In today's episode, Dr. Brian Hurley provides expert insights into the current state of stimulant use disorder, its implications across different regions, and available treatment options.

Publication Date: 04/15/2024

Duration: 30 minutes, 43 seconds

Transcript:

NOAH CAPURSO: Welcome to The Carlat Psychiatry Podcast. I'm Dr. Noah Capurso, the editor in chief of The Carlat Addiction Treatment Report and an associate professor of psychiatry at the Yale University School of Medicine. In this episode, we will explore the changing landscape of stimulant use disorder and its impact across different regions. We will be joined by Dr. Brian Hurley, who will share his expert insights on the current state of the stimulant drug supply, most commonly used drugs, and geographical variations in use patterns. We also explore the pharmacological and clinical distinctions between prescription stimulants and illicit substances like cocaine and methamphetamine, and shed light on the concerning uptick in stimulant related morbidity and mortality, delving into the complex interplay of various substances in the ongoing overdose crisis. Dr. Hurley, can you please introduce yourself and share some information about your background before we proceed?

BRIAN HURLEY: My name is Brian Hurley. I am an addiction physician. I am the president of the American Society for Addiction Medicine.

NOAH CAPURSO: Let’s start by having you give us an overview of the state of the stimulant drug supply, most prominent agents, and how these might differ by geography.

BRIAN HURLEY: There are three major categories of stimulants that are used throughout the United States outside of a prescription context. When we talk about non-medical use of stimulants, I am not talking about psychostimulants prescribed for medical reasons such as attention deficit disorder or other types of medical conditions. Psychostimulants have what is sometimes referred to as an abuse potential. That is a source of stimulants in the drug supply that people use is prescription stimulants that have been procured outside of a pharmacy context and outside of what we would call medical purpose. Then there is methamphetamine. I live in Los Angeles, California. Methamphetamine in my region is by far and away the most common stimulant we see used. In the United States, the other common stimulant is cocaine. We do see regional differences. I did my addiction psychiatry fellowship in New York City where cocaine far exceeds methamphetamine in terms of prevalence. That was also true in Boston where I was a psychiatry resident. Having grown up in Los Angeles and now back working in Los Angeles, here methamphetamine far exceeds cocaine. What we see across the United States are regional differences with cocaine being more prevalent in parts of the east coast of the United States and methamphetamine being more prevalent in the Midwest on westward to the west coast of the United States. Those are of course general rules. Individual people can use cocaine or methamphetamine. I am unaware of any part of the country that has zero of either. In terms of prevalences, we see the prevalence of cocaine use being more prevalent on the east coast and the prevalence of methamphetamine being more prevalent in the Midwest on westward.

NOAH CAPURSO: You started by talking about prescription stimulants and just like the opioid epidemic where we’ve seen this kind of evolution from prescription drugs into illicit substances and then a further evolution of those illicit substances. We’ve seen a similar path actually with stimulants. Can you outline some of both pharmacological and clinical differences that are important for clinicians to know about with prescriptions versus these illicit stimulants? And then differences between cocaine and methamphetamines.

BRIAN HURLEY: There is a really important difference between non-medical use of prescription psychostimulants and the overdose crisis caused by opioids. We did not see anywhere close to the same rates of psychostimulant-overprescribing as we saw during the beginning of the opiate overdose crisis. There are very material differences in clinician prescribing patterns that seem to cause or certainly substantially contribute to the opiate overdose crisis. We’ve not seen the same pattern again with prescription psychostimulants. That said, the clinical effects of amphetamines are similar whether you are talking about lisdexamfetamine which is a prodrug that metabolizes to amphetamine, dextroamphetamine and amphetamine salts that are mixed which doesn’t require the metabolism sap, that psychostimulant works faster. You might think of it as a higher impact amphetamine in terms of clinically it is a stronger pace of onset and also the pharmacology of it is such that it wears off relatively quickly and therefore comes in an extended-release formulation. Then drugs like methamphetamine which absorb into the brain very, very quickly. They are what’s called lipophilic, so they pass the blood-brain barrier faster, have a very quick effect and methamphetamine has a clinical effect that lasts much longer than many other amphetamine types. Those are some of the differences we’ve seen between prescription amphetamines and the illicit amphetamines we see on the market. Methylphenidate which is used a lot of the time as a medical treatment for attention deficit hyperactivity disorder actually has a similar mechanism of action to cocaine, the difference being that methylphenidate has a very different absorption pharmacology and a very different duration of action. Methylphenidate, again, affects dopamine reuptake out of the synaptic cleft but you don’t get nearly the same clinical activation for methylphenidate as you would see for something like cocaine. There are really important safety differences between the psychostimulants that are prescribed and the illicit stimulants that we see sold in our communities.

