Novel Psychoactive Substances (NPS): A Dangerous, Widespread Public Health Issue

Novel psychoactive substances (NPS): A dangerous, widespread public health issue

(PODCAST TRANSCRIPT)

Voiceover [00:00:02]:

Welcome to ‘The Results Are In’ from Quest Diagnostics. Conversations with diagnostics industry leaders who enable optimized care pathways for patients.

Jason Suomala [00:00:16]:

Good afternoon. My name is Jason Suomala. I'm the Product Director for Quest Diagnostics Drug Monitoring and Toxicology Division. I'm joined here today with my colleague, Dr. Jack Kain.

Jack Kain [00:00:25]:

Hi, I'm Dr. Jack Kain. I'm the director of Drug Monitoring and Toxicology here at Quest and Medical Science Liaison for Medical Affairs here at Quest Diagnostics.

Jason Suomala [00:00:35]:

All right, today we're here to talk about the growing crisis of novel psychoactive substances. And we're going to cover three learning objectives today, the first one of which is going to be the increase your knowledge of novel psychoactive substances and why you should be concerned with them. Hopefully gain a deeper understanding of the increasing prevalence and the characteristics of these NPS classes and specific classes and drugs, determine the clinical utility of NPS testing and how these test results can help you in a clinical setting. So the growing crisis of novel psychoactive substances. These substances have become more prevalent in communities and are providing a different challenge for providers in today's setting. I'd like to today talk about some of the specifics around these substances and I'll turn it over to Dr. Kain to get into some of the details.

Jack Kain [00:01:25]:

Yeah, thank you, Jason. As you know, as we always discuss, you know, the unpredictable nature of these novel substances, some can be, you know, very moderate adverse effects, health effects, but some are very severe, contributing to the overdose crisis that we've seen these past years. But they are novel. So they have flown under the radar of, let's just say, traditional drug casting, traditional prescribing practices. All of them are essentially illicit and, you know, span over multiple drug classes. So, you know, why are these substances made? Why have they been designed as such? Well, they're meant to mirror the psychoactive effects of traditional drugs of abuse or even pharmaceutical controlled substances. So your opioids, your benzodiazepines, now there are, think of it as like, you know, Xanax having a street version or street alternate version of itself, which would fall under a class called designer benzodiazepine. It's like flubromazolam being one example, but also fentanyl having other counterparts, similar in effect and chemical structure, but also varying potency.

Jack Kain [00:02:40]:

We call those that class fentanyl analogs. But a lot of people may have heard of arguably the most potent fentanyl analog known as carfentanil, which is more potent than fentanyl in and of itself. And just a reminder, you know, fentanyl is the most significant contributor of drug overdose deaths in this country. And so that's what's happening out there is these novel substances, they're mirroring the effects of these traditional drugs of abuse and in some cases, completely supplanting them. So, you know, Quest data shows that heroin is arguably not anywhere near as relevant as it was even five years ago. And in some areas in this country, heroin's been completely supplanted by fentanyl, completely replaced by fentanyl. And patients don't know, you know, if they're consuming these substances. You only know that these substances have passed through your body.

Jack Kain [00:03:36]:

If you consumed, if you've done a drug test, you know, truly what's passed through the body, because we see some of these substances, they form byproducts known as metabolites. Those metabolites can only be formed by passing through the liver in the body and then thereby excreted in the urine. And so you don't know, patients don't know what they are consuming. And even a provider does not know with these substances until a drug test is done to identify those unique byproducts of these substances. And as you can see, yes, the prevalence of novel psychoactive substances is increasing. It's increasing dramatically. I mean, we'll get into our data set right now. So we report our data via our Health Trends report.

Jack Kain [00:04:19]:

You can find this online. And so our Health Trends Report, we looked at, you know, 3730 randomly selected remnant urine specimens we tested for novel psychoactive substances using our new test panel, which Jason will get into later. But the most prevalent designer substance or novel substance that we have found was xylazine. You know, it was found in nearly one in 12 remnant specimens tested, Jason. You know, it's making it the most prevalent NPS that we have. You know, xylazine is most often found with fentanyl. It adds to it, potentiates the effects of fentanyl, but unfortunately, it also has contributed to more significant overdoses. And it's made the management of overdose toxidromes more difficult with naloxone, because naloxone isn't necessarily meant to reverse the effects of xylazine, while naloxone is meant to reverse the effects of fentanyl.

