KEY TAKEAWAYS
Nitazenes are new synthetic opioids 10x more potent than fentanyl and are used as recreational drugs in the UK, US, and other countries worldwide.
What Is Nitazenes Addiction?
Protonitazene is a strong μ-opioid receptor agonist with 1.29x higher efficacy and a strong potential for addiction compared with fentanyl [1].
Consumption leads to decreased consciousness, particularly in overdose.
71.4% of varied substances are mixed with nitazenes, causing nitazene addiction to go unnoticed [2].
An individual who has consumed nitazenes appears euphoric and relaxed but, in severe cases, will not be able to communicate because of depressed levels of consciousness.
Nitazenes Vs Other Opioids
Drug | Nitazenes | Heroin | Morphine |
|---|---|---|---|
Strength | 10x stronger than fentanyl [3] | 1.5x stronger than morphine [4] | 10x stronger than tramadol [5] |
Administration | Vaping, sublingual, injection, nasal | Vaping, injection | Injection, oral, rectal |
Lasting drug effects | 2 minutes-4 hours | 2-4 hours | Short-acting morphine lasts for 2 to 4 hours |
Reduces pain? | Comparable to morphine | Heroin acts quicker than morphine | Analgesic effects peak at 5-10 minutes |
Prescribed/illicit | Illicit | Illicit | Both |
Drug | Codeine | Fentanyl |
|---|---|---|
Strength | 1/10 of the strength of morphine [6] | 50 - 100 times more potent than morphine [7] |
Administration | Oral, injection | Injection, transdermal, nasal, oral |
Lasting drug effects | 3-6 hours | 72 hours |
Reduces pain? | Analgesic effects peak at 2 hours | Analgesic effects peak at 2-5 minutes |
Prescribed/illicit | Both | Both |
Drug | Methadone | Tramadol |
|---|---|---|
Strength | Equipotent to morphine | 1/10 of the strength of morphine [5] |
Administration | Smoking, nasal, injection, oral | Oral, nasal |
Lasting drug effects | 8 - 12 hours | Up to 24 hours in extended-release |
Reduces pain? | Analgesic effects peak at 3 hours | Analgesic effects peak at 2 - 3 hours |
Prescribed/illicit | Both | Both |
Nitazenes Side Effects
Physical Side Effects
Nitazenes cause a depressed respiratory rate of 38±2% from baseline, leading to hypoxia and subsequent coma [8].
Consumption leads to coughing in 45% of cases, similar to strong fentanyl doses (7µg/kg) [9].
Lightheadedness and dizziness from morphine consumption occur at the same rate in nitazene-related consumption, even when the dose is smaller.
Consumption results in dizziness and confusion, and an individual will appear relaxed but zoned out.
Combined consumption with methadone, lualprazolam, and flubromazepam results in cardiac and respiratory arrest.
Psychological Side Effects
Nitazenes act on the opioid receptors within the central nervous system, leading to a relaxed mood and sedation.
Fentanyl users experience hallucinations, akin to nitazenes that also elicit psychoactive effects on opioid receptors.
Nitazenes presence in the bloodstream promotes GI protein signalling, reinforcing drug-seeking behaviours in users.
Overexpression of GI proteins reduces rewarding efficacy in the brain, resulting in tolerance.
High lipophilicity also results in rapid absorption, leading to euphoria faster than morphine.
