Also known as

China white, synthetic heroin, drop dead, flatline, lethal injection, apache, china girl, chinatown, dance fever, great bear, poison, tango & cash, TNT, serial killer, shine, goodfella, jackpot, murder 8, percopop


Opioid analgesic


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This drug is extraordinarily potent (i.e. 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 measured by sight. Fentanyl can also be fatal when combined with depressants such as opiates, benzodiazepines, barbiturates, thienodiazepines or other GABAergic substances.

It is strongly encouraged to wear gloves while handling, and to not consume either moderate or heavy dosages of other depressants in combination with this drug.

Fentanyl is a narcotic analgesic with a potency at least 80 times that of morphine. Fentanyl and its derivatives (Alfentanil, Sufentanil, Remifentanil and Carfentanil) are used as anaesthetics and analgesics in both human and veterinary medicine (Carfentanil). They are subject to international control as are a range of highly potent non-pharmaceutical fentanyl (NPF) derivatives, such as 3-methylfentanyl, synthesised illicitly and sold as 'synthetic heroin', or mixed with heroin [1].

Fentanyl is a depressant drug, which means it slows down the messages travelling between the brain and body. It belongs to a group of drugs known as 'opioids' that are from the opium poppy. It is prescribed for the control of chronic, severe pain as a result of cancer, nerve damage, back injury, major trauma or other causes [2]. It is about 80 to 100 times stronger than morphine [3], [4].


In terms of Defined Daily Doses (S-DDD) the main consumers in the EU in 2008 per million inhabitants per day were Belgium (13,601 S-DDD), Germany (13,341 S-DDD), and Austria (10,143 S-DDD).

Illegally diverted Fentanyl is a relatively marginal phenomenon in most of the EU but not in Tallinn, Estonia, where as many as 70% of applicants for treatment services in 2009 reported fentanyl as their primary drug [1].

How long do its effects last?

Onset of effects

  • sublingual - 15 - 30 minutes [5], [6].
  • insufflated - 15 - 30 minutes [5].
  • transdermal - 2 - 4 hours [5], [6].

Duration of effects

  • sublingual - 1 - 4 hours [5], [6].
  • insufflated - 1 - 4 hours [5].
  • transdermal - 48 - 72 hours [5], [6].


Fentanyl is a narcotic analgesic acting predominately at the µ-opiate receptor. Apart from analgesia, the fentanyls as a group produce drowsiness and euphoria, the latter being less pronounced than with heroin and morphine. The most common side-effects include nausea, dizziness, vomiting, fatigue, headache, constipation, anaemia and peripheral oedema. Tolerance and dependence develop rapidly after repeated use. Characteristic withdrawal symptoms (sweating, anxiety, diarrhoea, bone pain, abdominal cramps, shivers or 'goose flesh') occur when use is stopped. Serious interactions can occur when fentanyls are mixed with heroin, cocaine, alcohol and other CNS depressants e.g. benzodiazepines. The use of HIV protease inhibitors such as Ritonavir has been reported to increase plasma levels and reduce elimination of co-administered fentanyl.

Overdose results in respiratory depression which is reversible with naloxone. Sudden death can also occur because of cardiac arrest or severe anaphylactic reaction. The estimated lethal dose of fentanyl in humans is 2 mg. The recommended serum concentration for analgesia is 1 - 2 ng/ml and for anaesthesia it is 10 - 20 ng/ml. Blood concentrations of approximately 7 ng/ml or greater have been associated with fatalities where poly-substance use was involved. While fatalities have been reported after therapeutic use, many deaths have occurred as a result of the misuse of pharmaceutical products. Both used and unused fentanyl patches have been injected, smoked, snorted or taken orally with fatal consequences [1].


Fentanyl is an opioid analgesic. Fentanyl interacts predominately with the opioid mu-receptor but also binds to kappa and delta-type opioid receptors. These mu-binding sites are discretely distributed in the human brain, spinal cord, and other tissues. In clinical settings, Fentanyl exerts its principal pharmacologic effects on the central nervous system. Its primary actions of therapeutic value are analgesia and sedation. Fentanyl may increase the patient's tolerance for pain and decrease the perception of suffering, although the presence of the pain itself may still be recognised. In addition to analgesia, alterations in mood, euphoria and dysphoria, and drowsiness commonly occur. Fentanyl depresses the respiratory centers, depresses the cough reflex, and constricts the pupils [7].


Bioavailability is 92% following transdermal administration and 50% following buccal administration [7].


7 hours (range 3 - 12) [7].


Fentanyl is metabolised primarily via human cytochrome P450 3A4 isoenzyme system and mostly eliminated in urine. Within 72 hours of IV fentanyl administration, approximately 75% of the dose is excreted in urine, mostly as metabolites with less than 10% representing unchanged drug [7].

