Psychiatry & Psychotherapy Podcast - Opioid Use Disorder with Dr. Cummings

Episode Date: June 8, 2023

This week's episode is on opioid use disorder and is the second in our series on addiction. We are once again joined by Dr. Michael Cummings.  Dr. Puder and Dr. Cummings discuss the history of opioids, the neurobiology of addiction, risk factors for opioid use disorder, and treatment options. By listening to this episode, you can earn 1 Psychiatry CME Credits. Link to blog. Link to YouTube video.

Welcome to the Psychiatry and Psychotherapy Podcast. I'm your host, David Puter. This is your gateway to the intriguing world of mental health. As one listener put it, this is the podcast that your psychiatrist listens to. And we're incredibly proud of that endorsement. Whether you're a loyal, active listener who's been kind enough to reach out, maybe send an email at DM or put in a review, or you're new to this community. We have an exceptional opportunity for you, not only to learn, but to also, earn continued medical education credits with each episode. Our credits are meticulously designed to empower you in your field, demystify complex mental health topics, and transform your learning journey into a truly rewarding experience. To access this and more, just visit Psychiatrypodcast.com. We're grateful to our valued subscribers who are already reaping the benefits of these credits. Your support is instrumental in allowing us to devote time each week to curate. this podcast, sharing cutting-edge insights, featuring top professionals, and exploring the latest

research. Whether you're here to learn, earn credits, or both, we're thrilled to have you with us. Get ready to deepen your understanding of psychiatry and psychotherapy, one enlightening episode at a time. All right, welcome back to the podcast. I am joined today, once again, with Dr. Cummings. We will be going over opiate use disorder, talking about the history of opiates, the mechanism, the neurobiology, drugs used to treat, opiate use disorder. We'll talk about detox. And this will be a CME that you can apply towards the DEA's new required CME requirement of eight units of CME on substance use disorders. So Dr. Cummings, welcome to the podcast.

Thank you. I'm happy to be back and certainly happy to talk about this very important. topic that the U.S. in particular has been struggling with these past several years. Yeah, so maybe take us through to the dawn of history and then bring us forward to where we are today. Okay, people indeed have been aware that derivatives of the poppy, poppy seeds from some species, contain animals. analgesic alkaloids. And those have been, records have been found of that, people making decoctions and teas and other remedies to relieve pain, going back literally for millennia.

In the 19th century, people began to make more purified forms of opiate medications. Things became available like Dilaudid, lauded, laudan. and later morphine, and still later diacetylmorphine, also known as heroin, although as things became more potent, it also became clear that these drugs could cause habituation and dependence. That ultimately led to the outlawing of heroin as a medication in 1924. And from that point forward, much tighter regulation over opiate medications, although illicit use continued at a low level for many, many decades until we got to the late 1980s, at which point there was a valid

concern that many people were not receiving adequate pain treatment. NIH estimated at the time that roughly a third of Americans suffered at some point, in their life from chronic pain, meaning pain lasting more than a month, to distinguish it from shorter-term acute pain. And there was indeed a great deal of concern that that was being under-addressed. That ultimately led to organizations like the Joint Commission on Accreditation of Health Organizations, JCO, and the World Health Organization proposing that pain be added as a fifth vital sign, and nurses began asking people to rate their pain. all well and good so far, except that in the decade of the 1990s, the number of

prescriptions for opiate analgesics increased threefold between 2011 and 2021, for roughly 79,000 prescriptions a year to just shy of 300,000 prescriptions per year. The unfortunate outcome of that was that about 4 to 5% of people who were prescribed an opiate for, say, post-surgical pain or other painful condition would go on to become addicted to the opioids. The other thing that happened that contributed to our current opioid epidemic is that the opiates used over time became more. and more potent. Things like oxycotton and hydromorphone became the dominant opioid medications on the market. And we've now wound up in the present time with an epidemic of fentanyl, which, because it's often a mixture of fentanyl in pure form, alpha-methyl fentanyl, acetyl fentanyl, can be anywhere from 50. to 100 times as potent as either heroin or morphine. And indeed, in pure form, two milligrams of fentanyl can be enough to kill somebody who is opioid naive.

Yeah, and then what I've heard is that once they started cutting back from giving opiates, people would go to the streets, and there was black tar heroin, which was a fairly pure form of heroin, coming through Central America. As people have cut back from prescribed opioids because indeed the medical community became alarmed

during the 2010s by the rising number of people who were addicted to opiate drugs and who then saw treatment, the rising number of opioid overdose deaths

that began occurring in fact the CDC just released the numbers for 2022 last year there were a little over 109,000 opioid deaths in the United States which is a horrible number because that's essentially in rounding numbers that's roughly 300 deaths per day you know so we are still doing dealing with a serious epidemic and indeed people who've been cut off from prescription opioids have turned to the streets where now fentanyl is rampantly available and is being used to cut or is being added to a number of other illicit substances such as methamphetamine,

cocaine, because essentially fentanyl comes in two forms on the street. It comes as a clear, colorless, odorless liquid, which can be dripped onto a number of vehicles. And it also comes as an off-white powder, which again is tasteless and odorless, which makes it for illicit drug use an ideal agent to be added to other things. Yeah. Think about that number, like 109,000 deaths in 2022. It's a huge amount. Yeah.

