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Protonitazene is a novel synthetic opioid Opioids are central nervous system depressants. They typically produce a range of effects including sedation,…
About Fentanyl and Fentanyl Analogues
Fentanyl is an extremely potent synthetic opioid, up to 100 times stronger than morphine.1,2 A dose of fentanyl that can cause death for most people is 2 mg, but as little as 0.25 mg may place a person at a high risk of overdose depending on their tolerance to opioids.3 Fentanyl can be injected, snorted, smoked, absorbed in the mouth/under the tongue or through the skin (via a patch), or taken orally in a pill/tablet.4 Fentanyl is widely manufactured both legally as a pharmaceutical drug and illegally as a drug or as an adulterant in other drugs (e.g. “lacing”).
Fentanyl was first synthesised in 1960 and has since been widely used as a medicine.1 In Australia, fentanyl is used to treat moderate to severe acute or chronic pain.5 Illegally manufactured fentanyl began to emerge in the mid-2000s in the US, causing a number of overdoses.1 In the 2010s, fentanyl-related deaths in the US skyrocketed and illegally-manufactured fentanyl began to spread globally.1,6 Fentanyl and other potent synthetic opioids are the main drivers of the overdose epidemic in the US, causing nearly 75,000 overdose deaths in 2023.7 Although Australia’s present situation is not as severe as the US’s, synthetic opioids including fentanyl were responsible for an estimated 215 overdose deaths in Australia in 2020.8
Pharmaceutical fentanyl is given as an injection in hospital settings, or it is commonly sold as transdermal patches used to treat chronic pain (e.g., Durogesic).2,9 The fentanyl in these patches is absorbed through the skin throughout the day, but some people choose to extract the content of these patches for injection.4,9 Extreme care should be taken if doing this as there is a high risk of overdose. The actual amount of fentanyl contained in these patches is far greater than the dose listed on the package (see the Dosing Fentanyl section below for more detail).10
Historically in Australia, fentanyl patches—in particular Duragesic and generic versions—are a widely diverted and injected preparation of fentanyl, particularly in regional or rural areas where illicit heroin supply is inconsistent and where opioid maintenance treatment programs are lacking or difficult to access.11-13 The injecting of fentanyl patches became an issue in Australia as the US grappled with overdose deaths resulting from the wide availability of OxyContin tablets. This is because many prescribers in Australia were encouraged to move away from prescribing OxyContin and some began using fentanyl patches as a safer alternative. This change was precipitated by transdermal patches becoming subsidised under the Pharmaceutical Benefits Scheme in 2006, principally because pharmaceutical companies changed fentanyl patch formulations to a “trans–dermal matrix” preparation which they stated was tamper proof and could not be injected.13,14 In reality, the new “matrix-based” preparation was much easier for people to extract and inject than the old patches where the fentanyl was mixed into a gel contained in a pouch . This caused an increase in overdose deaths in rural and regional areas in the early-mid 2010’s.13
The increase in overdoses prompted harm reduction and drug user organisations such as the AIVL National Network and the Medically Supervised Injecting Centre in Sydney to create harm reduction resources showing people how to measure dosages of fentanyl patch (including by converting fentanyl to morphine dose equivalent and then cutting the patch into pieces) and how to add citric or ascorbic acid and heat to the preparation to extract the fentanyl .10,15 It also precipitated NSPs and safe injecting facilities providing small sachets of acid specifically for the purpose of injection from Exchange Supplies in England, where they are commonly used for injecting brown heroin.
Due to the rise in overdoses and the subsequent efforts of harm reduction organisations, prescribers became more aware of the safety issues associated with “matrix-based” fentanyl patches.16,17 In the late 2010’s and early 2020’s, fentanyl patch prescriptions decreased and the guidelines were updated to restrict their medical uses.16,17. Fentanyl patches are still diverted for injection, but to a much lesser extent than during the 2010’s.