Lethal dosage

LD50 in mice - 62 mg/kg subcutaneously, 11.2 mg/kg intravenously [8]. Fentanyl has an LD50 of 3.1 milligrams per kilogram in rats, and, 0.03 milligrams per kilogram in monkeys. The LD50 in humans is not known [7].

Mechanism of action

Opiate receptors are coupled with G-protein receptors and function as both positive and negative regulators of synaptic transmission via G-proteins that activate effector proteins. Binding of the opiate stimulates the exchange of GTP for GDP on the G-protein complex. As the effector system is adenylate cyclase and cAMP located at the inner surface of the plasma membrane, opioids decrease intracellular cAMP by inhibiting adenylate cyclase. Subsequently, the release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine and noradrenaline is inhibited. Opioids also inhibit the release of vasopressin, somatostatin, insulin and glucagon. Fentanyl's analgesic activity is, most likely, due to its conversion to morphine. Opioids close N-type voltage-operated calcium channels (OP2-receptor agonist) and open calcium-dependent inwardly rectifying potassium channels (OP3 and OP1 receptor agonist). This results in hypopolarization and reduced neuronal excitability [7].

Mode of use

Intravenous injection (Sublimaze®), transdermal patches (Durogesic®), oral transmucosal lozenges (Actiq®), buccal tablets (Effentora ®). Non-prescribed fentanyl has been misused by injection; by oral ingestion of lozenges, patches (both used and unused) and 'trips' and fentanyl powder or patches have also been smoked or taken intranasally (snorted) [1].

The transdermal patch is applied to the skin and provides strong and consistent pain relief at an even rate over a 72 hour period [2]. The patch is the most commonly used form of fentanyl.

The lozenges are dissolved in the mouth and are used for breakthrough pain in patients already taking regular opiates for severe pain [2].

The IV solution is injected for pain relief and sedation during minor surgery and it's duration of action is short [2].

Some people use fentanyl illegally to become intoxicated by extracting the fentanyl from the patch and injecting it. This is very risky as there is little difference between the amount needed to get 'high' and the amount that causes overdose. It is also extremely hard to judge a 'correct' dose size [4].

Injecting Fentanyl

Due to the extreme potency of fentanyl users should not attempt to inject fentanyl. There is no safe way to inject fentanyl outside of a medical environment.

There is no way to safely measure a dose of fentanyl without an extremely sensitive scale which would be well outside the price range of the typical consumer. Fentanyl is so powerful that it only takes a tiny difference in dosagee to be fatal. Injection is an extremely fast and efficient method of administration with no recourse if the dose was too high, excepting a naloxone injection which would have to administered very quickly by trained medical professionals [8].


Fentanyl powder may be snorted, but it is not recommended [9].


The gel inside patches can be smoked. The powder also may be smoked, although it is not recommended [9].

Signs of usage

A family member or loved one may see some of the following signs that can suggest addiction to fentanyl -

  • irritability,
  • decline in activity,
  • increasing sleep disturbance,
  • increasing problems in relationships,
  • reports of lost or stolen pain-medication prescriptions,
  • frequent early renewal requests from pharmacists,
  • doctor shopping,
  • increasing complaints of pain,
  • reluctance to try non-opioid pain medications for any painful conditions,
  • requesting other prescriptions for medications with euphoric effects (e.g., other opioid drugs, benzodiazepines, or other sedatives),
  • unwillingness to provide medication history to prescribing doctors [4].

For parents or friends of adolescents, some of the following signs and symptoms of addiction may be helpful -

  • missing school and reports of bad behavior or poor academic performance,
  • constant itchy nose and 'sniffles',
  • pin-point pupils,
  • avoiding family activities,
  • reports of going out for long periods with 'friends' you never get to meet,
  • frequent vomiting, shivering, sweating, complaints of aches and pains, diarrhoea,
  • poor appetite, even for favourite foods,
  • reports from relatives on opioids that 'someone's been into the medicine cabinet',
  • evidence of injection drug abuse, such as wearing long-sleeved shirts in summertime to hide track marks or needle marks, missing spoons from the kitchen (for drug prep), or cutting the tops of cotton swabs to filter crushed tablets [4].


Long-term effects

Regular use of fentanyl may cause -

  • mood instability,
  • reduced libido,
  • constipation,
  • menstrual problems,
  • respiratory impairment [3], [4].

Physical effects

  • physical euphoria,
  • pupil constriction,
  • appetite suppression,
  • cough suppression,
  • orgasm suppression,
  • pain relief,
  • respiratory depression,
  • sedation,
  • constipation,
  • difficulty urinating,
  • increased perspiration,
  • itchiness [5].

Cognitive effects

  • cognitive euphoria,
  • compulsive redosing,
  • dream potentiation,
  • anxiety suppression,
  • decreased libido [5].


