What Is Nitazenes Addiction

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Nitazenes (NTZs, 2-benzyl benzimidazole opioids) addiction is:

Taking 3mg within 25 minutes and continuing to re-dose 5 – 10x daily to satisfy cravings [1]
Taking nitazenes to prevent withdrawal symptoms from developing 7 – 9 hours after the last dose [1]

What Is Nitazenes Addiction?

Nitazenes addiction is:

Having a “strong desire" to re-dose after consuming 500 µg etazene intranasally and taking 1.5mg every 30 minutes until falling asleep due to the development of tolerance and cravings within 2 weeks of heavy use (e.g. 5 - 10 doses daily) [1]
Taking 1 pill every 7 hours to avoid NTZs withdrawal symptoms (e.g. sweating, leg restlessness) or waking up early to “dose” to prevent acid reflux and shakiness from developing within 9 hours of the last use [1]

NTZs addiction develops after users continue to take benzimidazole-derived synthetic opioids to recapture the initial “euphoric glow” and drowsy sensation experienced within 30 minutes of taking a 1mg dose because [1]:

NTZs are 130x more potent than morphine (MOR) and 20x more potent than fentanyl (FEN), with a stronger binding affinity (Ki = 1.09 nM) at the mu (μ) receptor in comparison to both substances (Ki = 2.17 + 3.04 nM) [1]
Dopamine (DA) increases by 227 – 253% in the nucleus accumbens within 20 minutes of taking metonitazine and flunitazene, lasting up to 3 hours after consumption [2]

Physical Indicators Of Nitazenes Addiction

Rapid Weight Loss

Rapid weight loss (e.g. > 5% body weight in 1 month) is a physical indicator of nitazenes addiction because [3]:

NTZs bind to μ-receptors (Ki = 1.09 nM) in the hypothalamus and inhibit the release of neuropeptides (e.g. NPY/AgRP neurons) responsible for appetite stimulation [1]
The motivation to eat is diminished after the brain’s reward system becomes desensitised to natural rewards due to a 253% increase in dopamine after taking NTZs vs ~ 50% increase after eating ‘pleasurable’ foods (e.g. chocolate) [2][4]
Prolonged μ-receptor activation after some users re-dose 5 – 10 times a day, interferes with ghrelin and leptin signalling due to NTZs being rapidly metabolised (72 – 100% depletion within 30 mins) by cytochrome P450 enzymes (CYPs) [1][5]

NTZs addiction is likely to trigger weight loss at a faster rate than fentanyl (e.g. 39% of daily users lose >5% of body weight in 3 months) due to NTZ analogues (e.g. etonitazepyne) being 20 times stronger [1][3].

Skin Discolouration

Skin discolouration is a physical indicator of nitazenes addiction caused by bradypnea (e.g. 6 breaths/min) and hypoxemia (i.e. oxygen saturation = 65%), leading to a bluish-purple discolouration of the skin and mucous membranes within 90 minutes of use [6].

Skin discolouration occurs because NTZs are respiratory depressants, often causing breathing difficulties, blue lips or fingertips, and cold or clammy skin, although cases are typically associated with high blood concentrations (e.g. 286 ± 556 ng/mL) [1].

Schumann et al. (2022) studied a woman who was hospitalised due to cyanosis and an oxygen saturation of 50% after regularly taking protonitazene, although after 20 hours of supportive care (e.g. BVM), the patient was discharged [6].

Dehydration

Dry mouth is a physical indicator of nitazenes addiction caused by a 42 times greater agonism at μ-receptors than other opioids (e.g. morphine) that reduce salivary flow rates by 20 -27% after inhibiting parasympathetic nervous system (PNS) activity [1][7].

Xerostomia is likely to be exacerbated in 41% of protonitazene users who inhale the drug using a vape because the salivary flow rate of e-cigarette users is typically 2x lower than non-users (0.94 vs 1.92 mL/min), leading to hyposalivation (<1.0 mL/min) [8][9].

Dehydration is likely to be intensified in etonitazepyne users who experience “severe” sweating and vomiting around 7 hours after taking the last dose and etazene users who may forget to drink fluids during a 6-hour binge episode (e.g. taking 1.5mg every 30 mins) [1].

