The Analytical Zen Podcast

Cat and Mouse: How Toxicologists Chase Ever-Evolving Designer Drugs

Geraldine M. Dowling Episode 12

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In this compelling episode, Dr. Kayla Ellefsen—Deputy Chief Toxicologist at the Travis County Medical Examiner’s Office in Austin, Texas, United States-offers a rare look into the science of forensic toxicology and its critical role in death investigations. She dismantles Hollywood myths about quick test results and flashy labs, revealing the meticulous process toxicologists follow to identify substances in postmortem samples and determine their role in a person's death.

The conversation takes a deeper turn into one of the most urgent challenges facing toxicologists today: Novel Psychoactive Substances (NPS). These synthetic compounds are designed to imitate known illicit drugs while evading laws and standard detection methods. Dr. Ellefsen describes the evolving “cat-and-mouse” game between underground chemists and forensic labs, and how advanced tools like high-resolution mass spectrometry are crucial.

A particularly alarming trend she highlights is the rise of bromazolam, a designer benzodiazepine. Even more concerning is the emergence of “benzodope”—the deadly mix of benzodiazepines and synthetic opioids.

Dr. Ellefsen closes with a strong message: researchers must share data on NPS to build a clearer picture of the threat and support the development of harm reduction tools.

Whether you're curious about forensic science, concerned about public health, or trying to understand today’s shifting drug landscape, this episode delivers critical insight into a field on the front lines of modern substance misuse.

Introducing Dr. Kayla Ellefson

Dr Geraldine M. Dowling SFHEA

Welcome to the Analytical Zen Podcast, where we delve into the minds of leading scientists and professionals exploring forensics, toxicology, medicine and health in terms of mind, body and spirit. I'm your host, geraldine M Dowling. What should you expect in the Analytical Zen podcast? Well, we'll dive into cutting edge research and topics that inspire curiosity, the latest in forensic and clinical toxicology pursuits, and engaging conversations and perspectives from disciplines outside of these fields. We're thrilled to have Dr Kayla Ellefson as our guest on the Analytical Zen podcast. Dr Ellefson received an Honours Bachelor of Science in Forensic Science from Laurentian University in Canada, a Master of Science in Forensic Science from Sam Houston State University and her PhD in Toxicology from the University of Maryland Baltimore in the United States. Her doctoral research was conducted at the National Institute on Drug Abuse, or NIDA, and focused on advancing analytical methodologies for classic and novel stimulants. Additionally, she was part of the NIDA Designer Drug Initiative, tasked with studying the pharmacodynamics and pharmacokinetics of emerging novel psychoactive substances, or NPS.

Dr Geraldine M. Dowling SFHEA

For the last nine years, dr Ellefson has worked for the Travis County Medical Examiner, located in Austin, texas, usa. As the Deputy Chief Toxicologist, she helps develop and validate new and improved methods for the analysis of drugs, other chemical substances and emerging MPS in traditional and alternative biological matrices. She interprets analytical findings and reports toxicology findings to aid in the determination of cause and manner of death. She also serves as toxicology faculty for the University of Texas Medical Branch Forensic Pathology Fellowship Program. Dr Ellefson is the current chair of the Society of Forensic Toxicologists NPS Committee and has been a member of that committee since 2018. She's also a member of the International Association of Forensic Toxicologists, or TIAA, and the American Academy of Forensic Sciences, or AAFS. Kayla, it is my pleasure to welcome you to the Analytical Zen Podcast.

Dr E

Hi, Geraldine. Thank you so much for having me. It's a pleasure to be here today.

Dr Geraldine M. Dowling SFHEA

Kayla, how did you get into forensic toxicology, and was there a particular course, professor or internship that led you to pursue this path?

Dr E

Yeah, that's a great question. I don't necessarily think it was one thing that led me down this path. I originally had a general interest in forensic science after reading a fiction book on death investigations and specifically relating to medical examiners. So that's really what initially captured my interest. But then, I would say, my undergraduate research project with my toxicology professor at Laurentian, dr James Watterson, really drew me into forensic toxicology. The project was involved in examining the performance characteristics of a portable breath alcohol testing device called the Intoxilyzer 8000. And after measuring breath alcohol concentrations in healthy subjects under social drinking conditions, we then were able to assess the performance characteristics of this portable breath alcohol testing device. So that really kind of captured my interest in forensic toxicology and led me down the path I am today and thankfully I've been really blessed to have numerous mentors who have guided me throughout my career, including Dr Marilyn Hustis, and she was a big role in my PhD program and really teaching me the ins and outs of forensic toxicology that have allowed me to continue on this career today.

