Why Is Fentanyl Driving Overdose Deaths?

OxyContin contributed to a modern opioid epidemic with lasting repercussions, and now fentanyl has brought the overdose crisis to a new level.

Although both are highly addictive opioids (a class of drugs with pain-relieving and euphoria-inducing properties), fentanyl is purely synthetic, meaning it can be made easily and cheaply in a lab, and it is more potent—about 50 to 100 times stronger—than many prescription opioids.

In 2022, according to provisional data from the Centers for Disease Control and Prevention (CDC), close to 83,000 people died from opioid overdoses in the United States, the majority from fentanyl and other highly potent synthetic substances.

Fentanyl isn’t new; it has been used in the U.S. since 1960 as an intravenous anesthetic. It is still prescribed today by doctors, often in the form of patches and lozenges, for treating severe and chronic pain from cancer and other illnesses and injuries.

But fentanyl has shifted from exclusively being produced by pharmaceutical companies to now also coming from drug cartels and other entities, says David Fiellin, MD, a Yale Medicine primary care physician who specializes in addiction medicine. “We refer to it as illicitly manufactured fentanyl,” he says.

Drug dealers are increasingly mixing fentanyl into all kinds of drugs, including heroin, cocaine, and methamphetamines. They also put it in fake prescription pills, including oxycodone (OxyContin®—one kind of oxycodone), hydrocodone (Vicodin®), and benzodiazepines—a type of sedative medication used for anxiety—such as diazepam (Valium®), that are sold on the street.

“Dealers package it to look like a normal prescription pill that you would get at the pharmacy, but nobody can tell what's in it,” explains Dr. Fiellin. “So, someone buys from a drug dealer what they think is Valium, or cocaine, or OxyContin, but it has a small amount of fentanyl in it that the buyer is unaware of. This can cause an overdose because the individual doesn’t have the physical tolerance to fentanyl, even if they have a tolerance to, say, OxyContin.”

In many cases, however, people who use or overdose on fentanyl are knowingly taking the drug because of the intense high it delivers.

We spoke with Dr. Fiellin, who answered our questions about illicitly manufactured fentanyl.

The conversation below has been edited for clarity.

It’s important to acknowledge that the U.S. has, over the last 100 years, had an opioid in one form or another that people were misusing, and that has led to addiction—the formal term is opioid use disorder.

Over the years, the misused opioid changed from opium to morphine to heroin, which grew in prevalence during the 1960s and 1970s. And then, in the 2000s, we saw a surge of prescription opioids that were being diverted from those that were prescribed to people for chronic pain [to the illicit marketplace]; people started misusing the diverted supply instead of—or in addition to—heroin.

And now, since 2015 or 2016, the opioid street supply in the U.S. has shifted from primarily heroin and prescription opioids to illicitly manufactured fentanyl. One reason is that because fentanyl is easy to manufacture, it is easy to ship around the country.

And because of its potency, it takes a small amount of fentanyl to create the effect of analgesia [the absence of pain] or euphoria or to help people avoid the symptoms of opioid withdrawal. The potency also presents a high risk for overdose.

There is a phrase in medicine: ‘Consider the host.’ It means that an individual substance or disease will behave differently depending on the host—or person—exposed to it.

Some people use opioids daily for months or even years. Their level of physical tolerance, or the amount of opioids their bodies can process, is far higher than that of another person who has rarely or never taken the drugs.

Also, tolerance can rise over time. A person may start with a dose of one, two, or three milligrams and, over years of use, can take up to, say, 50 milligrams. As tolerance and, with it, physical dependence increase, people need ever-higher doses of a substance to get the same effect—be it pain relief, treatment of opioid withdrawal, or euphoria.

But an individual who doesn't use opioids regularly could overdose on a very small amount, and that's what we're seeing with fentanyl. Or, someone who regularly uses opioids might misjudge or be unaware of the amount of fentanyl in the supply they're using and get twice or three times as much as they anticipated, and they will overdose.

If you are exposed to fentanyl, tolerance to another opioid, such as oxycodone, does impact the effect it will have on you. You're then more likely to be okay than somebody who never takes these drugs, but there's a point at which fentanyl is so potent that you would experience overdose effects.

People use fentanyl patches for cancer or other types of pain, and we don't ever want to stigmatize that or say that's a bad idea. Others might get it in the emergency department, say, if they have a fracture. Under medical guidance, fentanyl is appropriate, and people should not be afraid of it.

Most of the time, it’s exclusively fentanyl, but over time and depending on what part of the country you live in, we also see what we call fentanyl analogues. Those are chemicals similar to fentanyl, but one part of their structure and chemistry is changed. They then have a different name, such as carfentanil or acetyl fentanyl.

Often, we refer to high-potency synthetic opioids as the ‘overarching group,’ and it includes fentanyl, fentanyl analogues, and even some other newly emerging synthetic opioids—called nitazenes.

Fentanyl test strips are small strips of paper treated with a chemical that detects the presence of fentanyl in different kinds of drugs. Though these are not legal in all states, we're very much in favor of fentanyl test strips in general because they help people be more aware of the drug supply and things that they may or may not want to be exposed to. That’s part of the principle of harm reduction [more on that below].

But they're not foolproof. If you test one corner of a pill, it may not have the same result as another corner of the same pill, because the pills aren't manufactured like something from a pharmacy—their content is not uniform.

The other thing about the test strips is they can be very useful if somebody only uses cocaine, for example; they can test the cocaine to make sure there’s no fentanyl in it. But as I mentioned, even if fentanyl is not in the substance, there may be something else, such as a nitazene or carfentanil, that the strips will miss. So, it's important for people to use the test strips but also to recognize that they're not always 100% accurate.

Test strips are mostly available through treatment or harm reduction providers. People can try NEXT Distro or their state's Department of Public Health. I don't believe they're reimbursed by insurance, but they're relatively inexpensive.

There could be, but it's a bit of a moving target. There's now a test for xylazine, which is a horse tranquilizer that has gotten into the drug supply, especially in areas around Philadelphia, but also here in Connecticut.

Xylazine is not an opioid and does not respond to Narcan® [see more below], but it has an effect that prolongs or modifies the impact of other drugs, such as fentanyl, so that's why some people may be interested in having xylazine in their drug supply. Most people, however, are not aware that xylazine is in the supply they are using.

Naloxone, best known by the brand name Narcan, is a nasal spray that can be used to reverse an opioid overdose and is now available over the counter. It seems that it's as effective with fentanyl as it is with other opioids. There had been some concerns that you needed higher doses or double doses of naloxone, but overall, it continues to be effective for fentanyl overdoses.

Harm reduction is a well-established concept in medicine in general. Despite receiving treatment, patients often will continue to have problems with controlling their disease—for instance, in a person with diabetes, their glucose may not be at ‘goal’ levels all the time. The same is true with high blood pressure or depression. Clinicians continue to provide treatment to their patients and try to reduce the harm of the disease with other interventions, such as exercise and diet. And that carries over into treating addiction, too.

Somebody may be doing much better while receiving treatment, but we also need to recognize that we want to do whatever we can to decrease their potential harm. So, making sure they have access to naloxone and test strips, or if they're injecting, that they're using clean needles—all of those things that, even if they've gone from using three times a day to using once a month, are in place to protect them from potential adverse effects.