It is. And to give you a comparison, before. the current opioid epidemic got started, the number of opioid deaths per year typically ranged from about 3,000 to 7,000 in the United States per year. And we've gone from that to 109,000. So it's been a gigantic increase. Yeah. I did an episode on this in episode 66, and we were way back then worried about the rising fentanyl use, seen as kind of the third wave, the first wave being commonly prescribed opias, the second wave being heroin, which really started to increase in 2010 and maybe all the way up to 2015. and then the third wave being fentanyl, which was really starting around 2013. We saw a huge spike in the deaths.

Yeah. There are some authors who are now proposing that a fourth wave is beginning, essentially referring to the addition of fentanyl to other substances, including in some contexts what are labeled as prescription medications, that the person may be entirely unaware that what they're buying may contain fentanyl, which is incredibly dangerous. Of course, that's also one of the things that makes it dangerous for people who may be thinking that they are buying cocaine or they're buying methamphetamine.

Fentanyl has become so ubiquitous because it is incredibly, cheap to manufacture. Presently, the DEA has described essentially the raw ingredients for fentanyl being imported largely from Asia, China in particular, to Mexico where a drug cartels then manufacture fentanyl in a variety of forms, including both liquid powder tablets, and then use the fentanyl. to make a variety of products, many of which the end user may be, frankly, unaware that what they're taking contains Ventana,

which, of course, is incredibly dangerous. Yeah, I know patients have told me, they know there's a person that puts a slurry of stuff into the Xanax pills. So they look like Xanax pills. They have a presser, but they put in a slurry of whatever, they have on hand.

Yeah, I've never understood why some people are under the impression that manufacturers of illicit drugs have any interest in quality control. They're simply interested in making the largest amount of profit per pill or per dose that they can, and fentanyl lends itself to that because it's incredibly potent and incredibly cheap. Yep. The DEA estimates that the cost

per dose for the drug cartels is probably under a nickel a dose. And it's so easy to transport because you don't

need huge amounts of it to make huge amounts of end product. Yeah. You know, a lethal dose looks like a

grain or two of salt. Yeah. Yeah, two milligrams, two, thousands of a gram is not a lot in terms of if it's in pure form. Yep. So here we are in the middle of an opiate epidemic. And so this is a timely episode to

kind of dig into some of the facets of it, the treatment. And yeah, let's start with. What is opiate use disorder? Okay. Opiate use disorder is when the person moves beyond the legitimate use of the opioid, which many people would argue that the opioids really have two very well-evidence-based uses, that is, for treatment of acute pain. You know, if you suffer severe tissue trauma, the opioids will block the pain centrally so that you're not suffering. Or cancer-induced pain, which particularly involving bone metastases, can be incredible. painful. Other uses for chronic pain are much more questionable in terms of evidence base,

but may be legitimate in some cases. But when somebody begins to become first tolerant of the opioid, they need more opiate to achieve analgesia. But then it moves beyond that to the person who is beginning to take the drug for the euphoric effects, and then eventually as they become tolerant to that effect of the opiate, they're then taking it essentially to stave off the ravages of opioid withdrawal. Yeah. And at that point, they have crossed over from using the opioid for the legitimate purposes into an opioid use disorder.

Yeah. So what were you saying before, like out of the people who are given an opiate, something like 5% will become addicted? Yeah, the estimate by the National Institute of Drug Addiction is that somewhere between 4 and 5% of people who are given an opioid initially, for a legitimate reason, they broke their leg, they had surgery, about 4 to 5% of those people will continue the opioid beyond the point where there's a medical indication for it, meaning that they're drifting into an opioid use disorder.

Yeah. And so these people often will have impaired control. They'll have some social consequences of use, such as failure to fulfill major roles at work, school, or home. They'll have risky use, meaning that they're putting themselves at risk maybe taking something from off the street, maybe something that would be potentially giving them diseases. they'll have a level of tolerance that will build up requiring larger opiates to give the same desired effect and they'll have withdrawal symptoms when opiates are reduced or discontinued which are awful absolutely awful yeah indeed and as you point out they get into a very dangerous situation where they can easily wind up dying as a result of their opiate dependence often not intentionally, but by accident, even opioid users may think that they're buying heroin, for example, but it may be heroin mixed with fentanyl,

which is 50 to 100 times more potent. And consequently, they may take what they think is their usual dose and wind up overdosing on the drug. You know, an important thing for people to understand is the mechanism by which opioids kill people. Essentially, all of us breathe because we get uncomfortable if our carbon dioxide levels and our blood begins to rise. That's why if you hold your breath, you have an increasing urge to breathe.