Dr Geraldine M. Dowling SFHEA

Kayla, what does your professional work involve and what type of samples do you analyze?

Dr E

As a forensic toxicologist, we're primarily responsible for performing routine chemical and biological analyses of bodily fluids and tissues to determine the presence and identity of toxicological substance in the body. So, whether that's determining the presence of alcohol, medications, illicit drugs and or other chemical substances that are foreign to the body. So, since I work for the medical examiner's office, we're primarily dealing with post-mortem samples in order to help the forensic pathologists in determining cause and manner of death by identifying these substances or combination of substances present in these biological samples. So we're really there to kind of help determine if their presence is sufficient enough to cause or contribute to the cause of death. For instance, after autopsy we generally receive a variety of specimens that are available to us that will need to be analyzed to determine what, if any, substances are present. So, for instance, you can receive a blood sample from after autopsy and then we'll test for alcohol and then we'll screen that blood with a variety of different analytical techniques and then, based on those screening results, we'll then confirm their presence of the substance with another analytical technique in order to determine how much drug is present in that sample, and then we'll interpret our findings in order to report these findings to the pathologist to help determine cause and manner of death.

Dr E

And then the second part of my job here at the medical examiner's office specifically involves developing and improving upon these analytical methods that we have to detect these substances. So instruments and techniques are constantly evolving, so it's really important for us to be able to adapt our methods in order to improve the detection and stay up to date with these advances. And then, second fold, drug trends are constantly changing, so new methods or updates to existing methods in order to be able to detect these emerging drugs or compounds that we previously weren't looking for is definitely a high priority for us.

Reality vs. TV Depictions

Dr Geraldine M. Dowling SFHEA

Kayla, what would you describe as the biggest difference between what you do as a forensic toxicologist and what is portrayed on TV shows?

Dr E

Oh gosh that's a great question. I think the main thing is that toxicology results cannot be determined in a matter of hours. I think on these TV shows they're depicting that it's you know, with the snap of a finger that we can detect what substances may be present. However, each case receives extensive testing, At least in our laboratory. You're getting four different analyses up front and then, if that case is positive for one or more substances, it then requires further testing to confirm their identity. It's not all that glamorous. We don't really necessarily have a lot of high profile cases that we're constantly dealing with, and I think that's one thing that these shows kind of depict on every episode.

Dr Geraldine M. Dowling SFHEA

Kayla, what are your main areas of interest and research now?

Dr E

My areas of interest in research are twofold.

Dr E

As I mentioned previously, I'm very interested in improving our analytical methodologies to keep up with advances made in the field, and this really stemmed from my PhD research, which involved an IV cocaine administration study. Study then allowed us to examine the pharmacokinetics and pharmacodynamics of cocaine in a variety of biological matrices whether that be oral fluids, breath, dried blood spots and then developing these analytical methods in order to be able to detect cocaine in these different matrices. And then the second fold of this research would be my involvement in novel psychoactive substances. I have been involved with NPS since my master's program and it's kind of followed me throughout my career. With my PhD research I was fortunate enough to help work with the NIDA Designer Drug Initiative, which involved looking at the pharmacokinetics and pharmacodynamics of these emerging substances in in vivo animal studies. So I was primarily responsible for developing these analytical techniques in order to be able to assess these specimens from these in vivo animal studies. So that was really a great opportunity for me and what really dabbled my toes into the NPS field.

Dr Geraldine M. Dowling SFHEA

Kayla, could you explain to our listeners what are NPS and what are the challenges associated with NPS?

Dr E

Of course, I think the term NPS has really kind of evolved over the last decade, but primarily they referenced a diverse group of synthetic substances that were designed to mimic effects of established illicit substances, often referred to as designer drugs or legal highs, and they're often misrepresented or in adulterated products. Often they involve a slight chemical modification of the chemical structure of a controlled substance in order to evade detection from traditional screening methods. Generally, these substances are not under any international and regulatory control, and they were initially designed to circumvent these legislative and regulatory efforts. It's like this cat and mouse game as soon as you schedule one NPS, another is created by slightly altering that chemical structure. So it's this constant cat and mouse game between learning more about one substance and then the next minute getting scheduled and another one popping out on the market. Nps consists of four main classes the synthetic cannabinoids, synthetic stimulants and or hallucinogens, the synthetic opioids and the NPS benzodiazepines. But more recently the definition of NPS has kind of expanded to also encompass substances that are being used in another manner than what was initially intended. For example, a drug may be prescribed therapeutically in another country but is recreationally misused at sub-therapeutic doses for a different type of effect here in the United States.

