinteractions||@@@@| }} {{#arrayprint:dangerousinteractions||@@@@| }}

Fentanyl
Chemical Nomenclature
Common names	common name:: Fentanyl, common name:: fentanil, common name:: Sublimaze, common name:: Actiq, common name:: Durogesic, common name:: Duragesic, common name:: Fentora, common name:: Matrifen, common name:: Haldid, common name:: Onsolis, common name:: Instanyl, common name:: Abstral, common name:: Lazanda
Systematic name	N-(1-(2-Phenylethyl)-4-piperidinyl)-N-phenylpropanamide
Class Membership
Psychoactive class	psychoactive class::Opioid
Chemical class	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. {{#arrayunique: SublingualDosage}} {{#loop: i | 0 | {{#arraysize: SublingualDosage}} | {{#arraydefine: val | {{#arrayindex: SublingualDosage | {{#var: i}} }} | ; }} }} {{#arrayunique: SublingualDuration}} {{#loop: i | 0 | {{#arraysize: SublingualDuration}} | {{#arraydefine: val | {{#arrayindex: SublingualDuration | {{#var: i}} }} | ; }} }} ⇣ Sublingual Dosage Bioavailability 50% [[Dosage_classification#{{#arrayindex: val | 0 }}|{{#arrayindex: val | 0 }}]] {{#arrayindex: val | 1 }} Duration [[Duration#{{#arrayindex: val | 0 }}|{{#arrayindex: val | 0 }}]] {{#arrayindex: val | 1 }} {{#arrayunique: InsufflatedDosage}} {{#loop: i | 0 | {{#arraysize: InsufflatedDosage}} | {{#arraydefine: val | {{#arrayindex: InsufflatedDosage | {{#var: i}} }} | ; }} }} {{#arrayunique: InsufflatedDuration}} {{#loop: i | 0 | {{#arraysize: InsufflatedDuration}} | {{#arraydefine: val | {{#arrayindex: InsufflatedDuration | {{#var: i}} }} | ; }} }} ⇣ Insufflated Dosage Bioavailability 89% [[Dosage_classification#{{#arrayindex: val | 0 }}|{{#arrayindex: val | 0 }}]] {{#arrayindex: val | 1 }} Duration [[Duration#{{#arrayindex: val | 0 }}|{{#arrayindex: val | 0 }}]] {{#arrayindex: val | 1 }} {{#arrayunique: TransdermalDosage}} {{#loop: i | 0 | {{#arraysize: TransdermalDosage}} | {{#arraydefine: val | {{#arrayindex: TransdermalDosage | {{#var: i}} }} | ; }} }} {{#arrayunique: TransdermalDuration}} {{#loop: i | 0 | {{#arraysize: TransdermalDuration}} | {{#arraydefine: val | {{#arrayindex: TransdermalDuration | {{#var: i}} }} | ; }} }} ⇣ Transdermal Dosage Bioavailability 92% [[Dosage_classification#{{#arrayindex: val | 0 }}|{{#arrayindex: val | 0 }}]] {{#arrayindex: val | 1 }} Duration [[Duration#{{#arrayindex: val | 0 }}|{{#arrayindex: val | 0 }}]] {{#arrayindex: val | 1 }} 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.
Interactions
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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 Psychoactive class::opioid substance of the Chemical class::anilidopiperidine 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 lower 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. It is also highly advised to use harm reduction practices if a user chooses to do fentanyl. Users are also advised to test all of their opioids (and substances in general) for fentanyl and other adulterants using reagent testing kits.

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.

Chemistry

Fentanyl is a member of the anilidopiperidine class of synthetic opioids. Its structure features a piperidine ring bound at its nitrogen constituent R_N 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 R_N.

Pharmacology

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.

Subjective effects

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 ☠.

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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:

• Erowid Experience Vaults: Fentanyl

Toxicity and harm potential

File:Heroin-Fentanyl-vials-NHSPFL-1024x576.jpg

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. It is Toxicity::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 [[Toxicity::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.

Fentanyl is very potent and around 1000 times more permeable than morphine. Even though fentanyl uptake through skin is rather slow, Toxicity::unintentionally transporting the substance from the skin by touching the mouth, nose or eyes is dangerous.

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 Addiction potential::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 Time to full tolerance::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 Time to half tolerance::3 - 7 days for the tolerance to be reduced to half and Time to zero tolerance::1 - 2 weeks to be back at baseline (in the absence of further consumption). Fentanyl presents cross-tolerance with [[Cross-tolerance::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.

Dangerous interactions

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.

• DangerousInteraction::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
• UncertainInteraction::Stimulants - 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.
• DangerousInteraction::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.
• DangerousInteraction::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.
• DangerousInteraction::GHB/DangerousInteraction::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
• DangerousInteraction::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.
• UncertainInteraction::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.
• DangerousInteraction::MXE - MXE can potentiate the effects of opioids but also increases the risk of respiratory depression and organ toxicity.
• UncertainInteraction::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.
• UncertainInteraction::PCP - PCP may reduce opioid tolerance, increasing the risk of overdose.
• DangerousInteraction::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.
• DangerousInteraction::Grapefruit - While grapefruit is not psychoactive, it may affect the metabolism of certain opioids. Certain opioids such as oxycodone and fentanyl 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, hydrocodone, and Tramadol 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.

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.

• DangerousInteraction::MAOIs - Such as banisteriopsis caapi, syrian rue, phenelzine, selegiline, and moclobemide.
• DangerousInteraction::Serotonin releasers - Such as MDMA, 4-FA, methamphetamine, methylone and αMT.
• DangerousInteraction::SSRIs - Such as citalopram and sertraline
• [[Wikipedia:SNRIs|DangerousInteraction::SNRIs]] - Such as tramadol and venlafaxine
• DangerousInteraction::5-HTP

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).
• 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.
• Switzerland: Fentanyl is a controlled substance specifically named under Verzeichnis A. Medicinal use is permitted.
• Turkey: Fentanyl is a 'red prescription' only substance and illegal when sold or possessed without a prescription.
• 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.

See also

• Responsible use
• Opioid
• Heroin
• Morphine
• Acetylfentanyl

External links

• Fentanyl (Wikipedia)
• Fentanyl (Erowid Vault)
• Fentanyl (Isomer Design)
  • Fentanyl landscape (Isomer Design)
• Fentanyl (DrugBank)
• Fentanyl (Drugs.com)
• Fentanyl (Drugs-Forum)

References

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