That's based on neurons in the brainstem that are sensitive to CO2 concentrations. The opioids can basically turn those neurons off in terms of their function so that the person is insensitive to rising levels of carbon dioxide and they then don't have a respiratory drive. And indeed, one of the ways you can spot somebody who's had an opioid overdose is their breathing may be shallow and very slow. You know, five, six respirations per minute all the way down to they're not breathing at all. They may have blue lips and fingertips because they're cyanotic, along with pinpoint pupils, because indeed the opioids also cause pupil constriction.

Yeah. And so what are some things that might be risk factors that would lead to someone developing like an opiate use disorder compared to maybe just using opiates transitually? Oh, I think one thing we need to be careful about is indeed how many opiates we prescribe. One of the nice things in California and many other states have very similar systems is that there's now a database run by the Attorney General's office where you can check whether your patient is obtaining analgesics from more than one source. there have been people who have become addicted who basically roam from pharmacy to pharmacy with prescriptions from multiple providers collecting opioids. The attorney, it's called the Cures Program in California.

That's an attempt to overcome that problem because it will tell you if your patient is obtaining more than what you're prescribing for them. And, of course, you can be careful about what you prescribe. interestingly, as the use of opioids went up in the 1990s, the use of non-opioid pain medications went down, dropping from around 38% down to 29%. So certainly we could look at other means for treating pain much more often than we do. I think one of the unfortunate characteristics of U.S. culture has been, we're a little too prone to reach for a pill.

And I know that sounds odd coming from somebody who's a psychopharmacologist, but, you know, there's a lot to be said for diet, exercise, physical therapy, and other means of dealing with pain other than prescribing an analgesic. Yeah, people will be surprised that you're saying that. I don't know, am I converting you with my podcast, all these exercise episodes and stuff? I don't know if you even listen to them. No, that's actually always been my opinion. People would be surprised if they read many of the consultations that I've done.

Often the majority of the recommendations have to do with what medications to taper and get rid of rather than adding medications. I'm a firm believer that medications are useful tools, but they are certainly not the answer to all of life's questions. Well, I think it takes a really good psychopharmacologist to actually know which one they can get off of without being an issue. I think that's where the nuance and the expertise really comes through. Yes. Yeah. Okay. So I guess what I'm thinking though, is or are there risk factors that could potentially lead to a higher rate of conversion to a substance use disorder like opiate use disorder?

Certainly there are risk factors. Younger age appears to be a risk factor. As we talked about in the previous episode, all of the addictions are in essence driven by the reward pathway, particularly the nucleus accumbens. That system develops earlier in adolescence than the prefrontal cortex does. So it's possible for adolescents to be much more reward-driven and at the same time not have the judgment to think that they perhaps ought not to make that choice. There's also, of course, the issue of family history. There are a huge host of studies suggesting that the vulnerability to substance addiction, including the opioids, is in part at least genetically determined.

So certainly collecting someone's family history and finding out whether there have been substance use disorders for either opioids or other substances can be very useful in guiding. prescribing. And while I'm certainly not an advocate of people saying, well, I'm never going to prescribe an opioid, there are contexts in which they are appropriate. I think it's one important to be careful about thinking when you're going to prescribe them, how much you're going to prescribe and what monitoring you have in place to be sure that the person is not getting in trouble with the opioid. there's also a very important element of patient education before you prescribe what may be somebody's first opioid they need to understand much of what we're talking about today that these can be very

habit-forming very addicting drugs and can cause an immense amount of misery in terms of the person's life okay and then yeah anything about the neurobiology of opiate use disorder that we haven't spoken about. The neurobiology, indeed going back to our discussion of the reward pathway, the reward pathway is driven by essentially two things. The dopamine, which we talked about to some extent, and also opioids. The cells, the spiny neurons of the nucleus incumbents,

do have opioid receptors on the cell. surface, both MU and Delta receptors. The mu receptors are responsible for that euphoria effect of the opioids, that sort of sensation people have of, oh,

I just feel absolutely wonderful, kind of warm, fuzzy, great feeling. The delta receptors appear to drive essentially goal-oriented behavior,

that is to set the person up to want to repeat the experience. And those two receptor types, indeed, can go a long way toward promoting dependence on an opioid. There are also a critical point at which we can interfere with the person who is craving either opioids or other substances, and that if we block the opioid receptors, we're essentially removing the drive, the reward for using the substance, and that can help some people who are wanting to become free of opioid dependence to have an easier time kicking the habit

to get rid of the cravings. The primary drug used in that context is not, TREXO, potent opioid antagonist. And fortunately, it comes in two forms. It comes as an oral tablet. It has to be taken daily to be effective, but it also comes as a long-acting injectable trade name Vivitrol, which is a once-per-month injection used in many substance use disorder programs.