Illegally-manufacture fentanyl and chemicals related to fentanyl (called fentanyls or fentanyl analogues) are sold as a pure powder (rarely), in counterfeit pills such as fake oxycodone or benzodiazepine pills, or as an adulterant in other drugs such as heroin and cocaine.1,4 Although they are rarer than fentanyl, some of the fentanyl analogues that have been detected in the US include acetylfentanil, furanylfentanyl, and carfentanil, which is up to 100 times more potent than fentanyl.1,6
Importantly, fentanyl is found as an adulterant in non-opioid drugs, such as counterfeit benzodiazepine pills and cocaine.1 This poses a high risk of overdose because many people who use these drugs have a low or no tolerance to opioids. Fentanyl has been detected in the ACT before, but it was first detected at Canberra’s fixed-site health and drug checking service CanTEST in September 2024 (for more info see here).18 In this case, fentanyl was found in a brown powder and was not expected by the person who submitted the sample.18
Fentanyl can be present in tiny amounts in drugs including powders and pills. As such, it is important to test your drugs either at home using a fentanyl test strip (e.g., https://dancesafe.org/fentanyl/), or by taking a small sample to a drug checking service such as CanTEST. Fentanyl test strips can detect very small amounts of the drug, but they may not be able to detect some fentanyl analogues.19 Additionally, fentanyl test strips cannot detect nitazenes (for more info on nitazenes, see here).19
Effects of Fentanyl
The effects of fentanyl are similar to other opioids and typically include:20,21
- Pain relief (analgesia).
- Sedation.
- Euphoria.
- Constricted pupils (miosis).
- Slowed breathing.
- Constipation.
- Diminished sex drive.
Although the effects can be similar to heroin, many users report that fentanyl produces noticeably less euphoria than heroin.20 The effects of fentanyl are relatively short-lived compared to other opioids, typically lasting 1-4 hours.20
Dosing Fentanyl
Harm Reduction
The potency of fentanyl can vary depending on the way you take it and a person’s weight, metabolism, and tolerance to opioids. It is always recommended to start at a low dose and wait before redosing recreational drugs (start low and go slow). Additionally, some people can have bad reactions to fentanyl, including a small number who have severe allergic reactions (i.e., anaphylaxis).22 As such, it is recommended to take a test dose and monitor for signs of adverse effects before taking a full dose.
Tolerance to opioids, including fentanyl, builds quickly and a larger dose may be required to produce the same intensity of effects following repeated use. Tolerance also fades, so if you’ve taken a break from opioids, start with a dose smaller than you would use previously. A break of only a week or two can cause a significant decrease in tolerance, so be careful!
The following dosage guide is for an opioid naïve person (someone with no tolerance) and assumes the fentanyl is 100% pure. This is only a guide. Everyone is different, and some people can overdose on a hit that another person would barely feel. If you are using fentanyl for the first time, or if you are inexperienced with using strong opioids, make sure you have a friend with you who is not intoxicated, and have easily accessible naloxone on hand. Naloxone is available either as intranasal or injectable forms, and it can be obtained for free at many pharmacies throughout Australia. It is also freely available at many needle exchanges and other Alcohol and Other Drug services.
Handling fentanyl can be dangerous as there is a risk of accidental exposure through inhalation, ingestion, and absorption through mucous membranes (e.g., mouth, eyes, nose, and anus).23 Avoid touching your eyes, mouth, and nose when handling fentanyl and wash your hands thoroughly afterwards.23 Fentanyl is also absorbed through the skin, although to a lesser extent.23 Consider wearing eye protection and powder-free nitrile gloves.23
Avoid mixing fentanyl and fentanyl analogues with other drugs. Many recorded overdoses have involved mixing fentanyl.14 Mixing fentanyl with:20
- Depressants (including alcohol, benzos, GHB and other opioids) can increase the risk of losing consciousness, respiratory depression, and vomit aspiration.
- Dissociatives (including ketamine) can increase the risk of losing consciousness and vomit aspiration.
- DXM may decrease a person’s tolerance to opioids and increase the risk of overdose.
- Stimulants (including meth and cocaine) can cancel out some of the effects of opioids, causing a person to take more than they would otherwise. If the stimulant wears off, the person may slip into an opioid overdose.