Jack Kain [00:05:23]:

So it makes managing these scenarios that much more complex going forward to identify.

Jason Suomala  [00:05:29]:

Those, too, huh, Dr. Kain?

Jack Kain [00:05:31]:

Oh, absolutely, absolutely. You know, you want to catch these risky behaviors before they occur, or you want to catch relapse in close proximity to when it actually occurs, and you want to do it in an objective way by using a drug test and using that in conjunction with the patient's clinical picture. And as you can see here, our data showed that fentanyl analogs were the second most prevalent NPS. Designer benzos came after, then designer stimulants, designer opioids, the nidazines or the nitazines, however you want to pronounce them, are novel. They mirror the effects of opioids and they're starting to, you know, we. We think they are increasing. Our data shows that they're prevalent, but the ebb and flow of these substances, it can change within a given quarter or a given year, Jason, as you know. And so it's important to just identify these.

Jack Kain [00:06:23]:

Synthetic cannabinoids are still prevalent as well. And so you could find this data in our Health Trends report. And as I mentioned earlier, thylazine was the most positive NPS of all the NPS that we tested. We had a 13.1% overall positivity. This is pretty significant compared to what we used to see even just a few years ago with some of our synthetic cannabinoids panels or some of our designer stimulant panel as well, which were really low in positivity. But the trend is showing that these designer drugs, these novel substances, really are increasing tremendously, and each of them ebb and flow throughout the given year.

Jason Suomala  [00:07:03]:

It looks like they were found a lot in combination, too.

Jack Kain [00:07:06]:

Oh, yeah. So I'll just say we rarely see xylazine by itself. We see these substances mixed together. It is essentially a cocktail. I mean, a patient, when they consume an illicit drug, do they really know what they're consuming? And the truth is, is our data shows that oftentimes these substances are co mixed to contribute to a more potent effect. It's concerning, Jason, because, you know, this person who was addicted to just opioids, now there might be designer stimulants mixed into it. So the old adage of, oh, you know, this person only uses opioids or is only addicted to opioids, may actually be addicted to multiple classes of substances unknowingly and, you know, eventually knowingly, but it just makes managing these patients that much more complex. So xylazine, we call it the poster child right now of novel psychoactive substances.

Jack Kain [00:07:57]:

But, you know, tomorrow it could be something else. And so you need, you know, you need a test that can identify these substances in a dynamic way to be able to keep up with what's being reported by the DEA, by Customs, and postmortem toxicology results. And Whatever resources that we could find that, you know, might point to the utility of testing for these substances as they ebb and flow through the US communities. And so xylazine, for those that don't know much about it, it was actually used as a veterinary tranquilizer, but it's not approved for human use nor scheduled as a controlled substance. So is it a novel substance in and of itself? No, it's been around for a while as a veterinary tranquilizer. But is it novel in human use or novel in human misuse compared to some of the traditional substances? Yes, absolutely. You know, it could cause sedation, difficulty breathing. Difficult sedation, difficulty breathing.

Jack Kain [00:08:54]:

Those are side effects of opioids. So you mix that with fentanyl, you mix these effects with fentanyl, and you get synergistic effects that lead to overdose symptoms. And then carfentanil, we are seeing a reemergence in carfentanil. You know, acetyl fentanyl is still one of the most prominent fentanyl analogs. But this is just concerning, Jason. I mean, this fentanyl analog has been called an elephant tranquilizer. It's more potent than fentanyl, and yet we're seeing it reemerge in various communities in this country, which is just scary. And so what is a doctor to do if they see a patient test positive for this? You know, you're going to.

Jack Kain [00:09:32]:

The provider, I imagine, is going to take steps to call this patient and alert them, you know, that they are essentially positive for the most potent fentanyl analog out there and assess for symptoms, signs and symptoms of overdose if the patient's currently present. But very important counseling point here. I mean, if you ask many patients that used, you know, cocaine, it was also found with fentanyl, would they still use the cocaine? You know, I think that would be up for debate, but I think there would be a lot of patients that wouldn't use it knowing that carfentanil is in their drug supply. And then we have designer benzos meant to mirror the effects of traditional benzodiazepines. So let's just say a clandestine laboratory, like, what if we combine the components of Xanax with the components of thalium, we make a new benzodiazepine. The answer to that question is yes. You know, the chemical structures look very similar to traditional benzodiazepines, and the effects are similar with varying potency that is just unpredictable and could lead to overdose on any given day for, for any patient, for any individual. And then you have designer Stimulants, I think, you know, Flakka was a popular one down in Florida, you know, aka Alpha PvP.

