Meet the fentanyls

With a vast range of forms and potencies, the fentanyl family bring too many unknowns. Kevin Flemen gives an essential guide.

Another day, another drug warning – lately we’ve had drug scare after drug scare. There was flesh-eating Krokodil, Bath Salt cannibals, Hippy Crack, Zombie Spice and, in the May issue of DDN, concerns about an increase in Xanax use.

Most recently came warnings about fentanyl-type drugs. Such bulletins can risk losing impact, but if the evidence from North America and elsewhere is anything to go by, fentanyl and its derivatives have the potential to become a huge problem and cause significant loss of life.

Although fentanyl-type drugs have featured sporadically in the UK drug scene for a while, concern about them has increased markedly in the past few months, leading to official warnings from the National Crime Agency (NCA) and Public Health England (PHE). So, it’s time (and some would argue, long overdue) to get up to speed with the fentanyls.

Fentanyls are opioids, with fentanyl (Duragesic) used for severe pain. It has numerous analogues and derivatives, with new ones emerging – Wikipedia lists 42 and this may be an underestimate. Several of the fentanyls have legitimate medical use and so are better understood in terms of potency, doses, and metabolites, but others have been developed to sidestep legislation or restriction on precursors. Less is known about these newer compounds.

The potency and half-life of different fentanyls varies massively. To illustrate relative potency, fentanyls are compared to morphine – but this is a crude indicator, especially when the composition and purity of street-sourced fentanyls is unclear.

To further complicate the issue, some analogues have more than one isomer, which in turn vary in potency. So 3-methylfentanyl ranges in potency, from 300 times the potency of morphine to 6,000 times stronger, depending on which isomer is present.

Given such a wide range of products and potencies, the risk of overdose cannot be understated. There is every chance of misidentification and mis-selling throughout the supply chain, from producers inadvertently supplying the wrong analogue or isomer through to suppliers mis-identifying their product.

To reduce the potency to usable levels, fentanyls need to be bulked out with a non-psychoactive filler agent, such as mannitol. This demands correct identification of the drug, careful calculation of the amount of filler to be added, and thorough mixing of drug and filler.

Such mixing is at best prone to errors. When fentanyl is mixed with more granular substances, such as brown heroin, it is impossible to achieve a thorough mix, and so the risk of separation and ‘hot-spots’ is greater still.

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Fentanyls – a comparative

Fentanyl is rated as approximately 100 times* the potency of morphine – so 1g of fentanyl is equivalent to 100g of morphine.

Some analogues are weaker: acetylfentanyl is around 15 times the potency of morphine. Others are far stronger: 4-fluorofentanyl is reported to be twice the strength of fentanyl – some 200 times the strength of morphine.

Carfentanil, legitimately used to tranquillise large mammals, is reportedly around 10,000 times the potency of morphine (100 times stronger than fentanyl). So, in theory, 1g of carfentanil is the equivalent of 10kg morphine.

*This dose equivalence is a very crude way of indicating relative potency. Variables such as speed of onset, duration of effect, level of analgesia versus level of sedation, and therapeutic index cannot be summarised by a simple drug A is x times stronger than drug B.

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Sources and supply

Synthesised in China and elsewhere, fentanyls have become increasingly available on the dark web. Products reputedly on sale included fentanyl, furanyl-fentanyl, carfentanil and other analogues.

Given their very high potency, they are an appealing option for international smuggling. They offer a low bulk/high potency alternative to heroin and are available via labs online, rather than engaging with heroin suppliers.

Fentanyls have become a very significant factor in drug deaths in North America and the major cause of opiate deaths in British Columbia, with the number almost doubling between 2015 and 2016. Closer to home they have been an issue in the EU, but it has primarily been Baltic countries, especially Estonia, which have seen the biggest problems.

There may also be some European production. In April, West Yorkshire Police raided a ‘drugs lab’ where fentanyl was involved, although is not clear from the reporting if the ‘lab’ was synthesising fentanyl, or compounding imported fentanyls with heroin for onward sale.

The UK market
Medically diverted fentanyl is abusable, but the combination of limited prescribing and transdermal preparations has meant it has not been a massive issue in the UK to date. Fentanyl analogues have been around here for a while, cropping up sporadically in drugs analysed (for example) by the drug identification service WEDINOS, but difficulties in detecting newer fentanyls make it hard to gauge their presence. It may be that they have been a factor in opiate drug deaths for longer than thought, and reviews of post-mortem samples are being conducted to see if this is the case. Routine drug testing and screening won’t show up fentanyls and even fentanyl-specific tests won’t detect all analogues.

