The Fentanyl Crisis

How Fentanyl Analogs and Derivatives Play a Role in the Epidemic

Unconscious young woman
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Although the medical use of fentanyl has declined recently, illicit fentanyl and its analogs and derivatives have become a significant part of the larger opioid crisis which has spread across the United States and Canada, as well as many other countries. The fentanyl crisis is claiming the lives of hundreds of people each month.

What Is Fentanyl?

Fentanyl is a high potency synthetic narcotic, sometimes called synthetic heroin.

The drug also has street names including "white heroin," "Perc-O‐Pops," or "Chiclets."

Fentanyl was created in 1959 as an intravenous surgical analgesic. It is 50 to 100 times more powerful than morphine. As an opioid drug, fentanyl is sometimes used deliberately by people who use other opioid drugs, such as heroin and prescription painkillers. But due to its potency, it has made its way into many other drugs that people use recreationally.

This has led to a huge increase in accidental consumption of fentanyl, and in overdose deaths, often by people who are not even aware they are taking it. If a user is new to taking opioids, the risk of overdose is even higher, because their bodies have not developed any tolerance to the drug.

However, even regular heroin and methadone users are at risk of overdose if they take fentanyl because it is so much stronger than these other opioids.

Increase of Use

Originally, fentanyl was rarely used, except in hospital operating rooms.

However, in the 1990s, a new transdermal skin patch was developed to treat chronic pain. Patients who used the patch were people who desperately needed pain relief, but regular opioid pain medications had become ineffective for them.

Although originally used only in these rare cases, the use of the fentanyl patch increased rapidly, due to its potency and effectiveness in managing pain in these hard-to-treat patients.

It was also used because of some unique advantages it offered over other drugs, including quick and short action, few cardiovascular risks, and low histamine release. This made it a good prescription choice for some patients, as it reduced some of the risks of medical complications that other pain relievers have.

As use of the fentanyl patch increased, it began to be prescribed for patients with chronic non-cancer pain. As its popularity increased, alternative forms of the drug, including lozenges, tablets, and nasal sprays were developed for medical use.

These alternative forms of the drug increased the potential for the drug to make its way into the illicit drug market, which wasn't really feasible when the drug was only available as a skin patch. This led to a dramatic escalation of its use as a cutting agent—a drug that is mixed with another drug to increase its bulk or potency and thereby the profit that can be made.

Even though fentanyl is an opioid drug, drug dealers began to use it to cut a variety of drugs including heroin, cocaine, and meth, because only a tiny amount was needed to produce a powerful euphoric experience. Unfortunately, this went hand-in-hand with an increase in illicit drug users dying or nearly dying from overdoses, even when they only took a tiny dose of the drug, and even when they did not intend to take fentanyl or another opioid.

The Fentanyl Crisis

The increasing availability of prescription fentanyl has provided a supply of this powerful drug. Fentanyl can be stolen from hospitals, pharmacies, and or from patients and sold on the street drug market.

In addition to pharmaceutical fentanyl being diverted from medical sources, Chinese labs began making and selling cheap fentanyl, which is imported to North America and cut with other drugs for a huge profit. In this way, both medical and illicitly made fentanyl has spread throughout the illicit drug market, massively increasing the number of drug-related deaths.

Analogs and Derivatives

Drug analogs are drugs that are developed to imitate a particular drug, but they are not identical.

Sometimes called novel psychoactive substances, they can be made to be similar in chemical structure, or similar in pharmacological effect to the original drug.

Creating drug analogs became popular in the 1990s, as illicit drug manufacturers tried to beat the legal system by making drugs that could not be listed as illegal or controlled drugs until they were recognized. Although this "designer drug" strategy did not beat the system, because any drug that was structurally similar to a controlled drug also became illegal, drug manufacturers have continued to develop new drug analogs in this way.

Carfentanil

The fentanyl analog carfentanil, which has begun appearing in street drugs, is a particularly dangerous analog of fentanyl. Whereas fentanyl is 50 to 100 times more powerful than morphine, carfentanil is 10,000 times more powerful than morphine. In fact, it was never even intended for use by humans but was only intended to treat large animals many times our size.

Furanyl Fentanyl

Another fentanyl analog, furanyl fentanyl, is often made illegally for sale on the illicit drug market and has been contributing to the fentanyl and opioid crisis. Researchers have developed a way to identify furanyl fentanyl in the urine specimens of pain patients and discovered that approximately 10 percent of samples from a set of 500 urine specimens which had been thought to contain heroin were found to also contain furanyl fentanyl.

Novel Fentanyl Analogs

The number of new psychoactive drugs that are introduced through the online recreational drugs market is also increasing. The Swedish STRIDA project conducted research which confirmed cases of people admitted to the hospital emergency department or intensive care unit with drug intoxication involving the novel fentanyl analogs acrylfentanyl, 4-chloroisobutyrfentanyl (4Cl-iBF), 4-fluoroisobutyrfentanyl (4F-iBF), and tetrahydrofuranfentanyl (THF-F), and cyclopentylfentanyl.