  • analgesia,
  • euphoria,
  • feelings of relaxation [9].


  • sedative effects,
  • changes in focus,
  • changes in attention [9].


  • respiratory depression,
  • diarrhoea,
  • nausea,
  • constipation,
  • dry mouth,
  • somnolence,
  • confusion,
  • weakness,
  • sweating,
  • headache,
  • fatigue,
  • dizziness,
  • nervousness,
  • anxiety,
  • urinary retention,
  • hallucinations [9].


  • confusion,
  • depression,
  • difficulty walking,
  • muscle stiffness,
  • slowed/altered heart rate,
  • laboured breathing,
  • weakness,
  • dizziness, lightheadedness, and fainting,
  • shaking,
  • sleepiness,
  • slurred speech,
  • weight loss,
  • visual hallucinations,
  • nausea and vomiting,
  • itching & scratching,
  • pinpoint pupils [10].

After effects

There is a risk of post-acute withdrawal effects which could include -

  • diarrhoea,
  • depression,
  • anxiety disorder,
  • psychosis, or even
  • suicidal ideation in extreme cases [9].


The following are some of the symptoms of a Fentanyl overdose -

  • slow, shallow breathing,
  • decreased urge to breathe,
  • breathing difficulties,
  • swallowing difficulties,
  • drowsiness,
  • dizziness,
  • confusion,
  • fainting [11],
  • respiratory depression,
  • chest pain,
  • cyanosis,
  • seizures,
  • passing out,
  • coma,
  • death [4].

If you experience any of these symptoms, stop using fentanyl and call your healthcare provider immediately or seek emergency medical treatment [11].


Signs of addiction to fentanyl

There are a number of signs that you are addicted to the drug - ones you might not always be willing to accept or notice. These include -

  • being incapable of making proper judgments (i.e., choosing continued drug taking over all other responsibilities),
  • experiencing difficulty in finding pleasure from everyday occurrences from friends and friends,
  • taking large doses of the drug for a long period of time,
  • doctor shopping or other questionable methods to make sure you get enough prescriptions of the drug to satisfy your compulsive use [12].

Apart from affecting the mind and how you may feel emotionally, fentanyl addiction takes a physical toll, which can manifest as a number of negative health effects. If you think you might be addicted to fentanyl or that someone you know might be addicted to the drug, you will want to look out for the physical symptoms associated with fentanyl addiction [12]. These include -

  • nausea,
  • constipation,
  • confusion,
  • sedation,
  • slowed breathing,
  • drowsiness,
  • intermittent loss of consciousness, and
  • coma [12].

Fentanyl addiction can dramatically increase the risk of severe respiratory depression or respiratory failure as a consequence of overdose [12].

Dangerous interactions


  • 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.
  • MXE - This combination can potentiate the effects of the opioid
  • 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.
  • Cocaine - Stimulants increase respiration rate allowing a higher dose of opiates. If the stimulant wears off first then the opiate may overcome the patient and cause respiratory arrest.
  • 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
  • GBL / GHB - 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
  • 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
  • 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 [6].


  • PCP - PCP can reduce opioid tolerance, increasing the risk of overdose.
  • Nitrous oxide - 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.
  • Amphetamines - Stimulants increase respiration rate allowing a higher dose of opiates. If the stimulant wears off first then the opiate may overcome the patient and cause respiratory arrest.
  • 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, diarrhoea, hypertension, tachycardia, seizures, and coma. Death has occurred in some cases [6].


Giving up fentanyl after using it for a long time is challenging because the body has to get used to functioning without it. Withdrawal symptoms usually start within 12 hours after the last dose and can last for about a week - days 1 to 3 will be the worst [4]. These symptoms can include -

  • goose flesh/bumps,
  • bouts of chills alternating with bouts of flushing and excessive sweating,
  • irritability,
  • insomnia,
  • loss of appetite,
  • yawning,
  • sneezing,
  • watery eyes,
  • runny nose,
  • vomiting,
  • nausea,
  • diarrhoea,
  • increased heart rate and blood pressure,
  • pains in the bones and muscle,
  • general weakness,
  • depression [3], [4],
  • fatigue,
  • fever,
  • headache,
  • muscle twitching,
  • muscle pain or cramps [12].

Harm Reduction

Fentanyl is considered one of the safest opioid medications on the market, as well as the least physically harmful to the body with long-term or life-term use. Still, fentanyl has caused overdoses and deaths, especially when mixed with other drugs.

Illicitly synthesized fentanyl powder has also appeared on the United States market. 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, consequently, very dangerous.

Sometimes fentanyl is sold as heroin. Some dealers may mix fentanyl powder with heroin to increase potency or compensate for low-quality heroin. If you have any concerns about your drug, please test it [9].

  • avoid driving and operating heavy machinery,
  • risk of post-acute withdrawal effects,
  • strong addiction potential due to short effects,
  • risk of overdose/death [9].

