With the current opioid overdose epidemic, there has been a LOT of discussion about fentanyl.

It seemed to pop up kind of out of nowhere, and has been a major cause of the increase in overdose deaths since about 2012. And it turns out that’s not just a coincidence.

Fentanyl is especially deadly because of the specific chemistry of the compound, and the tendency for people who use it illicitly not to know how much they’re taking at once. So in the ongoing fight to reduce opioid overdoses, we need to understand as much as we can about the specific threat of fentanyl, and how we can keep people safe from the dangers it poses. [♪ INTRO] To be clear, the fentanyl that’s causing so many overdose deaths is illicit fentanyl, which is the kind that is made illegally and not regulated. But to start, let’s explain exactly what the drug is.

Fentanyl is an opioid, which is a type of painkiller. It’s in the same class of compounds as opium, morphine, or heroin, but fentanyl is very strong, something between 50 and 400 times stronger than morphine. These drugs are also sometimes called narcotics, but for this video, we’re sticking with the term opioid.

Opioids mainly block pain by binding to something called mu-opioid receptors. These are basically small molecular switches on our nerve cells. Activating these receptors tweaks how easily and how often our nerve cells send electrical signals.

Imagine them kind of like volume knobs on your nerves. Activating the receptor essentially turns the volume down. The end result is that the cells are less responsive to stimulation.

Less response equals fewer pain signals, equals less pain. And this is often what we want these drugs to do! Opioids have been used in medicine for a long time.

Even fentanyl has been used as a medicine for decades. It was first introduced to the market in the 1960s as an anesthetic. Chemists had been looking for new painkillers that were stronger, safer, and with fewer side effects than previous ones like morphine.

One of the ideas was to look for compounds that could dissolve into fat better, the thinking being that this would help them get into the fat-rich central nervous system more quickly. And out of that research came fentanyl. Fentanyl wasn’t used all that much until the ‘90s, though, when there was a breakthrough in the ways that it could be administered that made it more appealing clinically.

It’s still used today for things like surgery, and chronic pain patients can get it in patches or lozenges to help with pain management. But like any incorrectly-used opioid, fentanyl’s effects on the central nervous system, that ability to turn down the volume knob on our nerve cells, can be dangerous. Opioids can also slow down respiration, since it turns out the same receptor that blocks pain is also found in the cells in the brainstem that control breathing rhythms.

The whole process is complex and still being studied, but it looks like opioids also make these cells less responsive to electrical stimulation, slowing down your breathing. And if you keep turning down the volume, well… eventually, you’ll get to no sound at all. What’s more, opioids can also tamp down a second breathing reflex we have to get rid of excess carbon dioxide in our blood.

This kind of one-two punch means that if you take too much at once, a person can be in real danger of suffocating. That said, doctors are aware of this danger and keep it in mind when they write fentanyl prescriptions. The problems come into play when fentanyl is used illicitly or without the supervision of a medical professional.

It’s also only dangerous if it gets into your bloodstream. You can’t overdose just from touching or being near fentanyl or any other opioids, despite what you might have heard elsewhere. And to be clear, all opioids have their dangers, not just fentanyl.

But fentanyl is particularly dangerous because it’s so much stronger, meaning the dose needed to overdose is much less than for other opioids. Experts say that as little as two milligrams of fentanyl, which is about one tenth of the weight of a penny, can be enough for a lethal overdose. As for why you need so little to get the same punch as other drugs, it comes down to two key factors: Fentanyl works fast, and it binds to your mu-opioid receptors in a weird way.

First up, its speed: remember how we said that fentanyl was created because scientists were looking for something good at getting into the fatty tissues of the nervous system? Yeah. Fentanyl’s what’s known as strongly lipophilic, meaning it dissolves well into fats and oils.

Because of this, it can quickly cross the lipid-rich blood brain barrier, a kind of biological shield that usually slows down or stops drugs from getting to the brain. That means that fentanyl can just straight up get to the receptors faster than morphine can. Again, that’s good if you’re a doctor looking for fast-acting pain relief.

But in an overdose situation, that means that breathing problems start sooner. This might mean that a person overdosing or even someone nearby might have less time to realize that something’s wrong before things get dangerous. Which brings us to the binding: fentanyl seems to bond to those mu-opioid receptors differently than other opioids do.

And it may come down to the shape of the molecule itself. Morphine, for example, is kind of short and squat. But fentanyl is long and skinny.

Both of these opioids fit into the receptor itself, which is how they bond there. Based on computer simulations, we think fentanyl forms a different kind of chemical bond that seems to activate the receptor more strongly. What’s more, fentanyl’s long, skinny tail also unlocks and interacts with a second, deeper pocket in the receptor that morphine can’t reach.

