Looking Back/Moving Forward: The Neurobiology of Addiction with Peter Kalivas, PhD

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[00:00:04] Loretta Lynch-Reichert: Good morning, everyone and welcome back to another addition of Medical University of South Carolina’s Science Cafe via podcast. I am your host, Loretta Lynch-Reichert, director of research communications here at MUSC. Today, our guest is Dr. Peter Kalivas, an MUSC distinguished university professor in the department of neurosciences. Dr. Kalivas’ research has been at the forefront of addiction science recognized around the world. Welcome back to Science Cafe Dr. Kalivas.

[00:00:35] Peter Kalivas, PhD: Thank you, Loretta. It’s a pleasure to be here.

[00:00:38] Lynch-Reichert: In 2017, we were privileged to have you and your wife, social worker Sue King, join forces at Science Cafe to explore the neurobiology of addiction and what the community can do with this understanding to better protect our children. You both presented compelling work on addiction and changes in the brain, how it happens, especially with regard to adolescents and exploring how to help addicts fix their brains and regain their lives. That was three years ago. What have you discovered since that time?

[00:01:10] Kalivas: Well, one of the primary discoveries that we keep making over and over again is that the disease, like all neuropsychiatric disorders, the disease of addiction is substantially more complicated in terms of its impact on the brain than we would have imagined. The brain itself is more complicated and the impact of the drugs to change the brain is much more complicated. I can give some examples of things that we’ve discovered at a biological level and then what I thought I would do is chat a little bit about some new clinical perspectives that evolved out of communication between the basic sciences and the clinical sciences; as you’re well aware here at MUSC, there are a lot of outstanding world class clinical neuroscientists in the field of addictions as well.

[00:02:03] Lynch-Reichert: That sounds wonderful. Please start.

[00:02:05] Kalivas: Sure. Yeah, at a basic level, you’re familiar with the concept of a synapse and the way neurons communicate with each other. We used to think that that was the essence of how the brain functions, that is, if you will, the microchip in the brain that allowed us to do everything that we do and what we’ve realized is that that synapse has a lot of help and in fact the helper cells, neuroglia, and the areas around the cells which turn out to contain lots of molecules are extremely important in keeping the synapses balanced. So what we’re starting to discover is that the drugs of abuse are impacting not just synaptic transmission, which is what there’s been the last 20 years of study on, but it’s really starting to imbalance areas around the synapse that keep the synapse balanced.

And so what you find is that it’s not so much the synapses don’t work, they just don’t regulate as well and as a result in some cases they can’t learn as well, which accounts for why addicts have more difficulty with learning new situations to change their behavior, their addictive behavior. The imbalance can also lead to long-term alterations in mood and emotion and that makes it all sound so hopeless, and I’ll talk a little bit about how we could use that to assist in substance use disorder and help people that are suffering from this disorder move back into what we call homeostasis.

The other big advance has been in, at least at a basic level, working with rats that have been using drugs, and mice, is in vivo cell imaging. So what we can do now is we have these mini cameras, very small cameras, with a lens that we can stick inside the brain, and we can actually watch the brain working at a cellular level. So we can watch these synapses fire, we can watch the synapses actually change in response to learning to take a drug like heroin, and they don’t change in response to learning to take, for example, sucrose. So we’re really, for the first time, starting to be able to actually watch the brain as it performs at a cellular level, so you’re aware and we can talk a little bit about that later if you’d like, about the neuroimaging work that’s being done in humans and in animals, but humans is the most relevant. And that is... the neuroimaging work in humans is at a very large level. So you can’t really see how the brain itself at a molecular level has changed in response to drugs, you can see how it’s changed at a more global level, and we can talk about that in a little bit.

The final, from our perspective as researchers, thing that I would like to bring up arose from us doing clinical trials with a substance called N-acetylcysteine. So this is a modified amino acid, and back in 2017 we had our fingers crossed that this was going to be a highly impactful compound in substance use disorder. There was a very positive trial that came out of MUSC with adolescents and cannabis abuse, and it decreased the amount of cannabis used by adolescents, and there were other positive indications from other trials. Well since that time, a large nationwide trial with this compound, there are five sites I believe, it failed to suppress cannabis use. So we’ve been studying that and trying to figure out why it works in adolescents, but doesn’t work in the global population which included mostly adults, not adolescents. When you actually went back in and examined the adolescents, it appeared that the compound was successful.