Mixing Nitazenes With Other Drugs
Heroin | Fentanyl | |
|---|---|---|
Why They Are Mixed With Nitazenes | Reduced heroin production means more demand for nitazenes Nitazenes are cheaper Nitazenes are sold online - more available 45% of heroin users supplementing use with prescribed opiates now use nitazenes instead [10] Reduces heroin withdrawal symptoms Nitazenes and heroin act on μ opioid receptors | Drug sellers lace nitazenes in illegally bought fentanyl Nitazenes are less restricted than fentanyl Fentanyl’s analgesic effects increase with nitazenes Both nitazenes and fentanyl act on κ type opioid receptors |
Physical Side Effects | Reduced lung function and respiratory depression >30% lowered body tissue oxygen [11] Hypoxia Inhibited pain Apnea and lowered SpO2 (<88%) Increased opioid tolerance Longer intoxication than heroin alone | Respiratory depression Depressed levels of consciousness Increased self-reported pain Increased opioid tolerance Bradycardia |
Psychological Side Effects | Depression and anxiety Psychosis and paranoia Blunt emotions Confusion Drug-seeking behaviour | Depression Visual hallucinations Cognitive and memory impairment Mental clouding and confusion Drug-seeking behaviour |
Oxycodone | |
|---|---|
Why They Are Mixed With Nitazenes | Drug sellers lace nitazenes in illegally bought oxycodone Enhances euphoria and subjective high Increased opioid dependency
Nitazenes are less restricted than illicit use of oxycodone |
Physical Side Effects | Shallow breathing and respiratory depression Serotonin syndrome Fever Unresponsiveness and sedation |
Psychological Side Effects | Euphoria Lowered episodic memory Reduced psychomotor functioning Drug-seeking behaviour |
What Settings Are Nitazenes Most Likely To Be Used In?
A history of mental health issues and substance misuse disorder are risk factors for combined consumption with oxycodone.
Individuals formerly prescribed narcotics for extreme pain relief seek illegal, stronger variations when a prescription is no longer available due to addiction.
The global decrease in heroin production encourages drug sellers to substitute with new synthetic opioids to meet the demand of drug users.
Drug sellers also cut nitazenes into heroin to generate more profit, as nitazene-related drugs are inexpensive in comparison.
Stricter measures in place for prescribing opioids have seen a decrease in narcotics prescriptions, leading to a heightened need to source illicit nitazenes for users who are addicted.
The production of nitazenes is less regulated than non-synthetic opioids, making them more readily available.
Test strips cannot detect nitazenes in fentanyl, making it challenging for the user to know what substance is being consumed.
Who Is More Likely To Take Nitazenes?
Profile Of Users Before Taking Nitazenes | Circumstances Leading To Nitazene Use |
|---|---|
Oxycodone users | |
Fentanyl users (prescribed/non-prescribed) | |
Heroin users | |
Poly-drug users |
At Risk Groups When Taking Nitazenes
Recently Detoxed
Tolerance decreases rapidly after detoxification of nitazenes, so if users administer the same high dose as before, this poses a hazard of side effects and overdose.
A lack of awareness of how much tolerance reduces in nitazene withdrawal leads to potentially fatal relapses, even if individuals take smaller doses of nitazenes than before.
Extended detox of nitazenes and other narcotics reduce respiratory tolerance, leading to respiratory depression and opioid-related overdose mortality during relapse.
Individuals who have been in prison for 2+ weeks have a 129x greater risk of severe opioid overdose upon release, and research demonstrates this rises when consuming of nitazenes [14].
Not Previously Taken Opioids
The volume of fentanyl required to cause 50% respiratory depression in opioid-naïve individuals is 333% less than in chronic opioid users, with this number rising in stronger opioid consumption [15].
Oxygen saturation can drop to SpO2 <88% within 4 hours of administration in opioid-naïve individuals beginning consumption [16].
Remifentanil-induced hyperalgesia rises by 180 ± 47% for opioid-naive patients with pre-existing pain, and this rises when stronger opioids are consumed [17].
Opioid-naïve individuals taking nitazenes experience immunosuppression and secondary infections compared to an individual who has been using the drug for longer.
Elderly
Opioid receptors are impaired in old age, making older people more susceptible to the factors commonly associated with beginner consumption.
Chronic consumption generates histamine release, reducing blood pressure and vascular resistance in elderly users.
Elderly individuals are more at likely to develop opioid-induced urinary retention, where urinary retention occurs in 1 in 3 men over 80 years old [18] [19].
A 77% reduction in metabolism in the elderly leads to neurotoxicity of opioid consumption, as the drug accumulates in their body for longer [20] [21].
Concurrent Prescribed Medication
There is a 1.23x greater risk of opioid overdose through the combined use of paroxetine or fluoxetine SSRIs and oxycodone, and research suggests this rises with more potent variations [22].
25% of reported cases of serotonin syndrome resulted from the combined consumption of SSRIs and opioid analgesics, and this rises with serotonergic nitazenes [23].