And then, of course, on the other side, we also have a very rapid acting antagonist naloxone, which I'm happy to see has become more widely distributed for people in acute overdose situations, administered most often as a nasal spray, and will reverse the effects of an opiate overdose within a few minutes. And indeed, there are some proponents that perhaps these should be distributed publicly, just like public automated defibrillators. I sort of somebody discovered somebody in overdose they can

give them a shot of naloxone. I know, I gave it to one of my patients who's in high school because she saw one day at a football game someone overdosed on something.

I said, hey, let me give you something that you can have in your pocket and if something like that happens, just go over there and squirt it in the nose, which I think, like, could be life-saving, you know? Oh, very much so. If you're minutes away from it,

compared to, like, you know, maybe it takes, like, 10 or 15 minutes for EMS to arrive. Yes. Well, the nice thing as well about the opiate antagonists is if the person is tolerant, you will put them into opioid withdrawal. But while it's miserable,

opioid withdrawal is typically not lethal. But beyond that, if the person is not tolerant, essentially the antagonists have no substantial medical effect on the person. Right. Yep. So, okay, we're getting through the neurobiological stuff. Anything else you want to add on that before we shift? Probably only a brief note from Greek mythology. that applies to the overdose situation we talked about the loss of sensitivity to co2 uh you'll

sometimes hear that referred to uh in historically oriented medical literature as on dean's curse in brief on dean was a greek goddess whose husband cheated she cursed him with having to think about everything he did and when he went to sleep of course he was not thinking about breathing wait okay so my gosh my brain is so slow so she cursed him to not to have to think about everything he did to think about everything oh okay oh so when he went to sleep of course he was no longer got it thinking about breathing so he stopped breathing oh man you know there's something about there's something about rage also that's so archetypal there where it's like we want in the midst of our rage we want the other person to suffer so that they can empathize with how we have suffered, right?

Yes. And it's like this like... The other moral of that story, of course, is that if you're married to a Greek goddess, don't tick her off. Yeah, that's good. Yeah. Okay, so, yeah, let's talk more about the medication. We're talking about naloxone. rapid antagonist.

We're talking about naltrexone, which is a pill that you would take, and then the long-acting version of that, which is Vivitrol. And what's the generic for Vivitrol?

I have forgotten its generic name. I've seen it typically described as long-acting injectable, naltrexone. Because it's the same medication. Yeah, yeah. Altrexone is the heart of it.

So it's Naltrexone for extended release, injectable suspension, 380 milligrams per vial, right? Yes. Okay. And it's a once-a-month injection, so the person need only take it once per month. What kind of success are people having with that once-a-month injection? Quite a bit. It's particularly useful for those people who are trying to establish and maintain their recovery, but they're still bothered by cravings and may at times be tempted to act

impulsively to take an opioid. Of course, if they do slip and they take an opioid, nothing happens because the naltrexone has a higher binding affinity than any of the psychoactive opioids. So that unless they take a truly massive dose, the naltrexone will effectively prevent the opioid from having any effect. And that's also been a component. Naloxone has also been used as a component of some buprenorphine preparation. Buprenorphine is an opioid partial agonist used in opioid treatment programs as a substitute for illicit opioid. Some of the preparations available also have a small amount of naloxone added. The reason being

that naloxone taken orally at the amounts they put into these formulations is not active. You don't absorb it very well from the GI tract. But should the person attempt to abuse the buprenorphine by taking a larger than prescribed dose, enough of the naloxone will be absorbed that it will essentially block the effect of the partial agonist. Got it. Got it. Okay, so let's move this into like stages. Let's talk about detox first.

So what are like the standard practices for detoxing someone off of opiates at this point? Typically detox, well, there are two ways of doing. You can detox somebody slowly, which usually means putting them on a drug like methadone or buprenorphine and tapering the dose to zero so that their tolerance declines over time. There are places that offer what's called forced detoxification where they essentially put the person into surgical anesthesia, give them essentially intravenous naloxone,

essentially force them into a full-blown withdrawal, but they're not conscious. And three days later, they wake them up, and they're no longer opioid dependent in terms of being physically tolerant or having withdrawal. Both approaches work. People also have used other classes of medication