NOAH CAPURSO: How do you think about the clinical differences between cocaine and methamphetamines—the two most prevalent illicit.

BRIAN HURLEY: The biggest difference is the duration of action. Cocaine, when somebody uses cocaine—and cocaine can be smoked, swallowed, injected, insufflated, there are a number of ways that people can use it—it lasts for anywhere between twenty and thirty minutes depending on the person. So, when somebody is using cocaine, they are typically using cocaine several times throughout a use episode, but a use episode might last hypothetically an evening or a day. It’s not necessarily lasting, well of course there are people who might use cocaine for longer than that, a typical use episode is relatively brief over the course of a day. Methamphetamine lasts twelve to fifteen hours after somebody uses it. So, just the duration of intoxication effect is much, much longer and when people use methamphetamine multiple times, you’ll see people who use methamphetamine over the course of a weekend, multiple days in a row, or half of a week. Now, that’s half of a week where people are not sleeping or have very diminished sleep. As a result, when I was training on the east coast and I saw people with cocaine intoxication, those intoxication syndromes tended to resolve relatively quickly. Keep an eye on somebody for an hour or two and their intoxication resolves. With methamphetamine you’ll see people intoxicated for hours. There are people that I’ve taken care of in the psychiatric emergency room for many, many hours where they have psychosis of unclear origin. I don’t know if they have an underlying psychotic disorder, but I do know they are exhibiting psychotic symptoms that seem to persist for hours and hours and it takes much longer for somebody to clear. That’s just one key difference between methamphetamine and cocaine. The duration and drugs that last longer and impact core brain functions like sleep functions tend to have more severe set of psychiatric comorbidities that I’ve seen.

NOAH CAPURSO: Would you say that longer time course of methamphetamine is related to what I think are seen as higher rates of some of these adverse effects that’s associated with long-term stimulant use?

BRIAN HURLEY: The physical comorbidities both from cocaine and methamphetamine are significant but if you look at drugs that land somebody in the coroner’s office here in Los Angeles, drugs that are involved in fatal overdose. Now, keep in mind that I live in an area where methamphetamine use is at baseline more common than cocaine use. But we see comparable amounts of methamphetamine and fentanyl involved in fatal overdoses here in LA county. Methamphetamine is a huge driver of overdose. That’s not to say that the people with methamphetamine-involved overdose weren’t also potentially impacted by fentanyl. I’m not saying the presence of a drug means that the cause of death was clearly due to that drug. What I’m saying is that the geography of where I live and work, methamphetamine is a huge driver of overdose. If you look at methamphetamine overdoses that don’t involve fentanyl, you see things like hemorrhagic stroke, heart attacks, you see a whole number of medical consequences of long-term stimulant use. Do people still have those consequences with cocaine? Sure, but that’s not what we’re seeing in terms of the actual frequency of overdose and death in our community. I’m not saying cocaine is safe and methamphetamine is not. That’s not what I’m saying. What I am saying is a longer acting stimulant has a longer risk of having a stronger effect on somebody’s physiological function.

NOAH CAPURSO: For sure. That makes intuitive sense as well. That sort of dovetails nicely with the next question, which is if you look at overdose death rates, we are seeing a very concerning uptick in stimulants. Just the number of people with morbidity, mortality, secondary to stimulants is really increasing. Why do you think that’s happening? Why are we seeing that?

BRIAN HURLEY: When we think of the overdose crisis in the United States—and I’ve stopped calling it the opioid crisis, I really do think it’s an overdose crisis. What we’re seeing is wave one being prescription opioids, wave two being heroin which is relatively short-lived, then the synthetic opioid fentanyl being the next driver. Fentanyl remains a huge driver, but I think what we are seeing is overdoses involving sedatives and overdoses involving stimulants on top of the existing high overdose rate related to fentanyl describes the fourth wave of the overdose crisis being multiple drugs. I’ll tell you, it’s not just stimulants. It’s also sedatives and opioids. In other words, there is something about the combination of these drugs in the drug supply that is particularly risky and dangerous. Again, I live and work in Los Angeles. In my community, it’s the synthetic stimulant methamphetamine and the synthetic opiate fentanyl that seems to be driving most of the public health risk. That’s what we are seeing here in LA. We know that there are people that use both, that co-use both fentanyl and methamphetamine, which appears to be quite risky. We also know of people who use a methamphetamine and sedatives, or they use other substances and there again is a risk associated with mixing drugs or using drugs around the same time as each other on its impact both on our overall brain health and physiologic function but also as a risk factor for overdose.