Dr E

Moving on to challenges, I think one of the main challenges with these emerging substances is their dynamic market that they exist in. These compounds are in a constant state of flux with the ones that are currently being used on the market, as well as new emerging NPS coming onto the market and others phasing out. So you have this constant fluctuation between what is actually present in this NPS market, which makes it very challenging to know which substances you should be testing for and what NPS trends are even prevalent in your population. Along with this, because they're such new compounds, little is known regarding their pharmacology, toxicology and potential health risks. So not only do you have these overarching challenges associated with NPS compounds, but you also have numerous analytical challenges they pose to toxicologists and being able to detect and identify these substances in casework. So they're a real challenging group of substances.

Dr Geraldine M. Dowling SFHEA

Kayla, why do you think it's important for laboratories to be monitoring for NPS?

Dr E

I think it's important for laboratories to be monitoring for NPS in order to ensure that we're not underestimating their prevalence in our casework, in order to allow us to better understand their threat to public health and safety and also to be able to help establish what concentration might mean in a variety of different case samples.

Current Trends in NPS Cases

Dr Geraldine M. Dowling SFHEA

How is your laboratory, Kayla, tackling testing for these emerging substances?

Dr E

So currently, our laboratory is screening for these compounds using high-resolution mass spectrometry, and this is because it offers us a level of sensitivity that we need to be able to detect these substances and the specificity to encompass all of the emerging NPS compounds.

Dr E

To encompass all of the emerging NPS compounds. High resolution mass spectrometry also allows us to perform retrospective data mining on cases previously analyzed in order to potentially identify the presence of a novel NPS that we weren't originally looking for. I don't think it's necessarily a one size fits all approach when it comes to NPS testing. I think we've come a long way with the resources that are available to us regarding these substances, and it's really just combining everything you have in order to do the best you can. We do have resources that are available to help in terms of what to look for, what limits of detection we should be using, what types of instrumentation might be beneficial for the various NPS classes and, in general, what we know about these compounds and their effects on the body, and what the body does to these substances, has really grown over the last decade.

Dr Geraldine M. Dowling SFHEA

Kayla, what NPS trends then are you seeing in your casework?

Dr E

In our casework. Nps positivity rates are about 2 to 5% over the last several years. Our NPS positive cases are primarily white males in their early 30s, which is also consistent with the observed demographics here in our population In terms of our positive NPS cases. Nps benzodiazepines are the most prevalent NPS class in our postmortem casework, primarily bromazolam in the recent years, and they account for almost half of our identifications that we make. Often these substances are found in combination with other substances such as CNS depressants or stimulants like cocaine and methamphetamine. Our next most prevalent class of NPS compounds are the NPS opioids and this is a result of primarily floral fentanyl detection Floral fentanyl is primarily found with fentanyl and really started taking off after the ban on fentanyl.

Dr E

precursors used to make illicit fentanyl, which then shifted the production of how illicit fentanyl was produced, and it is an illicit byproduct that is found in the formation of this illicit fentanyl was produced and it is an illicit byproduct that is found in the formation of this illicit manufacturing of fentanyl. Otherwise, we really haven't detected too many fentanyl analogs or the nitazine compounds that are currently dominating the synthetic opioid market. And then our next most prevalent class are the synthetic cannabinoids. Up until the end of 2021, this was our second most prevalent finding. However, we then noticed a significant drop in our synthetic cannabinoid cases, and this coincided with the China ban of synthetic cannabinoids, which has recently started seeing an uptick in these cases with the availability of the synthetic cannabinoid precursors. Interestingly, we really don't have a lot of cases involving NPS stimulants or hallucinogens, like other parts of the country, for example Florida, or even over in Europe, but when we do see them, we do see a wide variety of compounds.

Dr Geraldine M. Dowling SFHEA

Kayla, can you elaborate on what Bromazolam is and talk more about your recent findings you have observed in your population?