Drug testing

Several factors are involved in determining how long Fentanyl is detectable in the body, including which kind drug test is being used. Fentanyl - marketed under the brand names Abstral, Actiq, Fentora, and Onsolis - can be detected for a shorter time with some tests, but can be 'visible' for up to three months in other tests.

The timetable for detecting fentanyl in the system is also dependent upon each individual's metabolism, body mass, age, hydration level, physical activity, health conditions and other factors, making it almost impossible to determine an exact time fentanyl will show up on a drug test [11].

The following is an estimated range of times, or detection windows, during which Fentanyl can be detected by various testing methods -

How long does fentanyl stay in the urine?

Fentanyl can be detected in the urine for 8 - 24 hours [11].

How long can fentanyl be detected in blood?

A blood test can identify Fentanyl for up to 12 hours [11].

How long can a saliva test detect fentanyl?

A saliva test can detect Fentanyl for up to 1 - 3 days [11].

How long can a hair test detect fentanyl?

Fentanyl, like many other drugs, can be detected with a hair follicle drug test for up to 90 days [11].

Mixing with other drugs

The effects of taking fentanyl with other drugs - including over-the-counter or prescribed medications - can be unpredictable and dangerous and could cause -

  • Fentanyl + alcohol - adds to adverse effects and may increase the risk of respiratory depression.
  • Fentanyl + MAOI anti-depressants - may result in severe unpredictable reactions.
  • Fentanyl + benzodiazepines - may add to the sedative effects and diminished breathing [2], [4].


Detoxification refers to the process of gradually taking a drug-dependent individual off of a drug. The goals of detox are -

  • to allow the body to rid itself of the drug and, in doing so, gradually eliminate the dependence associated with chronic daily fentanyl use,
  • to help minimize the pain and discomfort of withdrawal and to reduce the risk of relapse,
  • to provide an environment that increases the likelihood of continued substance abuse treatment,
  • to identify any medical problems and to treat them or refer after detox to additional care,
  • to begin educating the person about issues related to his or her addiction as an initial step towards longer-term substance abuse treatment and lasting recovery [12].

Withdrawal from fentanyl without medically-assisted detox is not only very uncomfortable, but also potentially dangerous for the fentanyl user. Given the high risk of relapse for opioid users, fentanyl poses a particular risk due to its sheer strength. In withdrawal, tolerance levels drop so that the addicted person who relapses on the same doses that he or she reached before withdrawal can administer a fatal dose resulting in respiratory failure and death.

During medical detox, access to fentanyl and other drugs is removed, exposure to potentially triggering stimuli is minimized, medications may be given to reduce craving and to manage other troublesome withdrawal effects, and the person can be observed for medical problems or complications from fentanyl use. Specifically, methadone (Dolophine) and buprenorphine and naloxone (Suboxone) are options in preventing further withdrawal sickness and cravings for fentanyl. The drug clonidine (Catapres), which is used for treating high blood pressure, is also used to treat withdrawal associated with fentanyl cravings.

Medical monitoring of fentanyl detoxification is essential to minimise the risks of relapse and possible fatal overdose. People with a history of opioid abuse may additionally be dealing with various infectious diseases and other serious health issues, warranting the consideration of close medical supervision and intervention, if necessary. Seizures, while not usually a part of opioid withdrawal, may develop due to recent fentanyl abuse because of its similarity to the drug meperidine (Demerol) in lowering the seizure threshold [12].


  • According to the DEA, between 2005 and 2007, fentanyl abuse killed more than 1,000 people in the U.S.
  • According to the American Association of Nurse Anesthetists (AANA) Journal, nurses and anesthesiologists have a higher probability of abusing Fentanyl than the general public.
  • Per the DEA, over 12 varieties of drugs currently being trafficked have been produced illicitly in labs to resemble fentanyl.
  • Per a report by the CDC, those addicted to opiate painkillers are 40 times more likely to abuse or become dependent on heroin [10].


Fentanyl was first synthesised by Paul Janssen in 1960 [5] following the medical inception of pethidine several years earlier. Janssen developed fentanyl by assaying analogues of the structurally related drug pethidine for opioid activity [13]. The widespread use of fentanyl triggered the production of fentanyl citrate which entered the clinical practice as a general anaesthetic under the trade name Sublimaze in the 1960's. Following this, many other fentanyl analogues were developed and introduced into medical practice, including sufentanil, alfentanil, remifentanil, and carfentanil.

In the mid-1990's, 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 [14], [15]. In 2013, 1700 kilograms were used globally [16].

Fentanyl was first synthesised by Paul Janssen in 1960. Fentanyl was introduced in patch form in the mid 1990's, shortly followed by lollipop form. As of 2012 fentanyl was the most widely used synthetic opioid in clinical practice [9].


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