Jack Kain [00:10:47]:

It was described in a British patent in 1963. So some of these, they're not essentially novel in discovery. They're just novel at human use adjacent, right? So novel in their contributions to overdose toxidromes. I mean, and here you'll see what I mentioned earlier about structural similarity, the structures of traditional benzodiazepines versus designer benzodiazepines. So if you look at Xanax or Klonopin, look at those two chemical structures, this is what makes a benzodiazepine class. They look very similar, but it's also why you need to test, use definitive testing to differentiate between two substances within a same class, because it looks so similar. So. But do they have different molecular weights? Mass spectrometry or definitive testing can help elucidate that information.

Jack Kain [00:11:37]:

But then you have designer benzodiazepines, and you look at clonazolam on the right, it looks just like these traditional benzodiazepines. But you need a definitive test, you know, a very highly sensitive, highly specific methodology of testing to really be able to differentiate between designer benzodiazepine use, clonazolam use versus prescribed Xanax use. I mean, those are two different. Those could be two entirely different patients, right? Indications. One is using an illicit form of clonazolam. The other patient is compliant with their Xanax prescription. And so very different ways that you're going to respond to positivity in those patients. And then designer drugs and classes.

Jack Kain [00:12:19]:

Some additional ones are synthetic cannabinoids. Those have been around for a while. We are testing for some of the newer ones. You know, JWH18 was the original synthetic cannabinoid. One of the original, it's not very positive anymore. In fact, it was like less than 1% positivity. But there are other ones out there that are significantly more positive in very setting. Even in controlled settings, such as certain prison systems are seeing an inflow of synthetic cannabinoids because they fly under the radar of a traditional drug test.

Jack Kain [00:12:52]:

And then you have your synthetic opioids, such as the nidazines, 40 times more potent than fentanyl and up to 500 times more potent than morphine. This is a class of drugs and so they have varying potencies. Some of them are remarkably potent and could be contributed to the next wave of overdoses going forward. We will continue to monitor them. And then counterfeit pills. You know, laboratory testing indicates that seven out of every 10 pills seized by the DEA contain a lethal dose of fentanyl. A significant amount of fentanyl comes with fentanyl analogs. That's what our data shows.

Jack Kain [00:13:29]:

And the DEA has seized a record 74.5 million fentanyl pills to date in 2023, which already exceeds last year's total of 58 million pills. So we're seeing, you know, a lot of counterfeit pills out there. They could be sold as Xanax, but they're really fentanyl and then various designer drugs added to it as a cocktail. People just do not know what they're getting when they're getting it on the street. This is a blatant attempt to influence, you know, the next generation of substance use disorder as well by making these counterfeit pills look legitimate. And then they really contain some of the deadliest drugs out there on the market out there, you know, on the street, unfortunately. And so, Jason, why don't you talk about, you know, what Quest offers, what we've done at Quest, what does our test look for, and how do we plan to proceed with this panel going forward?

Jason Suomala  [00:14:25]:

Sure, absolutely. So Dr. Kane introduced quite a few interesting challenges that these novel psychoactive substances present to our providers. So what we've done is we've come up with a tool to hopefully address those and provide a useful tool for clinicians to treat their patients. We have a new novel, a novel psychoactive panel that tests for all six classes of novel psych or the major classes, the designer benzos, fentanyl analogs, opioids, designer opioids, designer stimulants, synthetic cannabinoids, and then other illicit additives, which would include things like xylazine. And our panel is done utilizing the LC-MS/MS to be able to detect these simultaneously.

Jason Suomala  [00:15:07]:

And what we do, which is kind of unique, is we update or research what substances are prevalent in communities. And we update our panel on a regular basis to include newly introduced substances and remove things that are less of concern as they going forward. If there is low positive or no positivity, we'll look to take things out, and then we'll add things that are important and the panel reports out at a class level. Because what we found in doing research with providers is that you know, which specific designer benzodiazepine is less important to the treatment of the patient than understanding the designer benzodiazepine was present. Because we know that based on the nature of these substances, it could change a patient could be positive for One type of designer benzodiazepine today, but tomorrow could be another one. But the treatment with a positive benzodiazepine or concern is the same.