Oedema

Pulmonary oedema (right lung = 1260g + left lung = 900g vs normal weight = 675 – 720g) after abusing around 1g isotonitazene per month is a physical indicator of nitazenes addiction because fluid accumulates in the alveolar tissue due to [11]:

Excessive release of antidiuretic hormone (ADH) from the pituitary gland after NTZ analogues bind to μ-receptors (Ki = 1.09 nM) in the hypothalamus with a 31 - 42x greater agonism than other μ-receptor agonists (e.g. FEN, MOR) [1]
A damaged alveolar-capillary barrier caused by low levels of oxygen (e.g. 55%) and high levels of carbon dioxide (i.e. hypercapnia = arterial PCO2 6.49 kPa [48.7 mmHg]) in the blood after NTZs misuse [10]

Losing Consciousness

Losing consciousness within 1 hour of consuming 4 protonitazene doses for “relaxation purposes” is a physical indicator of NTZs addiction caused by low oxygen (e.g. O₂ = 50%) in the blood and tissues due to [6][12]:

Bradypnoea (i.e. respiratory rate = 6 breaths/min) after abusing NTZs purchased from the internet, leading to inadequate oxygenation of the brain (cerebral hypoxia) [6]
Hypotension (e.g. blood pressure = 87/32 mmHg) and bradycardia (e.g. heart rate < 60 BPM), resulting in some users becoming totally unresponsive (GCS = 3/15) due to cerebral hypoperfusion [10][13]

Presyncope symptoms (e.g. dizziness) can occur immediately after consuming NTZs, followed by drowsiness within 30 minutes of use after neuronal activity is suppressed by a CNS depressant 3 – 10x stronger than other synthetic opioids (e.g. fentanyl) [1][12][14].

Abu-Rumeileh et al. (2024) studied a 19-year-old male who was found unconscious after taking metonitazene, although the patient’s level of consciousness improved (GCS = 3 to 15) within 4 hours of being intubated in hospital [13].

Gasping For Breath

Gasping for breath (indicated by RR = 6 breaths/min) is a physical indicator of synthetic opioid addiction because the normal inhalation-exhalation rhythm (12–20 breaths/min) is disrupted by the overstimulation of μ-receptors in the medulla and pons [8].

Hypoventilation (< 8 breaths/min) occurs in up to 94% of NTZ users due to the suppression of the brainstem respiratory centre during intoxication, leading to hypoxemia (SpO < 90%) and hypercapnia (e.g. PaCO2 >6.0 kPa /45 mmHg) [8].

The brainstem triggers agonal respirations to compensate for critically low O₂ (e.g. 55%) levels and high CO₂ (e.g. arterial PCO2 6.49 kPa [48.7 mmHg]) levels in the blood caused by persistent shallow breathing (e.g. 4 breaths/min) after abusing isotonitazene [10].

Burow et al. (2024) studied a 19-year-old who developed type 2 respiratory failure (hypoxemia + hypercapnia) after abusing NTZs, although after 2 days in ICU, oxygen levels (O₂ = 98.5%) and respiratory rate (20 breaths/min) normalised [13].

Psychological Indicators Of Nitazenes Addiction

Emotional Dysregulation

Feeling euphoric and drowsy for around 30 minutes after taking NTZs, and then becoming hypervigilant around 4 – 5 hours later, is a psychological indicator of being addicted to 2-benzyl benzimidazole opioids because [1][13]:

The brain struggles to regulate mood after dopamine levels begin to decline around 3 hours post-use, following a 227 – 253% spike in the mesolimbic pathway within 20 minutes of consuming nitazene analogues [2]
Heart rate (+10 BPM), body temperature (+1.5°C), and blood pressure (+26/32 mmHg) rise around 4 hours after taking the last dose, resulting in sweating, shakiness, and restlessness [1][13]

Mueller et al. (2021) studied an isotonitazene user who experienced cycles of euphoria and relaxation followed by “intense psychic stress", psycho-motor agitation, and episodes of cold sweating after using a vaporising pipe to consume around 1g per month [11].