We’re still learning exactly why these different bonds result in different potencies. Like, we still don’t know what mechanically is changing in there between the two drugs. And it’s worth noting that fentanyl can also affect other receptors on the cells too, so the story might not just be about mu-receptors.

But all in all, it seems to translate into a bigger response from the cell. So basically, it’s kind of like the difference between tapping the volume down button once and really hammering on it. So is there anything we can do to prevent or decrease overdoses of fentanyl?

Yes, but it may be difficult, and these ideas often ultimately start to get into questions of public policy, rather than public health alone, since that may mean addressing some of the social or medical issues that lead people to start using drugs like fentanyl. Unfortunately, going into the specifics of how to fix a major societal problem is a little beyond the scope of today’s episode, and maybe the scope of the whole channel. But, we do have methods of mitigation that have been extensively researched, so we can talk about which potential solutions have scientific data to back them up.

A lot of these are what’s known as “harm reduction strategies;” in essence, not how to prevent addiction in the first place or how to address it long-term, but what we can do to limit the harm and keep people as safe as possible if they are using drugs. Because preventing overdose deaths means saving lives. Which is always a good thing.

For starters, it’s vital to make sure that people are getting the medical care that they need. If doctors are able to treat people for their health issues like chronic pain, people are less likely to turn to illicit use of opioids to self-medicate. As one example, there are still pervasive racial disparities between who gets prescribed a treatment for their chronic pain; Black patients are less likely to be given a prescription opioid to treat chronic pain than white patients.

Pain management under the supervision of a doctor is critical, for everyone. Because when people in pain can’t get a prescription medication to treat their pain, but can easily access illicit street drugs, it’s no wonder that they’d take that option. Part of avoiding fentanyl overdoses may also be helping people know if they’re taking fentanyl in the first place.

See, a lot of overdoses happen when someone thinks they’re taking a drug of a lower potency but their drugs were tainted or spiked with fentanyl. Which means they were essentially tricked into taking fentanyl, and don’t modify the dose to reflect how much stronger that compound actually is. So we can prevent a lot of overdoses if we give people resources to screen their drugs for contamination.

For example, fentanyl test strips are a quick and accurate way to test if a substance contains even a trace amount of fentanyl, and they’re relatively cheap to make and distribute, too. Another option for harm reduction may be opening what’s known as safe injection sites. The idea behind safe injection sites is that people who inject drugs are allowed to do so while supervised by medical staff, who are trained to intervene in the event of an overdose.

It may sound like an outlandish idea, but safe injection sites have been around for a long time. The first safe injection site in North America opened in Vancouver in 2003, and after it opened, the fatal drug overdose rate in its vicinity dropped by 35%. And it’s not just that one site.

A systematic review from 2021 found that other facilities were associated with significantly fewer overdoses and fewer deaths from overdoses, and improved access to treatment programs. These are just one of many interventions aimed at preventing overdose deaths from all manner of drugs. And while not all fentanyl is injected, these sites can also offer fentanyl testing strips and other safety precautions.

Not only that, but we can even reverse overdoses after they happen, using a medication called naloxone. It’s what’s called a receptor antagonist, which means that it also binds to mu-opioid receptors but doesn’t actually activate them. All it does is physically block other opioids from binding to the receptors.

Naloxone can be given via needle or nasal spray, and can restore someone back to normal breathing within a couple minutes. But fentanyl’s potency and speed means that the window for someone to either administer naloxone or call emergency services is much smaller than with other opioids. There’s been a proof-of-concept study into a wearable/injected device that could detect an overdose and automatically administer naloxone.

It would activate when a significant decrease in heart rate was detected. And while getting a device like this out into the real world would no doubt be complicated, we wanted to include it to show that there are a lot of folks approaching harm reduction from a lot of different angles. So that’s the deal with fentanyl.

It’s an opioid painkiller. It’s a drug and, like many drugs, it does have legitimate uses. But it can also be addictive.

Its particular chemistry gives it speed and power that most other opioids don’t have. And all that spells trouble. Researchers hope that a better understanding of how fentanyl works at the cellular level will help prevent future overdoses.

In the meantime, if you want to learn more about how to recognize an overdose, or want resources about harm reduction and drug addiction, there are links provided in the video description. Thanks for sticking around this far. We couldn’t dig deep into these science stories without you.

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If you’d like to learn more about becoming a patron, head over to patreon.com/scishow. And, as always, thanks for watching. [♪ OUTRO]