So what is the difference there? Part of it is that they just haven’t been using drugs as long. Part of it is that they don’t have it as readily available. So this got us thinking about what we really discovered in the basic sciences which is that the drug is good for craving and if you think about what craving is, it’s a component of substance use disorder, it’s not the entire disorder. And so it turns out adolescents, who often are in a somewhat more controlled environment, in other words they don’t necessarily have as ready access to cannabis as say an adult who is maybe using cannabis for 20 years, they have to crave, so craving becomes a big part of why they’re going to relapse. If you take a 40- or 50-year-old person whose been suffering most of their life from substance use disorder, they have built a world around friends who will drop by with the drug, they might have drug at home in almost all situations, and as a result, those people relapse when they’ve taken this drug because craving is not as important, the drug is so readily available.

And we realized the importance of that because in one trial, about 25% of the people started abstinent, meaning they hadn’t taken the drug for at least two weeks prior to – their drug of abuse – prior to starting the trial with N-acetylcysteine. And what we found is those people did not relapse and so those were probably people who had already started to bring some control to their life if they’d been abstinent for two weeks. So this led us to doing a trial with veterans, it was a combination of post-traumatic stress disorder and substance use disorder. As you may be aware, many people suffering from PTSD, post-traumatic stress disorder, also have comorbid substance use disorder and if you have both, it’s very difficult, very very difficult actually, to treat either one independently. So they’re very intertwined and maybe in another podcast we can go into some of the biology that causes those two clinical situations to be... to co-express, but what we found, amazingly, is that the N-acetylcysteine completely wiped out post-traumatic stress disorder symptoms.

[00:10:00] Lynch-Reichert: Wow.

[00:10:01] Kalivas: Yeah, so we had a huge effect there. This is a trial that’s being headed by Sudie Back here at MUSC and I know she’s now, we’ve completed the pilot trial and published that, and now there’s a much larger trial and she’s running. And what that caused us to realize is that craving is what we would call an endophenotype. So it’s a symptom of substance use disorder, it is not substance use disorder per say. Well it’s also a symptom, a very profound symptom actually, of post-traumatic stress disorder. So one of the real triggers in post-traumatic stress disorder is that the person cannot stop thinking about the traumatic event that they had encountered that led to the post-traumatic stress disorder, so for example, if it was a combat experience or rape, as two examples, when a person gets into a situation that reminds them of this episode in their life, the episode comes crashing back, it creates a state of high anxiety and they can’t control it and in the field of people who study post-traumatic stress disorder, that’s called intrusive thinking.

And so what we’ve come to realize is that what N-acetylcysteine is doing is it’s working at a neurobiological level and some of the things I was talking about with the more complicated synapses, it works at that level to restore circuit function so that thoughts don’t intrude as much as they did before. You still think the thought, but it doesn’t intrude and become a dominant feature of your behavior, and in the case of PTSD, create a high state of anxiety to where you’re behaviorally not functioning as well, or in the case of addiction, it would cause you to really crave the drug and if you didn’t have drug readily available, to go out and seek the drug. So those are the two... a little closer look at neurobiology that new technologies have allowed us to have of how the brain is adapting and how going back and forth with this N-acetylcysteine, we’re starting to realize that probably the best treatments for addiction, for substance use disorder, are going to be combination treatments where you attack the different symptoms possibly with different compounds or different forms of psychosocial intervention.

[00:12:50] Lynch-Reichert: That is very promising, I mean, it brings up a whole world of opportunity for folks and I’m really amazed. I had no idea this was happening so kudos to you and the team in neurosciences and psychiatry. So let me see if I understand correctly: with adolescents, that craving is there but also the peer pressure, if I understand you correctly. Craving is just one symptom of addiction, so if they are taken away from an environment that encourages them to use drugs or alcohol or whatever, I’m assuming alcohol is also part of...

[00:13:37] Kalivas: Yeah, very much so.

[00:13:37] Lynch-Reichert: ...the kind of addiction you deal with, yeah. If you take them out of that environment, are they more likely, then, to have a hopeful future?

[00:13:46] Kalivas: So as near as we can tell, yes that would be the case. I mean that type of experiment, especially in combination with a compound that suppresses intrusive thinking or craving, has not actually been done, so to my knowledge anyway, that type of trial has not been done. What people are starting to do more is people have to be abstinent to enter a trial and just the nature of abstinence implies, meaning that they haven’t had the drug for a while, implies that they have some control over their environment already. Maybe they’re not... they’re trying not to see their friends that use drugs, but the bottom line is, the answer to your question I think is yes, that if you... a person is removed from the environment, they’re not going to encounter the things that would trigger craving – friends that they might see or situations that they would get into routinely where alcohol or cannabis might be available – and then taking N-acetylcysteine, it will suppress the intrusive nature, whenever they think about it because not all craving is driven by environmental cues, it’s also driven internally, so you start thinking about your friends and that can cause you to crave.

