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Science Diction Podcast | Fentanyl

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The Centers for Disease Control and Prevention estimates that in 2023, of the 112,000 Americans who died from a drug overdose, more than 70 percent were due to a synthetic opioid and the majority of those were due to fentanyl. In Episode 14, we discuss why fentanyl is so potent, the scale of the problem, and how we’re helping first responders do their job safely and effectively.

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SCIENCE DICTION PODCAST: Episode 14

Amy Manning-Boğ, Ph.D. 

The Centers for Disease Control and Prevention estimates that in 2023, more than 112,000 Americans died from a drug overdose. Sadly, this is a new annual record. Nearly 70 percent of these deaths were caused by synthetic opioids, and most were due to one that is particularly toxic. In fact, by the time you complete this podcast, more than two Americans will have died by overdosing on it.

Evan Durnal is a chemist and director at MRIGlobal who specializes in CBRNE. That’s chemical, biological, radiological, nuclear, and explosive related projects for commercial partners, the Department of Homeland Security, the Department of Defense, and other US government customers. This work includes testing and evaluation of drug detection equipment used by first responders, as well as site remediation products used by local, state, and national authorities. Today on the show – fentanyl – why it’s so potent, the scale of the problem, and how we’re helping first responders do their job safely and effectively. I’m Amy Manning-Bog, and this is Science Diction from MRIGlobal.

Evan Durnal, M.S.
In the late 1990s and for about the next 15 years, pain clinics across the country served as distributors for opioids, with Oxycontin being among the most popular. A significant increase in the number of overdose deaths attributed to this drug subsequently followed. This resulted in a crackdown on manufacturers, distributors, and ultimately users. Crack cocaine and heroin quickly filled some of this void, but also left users and the illicit manufacturers looking for a powerful and profitable alternative – enter fentanyl.

Amy Manning-Boğ, Ph.D. 

What is fentanyl?

Evan Durnal, M.S.
So fentanyl is a synthetic opioid, meaning it’s not naturally derived. It’s created in a lab or in a clandestine site. It targets the opioid receptors in the brain and reduces pain and elevating pleasure and relaxation. There are approximately 1400 known fentanyl analogs, 500 or so of which are of interest in today’s market. 30 to 40 of those are the most common that we see within the pharmaceutical industry and on the street. Based on the precursors used to make them, each has a different toxicity, some being much more potent than others. Unfortunately, because of its powerful opioid properties, both pharmaceutically and illicitly manufactured fentanyl can be diverted for abuse.

Amy Manning-Boğ, Ph.D. 

So fentanyl was originally manufactured for pharmaceutical use?

Evan Durnal, M.S.
Yes. When pharmaceutically manufactured fentanyl is used as prescribed, it can be a fast-acting opioid that has been described as a wonder drug by some. It can be beneficial for patients in addressing pain or those who are terminally ill, providing quick pain relief. This includes cancer patients, anyone recovering from a surgery, moms recovering from childbirth, athletes with a lingering sports injury. There’s actually a pretty good chance that many of us have had it after a surgery or in recovering from an injury. It’s these same populations of non-traditional drug users who become addicted, many times unknowingly. In fact, many first encounters with fentanyl are when it’s prescribed for a medical issue. Between three and 10 percent of people become addicted after only their first use.

Amy Manning-Boğ, Ph.D. 

Wow.

Evan Durnal, M.S.
So every time they refill a prescription, users are significantly more likely to become addicted, especially for those dealing with significant and chronic pain.

Amy Manning-Boğ, Ph.D. 

You just described legally made fentanyl. What about illegally made fentanyl?

Evan Durnal, M.S.
So for the illicit manufacturers out there, fentanyl offers numerous benefits. Foremost, it can be produced much more inexpensively than many illicit drugs, roughly 1/25th the cost of heroin, but with a similar or greater high for the users, so really a lot more bang for their buck, so to speak. Additionally, because fentanyl is synthetically produced, the production timeline is not as lengthy as a drug like heroin or morphine because it’s not dependent on that cultivation and the processing of poppies.

Amy Manning-Boğ, Ph.D. 

I see.

Evan Durnal, M.S.
For users, fentanyl doesn’t have the same stigma associated with it as a drug like heroin either. Because it can be prescribed by a doctor, continued use is often perceived as nothing more than a prescription refill, even if secured illicitly. It also is less expensive than many other drugs while still offering the high sought by users. As a result, when fentanyl first became popular in the early 2010s, it displaced a significant portion of heroin on the market. It also is sometimes used to cut various drugs and increase its potency, reducing its costs or to be disguised as a highly potent version of that drug. Unfortunately, it’s also much more toxic. An overdose death can occur when users believe they’re purchasing an illicit drug or a counterfeit prescription drug and don’t know that it has been cut with fentanyl.