Measuring Doses
The active dose of fentanyl is in the microgram range (< 1 milligram).2,20 Because the dose is so small, pure or semi-pure fentanyl powder is extremely difficult to dose accurately. If choosing to dose pure or semi-pure fentanyl, it is recommended to use volumetric dosing.20 This is where a larger quantity of fentanyl is dissolved in sterile water so that a smaller dose can be taken.20 A guide to volumetric dosing along with a calculator are available online.
Most scales are not sensitive enough to accurately measure a fentanyl dose.24 Gram scales, which measure tenths (0.1 g) or hundredths (0.01 g) of a gram are simply not good enough to weigh less than a milligram (< 0.001 g). A cheap set of milligram scales can theoretically weigh three decimal places (down to 0.001 g), but they will only be accurate for weighing 10 mg or more (> 0.010 g) due to the margin of error. Even if using expensive scales which can accurately weigh down to 1 mg (0.001 g), small disturbances will affect the readings, including breath, or other air movement. This means you will need to do volumetric dosing.
The following is an approximate dosage guide for fentanyl for an opioid naïve person:2,20,25
| LOW DOSE | 12-25 μg (= 0.012-0.025 mg) |
| MODERATE DOSE | 25-50 μg (= 0.025-0.05 mg) |
| STRONG DOSE | 50-100 μg (= 0.05-0.1 mg) |
The above dosage guide applies to intravenously injected fentanyl, sublingual/buccal fentanyl (i.e., under the tongue or in the mouth), and intranasal fentanyl (i.e., in the nose or snorted).2,20,25 When injecting drugs, it is always recommended to use safer injecting practices (see the Safer Injecting Handbook and AIVL’s Vein Care Guide).
As for fentanyl analogues, carfentanil is about 100 times more potent than fentanyl (that is, an active dose is 100 times smaller) and acetylfentanyl is about one third the potency of fentanyl.26
Dosing Fentanyl Patches
Multiple overdose deaths have been caused by consuming or injecting the contents of fentanyl patches.14,27 It is important to note that the actual amount of fentanyl in these patches is far greater than the dose listed on the package.14,27 The dose listed on the package is the dose that is released every hour, not the total amount of fentanyl in the patch. The total fentanyl contents are released over a period of 168 hours (one week).10 Hence, it is important to cut the fentanyl patch into squares of the desired dose before extracting and injecting the contents.10
If choosing to extract fentanyl from a patch, the best harm reduction practice is to measure the correct dose based on the strength of the patch, such as by using the table below, and dividing (e.g. with scissors) the patch accordingly. After this, the small segment of patch is dissolved in water along with ascorbic acid (Vitamin C), citric acid, or vinegar.10 Ascorbic acid is considered the best choice for this process, and sachets of acid are available at NSPs and injecting rooms.10 More water is added and the mixture is heated (e.g., using a lighter and a spoon) until the patch becomes clear and the water boils, then it is left to cool down.10 Extreme care must be taken when handling concentrated fentanyl to avoid accidental exposure. Other extraction methods, such as by using solvents or freezing and smoking the patches, carry a greater risk of harm and overdose.14,27 Injecting solvents is extremely dangerous and, although smoking is inherently less risky than injecting, inhaling the plastic in the patches can cause harm.The following is an approximate conversion table for the total amount of fentanyl in Durogesic patches:10,28
| Patch strength (as listed on package) | Total quantity of fentanyl in patch | Approximate equivalent dose of morphine | No. of 100 μg fentanyl doses per patch |
| 12.5 μg | 2.1 mg | 210 mg | 21 |
| 25 μg | 4.2 mg | 420 mg | 42 |
| 50 μg | 8.4 mg | 840 mg | 84 |
| 75 μg | 12.6 mg | 1260 mg | 126 |
| 100 μg | 16.8 mg | 1680 mg | 168 |
For example, if choosing to inject 500 μg of fentanyl, you would need to divide a 50 μg patch into 16 equal squares before extracting the contents of a single square.10
Fentanyl Overdose
Fentanyl overdose is a serious medical emergency. Fentanyl overdose causes life-threatening respiratory failure quicker than other opioids (less than two minutes after injection), so it is pivotal to seek help quickly.14 The symptoms of fentanyl overdose can include:29
- Loss of consciousness.
- Body going limp.