You’ll start thinking about the drug and then if you can’t regulate that, which is the issue, then it becomes an intrusive thought and it becomes to dominant your behavior and cause you to relapse. So it’s a combination of environment and we believe that this compound, N-acetylcysteine, the combination of the environment and N-acetylcysteine would be the best approach, which is why I think it works better with adolescents. Their environment is more in flux, it’s in a way – I know parents would agree with this [laughter], I had teenagers – but their environment is more controlled. They still...

[00:16:06] Lynch-Reichert: So, that kind of leads to a question maybe I should’ve started with: why is it that some teens are introduced to addictive substances... why are some teens able to walk away from it and other teens are almost immediately addicted? Is that a fair statement to begin with?

[00:16:33] Kalivas: Yeah, that’s a really good question and there’s no clean, clear-cut answers. You’re asking the question, the jargon we use is resilience. So why are some people resilient and other people are less resilient to these exposures? There’s genetic components, that’s been most clearly studied with alcohol, but most genetic studies would find that there’s a genetic component, so some people are genetically more vulnerable, but the genetic vulnerability is not overwhelming, in other words there’s a huge interaction with the environment.

[00:17:20] Lynch-Reichert: Okay.

[00:17:21] Kalivas: So some people with genetic vulnerability will never become addicted to substances and others are more susceptible. Exactly why one group is more susceptible, and another group is more resilient is a very difficult question. One is side effects, so some people are very sensitive to side effects so for example, the ataxia that you get with alcohol, some people find that extremely aversive.

[00:17:57] Lynch-Reichert: What is that, I’m sorry?

[00:17:59] Kalivas: Oh, I’m sorry. When you lose motor control.

[00:18:02] Lynch-Reichert: Ah, okay.

[00:18:04] Kalivas: Your motor systems aren’t working as well, and some people respond to that as that’s a very immersive event. When you think of cannabis, some people respond to cannabis with the loss of control over your thoughts becomes aversive. They may have paranoid thoughts, so they have a vulnerability there and many people, that will be their limit. Cocaine, for example, would be the sense of anxiety that the psychostimulants produce. Many people ultimately find that aversive and stop taking the drug or really cut back to the point where they’re not... it’s not going to interfere as greatly in their life.

But right now, we don’t really have a good way to fingerprint vulnerability versus resilience. So there’s some interesting studies being done here at MUSC, they’re being pioneered by Hesheng Liu, so he’s in the department of neuroscience here and he arrived from Harvard maybe two years ago, and his expertise, and he’s absolutely world-class in this, is imaging resting state brains. So what that means is a person gets put in a scanner, a magnetic resonance imaging scanner, and they watch brain function, but they don’t actually give the person any tasks. You just let the person free range and what you can see is that there are a number of circuits in the brain and he’s... it takes thousands and thousands of scans of people with well diagnosed disorders, such as depression or substance use disorder, and you can start seeing that there’s tendencies for certain circuits to be stronger and certain circuits to be weaker depending on the psychiatric disorder.

So I don’t think I would say that there’s an absolute thumbprint for each disorder, but we for example, in the case of substance use disorder, a weakness in the connection between the frontal cortex, which is decision making, and what we call the striatum, which is the habit area of the brain where the brain takes thoughts and puts them into action, and there’s a weakness there. It’s fairly well documented, not just here at MUSC but in other institutions as well now, that people that have substance use disorder often have a weakness in connectivity in that circuit and so to some extent that’s a potential biomarker. The problem is, it’s the old chicken and egg problem. They already have substance use disorder when they get imaged and there’s been some twin studies that have shown that if one person has it, another... a sibling, is more likely to have that and also siblings are more likely to have substance use disorder. So there is some reason to think that it maybe not just something that’s produced by the drug, the weakening of what we call cortical striatal function, but it could be actually something that is more generic to the person.

[00:21:58] Lynch-Reichert: That is, I mean it’s eye-opening. I know I’ve done a little reading myself on the neuroimaging and you see a lot of stuff in the popular press about such things as looking at the brain, let’s say when the patient sees cocaine or cannabis or sugar and I’m wondering are they making too... are they being too simplistic when they share that sugar can be just as addictive as a controlled substance? What’s your thought on that? The reason I ask is because I wonder if the research that you do would lead into other things such as weight management, I mean we all have addictions to something so I’m just really curious how your work could move other areas forward.

[00:22:49] Kalivas: No, that’s a really interesting question and a very popular question about how does substance use disorder translate into what appear to be addictive behaviors for other more natural compounds, sweet compounds, carbohydrates, etc. So because I’m a basic scientist by training and by almost all the work we’ve done, we collaborate with our clinical colleagues. We’ve tried to set up addiction models with high fat foods, with just regular sucrose pellets, the equivalent of a Milky Way bar or something, and you know, a certain,

interestingly, a subpopulation of rats will gain weight. Most won’t but some will eat the high fat pellets to the point where they gain weight and they have some of the characteristics in their brain that we find with, say an animal that’s been using cocaine, but not really as nearly as remarkable as what an addictive drug causes in the brain.