NOAH CAPURSO: It seems to be an emerging problem having people buying one drug and ending up with something either mixed in unknowingly or maybe something completely different. Oftentimes, fentanyl nowadays is tainting everything. So, somebody might go out trying to buy methamphetamine and experiencing a fentanyl overdose. Do you have a sense of the prevalence of this? How common is it that something like fentanyl is being found in methamphetamines?

BRIAN HURLEY: That is an excellent question with a somewhat complicated answer. There is the assumption that all methamphetamine, and for that matter all cocaine, has fentanyl in it. What I’m going to say is so paradoxical. If that were true, we could develop a better system for treating that. If we knew that that was true universally, then we could treat everyone that uses illicit stimulants as though they had a co-occurring opioid use disorder. We’ve got great treatments for opioid use disorder! We’ve got methadone and buprenorphine. For patients that [inaudible] extended-release naltrexone is an option. We’ve got good treatment. It’s the uncertainty of whether a given drug has fentanyl in it that seems to be the riskiest component of this. If everyone who uses a stimulant was equally tolerant to opioids, we would paradoxically see less overdose because we would see across the board increased opiate tolerance. It’s not that fentanyl kills every single person that takes it. It’s that fentanyl kills people, usually through respiratory arrest, for people who aren’t tolerant to opioids and because fentanyl is so high potency, it is so much less forgiving than other types of opioids between when somebody takes it and has an intoxicating effect and when they stop breathing. What does this have to do with stimulants? There was a pretty good article that came out last year in November these authors looked at what was the prevalence of fentanyl in methamphetamine and powdered cocaine samples. Again, we are just looking at methamphetamine and powdered cocaine, there is also crack cocaine which is a different composition of the way cocaine can be formulated. They came up with twelve to fifteen percent was the overall average prevalence. What’s interesting about that though was there was incredible variability between geographies. So, when I talk to my academic partners, we are seeing close to zero rates of fentanyl being found incidentally in other drugs which means there are other geographies where that is much more common. Across all of the drug tracking services, I think they were looking at twenty-five geographies, they came up with twelve to fifteen percent, I just wanted to highlight the variability. So, it’s not just the presence of fentanyl, it’s the unreliability of whether a drug that somebody buys has fentanyl in it that is in fact the riskiest part of using a drug from a non-pharmacy source where you don’t have any information about the supply chain. It’s just the uncertainty of whether fentanyl or another type of intoxicant might be present.

NOAH CAPURSO: One of the biggest challenges with stimulant use disorder, of course, and you sort of alluded to this relative to opioid use disorder, is what do you do for treatment? We don’t have a methadone or buprenorphine equivalent for stimulants. Can you go over some of the treatment options that are available?