Intrusive Images Of Nitazenes Use

Intrusive images of 2-benzyl benzimidazole opioid use are a psychological indicator of NTZs addiction because:

After repeated use (e.g. 5 – 10 doses daily for 2+ weeks), the brain associates drug administration methods (e.g. injecting, vaping) with euphoria and relaxation due to the 253% increase in dopamine within 20 minutes of drug-taking [1][2]
Vivid “flashbacks” are triggered by drug paraphernalia (e.g. e-cigarette devices) due to classical conditioning after 41% frequently vape and 19% inject or ingest NTZs to facilitate sleep or suppress withdrawal symptoms (e.g. sweating) [1][8]
Cravings and “strong desires" to re-dose provoke mental images of the drug-taking process (e.g. swallowing 1 pill), as users ruminate about the initial drowsy sensation experienced within 30 minutes of consumption [1]
Memories of drug-use patterns are encoded and rehearsed after taking NTZs daily and may be retrieved automatically due to the reactivation of hippocampal networks during and after binge episodes (e.g. taking 1.5mg every 30 mins) [1]

Hypnagogic Hallucinations

Hypnagogic hallucinations are a psychological indicator of NTZs dependence caused by the rebound of REM sleep during periods of withdrawal (e.g. 7 – 9 hrs after the last dose) after being suppressed for around 6 hours whilst intoxicated [1].

Hypnagogic hallucinations typically occur during the transitional period from wake to sleep due to the intrusion of REM features (e.g. dreams) at sleep onset after taking 1 - 1.5mg etazene every 10 – 30 minutes until falling asleep [1].

Ohayon (2000) found that opioid use increases the odds of having hypnagogic hallucinations ≥ 1x weekly by 2-fold, and visual, auditory, or haptic disturbances are likely to be exacerbated in those who abuse NTZs rather than traditional opioids due to [15]:

Stronger binding affinities (Ki = 1.09 nM) at the μ-receptor in comparison to MOR (Ki = 3.04 nM) and FEN (Ki = 2.17 nM), leading to the feeling of “falling down an abyss” or “being caught in a fire” due to sleep-wake irregularities and REM intrusion [1][15]
A 20x greater in vivo effect than fentanyl and a 130x greater antinociceptive effect than MOR, leading to a “dream-like state” and CNS depression with experiences of seeing and hearing imaginary people or objects [1][15]

Risks Of Nitazenes Addiction

Naloxone Not Working During Overdose

Naloxone (NLX) not working during drug overdose poses risks during addiction, as multiple high doses (e.g. 3x 400 µg IM/IV doses + 600 µg/h infusion for up to 10 hours) are required to block the toxic effects of NTZs (e.g. GCS = 3/15 + sO2 = 55%) because [10]:

Some patients remain unresponsive and bradypnoeic after receiving 2 intramuscular 400 µg NLX injections following an isotonitazene overdose due to the drug being 250 times more potent than heroin [10][16]
3 NLX doses (0.8mg IV + 0.8mg IM + 0.4mg IM) plus 25 minutes of cardiopulmonary resuscitation are needed to reverse respiratory arrest during protonitazene overdose due to the drug’s high affinity (Ki = 1.09 nM) for mu-opioid receptors [1][12]

Around 36% of patients who are hospitalised after overdosing on 2-benzyl benzimidazole opioids require NLX infusions following the initial 800µg dose due to severe, persisting symptoms (e.g. 4 breaths/min) caused by NTZs up to 500x stronger than heroin [10][16].

Roberts et al. (2025) found that 45% of protonitazene and isotonitazene overdose cases required repeated parenteral or intranasal NLX doses after the initial 400μg dose failed to reverse hypoventilation (8 breaths/min) and miosis (pupil diameter ≤ 2mm) [8].

Unknown Potency Levels

Unknown potency levels pose risks during addiction because varying amounts (e.g. 3.7 – 4.0 mg) of NTZ analogues (e.g. protonitazene) are found in the tablets taken daily by users who purchase the illicit drugs from the "darknet" or phone-based "dealers" [17].

Schumann et al. (2023) studied a woman who overdosed due to butonitazene being mixed into the same formulation as tablets listed as 'protonitazene' online, resulting in 20 hours of hospitalisation after receiving CPR, bag-valve-mask ventilation, and 2mg IV NLX [6].