to blunt the withdrawal effect. such as giving the person sedative hypnotics to at least make them more comfortable during the withdrawal process or anti-apoleptics to do much the same thing to make that subjectively not as difficult. For most people, acute opioid withdrawal can take anywhere from as little as three to four days up to about a week. so if they can make it through that period of time, then they are no longer physically dependent on the opioid, but they're very likely to continue to be psychologically dependent and to crave the opioid,

at which point the treatment shifts to first a good substance use disorder program to support them in their recovery and to teach them about addiction. and at the same time, use of drugs like buprenorphine or naltrexone to help them manage their addiction and to not fall back into use of illicit opioids. Methadone used to be used more commonly than it is now for that purpose. Methadone, because it's a full opioid agonist, however, has become less desirable than buprenorphine. Yeah, Suboxone or buprenorphine, we would use that in our detox protocol, the place I trained, and as an attendant, I would go in there and cover the weekend sometimes, or cover a couple weeks for my colleague there.

So we would use that to detox people. So usually patients come in, we give them a little bit of time for them to start to enter into withdrawal. because once you give the suboxone or buprenorphine, it will slam the opiates off of them and send them into withdrawal a lot faster if you don't kind of have a pause from the last dose of their opiate. And then we would use clonidine

for the noradrenergic sort of outpouring that happens. Can you want to speak to that at all? Yeah, clonidine or guanphasine have both been used. They're both alpha-2 agonists. They stimulate the auto-receptor in the locus ceruleus in the brainstem and essentially fool it into secreting less norapinephrine. The reason that's important in this context is as people use either sedative hypnotics or opiates, all of which are sedating, the brain tries to compensate by ramping up the amount of norapinephrine that's secretive.

When, of course, the sedating agent goes away, those that revved up noradenergic system is now unopposed. And many of the signs and symptoms of withdrawal for many substances from alcohol to opiates to benzodiazepines to barbiturates are essentially a storm of norapine. so the alpha-2 agonists can help blunt that by decreasing the amount of norapinephrine secreted. Yes, it's pretty commonly given. You could either take point one or point two every four hours. You can monitor blood pressure to determine how much you would give. And we would also usually give hydroxazine for anxiety. You want to talk about hydroxazine out of this one of your...

Yeah, hydroxazine was the second antihistamine produced. The very first one approved was diphenhydramine benadryl. Hydroxazine has the advantage of not being anticholinergic. It has essentially no affinity for the acetylcholine receptor, so it doesn't cause anticholinergic side effects. It's a very pure H1-H1-hystic. histamine receptor antagonist and essentially produces a decrease in cortical activity by blocking histamine receptors. For most people, that produces sedation. And in the context of somebody who's

undergoing withdrawal, it helps counteract the excessive arousal that's trying to occur because of the increased norapinephrine that's common in that context. A note on the clonidine, once you establish how much clonidine somebody needs over a 24-hour period, one of the nice things about clonidine because it's a very old drug, is that it's available in a wide range of formulations. In addition to the immediate release tablets, you have extended release tablets so you can consolidate to once-a-day dosing, and it also comes in a seven-day patch so that once you determine how much the person needs, they don't necessarily have to go on taking multiple doses per day. Yeah, and the patch is nice because it's self-tapering as well, I think, right?

It just slowly comes out. Yes, yes. Yeah, they can leave the patch on and it will gradually sort of, as the patch begins to run out of active medication, the amount they're absorbing, of course, will go down. And remember, you're not, for heroin or, other opioid withdrawal, you're not having to treat the person for the dependence, the tolerance long term. The withdrawal is fairly brief as drug withdrawals go so that the worst over it will be

over within 72 to 96 hours, and then they will be gradually on the mend after that. Usually by the time people are out a full week, they're pretty much over. the bulk of the opioid withdrawal. Yeah, so usually in our detox center, we try to figure out the first 24 hours how much suboxone or buprenorphine they needed, and then we would go down slowly over the next four to five days on the dose,

maybe decreasing two to four milligrams per day while we treat other things that come up, like insomnia, GI issues, diarrhea, anxiety, agitation, and yeah, any other sort of pearls you want to throw out there about the detox process? Yeah, just to note the dose range for the buprenorphine is for the withdrawal, it can range anywhere from 2 to 24 milligrams. The more severe the withdrawal appears it's going to be the high.

higher the dose you start with, and then as you say, you simply stare, step it downward over time. If this is a person who's going to ultimately wind up on buprenorphine maintenance, then instead of tapering them off, you taper them to the lowest effective dose that prevents withdrawal, and that then becomes their maintenance dose. Yeah. In terms of selection of patients that you would try to get off, or leave on? Is there a difference and how you would?

Largely that's driven by history. If the person, if this is one of their first attempts to become free of opioids, that's usually the better goal, getting them off of the opioid and keeping them off. Ultimately, if need be transitioning them to something like naltrexone, either short or long acting to help them maintain their recovery.