Amy Manning-Boğ, Ph.D. 

Why is fentanyl so deadly?

Evan Durnal, M.S.
Fentanyl is so deadly because of its potency primarily. It simply doesn’t take much to cause an overdose. There’s a wide range of doses that can be safely administered to elucidate the desired physiological responses like pain relief. The issue is that while fentanyl has a relatively wide index, that entire range is within a very small amount. Ideal therapeutic indexes are roughly in the 10x range or greater. For example, Tylenol, roughly 500 milligrams of acetaminophen. It would likely take over 20 times that to be a toxic dose, which is quite a bit of mass, right? Quite a few pills, right? So for Tylenol, that therapeutic index is about 10x. Fentanyl’s therapeutic index is in the ballpark of 400x, so a lot bigger, but that range ends more than 50,000 times lower for fentanyl versus Tylenol. It’s that two milligrams of fentanyl versus about 10 grams or more. Humans can very readily distinguish between around 500 milligrams of a white powder and 10,000 milligrams of a white powder.

Amy Manning-Boğ, Ph.D. 

It sounds really easy to accidentally overdose.

Evan Durnal
Yeah, for that reason. And another critical factor being toxicity when assessing the toxicity of various drugs, oral morphine is typically used as the baseline because it’s been studied extensively. Morphine has been around a very long time. Tylenol is 360 times less toxic than morphine. Advil around 222 times less toxic than morphine. Heroin being about four to five times more toxic than morphine and fentanyl being described sometimes 50 to 100 times more toxic than morphine.

Amy Manning-Boğ, Ph.D. 

Wow.

Evan Durnal, M.S.
A large animal tranquilizer known as carfentanil, which is used for elephants, horses, and other large animals, particularly in the veterinary fields, which is actually the most potent known fentanyl analog is about 10,000 to a hundred thousand times more toxic, and unfortunately, people can get their hands on it too, often with deadly results.

Amy Manning-Boğ, Ph.D. 

So given its high potency and that really small amounts can be toxic, the production of illicit fentanyl must contribute to its danger too, yeah?

Evan Durnal, M.S.
Absolutely. Clandestinely produced fentanyl is primarily manufactured in Mexico, India, or China, and imported into its country of use for further processing. That’s not to say it’s not made here in the U.S. also, that’s just where a large portion comes from. In North America, it’s often cut with baby powder or other inert materials, so think other ingredients that don’t really have an active pharmaceutical purpose and that it’s pressed into pills for further processing or consumption. This processing itself can result in highly inconsistent product as the amount of fentanyl in each dose can vary widely and pose a significant danger to users. They never know whether the next dose will deliver a high or a death.

Amy Manning-Boğ, Ph.D. 

Unfortunately, first responders and authorities responsible for cleaning up after interdictions and seizures are putting themselves in harm’s way as exposure to some of these drugs can be harmful and even fatal.

Evan Durnal, M.S.
Though most fentanyl is manufactured outside the U.S. and then imported. manufacturing sites are still a problem in this country. Since around 2020, in the U.S. alone, there have been more than 650 locations where law enforcement agencies reportedly found chemicals or other items indicating the presence of either clandestine drug laboratories or dump sites for post-production byproducts and precursors, some of which may be even more harmful than the drug itself. Since 2021, over 61,000 pounds of fentanyl have been seized in nearly 5,000 separate seizure events.

Keep in mind, a potentially lethal dose of fentanyl is approximately two milligrams, which would fit on the lead of a pencil. There are more than 450,000 milligrams in a pound. So 61,000 pounds is more than 13.7 billion lethal doses, and that’s just what was seized that we know about.

Amy Manning-Boğ, Ph.D. 

So 13.7 billion lethal doses. And then when we consider the number of people in the U.S., help me do the math here. What are we talking about?

Evan Durnal, M.S.
Yeah. That comes to roughly a little more than 40 lethal doses per person in the United States.

Amy Manning-Boğ, Ph.D. 

In what was seized in 2021.

Evan Durnal, M.S.
Yep.

Amy Manning-Boğ, Ph.D. 

What can you tell me about what these sites really look like?