Dugues et al. (2025) investigated the strength of NTZ tablets manufactured without dosage control and found that the metonitazene content ranged from 3.2% to 6.0%, equivalent to approximately 23mg fentanyl (10x the lethal dose) [17].

Polydrug Use

Mixing stimulants with NTZs poses risks during addiction because oxygen levels become dangerously low (e.g. 50%) after the body demands more O₂ than can be supplied to compensate for an overactive sympathetic nervous system (SNS) [6].

Greene et al. (2023) studied two hospitalised females who lost consciousness (GCS 3/15) after consuming etodesnitazene and protonitazene with stimulants (amphetamine + methylamphetamine) due to:

Low oxygen levels (O₂ saturation = 50 – 65% vs normal levels = 95 – 100%) and respiratory depression (e.g. RR = 6 breaths/min), requiring CPR followed by the provision of oxygen and ventilation via bag-valve-mask at 15 L/min
Cardiac complications (e.g. hypotension = 90/50 mmHg) and cyanosis, although patients were discharged 8 - 20 hours later after O₂ levels (98%) and respiratory rates (17 breaths/min) normalised [6]

Roberts et al. (2025) investigated 20 cases of acute NTZ poisoning and found that 90% of biological samples (e.g. urine, blood) tested positive for codetections, including cocaine, MDMA, and amphetamines, resulting in:

Sedation in 100% of cases, hypoventilation (< 8 breaths/min), miosis (pupil size ≤2 mm), serotonin toxicity, ventricular tachycardia (HR > 100 BPM), rhabdomyolysis (peak creatine kinase = 18,500 U/L), and type 2 non-ST-elevated myocardial infarction
Extracorporeal membrane oxygenation (ECMO), CPR, and repeated NLX doses due to the recurrence of sedation and hypoventilation between 30 minutes and 4 hours after the initial 400 μg reversal dose failed [8]

Who Is More Likely To Develop Nitazenes Addiction?

Demographic More Likely	Why?
Heroin/Fentanyl Addicts	Taken as a “step up” after tolerance develops to a weaker opioid NTZs are 20 - 500x stronger [1]
Prescription Drug Users	≤ 4mg ingested accidentally via counterfeit OXY pills [17] Continued use due to "strong effect" [17]
Under 30s Seeking MDMA Or Ecstasy	NTZs poisoning in 15% of 27 y/o after intending to take MDMA [8] 41% increased opioid + stimulant use vs over 50s [18]
Homeless Individuals	100-500x cheaper & stronger than heroin used in homeless populations [1]
Pre-existing Mental Health Disorders Self-medicated With Opioids	Mental illness & illicit drug use in 66 - 94% of fentanyl users [19] May seek NTZs 20x higher strength for escapism [1][19]

Nitazenes Addiction Vs Fentanyl Addiction

	Nitazenes Addiction	Fentanyl Addiction
Potency	Up to 500x stronger than heroin [16]	50x stronger than heroin [16]
Average Onset & Duration Of Euphoria	Within 30 mins, lasting ≈ 4-6 hrs [1]	5 - 15 mins, lasting ≈ 2-4 hrs [20]
Number Of Redosings Per Day	5 - 10 [1]	3 - 4 [21]
Overdose Risk	50% of overdoses are fatal [22]	9% of overdoses are fatal [22]
Cognitive & Behavioural State	Intense psychic stress + insomnia after 1g p/m [11]	Anxiety & agitation after 1 - 3g p/d [21]

How Does Using Nitazenes With Other Drugs Affect Nitazenes Addiction?