Jack Kain [00:15:58]:

I'll add Jason too. It's like you ask a provider if a patient's positive for Bromazolam or flu Bromazolam, well, knowing the difference between those two, change how they manage the patient as it corresponds to the result. And the answer to that question is no. But we do acknowledge that there are some NPS such as Xylazine, where you know, you might need to change management of the patient or consider using other resources, such as wound care for certain NPS. But for most NPS, knowing individual NPS within a class, is that going to change how they manage the patient? Probably not.

Jason Suomala  [00:16:32]:

Yeah. So one of the key things and one of the factors of these substances is the fact that they're ever changing and on a regular basis there being new substances are being introduced. So how are we keeping up with what's out there? So we're using internal surveillance data as we're conducting our own testing, but we're also utilizing testing from law enforcement, information from public health organizations and also public safety agencies to keep up with what's out there and what's becoming more prevalent. So we have a panel or tool that's up to date and the providers can introduce this test code into their ordering pattern. And they don't have to change because we change what we're testing for, but we keep the test code the same. So in today's electronic world, having to change test codes all the time and updating EMRs is a challenge with our offering, they don't have to do that. They can introduce this panel into their system and order it and know that they're getting the most up to date testing possible. So if you look at our reporting, one of the things that we've done is we've introduced a really easy to understand report where we take and give you a nice summary on the top that introduces a definitive qualitative result whether which class is positive.

Jason Suomala  [00:17:46]:

And then on the bottom we include all of the substances that we've tested so far. So as we introduce new substances, the list on the bottom will include the list of things that we're looking for. So as a provider you can look down and understand what substances and if there is a specific substance of concern, you know, if we've looked for it or not. And one of the things that we're introducing in some of our updates, as we update this on an annual basis is introducing some additional notes that will highlight some substances of concern like Xylazine. If Xylazine is detected, we'll note on the bottom whether or not that is there. So that's an upcoming change that's going to occur with our next generation of distance. And then if you look at just from a cutoff standpoint, there's a cutoff value. So it indicates at which level things were detected.

Jason Suomala  [00:18:32]:

Then if we move into the kind of the next generation of this testing, we're going to look at what types of things we need to add or what types of substances are of concern. There's actually 26 new analytes that we're looking to add in 2024 when we introduced generation two to over the six different categories we're going to be taking and adding the availability of ordering individual classes. So although with the combination of substances, we found that most of the time providers found the panel was the appropriate test to use, there are situations where the individual classes may be needed. We're also taking and adding that report, that update that I mentioned where we're going to indicate certain specific substances of concern like Xylazine. So what's going to stay the same is that panel test code that I told you about. The test code will not change. So we're making all of these changes, but the providers aren't going to have to update their EMR to have different codes in there. And then we'll continue to deliver great turnaround time.

Jason Suomala  [00:19:32]:

So a great tool that's going to continue to expand and change with the times that it's needed for these substances.

Jack Kain [00:19:39]:

Yeah. And Jason, I mean, you think about it, it's like we do have these individual orderable designer drug classes, which is appropriate. But you know, how often are patients going on the street saying, I just want designer Benzo, you know, and if they do, do they actually just get the designer benzo? Is it exactly what it is?

Jason Suomala  [00:19:58]:

It's like, no.

Jack Kain [00:19:59]:

Our data shows that all this stuff is mixed together. So if you're asking for one of them, you should probably be thinking about all of them. Now, is this an every single patient, every single time test? Now these are high risk patients should be used selectively. But you really should be thinking about all of these because patients just don't know what they're getting and the providers don't know either until they do the actual drug test that is sensitive and specific enough to identify these novel substances. Great.

Jason Suomala  [00:20:29]:

And maybe you can take us through a couple of case scenarios where this testing is useful.

