Nitazenes
Nitazenes, or benzimidazole opioids, are a class of potent (very strong) synthetic opioids. They are similar to heroin and fentanyl, but are much stronger. They range from 50 to 500 times more potent than street heroin.
They were originally developed in the 1950s as painkillers, but were never approved for medical use or made into a product. Recently they have appeared in the illicit drug supply chain, mostly added to illicit heroin powder to make it appear ‘stronger’. Nitazenes have also been detected in illicit benzodiazepines and synthetic cannabinoids which may affect a larger group of people in society.
The supply of nitazenes in the UK and Europe is possibly driven by the Taliban’s ban on opium poppy production in Afghanistan. Previously Afghan opium accounted for around 95% of European heroin production and without that supply producers and traffickers must look elsewhere to fill the void.
There are many different nitazenes currently on the market, and the potency varies greatly depending on the specific nitazene in question. The most common examples are protonitazene, metonitazene, isotonitazene and etonitazene. Most people who take nitazenes aren’t aware that they are taking them.
Nitazenes on the street typically appear as adulterants to other drugs, either being mis-sold or in addition to another drug in powder or pill form. Nitazenes don’t have a particular look or colour and can be bought as a powder or pressed into pills.
WEDINOS, a drug testing lab in Wales, has detected nitazenes as a contaminant in drugs sold as benzodiazepines (diazepam (Valium), zolpidem, temazepam, alprazolam (Xanax) and flubromazolam), opioids (heroin, oxycodone, fentanyl), 2C-B, synthetic cannabinoids (5F-ADB, 5CL-ADB-A, spice), THC vape liquids, promethazine.
Further research is needed in establishing the exact methods by which nitazenes act. Nitazenes are potent activators of mu-opioid receptor (MOR), in the brain. This is the same receptor which other opioids, like heroin, methadone and fentanyl bind to. However, nitazenes are much more selective and have a higher affinity for these receptors. This means that their effects on the body last longer.
The mechanism of action and duration of action may vary depending on which nitazene is in question.
Nitazenes are highly lipid soluble, which means they cross the blood brain barrier quickly and get to the brain. Nitazenes are highly selective to MOR over other opioid receptors such as κ-opioid receptors and δ-opioid receptors (with between 1000 - 15,000 times greater relative potency at MOR depending on which nitazene is investigated). It is worth noting however that the potency and mu-opioid specificity varies greatly between different nitazenes just as it does between different fentanyls, but those present in illicit drugs are generally more potent.
The time of onset and duration of effects from nitazenes is not well understood and is varies depending on which nitazene is used. The effects are often felt more quickly when injected or smoked. The effects may take longer to be felt if snorting or swallowing the drug. The duration of the ‘high’ experienced also depends on the route of administration and nitazene used but can be expected to last for longer than heroin or fentanyl.
Subjective effects of nitazenes are often like those of traditional opioids, and can include mental euphoria, a feeling of bliss, lethargy and tiredness (which can cause users to ‘nod’ and fall asleep due to the effects) and reduced anxiety.
Physical effects include analgesia, constipation, dehydration, pinpoint pupils and respiratory depression.
Although nitazenes were initially developed as analgesics in the 1950s, their development was stopped due to their extreme potency. As a result, no nitazene has been approved for medical use in any country.
Overdose
Taking an overdose of a nitazene may lead to respiratory depression, or death from a severe overdose. Where respiratory depression leads to hypoxia this may cause brain damage, especially on repeated overdose. The potency of nitazenes varies, however they are generally 50-500x times more potent than heroin, and very small amounts can be lethal.
An overdose can be temporarily reversed by administering naloxone. Because nitazenes bind more strongly to opioid receptors in the brain, their effects last longer and as a result multiple, repeated doses of naloxone are often required. It may be necessary to administer more/higher doses of naloxone to reverse nitazenes than for heroin. Medical assistance should be sought immediately if an overdose is suspected.
Due to the extended duration of effect of nitazenes there have been reports of naloxone wearing off before the nitazenes, leading to another re-overdosing. It may be necessary to administer naloxone over a greater length of time than for traditional opioids, and people should be monitored for up to 24 hours following an overdose. Therefore, it’s important to call the emergency services, together with administering naloxone, in case of suspected opioid overdose of any type.