Drug Mixed With Nitazenes	Interaction With Nitazenes
HIV medications	May raise NTZ's plasma concentrations via CYP3A4 inhibition [23]
Antidepressants	5-HT1/2A agonism (NTZs) + SERT inhibition (SSRIs)
Benzodiazepines	Enhanced GABAergic activity & μ-receptor agonism = additive CNS depression
Alcohol	NMDA inhibition exacerbates NTZ's effects (e.g. RR = 4 breaths/min)
Antihistamines	ACh & H1 receptor blockade + strong μ-receptor binding (Ki = 1.09 nM) = oversedation [1]
Antibiotics	Disrupts CYP3A4 activity & slows NTZs metabolism
Corticosteroids	CYP3A4 enzyme induction lowers NTZs blood levels
Antipsychotics	Psychomotor slowing via MOR activation & H1 + alpha-1 + D2 antagonism

Drug Mixed With Nitazenes	How It Changes Nitazenes Addiction
HIV medications	Excessive drowsiness + quick tolerance (e.g. 14 days) [1]
Antidepressants	Depressive crash + possible serotonin syndrome
Benzodiazepines	Contributes to 52% of fatal overdose cases [24]
Alcohol	Dual-dependence & intensified physical symptoms (e.g. sweating after 7hrs) [1]
Antihistamines	Ritualised behaviour & psychological addiction after initial relaxant effect
Antibiotics	Initial “high” indirectly reinforces use despite risks
Corticosteroids	Weakened effect = re-dosing 10x p/d to achieve euphoria [1]
Antipsychotics	Falls/accidents after dose escalation (e.g. 1.5mg every 30 mins) [1]

