Author: John Carter

Carfentanil Side Effects and Overdose Risk 100 Times More Potent Than Fentanyl

Secondary analysis of drug overdose deaths from the Center for Disease Control and carfentanil exhibit data from drug seizures submitted to drug crime labs and published by the Drug Enforcement Administration (DEA). Trends in overdose deaths were compared in states with high carfentanil exhibits with states with low or no carfentanil exhibits. The selected case reports below detail the unique challenges with detection, management, and clinical presentation of acute intoxication with various synthetic opioids.

Carfentanil and the Rise and Fall of Overdose Deaths in the United States

Due to inexpensive manufacturing and high potency, carfentanil has been added as a filler to other illegal drugs, such as heroin and cocaine. Carfentanil was structurally similar to lofentanil and also had high affinity and potency. It was surprising that carfentanil, a potent full agonist, would function as an in vivo receptor binding ligand; usually agonists shift their binding to a lower affinity in the presence of physiologic concentrations of sodium. These mu-binding sites are discretely distributed in the brain, spinal cord, and other tissues. Carfentanil also depresses the respiratory centers, depresses the cough reflex, and constricts the pupils. In its powdered form, carfentanil is virtually indistinguishable from heroin or cocaine.

Associated Data

The higher concentrations of isotonitazene distributed throughout the body compared with the femoral blood and his significant history were highly suggestive of isotonitazene intoxication leading to his death 35. Due to low molecular weight and high lipophilicity, carfentanil can be absorbed through the skin or inhaled. Contact with mucus membranes is more dangerous, but the exposure to a high dose would have to be prolonged to cause toxicity. Nevertheless, it is recommended that general occupational hygiene measures and personal protective equipment should be used by persons who may be exposed to carfentanil. For routine handling of the drug, nitrile gloves along with N95 mask and safety glasses provide sufficient protection.

1. Some opioid use disorder experts now recommend that healthcare professionals interview family members as part of routine follow-up care for a person taking opioids.
2. Like protonitazene, the primary source of isotonitazene is China, where manufacturers synthesize the product and market it overseas 24.
3. Advanced and expedited pharmaceutical research is of utmost need to identify effective alternative reversal remedies for overdosages and alternative pain-reducing formulas/medications 44–46.
4. Due to low molecular weight and high lipophilicity, carfentanil can be absorbed through the skin or inhaled.
5. Naloxone is an effective treatment against lethal doses of carfentanil in animal models.

In a recent case study, the t1/2 values for carfentanil and norcarfentanil after recreational exposure were estimated to be 5.7 and 11.8 h, respectively. However, the kinetic profiles of both analytes were incomplete as Cmax values were not calculated 30. According to the DEA, naloxone should be administered every two to three minutes until the person is breathing on their own for at least 15 minutes or until emergency help arrives. Carfentanil’s immense strength makes it about 100 times more potent than fentanyl and poses extreme danger.

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If someone is casually using any of these names, looking to buy carfentanil online, or interested in taking heroin, fentanyl or cocaine, they might be misusing carfentanil. If so, they are in danger of not only overdosing but of building a physical dependence and addiction to opioids. Fentanyl test strips can indicate the presence of fentanyl but cannot tell which type of fentanyl or fentanyl derivative, such as carfentanil, may be present in a sample.

How to tell if a loved one is abusing opioids

Another challenge is found in internet distribution, which makes these drugs more attainable and can cause confusion between pharmaceutically and illicitly manufactured opioids 5. To combat these growing challenges, clinicians should recognize the hallmark signs of opioid toxicity, such as respiratory distress, altered mental status, and miosis 4. This is related to the fact that fentanyl is very potent, allowing it to outcompete naloxone for the mu opioid receptor (MOR).

If someone can take carfentanil without coma or death, some of the common symptoms of misusing this drug are similar to other synthetic opioids or morphine. Carfentanil is a potent fentanyl derivative and is one of the strongest opioids in existence. Even touching or inhaling small amounts of carfentanil can be dangerous to humans, with a dose as low as 2 mg able to sedate an elephant and kill 50 people. The results demonstrated a binding pattern that was consistent with that of mu-opioid receptors, which was displaceable by naloxone, an opiate antagonist 17.

At present, there is still limited data regarding how often isotonitazene is implicated in drug overdoses. Given the lack of data, there have yet to be any studies addressing the recommended dosage of naloxone needed to reverse isotonitazene overdose. It is suspected, however, that a higher dose than that usually employed for opioid overdose may be required 25. Table 1 lists the synthetic opioids reviewed in this section and their strengths relative to both fentanyl and morphine. Fentanyl and its analogs cause severe central nervous system (CNS) and respiratory depression, which may lead to death, especially in an unsuspecting, opioid-naive person 4. Fentanyl analogs are emerging at an alarming rate, and their detection can be difficult since they often have novel chemical structures 4.

Further, because it is very lipophilic, it will stay in the body longer than other opioids. This narrative review, therefore, aims to highlight the clinical challenges presented by these new synthetic opioids. New synthetic opioids, carfentanil, protonitazene, and isotonitazene, play a detrimental role in the opioid epidemic. The potency and efficacy of these synthetic opioids increase the overdose potential substantially and have raised fatalities.

They include euphoria, relaxation, analgesia, myosis, drowsiness, sedation, bradycardia, hypotension, hypothermia, loss of consciousness and respiratory depression. Importantly, due to its extraordinary high affinity to opioid receptors, even very small doses are pharmacologically active. The most serious acute health risk from using carfentanil is a rapid and severe respiratory depression, which could lead to apnea, respiratory arrest, and death in overdose 11. This report examines the relationship between trends of carfentanil exhibits submitted to state crime labs and overdose deaths by state.

Since the early 2010s, synthetic opioids have significantly contributed to overall opioid-related overdose mortalities. For reference, of the 68,630 opioid-related deaths recorded in 2020, 56,516 involved synthetic opioids (primarily fentanyl and its analogs) 6, 7. This rise in synthetic-opioid related use in recent years has been accompanied by a corresponding, decrease in the use of other illicit opioids such as heroin 8. Some potential reasons why synthetic opioid use has become so ubiquitous have been postulated to include lower production costs, stronger or longer lasting highs, and increasingly efficient synthesis by manufacturers 8, 9. As noted by the US Drug Enforcement Agency, a relatively common factor in synthetic opioid overdoses is their utilization as cheap adulterants in preparations of other illicit drugs 10. This is not to say that there are not users who intentionally seek out synthetic opioids.