When combined with benzodiazepines, there is a 21.4x greater chance of emergency hospital admissions and opioid overdose [24].
Concurrent use of opioids with warfarin raises INR by 17.7%, leading to impaired blood clotting, especially when nitazenes are taken [25].
Mixing amphetamines with non-synthetic opioids enhances the analgesic effects.
(Read about amphetamine rehabilitation.)
Pregnancy
Narcotics use during pregnancy leads to a 6.4% rise in caesarian section births, and this increases when nitazenes are used [26].
3.1% of offspring from narcotics users required respiratory intervention for 7 days postpartum, with this increasing with potent strains [27].
Opioid use during pregnancy leads to neonatal syndrome, and this is 10x more likely when nitazenes are used throughout pregnancy due to their potency [28].
There is an elevated risk of stillbirth when the mother uses synthetic opioids during pregnancy, with this risk varying with the concentration of use.
Neonatal exposure to narcotics leads to a 68.4% heightened chance of developing chronic pain during childhood, with this risk being similar with nitazene consumption during pregnancy [29].
10% of pregnant women who inject their drugs develop HIV, and this is transmitted to their offspring in 1 in 20 cases [30].
Use Around The World
United States | United Kingdom | |
|---|---|---|
Prevalence | 22% of illicit opioid cases [31] | 36% of illicit drug cases [32] |
Drug use/possession laws | Schedule I | Class A |
Mortality rate | 42 deaths in 2021 in Tennessee [33] | 54 deaths in the last 6 months [34] |
Cost of addiction treatment | Up to $20,000 (private) | Free (NHS) |
Production/ trafficking route | From China | From China |
Public Awareness | 5 public announcements in 3 years | 7 public announcements in 3 years |
Demographics | Urban areas Mostly males White/black race Low socioeconomic status Homelessness | Urban areas Homelessness Low socioeconomic status |
Nigeria | Brazil | |
|---|---|---|
Prevalence | 83% of illicit drug cases [35] | 95% of illicit opioid cases [36] |
Drug use/possession laws | Monitored by United Nations | Class A1 |
Mortality rate | Data not available | Data not available |
Cost of addiction treatment | £200 (private - GBP equivalent) | £1400 (GBP equivalent) |
Production/ trafficking route | From China | From China |
Public Awareness | 1 public announcement in 3 years | 1 public announcement in 3 years |
Demographics | Urban/rural areas 21 - 30 year olds Mostly males Low socioeconomic status | Mostly females Low socioeconomic status Unemployment Low family income |
Legality
As of 22nd February 2023, 10 forms were made illegal in the UK:
Desnitroetonitazene and etonitazepyne are not officially controlled by the UK's Misuse of Drugs Act (1971), though these regulations are continually updated.
Individuals caught possessing, importing, or supplying any form of nitazene are subject to criminal charges under the Psychoactive Substances Act 2016.
As soon as one variant becomes illegal, new strains appear in the illicit drug marketplace, taking up to 5 years to be made illegal.
A lack of knowledge makes it challenging to identify this synthetic opioid, especially when mixed in other substances.
Nitazenes Recovery Challenges
The extent of withdrawal symptoms during immediate cessation is unknown, complicating detoxification care plans.
64% of oxycodone users inadvertently take nitazenes that are laced in the drug [37].
A 50 times rise in narcotic potency increases the chance of relapse [38] [39].
Recovery From Overdose
10mg of naloxone for metonitazene overdose reverses cardiac arrest symptoms in 50% of cases, whereas up to 8mg reverses respiratory depression symptoms in 100% of N-piperidinyl etonitazene overdoses [40].
97% of overdoses require stronger and more frequent naloxone doses (1+) compared with fentanyl overdoses [41].
Intake of naloxone results in tachycardia, hypotension, or hypertension in 1-10% of individuals, and with large doses of naloxone required during nitazene overdose, these risks are increased.
Cerebral edema is seen in 22% of overdose cases, resulting in reduced brain functioning and ability to maintain detoxification programmes [42].
4.4mg of naloxone during opioid overdose increases the pulmonary complications risk by 62%, and this is further complicated in nitazenes overdose, where ~10mg is required [43].