Jack Kain [00:20:34]:

Yeah, absolutely. And so high risk patients, you know, those who have a history of using injection drugs or have admitted to using counterfeit prescriptions if they know that they are counterfeit in the first place, or have just had experiences with counterfeit prescriptions because they were admitted to the ER experience the side effects associated with NPS that was found in a counterfeit prescription. Also, those who have been incarcerated experience homelessness or unstable housing, school aged young people are very, very concerned for adolescents because of what we talked about, these counterfeit tablets. I mean, have you heard of rainbow fentanyl, Jason? I mean, colorful pills that are actually contain fentanyl. They're meant to look appealing to our youth. And they contain fentanyl and fentanyl analogs and other designer drugs, sometimes not even what they're supposed to be. Like some of these pills, they're sold as they might be sold, knowing that or claiming that there's fentanyl in it, but it's actually just the designer benza. And so you think about what's happening to adolescents, it seems like a deliberate attempt to target the next generation of substance use disorder.

Jack Kain [00:21:49]:

And it will to some extent be successful, unfortunately. So individuals suitable for testing, right, those exhibiting signs and symptoms of NPS poisoning, those patients exhibiting aberrant behaviors, something is off, but a traditional drug test just isn't picking it up in some way, shape or form. Maybe a point of care test isn't picking it up because a lot of them don't even look for these novel substances. And if they do, they're probably not clear, waived or, you know, and so those being considered for opioid therapy or change in treatment, patients who need advocacy to verify their abstinence, patients in recovery from a substance use disorder. And so here's a patient case. So patient reported compliance to medications. I mean, this happens, but you know, the patient has a history of opioid use disorder. I mean, the patient is on a daily regimen of Suboxone as part of his treatment for opiate dependence.

Jack Kain [00:22:43]:

And during one of the clinical interviews, the patient intermittently fell asleep, demonstrated limited engagement, attributed this pronounced sedation to buprenorphine and naloxone, which I thought is pretty clever because opioids do have sedative effects. But something's off, something is just off. And so when awake, the patient appeared to be reacting to external stimuli, frequently diverting his attention to the door throughout the session, but also agitated. Signs of withdrawal and relapse, unfortunately. But we can only really know until a drug test is is. And so a screen the patient was sent to the er. Screening was performed as the. The immunoassay screens are often found in these ERs.

Jack Kain [00:23:28]:

And yes, the patient was positive, a presumptive positive, a screen positive for buprenorphine and negative for other illicit substances. But something is still off. You just know you use the patient's symptomatology matrix. Something was off. And so they did a definitive test, and they sent it off to Quest for a definitive test. And the patient was positive for synthetic cannabinoids and bath salts. So these are substances you don't find on a traditional drug test, you won't find on an immunoassay, a standard immunoassay in the ER so you need specialized testing. And what did we find? We found synthetic cannabinoids in bath salts.

Jack Kain [00:24:07]:

So subsequently, the patient acknowledged purchasing a K2 blend and using it regularly for the past six months. Here's the thing about K2 blend is that it's supposed to be synthetic cannabinoids only. And of course, only after the drug test revealed the truth did the patient begin to admit to using other substances. This happens often with drug testing. It's meant to open up dialogue, objective dialogue with the patient, and it certainly did here. But patient admitted to using K2 blends supposed to be synthetic cannabinoids. But guess what? It also contained bath salts, which are designer stimulants. And that was also contributing to the Simon symptoms that the patient was exhibiting, the aberrant behaviors that the patient was exhibiting.

Jack Kain [00:24:50]:

And only an NPS test would have caught that and helped this provider manage the patient accordingly, realizing that the patient is now in a relapse protocol. So we hope today that learning a bit more about mps. I know Jason and I can keep talking about this all day, and if you use Quest’s novel psychoactive substances test, we could talk about it, too. But also we do provide, you know, interpretation. We do provide tox line support for these types of results if they are used at Quest Diagnostics to help reveal what has been discovered from these results, but also so that ultimately providers can manage their patients accordingly and catch relapse in close proximity to when it occurs, in an effort to hopefully save the patient's life and reduce harm.

Jason Suomala  [00:25:38]:

Great. The information today was great, Jack. The other thing that I'd like to share is that if you would like to get some more information about the novel psychoactive substances and our Quest NPS panel, you can visit questdrugmonitoring.com you'll find information on the NPS panel plus our complete drug monitoring test directory and offerings, as well as you'll find a whole host of educational resources and insights from our team of toxicology experts like Dr. Kain. I want to thank you for your time today and enjoy your day.

Jack Kain [00:26:13]:

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