- Slow, abnormal, or no breathing.
- Choking, gurgling or gasping sounds.
- Cold, clammy skin.
- Blue nails or lips (cyanosis).
- Constricted pupils (miosis).
If you suspect someone has overdosed on fentanyl, try waking them up with a loud voice, pinching their shoulder or rubbing your knuckle over their chest. If they don’t respond, give the person naloxone and call 000 immediately.
If naloxone (a.k.a. Narcan) is available, administer it to the person who is overdosing as soon as possible, even if you are unsure that overdose is the problem. Fentanyl is more resistant to naloxone than other opioids, so multiple administrations may be required and it may need to be re-administered at regular intervals for some time.14 For more information about opioid overdose and naloxone, contact CAHMA or your local harm reduction service provider.
In the meantime, if they are breathing, try to place them in the recovery position and wait with them until they recover.
If they are turning blue, or obviously not breathing, they will need oxygen or Expired Air Resuscitation (E.A.R., otherwise known as mouth-to-mouth resuscitation).
This is fairly straightforward, but the first thing to remember is not to panic.
After calling 000, with the overdose patient on their back, the head should be tilted back slightly to open the airway. From here, pinch the nose closed and give a couple of good breaths directly into their mouth. You will need a good seal around the mouth so press firmly and exhale strongly. You should see their chest rise when this works. Often it will only require one or two breaths to get someone roused enough to breathe on their own.
If they do not start breathing by themselves, you will need to keep going until help arrives; a person who is not breathing will die within three or four minutes if no oxygen (or E.A.R.) is provided.
Naloxone breaks down in the body fairly quickly (30-90 minutes), after which the overdose symptoms may return.30 Hence, it is important to seek emergency medical attention even if you administer naloxone. Naloxone can sometimes cause withdrawal symptoms (e.g. agitation) when given to someone who is opioid-dependent.30 These symptoms will subside after an hour or so as the naloxone wears off. even if you administer naloxone. Naloxone can sometimes cause withdrawal symptoms (e.g. agitation) when given to someone who is opioid-dependent.23 These symptoms will subside after an hour or so as the naloxone wears off.
References
[1] https://doi.org/10.1016/j.neuropharm.2017.10.016
[2] https://www.ncbi.nlm.nih.gov/books/NBK459275/
[3] https://oregonstate.app.box.com/s/7cxt86s4mqfu0miorqo3l7ouzxxvsfvy
[4] https://www.dea.gov/sites/default/files/2023-06/Fentanyl%202022%20Drug%20Fact%20Sheet-update.pdf
[6] https://doi.org/10.1097/YCO.0000000000000717
[7] https://www.cdc.gov/nchs/pressroom/nchs_press_releases/2024/20240515.htm
[9] https://www.nps.org.au/radar/articles/fentanyl-patches-durogesic-for-chronic-pain
[10] AIVL, Injecting Fentanyl – Minimising the Risks
[11] https://doi.org/10.1111/dar.12668
[12] http://dx.doi.org/10.1016/j.sapharm.2017.04.002
[13] https://doi.org/10.1111/dar.13391
[14] https://doi.org/10.3390/toxics11010046
[15] MSIC Staff Client Resource – Fentanyl patches
[16] https://doi.org/10.1016/j.drugpo.2024.104666
[19] https://dancesafe.org/fentanyl/
[20] https://psychonautwiki.org/wiki/Fentanyl
[21] https://wiki.tripsit.me/index.php?title=Fentanyl
[22] https://doi.org/10.4103%2F0974-2700.99703
[23] https://stacks.cdc.gov/view/cdc/52812/cdc_52812_DS1.pdf
[24] https://psychonautwiki.org/wiki/Volumetric_dosing
[25] https://www.drugs.com/dosage/fentanyl.html
[26] https://doi.org/10.3389/fphar.2019.00238
[27] https://doi.org/10.1111/bcpt.12412
[28] https://doi.org/10.2165/00003495-200868120-00008
[29] https://www.healthline.com/health/drugs/fentanyl-overdose-symptoms
[30] https://adf.org.au/drug-facts/naloxone/
Written by Darcy Lynch