If a person has taken an overdose, they may fall unconscious and become limp. Their skin may also become clammy, and the fingertips and lips of lighter-skinned people and the inside of darker-skinned people’s lips may turn blue. Pin-point pupils are a symptom of all opioid overdoses, including nitazenes.
To reduce the risk of overdose, users should start by taking a small dose and see how they feel, rather than taking a large dose all at once. It is also advised to have a trusted person who, has a supply of the antidote naloxone, around when using nitazenes, so that they can administer it in the event of overdose.
Addiction and dependence
Nitazenes should be considered highly dependence forming due to their high potency, rapid onset and euphoric effects. Dependence can form following prolonged nitazene exposure.
Withdrawal symptoms may include:
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Muscle and bone pain
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Difficulty sleeping
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Diarrhoea and vomiting
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Cold flashes
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Uncontrollable leg movements
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Severe cravings
If you are using nitazenes, it is important to be aware of the signs of addiction and tolerance. For example, experiencing strong cravings and requiring increasingly higher doses to produce the same effects. Medical help is available to those experiencing addiction.
Loss of consciousness/not responding to pain
High doses of nitazenes can cause the user to pass out in dangerous positions and stop the user from recognising that this is causing pain, leading to the user spending an extended period of time in this position. This can lead to pinched nerves, which may have permanent symptoms and reduced movement of the effected area. Whilst pinched nerves following the use of opioids are uncommon, when it does occur it presents most commonly in the arms and legs.
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There are a few health conditions which may make using nitazenes more dangerous. For example, any lung conditions (such as asthma) and arrhythmia (irregular heartbeats).
Avoid mixing nitazenes with other drugs or alcohol.
The specific interactions between nitazenes and other drugs are not well studied, but extrapolation from other opioids suggests that mixing nitazenes with depressant drugs, such as alcohol, benzodiazapenes or gabapentinoids is especially dangerous. This combination can greatly increase the risk of life-threatening respiratory depression.
Mixing nitazenes with stimulants (such as amphetamine) can mask the effects of the nitazene, causing the user to take too much, and cause overdose when the stimulant wears off.
When nitazenes are used as an adulterant for other drugs, the risk of overdose is increased as the user is most likely unaware of the amount of the nitazene present. Nitazene test strips are available at drug treatment services. It is always worth having testing equipment available and strips can be purchased using this link https://www.exchangesupplies.org/shopdisp_SC103.php. Professional drug checking services offer more accurate results and should be used where possible.
When nitazenes are used as an adulterant for other drugs, the risk of overdose is increased as the user is most likely unaware of the type, strength or amount of the nitazenes present.
Drug testing services (i.e. The Loop, WEDINOS) can detect nitazenes in drugs and are free to access. Nitazene test strips are available which can identify if a nitazenes is present. It is always worth having testing equipment available and strips can be purchased using this link https://www.exchangesupplies.org/shopdisp_SC103.php. Professional drug checking services offer more accurate results and should be used where possible.
Naloxone – if you are using opioids, it is important to have naloxone available to reverse an overdose.
Avoid injecting – it is less dangerous to take opioids by mouth or smoking them rather than injecting them. However, if you are determined to inject opioids, then do not share or reuse needles – clean needles can be obtained from many community pharmacies.
Nitazenes are not reversed by naloxone
Whilst more naloxone may be required to reverse a nitazene overdose compared to heroin naloxone should always be given to anyone suspected of a nitazene overdose. However, due to the potency and duration of some nitazenes, more doses may be required than for overdoses to other opioids and the user may require observation for up to 24 hours with repeat administration of naloxone. Administering naloxone does not harm the user, even if they have not used any opioids, but will cause an immediate reversal of an opioid overdose.
All nitazenes are the same
There are many nitazene analogues in the illicit market, and many more still confined to laboratory research and not yet in the illicit supply chain. Not all of these nitazenes are equally potent and not all carry the same risks. However, extreme caution is advised with all nitazene compounds as they are not well studied and the long-term harms are not known.
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