References

[1] World Health Organization. WHO Expert Committee on Drug Dependence. Forty-Fifth Report. 8 Mar. 2023. Accessed 5 Sept. 2025. “One person reported a “strong desire to redose” (22). This 16-year-old male, weighing 85 kg, started by taking 500 µg of etazene and 10 min later took 1 mg more; 15 min after the last dose, he took 1.5 mg and repeated this dose every half hour until he went to sleep about 6 h after the first dose. All the doses were taken intranasally. He used etazene every day (about 5–10 doses a day) for the following 2 weeks.”
[2] Hataoka, Kyoko, et al. “Evaluation of Rewarding Effects of Nitazene Analogs: Results from Conditioned Place Preference Tests and in Vivo Microdialysis Experiments in Mice.” The Journal of Toxicological Sciences, vol. 50, no. 1, 2025, pp. 33–43. Accessed 5 Sept. 2025.“Significant increases in the DA levels were observed from 20 min to at least 80 min after the administration in all four nitazene analogs-treated groups (Fig. 3b). Elevated levels of DA in the NAc shell were comparable among the four groups with a peak range of 227–253%. Metonitazene and flunitazene significantly increased the extracellular DA levels in the NAc shell from 20 min to 180 min and 40 min to 160 min post-administration, respectively.”
[3] Takahashi, Hiroaki, et al. “A Retrospective Study on the Influence of Nutritional Status on Pain Management in Cancer Patients Using the Transdermal Fentanyl Patch.” Biological and Pharmaceutical Bulletin, vol. 37, no. 5, 1 Jan. 2014, pp. 853–857. Accessed 8 Sept. 2025.“Table 1. The NRS 2002 Screening System.”
[4] Sabitoni, Hannah . Dopamine: An Introduction to the “Feel-Good Chemical” - LHSFNA. 27 Jan. 2023. Accessed 8 Sept. 2025."It’s important to note that illicit drugs and alcohol release a much more intense flood of dopamine than natural rewards do. For example, eating chocolate raises dopamine levels around 50 percent above your baseline. Alcohol increases dopamine levels by around 150 percent. Amphetamines (like meth) raise levels 1,000 percent."
[5] Jadhav, Gajanan R, and Pius S Fasinu. “Metabolic Characterization of the New Benzimidazole Synthetic Opioids - Nitazenes.” Frontiers in Pharmacology, vol. 15, 18 July 2024. Accessed 8 Sept. 2025." Within 30 min of incubation, CYP2D6 depleted butonitazene (99%), isotonitazene (72%) and butonitazene (100%) significantly, ... All three nitazenes were rapidly metabolized in both HLM and HS9 with over 95% depletion within 60 min."
[6] Schumann, Jennifer L., et al. “Intoxications in an Australian Emergency Department Involving “Nitazene” Benzylbenzimidazole Synthetic Opioids (Etodesnitazene, Butonitazene and Protonitazene).” Journal of Analytical Toxicology, vol. 47, no. 1, 21 Feb. 2023, pp. e6–e9. Accessed 8 Sept. 2025.“Ambulance paramedics found the patient unconscious (Glasgow coma score 3), with a respiratory rate of six, pulse-oximetry oxygen saturation of 65%, heart rate 96 beats per minute and blood pressure 90/50 mmHg., ... cardiopulmonary resuscitation (CPR) was commenced by a friend, and upon arrival of paramedics, the patient was observed to be cyanotic with minimal respiratory effort and a pulse-oximetry oxygen saturation of 50%.”
[7] Fortuna, Giulio, et al. “Impact of Medications on Salivary Flow Rate in Patients with Xerostomia.” Clinical Oral Investigations, vol. 27, no. 1, 21 Oct. 2022, pp. 235–248. Accessed 10 Sept. 2025.“Table 3.”
[8] Roberts, Darren M., et al. “Clinical Experiences with the Nitazene Class of Synthetic Opioids: A Cohort Study.” Annals of Emergency Medicine, 14 Aug. 2025. Accessed 10 Sept. 2025.“A range of routes of exposure were noted, most commonly vaping (through refillable e-cigarette devices using refill liquid) in 11/27 cases (41% overall; but in 100% of acute opioid withdrawal cases) followed by ingestion and injection in 5/27 (19%) each.”
[9] Nourah, Dalia, et al. “Comparative Assessment of Oral Health Findings among E-Cigarette Users, Conventional Smokers, and Non-Smokers in Makkah City: A Cross-Sectional Study.” The Open Dentistry Journal, vol. 19, no. 1, Aug. 2025. Accessed 10 Sept. 2025.“Table 1.”
[10] Pucci, Mark, et al. “N-Desethyl Isotonitazene Detected in Polydrug Users Admitted to Hospital in Birmingham, United Kingdom.” Clinical Toxicology, vol. 62, no. 1, 1 Jan. 2024, pp. 19–25. Accessed 11 Sept. 2025.“Only one patient had no other substances detected apart from N-desethyl isotonitazene. This patient stated he had smoked heroin. He presented with coma (GCS 3/15), miosis, bradypnoea (respiratory rate 4 breaths per minute), hypoxia (oxygen saturation 55%) and hypercapnia (arterial PCO2 6.49 kPa [48.7 mmHg] on admission).”
[11] Mueller, F., et al. “Isotonitazene: Fatal Intoxication in Three Cases Involving This Unreported Novel Psychoactive Substance in Switzerland.” Forensic Science International, vol. 320, Mar. 2021. Accessed 12 Sept. 2025.“The individual explained that his addiction developed rapidly after about 1 g of isotonitazene consumed in 1 month, ... with the right lung weighing 1260 g and the left lung 900 g.”