BRIAN HURLEY: Absolutely. At the risk of appearing as though I’m trying to sell you something, ASAM and the American Academy of Addiction Psychiatry, so ASAM being the American Society of Addiction Medicine and the American Academy of Addiction Psychiatry have actually published a national clinical guidance document that describes what clinicians should know about treating stimulant use disorder. I would just refer everybody to that because it goes through stimulant use prevention and other secondary and tertiary prevention steps around mental health, harm reduction. There is a whole lot that clinicians can do working with people who are using stimulants that can help protect people’s health and wellness. That’s one thing. The second thing is diagnosing stimulant use disorder is not actually fundamentally different than diagnosing any other substance use disorder. There is a set of eleven criteria. Those criteria are generally considered across all substance abuse categories including stimulant use disorder. And the treatments for stimulant use disorder fundamentally are biopsychosocial. So, medications with counseling and then you have other types of support. Specific to stimulant use disorder, we have seen a huge response from a treatment called contingency management where somebody is provided an incentive for urine toxicology, verified stimulant abstinence that seems to significantly increase the rates of stimulant abstinence. It looks, from the evidence contingency management programs that last at least four months that are doing toxicology testing at what I’ll say is a reasonable frequency—twice a week is pretty common because most stimulants have a relatively short window for detection—do a good job of supporting peoples’ remission from stimulant use disorder. Our guideline is very clear on contingency management being a treatment of choice. One of the nice things about contingency management is that you can combine it with high intensity outpatient services as usual. So, somebody goes to groups and counseling and gets other types of psychoeducation and psychotherapy to treat their stimulant use disorder. There is actually a manual, called The Matrix Manual, and it is a manualized treatment for stimulant use disorder. Cognitive behavioral therapy, a well-known, validated, psychosocial treatment for a whole number of conditions is also effective at treating stimulant use disorder. You mentioned we don’t have a methadone or buprenorphine or extended-release naltrexone equivalent which treat opioid use disorder to treat stimulant use disorder, and that is true. But there are medications, despite the fact that they are not FDA-approved to treat stimulant use disorder, that are clinically effective at treating methamphetamine and cocaine use disorders. We also describe those in our guideline. They include both non-controlled substances, so medications such as topiramate, naltrexone, bupropion, or mirtazapine have all been identified as promising candidates that seem to help people reduce their stimulant use. That’s really what we see in most of our trials is reduced stimulant use. As well as psychostimulants, so psychostimulants such as methylphenidate or mixed amphetamine salts also can be considered in the treatment of methamphetamine and cocaine use disorder, respectively. But to the point that you brought up earlier, a clinical practice guideline has a caveat around the use of psychostimulants to treat stimulant use disorder because there is this presumed equivalence, right? If methadone works for opioid use disorder, shouldn’t X psychostimulant work for stimulant use disorder? That is absolutely not the case, by which I mean it isn’t true that any particular psychostimulant works as a substitution therapy. That is not what we are seeing with the data. If a clinician is going to use a psychostimulant outside of its FDA-approved indication to treat stimulant use disorder, ASAM and AAAP’s opinion is that clinician should be a board-certified addiction physician or somebody who is in consultation with or in supervision with a board-certified addiction physician who has commensurate training because you really do need to know what you are doing. What we don’t want to see is a huge rise of psychostimulant prescribing like we saw with the opioid overdose crisis. Patients are being comprehensively assessed, it is part of a comprehensive treatment program that really supports people’s health and wellness. People’s safety is being monitored and [inaudible] is being monitored. Those are all the things that we know board-certified addiction physicians are pretty familiar with, so that was caveat language that we put in related to off-label psychostimulants to treat stimulant use disorder. There are non-psychostimulant, non-controlled substances options we would we want every physician to at least consider. Again, with the caveat that they help people reduce their stimulant use, they don’t have the effect size that we see for methadone, buprenorphine, and extended-release naltrexone for opioid use disorder. We are not seeing that same impact from the off-label medications for stimulant use disorder.

NOAH CAPURSO: It is unfortunate that it doesn’t translate so well. Similarly, I have had trainees ask me, “why don’t we give benzos to people with alcohol use disorder? If we use methadone for opioid…” It’s like well the approach doesn’t quite translate all the time.

BRIAN HURLEY: It just doesn’t work. If substitution therapies across the board, across all intoxication categories, worked equivalently, things would be easier. But there are real differences in the way that different substances work on the brain. The mu opioid receptor being a singular target, you do things to either activate or partially agonize or antagonize that receptor, which seem to impact stimulant use. Whereas alcohol and benzodiazepines have different binding points on the GABA chloride channel. Psychostimulants, some of them work on the dopamine receptor, some of them work on the vesicular monoamine transporter, some of them work on the dopamine receptor right? You don’t have that final common pathway for all mechanisms for those drugs that make substitution therapies harder. What you are left with is what can we think would work adjacent or alongside or in combination with that seem to impact substance use? I might suggest, rather than thinking what is the medication strategy for everything. Particularly for non-opioid use disorders where medications just don’t seem to be as universally effective, the medications can be helpful. To make it clear, meds, even off-label meds, can help, but really the task is how do I support the patient in front of me learn a healthier way of navigating their lives. That could be everything from what is the harm reduction strategy? I might offer that to somebody to help protect their health and wellness. If they are interested in changing their substance use, how can I support them changing it in the most helpful way possible? If they are committed to abstinence, how do I provide the appropriate structures and supports which get everything from residential care which is a contained environment, plus psychoeducation, plus psychotherapy, plus linkage to vocational rehab and connecting somebody to a network of people that don’t use drugs. There are a whole number of things that we do in addition to our medication treatments that can have a huge impact on supporting people’s health and wellness.

NOAH CAPURSO: Can you tell us about some harm reduction approaches to consider for patients with stimulant use disorders?