If the person has been through substance use treatment a number of times, they've tried to get off of the opioid repeatedly, but they keep failing and winding up becoming re-addicted. That may be somebody who's a more appropriate candidate for long-term maintenance therapy, Historically, it would have been with either buprenorphine or with methadone. Buprenorphine, as we said, though, before has become the preferred agent because it's a partial agonist rather than a full agonist. It also doesn't have some of the legal restrictions that methadone prescribing has. Methadone prescribing typically has to be done in methadone clinics with observed dosing and a number of restrictions.

buprenorphine can be prescribed in the office setting. Yeah, and do you have any thoughts on why there's a special license that's required for buprenorphine? Like, do you think that's a good thing? Well, there used to be that licensing just got dropped about two months ago. that the X designation is now gone. Wow, okay. They no longer require that. They still do require that the person complete essentially a self-training

to educate themselves about how to prescribe buprenorphine. But I think the FDA and DEA have recognized that there is value to be had in having a larger range of, of clinicians know how to and to prescribe these drugs. They do, if you go to the website, one of the first things they'll ask is, well, how many such patients do you anticipate having, which, you know, if you're an ordinary prescriber and you're not operating a substance use program, odds are it's going to be a very small number. And for you, there'll be almost no requirements other than very basic education.

For people who are more involved in running a substance use disorder program where the number of prescriptions, the number of patients is likely to be larger, then I believe there are some reporting requirements. Great. Very helpful, yeah. So, okay, so patient selection, we talked about that. We haven't really talked about treatment programs, probably the value of that. So along with treatment with the medications, often I will recommend that they go to like an IOP or a partial program. Yes. I think, you know, one of the things that comes up over and over again about not just for the opioids, but for all of the substance use disorders is people have a much greater probability. of success if they are engaged in a psychosocial treatment program that helps them deal with

many of the issues that are going to arise as they attempt to become clean and sober. Most of these individuals, by the time they arrive at treatment, they, frankly, their life is often a wreck. they're socially isolated, they've lost jobs, they've lost family, things are not going well. And for them having essentially a treatment program that helps support their recovery and also frankly helps them problem solve some of the issues that are likely to arise as they attempt to recover. We'll go a long way toward helping them stay away from the substances. Excellent, yeah.

And we haven't really talked about pro bupheiferin, which is a buprenoprinoerphine implant. Do you want to mention that at all? Yes, it's another approach to, in this case, not having to take a daily pill. it has the advantage like many long-acting delivery systems do of providing the person with an ongoing stable plasma concentration without their having to indeed be adherent to medication on a daily basis. So far, the early reports I've read about it suggest it's useful for many patients who are prone to, not be stable in taking medications. So in that sense, I think its major advantage is going to be improved adherence.

Yeah, it's good for six months. So imagine, you know, you have a patient who's really struggling on and off with opiates, buprenorphine, they're not completely compliant, they're on back and forth, you know, you know that the high-risk of fentanyl may lead to their demise, and so this is another option, along with the naltrexone

injection. Yes, very much so. You know, the naltrexone injection works well for the person who's off of opioids completely, and they want to block the effect if they get tempted. This implant is very useful for those people who need a maintenance program, but still slip, even despite being in a maintenance program with buprenorphine. And I think most of the people who've been recruited for this formulation are those who've already been taking buprenorphine, but have not been taking it, as you suggest, reliably. Yeah, I think, okay, so we talked a little bit about IOP partial, But I think the real effectiveness of the IOP and the partial is the acquisition of, you know, how do they overcome stresses in life without going to substances?

And then also how do they process through the traumas that have happened while under the influence or before they were under the influence? You know, to me, that's where the magic happens. Like when someone really goes through a treatment program that's using everything. evidence-based psychotherapy and helping them get to that next level of understanding. So I see the detox. It's like for me, working with someone in the detox was about building up enough alliance that they would be willing to do the IOP and the partial because I knew like if that's, if they did that, then their chance of relapse would go way down.

Yeah, very much so. And in many ways, again, we're back to talking about. overcoming what I see is a fault in U.S. culture of as a society, we've been much too prone to, oh, if you have a problem, reach for a pill.

There are cases where pills of various sorts may be helpful, but they should not be an attempt to answer every question. Life consists of much more than medication. The other benefit of the group and from what I've witnessed is the bringing in the family.

And the families often have been in a state of fight and flight trauma for a long time with their loved one. And so if you can help the family reconnect, it adds a layer of social support. I'm reminded of this study where Vietnam vets came home. And there was a high degree of addiction. And after they went back to their home environments, you know, in the Midwest, pretty much all of them detoxed and a very small percentage continued in the addiction. Yes.

