The fentanyl crisis: Why are people dying?

Since 2022 or so, the media has too often shocked us with the news of a new death in the world caused by fentanyl. This creates confusion because it is something relatively new that did not happen before or happened very rarely, expectation because we do not know what is happening for this to occur, and even distrust and fear, since fentanyl is a common drug used in medicine to fight severe pain.

It has a very simple explanation, but first we need to understand some concepts.

What is fentanyl?

Fentanyl is a very potent opioid used in medicine, with a potency about 100 times greater than that of morphine. It is used in the operating room as an anesthetic in some interventions and as an analgesic to treat severe post-operative pain, extreme pain and pain in terminally ill patients.

Fentanyl has a very fast action but is also eliminated very quickly through the liver, so it has a very potent and brief effect, and is extremely addictive; even controlled patients can develop addiction with few doses.

Fentanyl safety

Fentanyl is a drug used in controlled medical settings because of its high potency. It is administered in very precise doses by anesthesiologists or pain management specialists to avoid adverse effects and overdoses, so it is always closely monitored. Although it is very effective for treating pain, it requires close monitoring because small variations in dosage can lead to serious consequences.

Fentanyl is very safe for medical use, so you can trust your doctor if he prescribes it to treat any ailment, as he will very accurately calculate the dose and frequency with which you should take the medication.

Fentanyl administration

Intravenous

• Usual dose: 0.05 - 0.1 mg.
• It takes effect in 1-2 minutes, reaches peak analgesia in 2-5 minutes and lasts 30-60 minutes.
• Main use: It is used in hospitals, especially in surgical procedures and in intensive care units for acute pain control. Also in emergencies for rapid pain management.
• Administration: Fentanyl is injected directly into a vein using an intravenous catheter or injection.
• Advantages: Provides almost immediate pain relief and allows for tight dosage control.

Transdermal patch

• Usual dose: 0.012 - 0.1 mg/hour (depending on the level of pain and the patient's tolerance).
• It takes effect in 12-24 hours, reaches peak analgesia in 24-72 hours and lasts 48-72 hours.
• Main use: Treatment of chronic pain, usually in patients with cancer or persistent pain not controlled by other opioids.
• Administration: The patch is applied to the skin and releases fentanyl continuously.
• Advantages: Provides consistent pain relief over long periods, reducing the need for frequent doses.

Tablets, lozenges or buccal tablets

• Usual dose: 0.1 - 1.6 mg (depending on the level of pain).
• It takes effect in 5-15 minutes, reaches peak analgesia in 20-30 minutes and lasts 60-120 minutes (1-2 hours).
• Main use: Treatment of breakthrough pain in patients with chronic diseases, especially cancer.
• Administration: They dissolve slowly in the mouth, allowing absorption through the oral mucosa.
• Advantages: They offer fast pain relief and are easy to use without the need for injections or devices.

Nasal spray

• Usual dose: 0.1 - 0.8 mg (depending on the level of pain).
• It takes effect in 5-10 minutes, reaches peak analgesia in 20-30 minutes and lasts 60-120 minutes (1-2 hours).
• Main use: For the treatment of breakthrough pain in patients with chronic diseases such as cancer, who cannot take oral medications or prefer a faster route of administration.
• Administration: It is sprayed into the nasal cavity and is rapidly absorbed through the nasal mucosa.
• Advantages: Provides fast pain relief without the need for injections or pills.

Intramuscular injections

• Usual dose: 0.05 - 0.1 mg.
• It takes effect in 7-8 minutes, reaches peak analgesia in 20-30 minutes and lasts 60-120 minutes (1-2 hours).
• Main use: Management of acute pain in emergency situations or during surgical procedures, when an intravenous route is not available.
• Administration: Fentanyl is injected into a large muscle, such as the thigh or buttock.
• Advantages: Easy to administer in situations where intravenous access is not possible.

Inhaler

• Usual dose: 0.1 - 0.4 mg (depending on the available formulation).
• It takes effect in 1-5 minutes, reaches peak analgesia in 10-20 minutes and lasts 60-120 minutes (1-2 hours).
• Main use: Treatment of breakthrough pain in patients with chronic illnesses or postoperatively, suitable for situations where the patient requires immediate pain relief but is unable to use other routes of administration.
• Administration: The patient inhales fentanyl in aerosol form, allowing rapid absorption through the lungs.
• Advantages: Provides extremely fast relief, without the need for oral administration or injections.

The fentanyl crisis

The so-called fentanyl crisis is motivated by 5 key factors, which when combined make fentanyl a death sentence if administered as a recreational drug.

Point 1: Safety profile, analgesic dose VS lethal dose.

Fentanyl also has a very tight safety profile: the difference between a therapeutic dose and a lethal dose is alarmingly small, so if administered by untrained personnel it can very easily lead to an overdose.

The analgesic dosage of fentanyl usually ranges from 0.05 mg to 0.1 mg to provide fast and effective pain relief. This type of dosage is carefully adjusted to avoid serious side effects, and its administration should always be under medical supervision.

The lethal dose of fentanyl is surprisingly low compared to its analgesic dose. It is estimated that just 2 mg of fentanyl can be enough to cause death in an adult. That's the equivalent of 10 grains of salt.

Fentanyl is so potent that even tiny amounts can have devastating effects. Respiratory depression, where the body simply forgets how to breathe, is one of the most common causes of overdose death.