Bromazolam and Benzodope Phenomenon

Dr E

Talk more about your recent findings you have observed in your population, no problem. So bromazolam is a novel benzodiazepine and it is the brominated counterpart to the chlorinated alprazolam that's often misrepresented or found in adulterated products such as illicit oxycodone or benzodote. Although its pharmacology has been largely understudied, it is believed to act similarly to traditional benzodiazepines, with those sedative and CNS depressant-like effects. So your loss of coordination, dizziness, drowsiness, slurred speech, muscle relaxion, amnesia and even respiratory depression. Typically, benzodiazepines on their own have a low toxicity profile. However, they're often found in combination with other products and compounds, which enhances their risk for adverse events and overdoses. So, relating this back to our findings in our casework, since 2021, we've observed a significant increase in bromazolam-positive postmortem cases. We've had almost a 307% increase in cases from 2021 through 2023, although we have noticed a decrease in these cases since its international regulation in March of 2024. Bromaze lamb is almost always found in combination with other substances. In our population, it's primarily fentanyl, methamphetamine and cocaine.

Dr Geraldine M. Dowling SFHEA

Kayla, you mentioned the benzodope phenomenon. What is it for our listeners and how does it relate to your case findings?

Dr E

Benzodope itself is not really a novel concept. Benzodiazepines and opioidsazolam and synthetic opioids such as fentanyl or some of the nitazine compounds and reports of benzodope replacing fentanyl on the streets have started emerging in recent years. Benzodope often offers a better high, a quicker hit. It's more addicting, and users have said that it's needed now in order to reach that desired nod that they're looking for, that it's needed now in order to reach that desired nod that they're looking for. The problem with benzodope really lies in users expecting to be using opioids and inadvertently increasing their risk for overdose from the benzodiazepine adulteration. Additionally, benzodiazepines are slower to take effect, so someone can experience delayed overdose symptoms.

Dr E

Now relating this back to our casework Travis County largely avoided the fentanyl epidemic that the rest of the United States saw until 2020. Since 2020, fentanyl-related deaths had increased by 305% through 2023, which accounted for 11% positivity in our casework, so that was rather worrisome for us. So in fighting with this increase in fentanyl-related deaths, we were also observing a significant increase in bromazolam-related cases. So we really wanted to look at the co-positivity of these substances to see if we were maybe seeing the emergence of benzodope. And when we looked at the co-positivity of fentanyl with our bromazolam cases, we've seen a 70% co-positivity rate since 2022. However, without aggregate drug type checking data, it's hard to say for certain if this is strictly a result of benzodote formulation or if it's really the combination of users using both of these substances.

Dr Geraldine M. Dowling SFHEA

Kayla, what are some of the take-home messages and the dangers associated with NPS use then?

Dr E

I think some of the take-home messages and dangers associated with using these NPS substances is that oftentimes, users are unaware of the products they're often using.

Dr E

Nps are often misrepresented and adulterated with other substances, increasing the risk for drug toxicity, and this is especially the case with naive users. Additionally, we really don't know much about these NPS compounds and the risks they may pose. I came across a poster a few years back and it was depicting a lab mouse that was saying I haven't even tried methadrone yet, so why have you? And I think that's a really great representation of the dangers that these users are facing by using these novel substances that we really don't know much about. I think it's also important to continue to adapt and improve our methodologies to keep pace with this ever-changing drug market, as they are often reported, in order to be able to understand the risks they pose and their potential threat to public health and safety, and to try and minimize the public health risks and investigate more harm reduction strategies, such as legalizing drug testing kits, in order to try to reduce the risks of unknowingly taking these unexpected substances.

Dr Geraldine M. Dowling SFHEA

Kayla, before we conclude, is there anything else you'd like to share with our listeners?

Dr E

Sure, I guess my PSA would be that if you have any data regarding NPS, please publish it. I feel like every little bit helps us to establish the extent of the problem and also to learn more about these novel compounds. So it's really important to get that information out there to other toxicologists and forensic pathologists and even the public.

Dr Geraldine M. Dowling SFHEA

Kayla, that's a really great point. Thanks for joining us on the Analytical Zen podcast and sharing your personal experience. Thank you.

Dr E

Geraldine, this has been such a fun time discussing this topic with you and I'm so thankful for this opportunity and I'm really excited to see what you do next.

Dr Geraldine M. Dowling SFHEA

Thank you, and likewise Kayla, and to our listeners, thank you for tuning in to an episode of the Analytical Zen Podcast. Be sure to join us next time and stay curious.