Whereas if you have a population who is like in the inner city, they go through a detox, the percentage that are going to relapse is very high. Very high. So it's like environment is so important to long-term change. Oh, very much so. Oh, as we talked about in our last episode, the response of the reward system is not only to the substance itself,

but to cues related to the substance use. So if somebody who has opioid dependence goes back to where opioids are being sold, they get to watch people using, that's going to ramp up their craving for the drug immensely. Much different than if you go back to the Midwest where there's not a drug dealer on the corner. Although our opioid crisis has gotten so bad that I'm fearful that even in the Midwest, there are indeed fentanyl dealers on every corner. yeah it's it's tragic i mean it's sometimes the the small towns are actually the worst at this point yeah well that's been one of the notations is that rural america has really suffered

immensely from the what has now become a fentanyl crisis yeah absolutely there's also this one study i was looking at with like mice and it's like or rats They created this like environment where they could, you know, push the button and get some opiates. But if they were in this area where they had like all of the features that they wanted, you know? Like it's kind of like a mouse or rat heaven, you know, like with lots of things to do, nature and playmates and stuff like that, they would rarely push the button. Any thoughts on that? Yeah. Again, as we talked about, those people.

seem most vulnerable to addiction for anything, whether it be a behavior or a substance, are those people who are somewhat chronically and hedonic. They don't derive enough joy. So certainly loading their environment with more joyful, healthy stimuli may be a way of helping to protect them against turning to substances. I was very impressed with work in this area where they've looked at, adopted away children from addicted families versus non-addicted families, and the genetics are very prominent in predicting who's vulnerable. Getting back to the idea of, well, for some people, they will try things when they're adolescents, and they'll kind of move on. Other people, they try things, and they're trapped.

and I think that's where we need people to build part of the recovery program is to help them build safeguards against becoming re-entrapped yep this is where I think the relational like the normal pleasures of life it's like how do we get them back to enjoying that if they can and if they can't then maybe treating

underlying depression or underlying mood disorders that are there. Any data that you've seen where antidepressants or medications that increased dopamine were used to treat this population, anything hopeful there from your perspective? Well, clearly if people develop signs and symptoms of anxiety or depression, then treating those comorbid conditions, is important to maintaining the person's substance recovery as well.

I am one of the things the group I work with does, we collaborate with some of the groups in Australia, and Australia right now is experimenting with controlled use of stimulant medications for people who are methamphetamine or cocaine, addicted, essentially a tempting model similar to buprenorphine or methadone, except in this case, with controlled amounts of stimulant. Early days still, so they don't have long-term results, but the early data appear promising that for some people who are hardcore speed and cocaine users, there may be approaches similar to the buprenorphine that may turn out to be helpful and helping some of those individuals get free of their substance use disorder.

Yeah, I've seen some of those early studies or, I don't know, like years ago when I was looking at this, I mean, there wasn't huge studies. So I'm very curious to hear about the bigger studies. Yeah, I imagine they're going for now. they're trying to, as in most cases, most early research is short term because funding is limited. But now they've gotten to the point where some of the research groups in Australia are now pursuing studies that will have five, 10-year follow-ups. So they'll be able to evaluate what the long-term results of those treatment approaches are. Now, how are they giving, like, I imagine they're giving like Concerta or Vivian,

because those have less ability to be abused. Yes. Is that right? Yes, they're choosing formulations that are difficult to abuse things like Vivance, which of course is a pro-drug. It's until it's cleaved from its amino acid. It's not active. That occurs in red blood cells.

So there's, you know, unless you're a very good chemist, you won't be able to make an active drug you can take. Some of the other formulations, like Lestexamphetamine vivance, that are encapsulated in ways that, again, unless you have access to a laser drill, you'd have very difficult time abusing the drug. Some of those they're using,

they're also not in a proof form, but they're also looking at silastic capsule implants as a way of releasing a controlled amount of stimulant. So there may be some parallels to the opioid treatments down the line. And what frequency are they giving the pills? Is it like here's your pills for the next seven days? Well, they started out in the very early studies. They were having the person come in daily, just like a methadone clinic.

They've now gotten to the point where the person has to start there, but they graduate to a longer prescription period. with very careful monitoring of they can't be running out of pills. And of course, I think they're hoping that if they can develop viable, long-acting or implantable formulations, that then that may get around the problem of the person saving pills or abusing pills. Like I said, early days still, so I'm not sure how that will turn. out, but it appears promising. Because we're looking at like orders of magnitude, like with what they would be using,

if they were using meth, for example, compared to something like concerta. Yeah, well, that's something a lot of clinicians don't appreciate. It confuses some people that, you know, yeah, we use drugs like Lestexamphetamine or methylfinidate or various formulations of amphetamine to treat illnesses like ADHD. and they say, yeah, but you guys are using it for these people. How come you're worried about people using it on the street? The difference is, as you know, the doses that are given to treat illness are fairly small. If you were just talking about amphetamine, usually well under 100 milligrams a day.