It is therefore one of the most dangerous drugs if not used correctly. The difference between a dose that relieves pain and a dose that can cause death is very small, making it a high-risk substance outside of medical control.

Opioid	Analgesic dose (mg)	Approximate lethal dose (mg)
Fentanyl	0.05 - 0.1 mg	Less than 2mg
Morphine	10 - 30 mg	120 - 200 mg
Oxycodone	5 - 15 mg	80 - 160 mg
Hydromorphone	2 - 4 mg	50 -100 mg
Codeine	30 - 60 mg	240 - 500mg
Methadone	5 - 10 mg	50 - 100 mg
Buprenorphine	0.3 - 0.6 mg	70 - 100 mg
Tramadol	50 - 100 mg	2000 mg

Point 2: Capacity to generate addiction

Its addictive capacity is so powerful because of how it interacts with the central nervous system, particularly the brain's reward circuitry.

How does fentanyl cause addiction?

When fentanyl binds to opioid receptors in the brain, it triggers a series of chemical reactions that have a profound impact on the release of dopamine, the neurotransmitter associated with feelings of pleasure and reward. This release of dopamine is the key to its addictive potential. In simple terms, the brain quickly learns to associate fentanyl use with pleasurable sensations, triggering a desire to repeat the experience.

Dopamine dosage and comparison with other substances

Fentanyl, like other opioids, has the ability to cause a significant increase in dopamine levels in the brain. Studies indicate that opioids can increase dopamine levels by more than 200% compared to normal levels. This increase is much greater than that obtained from natural activities that also release dopamine, such as eating, exercising, or having sex.

To put it into perspective:

• Food: A moderate increase in dopamine, around 50%.
• Intense physical exercise: An increase in dopamine of approximately 100%.
• Sexual intercourse: An increase in dopamine of between 100-200%.
• Fentanyl and other opioids: A dopamine surge that can exceed 200%, creating a feeling of intense euphoria.

This increase in dopamine levels is comparable to that of other highly addictive drugs such as cocaine and methamphetamine, although opioids such as fentanyl act through different receptors in the brain. The main difference is that while cocaine or methamphetamine affect dopamine reuptake, opioids such as fentanyl directly cause its massive release by binding to opioid receptors.

Tolerance and dependency

Fentanyl addiction does not develop solely because of its ability to release large amounts of dopamine. Over time, the brain adapts to these high amounts of dopamine and becomes less sensitive to its effects. This process is known as tolerance – the body needs increasingly higher doses of fentanyl to achieve the same effects as those obtained initially.

Dependence occurs when the body becomes so adapted to the presence of fentanyl that it can no longer function properly without it. If an addicted person suddenly stops using fentanyl, they may experience withdrawal symptoms, such as:

• Intense anxiety.
• Insomnia.
• Nausea and vomiting.
• Muscle and joint pain.
• Sweating and chills.

Comparison with other opioids

While all opioids have a high addictive potential, fentanyl is particularly dangerous due to its potency. Being 50-100 times more potent than morphine, users can develop tolerance and dependence much faster. This means that while other opioids such as oxycodone or morphine are also addictive, the risk of developing addiction with fentanyl is significantly higher due to its fast action and intense effect.

This release of dopamine causes a feeling of euphoria that can lead to compulsive repeat use, and as tolerance increases, the user becomes trapped in a cycle of dependence.

Point 3: Illegal manufacturing and use as a recreational drug

Fentanyl, being cheap and easy to produce, has become a common choice for illegal drug manufacturers. Its high potency allows small amounts to go a long way, making it ideal for mixing with other drugs like heroin or cocaine, reducing the amount of these but enhancing their effect. However, on the illegal market, the purity of these mixtures is extremely low and varies unpredictably. This leaves users unsure of exactly how much fentanyl they are taking, dramatically increasing the risk of overdose, as even small, miscalculated doses can be lethal.

Point 4: Very serious adverse effects when mixed with other drugs

When fentanyl is mixed with other substances, the adverse effects can become extremely dangerous. Depending on the type of drug it is combined with, the risks are multiplied:

• With central nervous system depressants (alcohol, benzodiazepines): The mixture enhances the sedative effect, which increases the risk of severe respiratory depression, coma and death. This combination is the most dangerous, since both substances slow down the nervous system, which can quickly lead to respiratory arrest.
• With stimulants (cocaine, methamphetamines): This mixture causes contradictory effects on the body, causing an overload of the cardiovascular system. It increases the risk of arrhythmias, cardiac arrests and convulsions, as well as worsening neurotoxic effects.
• With other opioids (heroin, oxycodone): The addictive and central nervous system depressing effect is intensified, increasing the likelihood of overdose. Fentanyl doses are often difficult to calculate, which increases the risk of death.

Conclusion

Fentanyl, as we have seen, is a very potent and safe drug when administered by medical personnel, so that pure fentanyl is administered and the administered dose can be accurately calculated.

The fentanyl crisis of recent years arises from combining the 4 key factors mentioned above:

• Drug with a very low safety profile. A slightly higher dose than correct can cause death.
• It is a very cheap drug that is easy to manufacture illegally, so it is used to reduce the quantity of other more expensive drugs sold and increase their potency. Its purity is unknown and therefore overdose is almost guaranteed.
• Drug with very serious adverse effects when combined with other drugs, so when sold mixed and without purity control, death is very likely.
• A terribly addictive drug, probably the one that generates addiction and dependence the fastest and most strongly of all those that exist.

And the post is over :(

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