[12] Stangeland, Marcus, et al. “Non-Fatal Overdose with a New Synthetic Opioid.” Tidsskrift for Den Norske Legeforening, vol. 144, 25 Jan. 2024. Accessed 15 Sept. 2025.“He claimed to have taken two doses without noticing any effect and subsequently took two more doses in quick succession. The time between the first dose and when he was found by his family was likely just under an hour.”
[13] Abu-Rumeileh, Samir, et al. “Clinical and Biochemical Profile of a Patient with Acute Metonitazene Intoxication.” Journal of the Neurological Sciences, vol. 458, Mar. 2024. Accessed 15 Sept. 2025.“Table 1.”
[14] De Baerdemaeker, K. S. C., et al. “Isotonitazene, a Novel Psychoactive Substance Opioid, Detected in Two Cases Following a Local Surge in Opioid Overdoses.” QJM: An International Journal of Medicine, vol. 116, no. 2, Mar. 2022. Accessed 15 Sept. 2025.“The patient reported smoking his usual amount of ‘heroin’ and immediately feeling dizzy following a few inhalations. He sat down on the street after which he lost consciousness, ... Analysis of the patient’s serum collected at the time of arrival to the ED (3 h 30 min after the ambulance was called), detected the presence, ... isotonitazene at a concentration of 0.18 ng/ml.”
[15] Ohayon, Maurice M. “Prevalence of Hallucinations and Their Pathological Associations in the General Population.” Psychiatry Research, vol. 97, no. 2-3, Dec. 2000, pp. 153–64. Accessed 18 Sept. 2025. “Table 2.”
[16] Holland, Adam, et al. “Nitazenes—Heralding a Second Wave for the UK Drug-Related Death Crisis?” The Lancet Public Health, vol. 9, no. 2, Elsevier BV, Jan. 2024. Accessed 18 Sept. 2025.“Table 1.”
[17] Dugues, Paméla, et al. “Emergence of Counterfeit Oxycodone Tablets Containing Nitazenes in France: First National Alert and Analytical Characterization.” Toxicologie Analytique et Clinique, Elsevier, July 2025. Accessed 19 Sept. 2025.“The estimated metonitazene content averaged 3.7 to 4.0 mg per tablet, whereas protonitazene content was below 0.1 mg per tablet, ... tablets contained an average of 3.9 mg of metonitazene, equivalent to approximately 23 mg of fentanyl, over ten times its estimated lethal dose.”
[18] Palis, Heather, et al. “Concurrent Use of Opioids and Stimulants and Risk of Fatal Overdose: A Cohort Study.” BMC Public Health, vol. 22, no. 1, Nov. 2022. Accessed 19 Sept. 2025.“Table 1.”
[19] Kilwein, Tess M., et al. “A Descriptive Examination of Nonmedical Fentanyl Use in the United States: Characteristics of Use, Motives, and Consequences.” Journal of Drug Issues, vol. 48, no. 3, Apr. 2018, pp. 409–20. Accessed 19 Sept. 2025.“Table 1 - 2.”
[20] Stanley, Theodore H. “The Fentanyl Story.” The Journal of Pain, vol. 15, no. 12, Dec. 2014, pp. 1215–26. Accessed 24 Sept. 2025.“Figure 4.”
[21] Azar, Pouya, et al. “Case Report: Acute Care Management of Severe Opioid Withdrawal with IV Fentanyl.” Addiction Science & Clinical Practice, vol. 17, no. 1, Apr. 2022. Accessed 24 Sept. 2025.“She was injecting approximately 0.25 g of street fentanyl 3–4 times per day. In the three days leading to admission, she increased her dose to approximately 0.75 g due to lower extremity pain secondary to her cellulitis that prevented her from attending her iOAT appointments. When asked about her fentanyl use despite receipt of DAM, she described a preference for fentanyl due its superior effect relative to other opioids.”
[22] Amaducci, Alexandra, et al. “Naloxone Use in Novel Potent Opioid and Fentanyl Overdoses in Emergency Department Patients.” JAMA Network Open, vol. 6, no. 8, American Medical Association, Aug. 2023. Accessed 19 Sept. 2025.“Table 3.”
[23] Krashin, Daniel. “Opioids in the Management of HIV-Related Pain.” Pain Physician, July 2012. Accessed 13 Nov. 2025.“Table 4.”
[24] Vandeputte, Marthe M., et al. “Pharmacological Evaluation and Forensic Case Series of N-Pyrrolidino Etonitazene (Etonitazepyne), a Newly Emerging 2-Benzylbenzimidazole ‘Nitazene’ Synthetic Opioid.” Archives of Toxicology, vol. 96, no. 6, Apr. 2022, pp. 1845–63. Accessed 24 Sept. 2025." Of the 21 cases, N-pyrrolidino etonitazene was found in combination with fentanyl in 57% of cases (n = 12), with methamphetamine in 57% of cases (n = 12), and with NPS benzodiazepines in 52% of cases (n = 11)."
[25] Katri Abel-Ollo, et al. “The Nitazene Epidemic in Estonia: A First Report.” European Journal of Public Health, vol. 35, no. 6, Oxford University Press, Sept. 2025. Accessed 20 Jan. 2026.“Table 2.”

About the author

Mischa Ezekpo

Mischa Ezekpo has a Bachelors degree in Psychology from Northumbria
University, and a Masters degree in Childhood Development and
Wellbeing, from Manchester Metropolitan University. Since 2018, Mischa
has written and published work on Addiction, Mental Health, Depression, and Eating Disorders. Content reviewed by Laura Morris (Clinical Lead).

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Last Updated: February 3, 2026