These people typically experienced symptoms of decreased consciousness (difficulty staying awake or passing out), respiratory depression (difficulty breathing), and miosis (constricted pupils of the eyes). These people all required acute and intensive hospital treatment, which, unfortunately, was not always successful.

Fentanyl Derivatives

A derivative is a drug that is made from another drug. Several fentanyl derivatives, initially sufentanil, alfentanil, remifentanil, carfentanil, and, more recently, acetylfentanyl, 6‐butyrfentanyl, 4‐MeO‐butyrfentanyl, isobutyrylfentanyl, furanylfentanyl, α‐methylfentanyl, 3‐methylfentanyl or TMF, p‐methylfentanyl, methylacetylfentanyl, acrylfentanyl, 2‐fluorofentanyl, fluoroacetylfentanyl, ocfentantanyl, and many others, are illegally manufactured. These derivatives do not have recognized medical uses, and have worsened the opioid crisis and the number of drug-related deaths.

Fentanyl Analogs and Derivatives in Other Drugs

One of the differences between the current opioid crisis and previous drug crises is the large number of accidental deaths, of people who did not even intend to take the drug that killed them. Because illicit drugs, by their nature, are unregulated, it is usually impossible for people to know if the drugs they purchase from a dealer contain fentanyl.

Given the pharmacological strength and therefore, the cost-effectiveness of using fentanyl and its analogs and derivatives as a cutting agent, the risk of fentanyl being mixed with other drugs is higher than ever. This has led to an unprecedented number of people dying from opioid overdoses—people who never thought they were at risk because they did not knowingly take opioids.

Opioid Addiction

It is currently thought that about 10 percent of people prescribed opioids become addicted, although the actual numbers are difficult to calculate, as addiction is such a stigmatized condition.

Fentanyl does not typically start out as the drug of choice for opioid users, as the dosages are so small and the overdose risk is so high. However, people who have been using heroin or other opioids for a long time, and no longer get the effect they want from small doses, may be attracted to fentanyl for its potency and cost-effectiveness compared to other drugs. This will greatly drive up their tolerance, producing an intense physical addiction to opioids.

Many of the people exposed to fentanyl do so unknowingly; they may think they are using cocaine or meth, and actually be taking fentanyl as well if it has been used as a cutting agent. If taken over a long period of time, these people are also at risk of developing an opioid addiction, as the body develops a tolerance for opioids. They may begin to experience cravings for the drug and experience opioid withdrawal symptoms if they do not take a substance containing opioids.

Opioid Overdose

Taking an overdose is one of the most significant risks of using fentanyl. The current opioid crisis has resulted in a massive increase in deaths by overdoses on opioids, many of them involving fentanyl, fentanyl analogs, or fentanyl derivatives.

Although an opioid overdose can potentially be reversed if caught in time, a person can only stop breathing for a few minutes before they die. Therefore, an overdose can only be reversed if the person continues to breathe, or is administered the correct medication within a few minutes of stopping breathing. They may also require CPR if their heart has stopped.

A fentanyl overdose happens very quickly. People who overdose on fentanyl have the same clinical symptoms as those who overdose on other opioids, such as heroin or opioid painkillers. They become unresponsive, and their breathing slows down, becomes very shallow, and may even stop completely.

During an overdose, a user may have an erratic or weak heartbeat, or their heart may even stop completely, so you can't find a pulse. As their body is deprived of oxygen, their skin becomes pale and "ashen" in color, while their lips, fingertips and under fingernails change to a blue or purple color.

An opioid overdose, including an overdose of fentanyl, fentanyl analogs. or fentanyl derivatives can be treated by administering a medication that blocks the opioid receptors in the brain. This medication is called naloxone or NARCAN. Naloxone is available either as an intramuscular injection or as a nasal spray.

If the person's heart has stopped, CPR will be needed to re-start the heart.  Additional doses of naloxone can be administered at three- to five-minute intervals if the person who has overdosed does not wake up. As fentanyl is such a strong opioid, an overdose is more difficult to reverse than many other opioids, and several doses of NARCAN may be required to revive them.

Unfortunately, as many people use opioids on their own, people who take fentanyl, fentanyl analogs, or fentanyl derivatives may simply die alone, with no-one to administer naloxone or call 911. Therefore, it is very important not to use drugs which may contain fentanyl alone, and ideally, for a companion to have access to NARCAN.

It is also important if two people are using drugs together, not to take the substance at the exact same time, because if both overdose immediately, there will still not be anyone conscious to administer NARCAN or call 911.

A Word From Verywell

Many lives have been lost due to drug users taking too much fentanyl, and no-one being available to help. Also, even if an overdose is reversed, the oxygen deprivation that happens during an opioid overdose can have lasting effects on the brain, so it is not a situation to be taken lightly. There has never been a worse time to experiment with drugs.

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