A lethal dose of heroin compared to a lethal dose of fentanyl. This is just an illustration—the substance actually shown in this photo is an artificial sweetener. © Bruce A. Taylor/NH State Police Forensic Lab

Overdose deaths from opioids, including prescription opioids, heroin, and synthetic opioids like fentanyl, have increased more than 5 times since 1999. Fentanyl has now become one of the drugs most frequently responsible for overdose deaths.

Looking at death certificates from 2011 through 2019, researchers identified patterns in specific drugs most frequently involved in drug overdose deaths. They found that synthetic opioids, primarily fentanyl, were the main cause of drug overdose deaths, which have increased 14-fold from 2012 to 2019, greatly outnumbering all other types of drug overdose deaths.

In 2020, more than 56,000 deaths involving synthetic opioids other than methadone (Dolophine) occurred in the United States, accounting for 82 percent of all opioid deaths.

What Is Fentanyl?

Fentanyl is a powerful, synthetic opioid that is part of the class of drugs called opioid analgaesics. Developed in the early 1960s, fentanyl was first used as an intravenous anaesthetic but is now prescribed and administered to treat chronic severe pain, for instance, with cancer or end-of-life care.

Fentanyl is prescribed under trade names such as Duragesic, Actiq, and Subsys. Names for illegally used fentanyl include Goodfellas, Dance Fever, and Apache.

The drug comes in several forms: a transdermal patch, a lozenge, a tablet that goes under the tongue, a nasal spray, and a sublingual spray. Side effects include euphoria, drowsiness, nausea, confusion, constipation, sedation, tolerance, addiction, respiratory depression and arrest, and unconsciousness.

How Fentanyl Works in the Body

Fentanyl works by binding to nervous system proteins called opioid receptors. This blocks pain signals to the brain but boosts levels of dopamine, a chemical messenger between brain cells that controls the reward and pleasure centre in the brain.

Because of its high potency – it’s 50 to 100 times more powerful than morphine and 50 times more potent than heroin – fentanyl can quickly enter the brain tissue, causing an intense and euphoric “high.”

Potent opioids such as fentanyl can cause breathing to stop completely, which can lead to death.

Why Is Fentanyl So Dangerous?

Fentanyl sold on the street is manufactured illegally in labs, primarily in countries like China or Mexico, where they synthesise a less pure, potentially more dangerous form of fentanyl. Since it comes in a fine powder, fentanyl is often added to fake prescription pills and illicit drugs like heroin, cocaine, or methamphetamine.

Even 2 milligrams (mg) of fentanyl can be lethal for people who aren’t opioid-dependent.

The drug has also been used in counterfeit prescription pills, made to closely resemble oxycodone (Oxycontin), alprazolam (Xanax), and acetaminophen and hydrocodone (Norco).

The amount of fentanyl in each counterfeit pill varies, but it’s estimated that as many as 6 in 10 fentanyl-laced fake prescription pills now contain a potentially lethal dose of fentanyl.

“People can be unintentionally exposed to fentanyl,” says Lindsey Vuolo, MPH, vice president of health law and policy at the Partnership to End Addiction. “Overdoses can happen very quickly, in a matter of minutes.”

How and Why Is Fentanyl Abused?

Fentanyl can be injected, snorted, sniffed, smoked, taken orally by pill or tablet, or spiked onto blotting paper. Fentanyl patches are abused by removing its gel contents and then injecting or ingesting it.

Fentanyl is classified as a Schedule 2 controlled substance by the U.S. Drug Enforcement Administration (DEA). Schedule 2 drugs have a high potential for abuse and addiction, despite their specific medical uses.

What makes fentanyl so addictive is that it’s cheap and it can produce an intense high with just a small amount, even at a much lower dose than heroin.

Abusing fentanyl can build up a tolerance to the drug, which increases the risk of overdosing. Many people may not even be aware they are abusing fentanyl. They may think they are taking heroin, Percocet, or Xanax.

An overdose can result in a stupor, cold and clammy skin, or even a coma and death.

Are Fentanyl-Related Compounds Just as Dangerous?

Fentanyl-related compounds, like acetyl fentanyl, carfentanil, and butyrfentanyl, pose an even greater threat because they’re designed to be more potent.

Carfentanil, typically used as a sedative for large animals like elephants, is estimated to be 10,000 times more potent than morphine and 100 times more potent than fentanyl.

It’s considered one of the most potent fentanyl analogs detected in the United States, and there have been a number of carfentanil-related deaths in states like Florida, Michigan, and Ohio. In just one year, 1,181 people died in carfentanil-involved overdoses in Florida.

Acetyl fentanyl, though less potent than fentanyl, has been linked to fatalities in several states, including California, Louisiana, North Carolina, Oregon, Pennsylvania, and Rhode Island.

In 2019, preliminary data shows that DEA labs’ databases identified 10,798 items as acetyl fentanyl.

How to Recognise and Help Someone Who Is Overdosing on Fentanyl

Because fentanyl overdose can be fatal, it’s imperative that a person overdosing on fentanyl get immediate medical help. The following are signs of an opioid overdose:

  • Loss of consciousness
  • Unresponsiveness
  • Awake but unable to talk
  • Breathing that is very slow and shallow, erratic, or has stopped
  • Choking sounds, or a snore-like gurgling noise (sometimes called the “death rattle”)
  • Vomiting
  • Body that is limp
  • Face that is pale or clammy
  • Small, “pinpoint” pupils
  • Lips or nails turning blue

Naloxone (Narcan) is a medication that rapidly reverses the effects of opioid overdose. The drug can potentially save a person’s life, although multiple doses may be required for it to work successfully. Naloxone works only on people who have opioids in their system and has no harmful effects if given to someone who does not have opioids in their system. You don’t need to be a medical professional to administer naloxone to someone having an overdose.

The U.S. Food and Drug Administration has approved naloxone in three forms: an injectable, an auto-injectable, and a pre-packaged nasal spray.

The drug works by binding to opioid receptors, reversing and blocking the effects of other opioids, and quickly restoring normal breathing in someone whose breathing has slowed or stopped as a result of an overdose.

Because naloxone has a relatively short duration of effect, overdose symptoms may return. Therefore, it is essential to get the person to an emergency department or other source of medical care as quickly as possible, even if the person revives after the initial dose of naloxone and seems to feel better.

In 2016, the Centers for Disease Control and Prevention (CDC) began recommending naloxone be co-prescribed with opioids in certain cases. According to the United States Government Accountability Office, as of March 2021, 47 states and Washington, D.C., had enacted Good Samaritan laws that provide legal immunity for people helping reverse an overdose. All 50 states have passed legislation to increase access to naloxone, allowing laypeople to get the drug at pharmacies.

The effect of naloxone distribution is undeniable. One study published in 2018 found that opioid overdose deaths decreased by 14 percent in states where naloxone was easily accessible.

And in a study published in 2019, statistical modelling found that increased distribution of naloxone could prevent 21 percent of overdose deaths.

There are various treatment options for fentanyl dependence, including medication, counselling, and cognitive behavioural therapy. It’s important to remember that opioid addiction is a chronic condition. Treatment will likely require a combination of approaches and long-term follow-up.

Additional reporting by Shira Feder.
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