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 opiods 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. It’s stories like this one that are some
of the hardest to get right, and aren’t the most advertiser-friendly. That’s why we’re so grateful to our patrons
on Patreon who make it possible for us to take these
big swings. Our community of patrons sees the value in
the work we do to make informative, accurate content on all kinds of scientific
topics. If you’d like to learn more about becoming
a patron, head over to patreon.com/scishow. And, as always, thanks for watching. [♪ OUTRO]