BRIAN HURLEY: Sure. With stimulant use disorder, one of the things that clinicians should consider is modifiable cardiovascular risk factors. This is all the stuff that primary care clinicians know around cholesterol, blood pressure, supporting, if somebody is using stimulants regularly, potentially considering modifying modifiable cardiovascular risk factors to reduce risk. The other thing that happens with psychostimulants, and for anyone that has prescribed a psychostimulant, you’ll be familiar with dry mouth. What we see with stimulant drugs of abuse, particularly methamphetamine works a long time is a lot of dental problems. Dental care can be actually an important harm reduction strategy so that people can continue to eat and talk and have appropriate dental function. Encouraging people to consider trials of abstinence. That isn’t to say that people will stop using forever, but to be intentional about when they are using and when they are not using. If you can give people a break from the stimulant, it can actually have a helpful impact on sleep and mood and overall quality of life and function. There is a lot of focus in the harm reduction community around route of administration. If somebody is going to inject a stimulant, that they use a clean needle every time to avoid spreading infectious disease. And a clean needle every time using as sterile of a technique as is manageable helps reduce things like wound infections. Injecting into smaller veins versus bigger veins are things that help reduce sepsis and other systemic infections. It is always safer to smoke a drug versus inject a drug because usually people that inject can inject various variable amounts whereas if you smoke a drug, you are usually taking in smaller amounts at a time so that allows for a titration element to substance use. Making sure people have access to smoking equipment in addition to injection equipment can be a harm reduction strategy. Our other harm reduction strategies include from the classic harm reduction moniker of “meet people where they are.” Connect to people where they are. Serve as an engagement connector for people to a whole variety of services. So, do people need other types of medical care? Need other types of mental healthcare? Do people want substance use treatment and if so, how do we connect them to it? Low threshold access to addiction medications can be a harm reduction strategy. Are we connecting people to housing and social services? Those are all, in and of themselves, you might say well these are medical services, but when they are offered in a low threshold context for people that are using drugs, can be an important part of a harm reduction strategy.

NOAH CAPURSO: I do my clinical work through the VA and there is a huge push at the VA recently for naloxone availability for patients with stimulant use disorders. Is that something that you practice?

BRIAN HURLEY: Absolutely and not just in a use disorder. From my vantage point, anyone that’s using any category of intoxicant should be offered naloxone which can reduce opioid overdose. Particularly for people with opioid and stimulant use disorders because that’s where we are seeing a lot of overdoses. I would say people with sedative use disorders, particularly if they are buying sedatives off the street. We are seeing a lot of fentanyl involved in pills that are pressed and sold as though they are sedatives but in fact have fentanyl in them. That is also a higher risk population. But let’s say somebody is coming into treatment and they are only using cannabis or only drinking alcohol. The overdose rates across the United States are so high and overdose is such a threat to public health. You just never know when you are going to be around somebody that overdoses. I think of naloxone access as a public health strategy that should be universal. I actually prescribe naloxone to every patient that I see who is receiving substance use treatment. Not because of the expectation that every single patient is going to overdose, but I don’t know when that person is ever going to be in a context where they could save somebody’s life. I would like every person in the United States to have access to opiate overdose antidote medication that can be applied in an emergency medication, because as you know, when somebody overdoses you don’t have enough time to get them to the hospital to reverse it before they are going to begin to experience brain death. You have a few minutes. That’s why universal access to naloxone is so important.

NOAH CAPURSO: Fantastic. I think that’s everything I wanted to cover. I always ask at the end is there anything that you think would be helpful to add that I didn’t touch on?

BRIAN HURLEY: There is sometimes an assumption, “oh my goodness! Methamphetamine is so bad. We don’t have the methadone equivalent. Gosh drugs are terrible. What do we do?” I’ll say if you look at just the natural history of substance use, what we know from the cocaine epidemic is we saw huge rates of cocaine use in the United States and then they went down. And they didn’t go down because everyone died. They went down because people stopped using cocaine. I think we are going to see the same thing with stimulants. We are seeing huge rates of stimulant use. They are going up. But I expect that the overdose crisis related to stimulants which is again driven both by the presence of fentanyl in the drug supply and due to the nature of stimulants themselves is also… people do recover is the point I am making. Yes, these drugs have risks, but if we can keep everyone alive through this overdose crisis, people do recover. About seventy-five percent of people with SUD at some point in their lives they do recover. It’s not that people forever have active substance use their entire lives. We’ve got really good tools to help with that recovery. Contingency management, cognitive behavioral therapy, high intensity outpatient treatment, and residential treatment can be helpful. We have got these off-label medications. We do have tools that are available. My message is that although stimulant use is worrisome, it is not untreatable. Recovery is possible and we owe it to our patients to offer the most effective, evidence-based tools at our disposal.

NOAH CAPURSO: I actually like closing on that message with a little bit of hope because you are right, sometimes especially when you don’t have a silver bullet it feels hopeless.

BRIAN HURLEY: Thank you very much.

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