The average person on the street who's using methamphetamine may use anywhere from 500, to a thousand milligrams and a single speed run. So an order of magnitude difference. It's like 10 times more, is what you're saying? Yeah.

And of course, like any molecule, the effect is, you know, can be vastly different depending on how much the person takes. Do you think

if someone was doing this in the U.S., is there is there current hesitancy to doing this if you're an addictionologist, or what is the addiction medicine groups stating about this? We've typically had a harder time coming to grips with substitution. It took eons for simply methadone clinics to be accepted for opioid treatment. And indeed, you know, one of the current struggles going on, at least for the current opioid crisis is a number of jurisdictions have proposed establishing safe administration settings where the person brings their own drug, they self-administer it, but they do it in a context

where there are basically nursing staff watching them. That is being promoted in some areas, and in other areas it's being treated as politically anathema, and that will never happen, and we'll never do that because it's supporting illicit drug use. So, you know, as a society, we're in many ways very divided on some of these topics. Okay. Okay. Yeah, this is good. This was like a good, I like that segue.

I'd be interested to hear with these studies show in the future, looking at five-year follow-ups. Wow. Me too. Yeah. How close are we to getting some data on that? Or is there early data that you're aware of? They're telling me they expect to publish some longer-term studies within the next year or two. Well, let's have them on the podcast.

How about we arrange that? Sounds good. When it comes out, it would be fun to talk about that. I'm all for creative ways of helping people stop using. It's like, what's worse? Someone having a relapsing use disorder, chronically relapsing on meth and cocaine or cocaine. cocaine or taking, you know, concerta.

Yeah. It's pretty obvious. Because, especially with... I agree. I mean, and I, there, you know, we have the example, especially with the buprenorphine, that there are people who clearly cannot just kick their opioid addiction. But with a substitute that is given at reasonable doses and does not cause

psychological effects, they can maintain a normal, productive life, which for psychiatry, that's our goal is to try to help the person lead as good a life as they can. Yeah. And I think that my viewpoint is also shaped by when someone gets cocaine or meth off the street, there's a high chance in my mind now that there's going to be fentanyl in it, that they could die. So we have to think a little bit about that risk and how that risk of death is there. And that should be for us as well.

If somebody's a methamphetamine user or a cocaine user, they may have zero tolerance for opioids because they don't use them. routinely. They come across a dealer who gives them cocaine or methamphetamine mixed with a little bit of fentanyl, two milligrams of fentanyl may be all that takes to do away with them. Yeah. Good. Well, I, yeah, coming back to the opiates, anything that you feel like we didn't cover that you would like to cover before we wrap this thing up? No, I think we have more or less covered the opioids. Oh, I did one last thing.

I have had people ask me, what's the difference between an opioid and an opiate? The terms often are these days used interchangeably. Originally, an opiate was derived from a plant source like poppies, whereas an opioid was a semi-synthetic or fully synthetic molecule. But as time has gone on, that distinction has become more blurry. Okay, here's a fun little thing I'd be curious to get your take on. What do you think of some of the lawsuits against the pharma companies that were pushing these opiates like they were candy? I hope it costs them dearly, in particular since.

the initial lawsuit, which was Oklahoma versus Purdue Pharma, which Purdue Pharma settled for $270 million. Several other states have now filed suit against Purdue Pharma, including California. And I frankly hope, as I said, that they paid dearly for the fact that in the 1990s, they not only promoted more potent opioids, and their medication was oxycodone, oxycotton, trade name. They also basically had their drug reps tell physicians, oh, this is not addictive, although that's been a very old story with the opioids. If you go back to the 1920s, morphine was originally marketed as a non-addictive substitute for dilaudid. Yeah, so, okay, they got into issues due to deceptive marketing practices to downplay the risks of addiction

and overstate the drug's benefits. And, you know, we think about 270 million. Sounds like a lot of money, but probably not. that much, right, in the big picture of them? Not for them. They made billions of dollars from doing that, which is why I hope, because the Oklahoma lawsuit was successful in getting them to settle, that many other states jump on that bandwagon and cost them more. Because, frankly, in my view, they need to be punished, frankly, for killing a lot of people. And sweeping in the opiate epidemic. I mean, that was a big part of it.

Yeah, that was the early days that swept it in and across that single decade, opioid prescriptions tripled. Yeah. Awful.

Well, there we go. We've tantalized people's curiosity and talked about some current events, political stuff. And we will wrap it up here, I think. This is really good. Okay, great.

All right. Thanks for your time, Dr. Cummings. Okay, thanks. Glad to be here.