At street level, fentanyl is most likely to end up as a component in another drug, usually heroin.

While fentanyl is most likely to appear as a cut in heroin, it is also sold online as a white powder and has been offered in liquid and blotter forms. It can be smoked, snorted, injected, or taken rectally, and while all routes are risky, smoking carries the lowest risk of fatal overdose. At street level in the UK, it is most likely to end up as a component in another drug, usually heroin. This may be in the form of typical brown heroin, with fentanyl added to make it feel more potent.

Fentanyl is sometimes referred to as ‘synthetic heroin’ or ‘China white’. It is therefore essential to stress that buyers offered ‘white heroin’ or ‘China white’ are at present very likely to be getting fentanyl rather than old-school white heroin.

People seeking heroin are clearly the group most at risk of encountering fentanyls. However, they have cropped up in place of other products including benzodiazepines and stimulants such as MDMA or cocaine in the UK and Europe, and sold internationally mixed with crack cocaine. Becoming more widespread could impact not solely on heroin users, but people using any white powder drug – populations that are likely to be harder to reach with harm-reduction messages and less likely to have naloxone at point of overdose.

Issuing warnings about fentanyls is a finely balanced judgement call, as premature warnings about ‘dangerous drugs’ can be counterproductive. On the one hand, they raise awareness and highlight the dangers; on the other, they risk publicising a high-strength, low-cost alternative to street heroin and can make it a sought-after product. However, the string of deaths in the north of England, more frequent reports from around the UK and increased police seizures have acted as a catalyst for the NCA and PHE to issue alerts about fentanyls. This has triggered a flurry of articles in the mainstream media, so the cat is well and truly out of the bag.

This still doesn’t mean that fentanyls are widespread or have penetrated the market at all levels. We need to try and develop locally relevant messages that don’t inadvertently promote fentanyl: references to ‘super strong’ or ‘high strength’ are probably phrases to avoid.

Where next?
We need to look urgently at the experience of North America, especially Canada, in the face of escalating fentanyl use. Experience in terms of detection, first response and educative messages will be invaluable.

In response to rising fatalities, drug consumption room provision is being expanded in Canada. Such measures are long overdue in the UK and in the context of escalating deaths in the UK and the advent of fentanyls, similar measures are required here.

There’s no evidence that harsher legal sanctions for adding fentanyl to heroin will deter suppliers. However, fear of police action may mean that suppliers holding fentanyl supplies try to offload stock quickly, with the risk that the drug will crop up in a more random fashion.

Ultimately, such measures are of course sticking plasters. We keep seeing the evidence that prohibition begets increasingly dangerous substances. The long-term solution is drug legislation reform, but until this happens we are obliged to wait for the next alert to flash up as a new, more potent substance enters the drug stream.

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Harm reduction

While all use of street opiates brings a risk of overdose, the potency and variability of fentanyls bring an unparalleled level of risk. Scattergun warnings can reduce their credibility, and so assessing what is going on locally is important:

• Engage with people who are using to determine what is being offered, and if ‘white heroin’ or other potential fentanyl-laced products are appearing on the market.

• Make bulletins up to date and locally relevant.

• Ensure that facts are established before cascading information by developing a local drugs warning protocol in conjunction with user groups, police and public health.

‘Fentanyl=death’ messages are inadequate as, without access to licit compounds, people will still access the street market and so harm reduction is also essential.

Core opiate harm reduction messages remain relevant, and need to be re-stressed:

• Smoking represents the lowest risk of fatal overdose and this should be emphasised, alongside provision of foil.

• Overdose risk increases when opiates are used alongside alcohol or other sedating drugs including benzodiazepines, z-drugs or gabapentin/pregabalin.

• Sampling batches before use and injecting slowly can reduce risk.

• Fentanyl overdoses can reportedly be very rapid.

• Use with company who can respond in the event of an emergency; if using together don’t all use at the same time.

• Ensure availability of naloxone and a phone that works.

• It is imperative that an ambulance is called in the event of an OD.

• OD may require larger doses of naloxone than a heroin OD and distributors may need to review training and the number of kits distributed if fentanyl is a local issue.

• Encourage retention and submission of samples post OD for analysis.

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Kevin Flemen runs the drugs education and training initiative, KFx. Visit www.kfx.org.uk for information and free resources.