Evan Durnal, M.S.
It really is a broad scope of what they look like, and that hammers home the importance of testing properly because it’s not just a pile of powder or a trace residue on a glass surface that’s really easy to clean off. It’s on porous surfaces, it’s on wood, it’s on tile, it’s on carpet, it’s on curtains, it’s on couches. So there is a broad difference between how you treat those surfaces in order to get them clean.

Amy Manning-Boğ, Ph.D. 

When authorities clean up a site like this, what is the goal?

Evan Durnal, M.S.
So obviously the goal for remediation of any site is a rapid return to normalcy. Since many of these sites include public ports, private residences, single and multifamily housing, and other facilities, that normalcy should involve the ability to prove a site as free of any hazards to the next person entering and trying to live their day-to-day life. Sometimes the hazard is respiratory. Did I breathe it in? Sometimes it’s a contact. Did I touch it? Both of these exposure situations should be addressed depending on what the hazard was, whether it’s a solid white powder like fentanyl or a liquid precursor or byproduct.

Amy Manning-Boğ, Ph.D. 

So tell us about remediation of these sites and the process that’s involved.

Evan Durnal, M.S.
Sure. So think of the terms we use to describe cleaning something up – removal, disinfection, neutralization, destruction, decontamination, mitigation, remediation, treatment. The list goes on. We rarely pause to think about what these terms actually mean and what the implications of those definitions are. Do they really all describe the same thing? So think of a child stating “My room’s clean.” I think we all agree that “clean” to my teenager means something very different than cleaning to a parent.

Amy Manning-Boğ, Ph.D. 

Yes.

Evan Durnal
It is all about setting the expectation. The same ambiguity can exist when inequitable testing methods and rigor are used to support claims of product efficacy. This product can be used against fentanyl. Okay. Does it physically remove it? If so, what do I do now with the contaminated wipe or liquid? Does it chemically degrade it? If so, what does it turn it into? Is that more dangerous than what we started with? Does it do some combination of the two? There’s really a spectrum of clean out there and it’s important to know what products provide, what results, and then what operational scenarios or environments to apply those products.

Evan Durnal, M.S.
How much of that product did you apply? How long did you let it sit on the surface? I think one common misconception is the fact that you could just like a Lysol at home, you spray it and wipe it two seconds later, everything’s clean and gone. Technically for different, whether it’s a biological pathogen, when you’re talking about Lysol or in this instance we’re talking about chemicals, the same theories apply where there’s that resonance time that a chemical needs to be in contact with the treatment method for it to actually work and actually decontaminate the surface like it’s supposed to.

Amy Manning-Boğ, Ph.D. 

Now, how does our work at MRIGlobal help with that?

Evan Durnal, M.S.
So nearly every day we’re working multiple angles to help solve this problem. We’re working to set the standard for efficacy testing. We’re working to make sure field portable equipment and users can quickly and accurately identify the hazards in the field. We’re working also to make sure that PPE protects those working in those hazardous conditions. Efficacy is kind of a foggy term that is relatively ill-defined when it comes to decontamination testing for clandestine chemicals. It is time that we have a universal test method and standards by which these decontamination products are measured by adhering to our rigorous test methods, we provide the apples-to-apples comparison between products that enables appropriate operational decisions.

We also help develop the equipment, both the hardware and software that field users rely on for timely answers. We help generate the onboard library entries used to determine the identity of the chemical threat and therefore start the process to render safe. It’s really hard to remediate a site if you don’t know what the hazard is to start with. And finally, we help evaluate fielded products and provide training for both commercial and government partners so they have confidence in the results they obtain, that they sample the right spot, and they understand how to interpret those results. Some of these pieces of equipment are not always straightforward in terms of the output.

Amy Manning-Boğ, Ph.D. 

Hence your call for universal standards. I really appreciate the rigor that’s involved in deeming a site clean.

Evan Durnal, M.S.
Absolutely. There are a lot of universal standards out there for other things. We’re talking about having that same level of rigor. If I say I tested your product and someone else tested your product, we should be able to compare those and get the exact same numbers and have that reproducible science that the public end user should demand.

Amy Manning-Boğ, Ph.D. 

That sounds like quite a bit of expertise involved.

Evan Durnal, M.S.
So our experience in not only the laboratory science but the field operations and real-world use of these methods and equipment allows us to give you and the folks using this confidence the threat was truly mitigated and wasn’t just shoved under the bed with the dirty socks like a teenager would do.