[00:24:18] Lynch-Reichert: That is fascinating.

[00:24:19] Kalivas: We can actually use that as a control. So if we get an effect by heroin on one of these synapses or a circuit and it’s not happening with our sucrose use, so an animal that goes in and takes sucrose every day, then we assume that that’s a true addictive trait and that everything else is not so much. So it’s an assumption we make to try to pull out the things that are related more to substance use from the use of highly palatable foods. So does that mean the highly palatable foods are not addictive? Not really, they’re not as addictive.

[00:25:10] Lynch-Reichert: Okay, so there’s hope.

[00:25:12] Kalivas: That’s the safest thing we could say, we’ve got our... the circuits that are set up in the brain to seek and use food are very resilient and so necessary to life. The adaptations to that circuitry that opioids produce, that’s not a natural process so we’re not as protected endogenously from something like opioids as we would be from food.
[00:25:44] Lynch-Reichert: Okay.

[00:25:44] Kalivas: And so the systems can get out of balance from an addictive drug much more quickly and, from our observations, much more thoroughly from an addictive drug than it will a natural substance like sucrose.

[00:26:02] Lynch-Reichert: Okay, that makes sense. The body needs certain things and so if I understand you correctly, food, as being a part of our life support, can be better balanced even when it becomes addictive as opposed to these substances that are not really part of the natural life cycle. Does that make sense? I mean, am I saying that correctly?

[00:26:25] Kalivas: Yeah, no that’s... that’s how we think about it is that the drugs directly influence the linkage between the frontal cortex and habit circuitry in the brain. Food does not. So people can still develop – and I’m sure there are vulnerabilities associated with this – intrusive thinking about food. So that intrusive thinking characteristic can definitely occur. It can occur with us – because intrusive thoughts are not necessarily abnormal, sometimes it’s important to have thoughts intrude – they can guide daily behavior. It’s when you lose control or the ability to regulate those intrusive thoughts and I think something like highly palatable foods can create that intrusive behavior – intrusive thoughts and behavior – but they don’t necessarily have access to really dramatically changing the circuitry and the synaptic topography the way addictive drugs do.

[00:27:47] Lynch-Reichert: Okay. My next question, just moving a little bit away from adolescents but kind of parallel to it. So you know, we all know COVID-19 is just a very compelling feature of our world today and another again popular media article I’ve been reading about is faced with these challenges, a lot of adults are now seeing themselves getting engaged in addictive behaviors, you know, drinking more, that’s been the predominant thing I see in the media, who subsequently or previously had no issues with it. So my question to you is for those folks who never had an issue with substance abuse but now find themselves in an environment that really almost like, I guess, PTSD – you're seeing adults drinking a lot more – are those people prone – drinking a lot more or maybe smoking cannabis or whatever a lot more – are those people prone to a long-term addiction cycle or is this just... would you suggest these people who have never had the issue previously are they... will it be easier for them to pull themselves away from these substances? Does that make sense?

[00:29:11] Kalivas: Yes. Yes, I understand, that’s a good challenging question because hard data is not going to be easy to come by. The data that we do have, the information, is that these drugs, the more you use, the higher the quantity on a daily basis, the more your brain is going to change, there’s no question about it. Your brain will adapt to these substances just like it adapts to all sorts of things. In fact, as you’re implying, the use of substances is an adaptive response to the COVID-19 situation where there’s an increase in stress and there’s boredom in some people, you know, so this combination would cause people to seek out the stimulation from drugs or the attenuation of stress that a drug especially like alcohol, which has anxiolytic qualities, would bring. The higher the quantity, the more your brain is going to change.

We talked earlier about – some people are more resilient to this change. Nobody’s immune to this change and so the higher the quantity the more likely you are to develop substance use disorder and I don’t think that there’s anybody, there’s no super humans out there that are 100% resistant to developing intrusive thinking about ‘oh I’d really like a beer right now’ or to just start developing these behaviors and again there’s... some people are more resilient and can control it to a deeper level than others but eventually they become a part of your life and you start to miss them if they go away and you develop intrusive thinking about them. So the increase that we’re seeing is a danger, it’s not a wipeout, you know, alcohol is among the least– there's a lot of alcohol addiction, I’m not trying to say that it’s not a problem, but it’s not cocaine or heroin or opioids. It’s not as addictive as those substances.

[00:31:45] Lynch-Reichert: Where would you see where public health could be useful for us?

[00:31:51] Kalivas: Yeah, so my own sense is that there is a... so there’s a couple of things from a basic way that we handle our research on addictive substances. So the FDA is... it’s relapse prevention only. So if you’re drug treatment or your trial or your TMS, transcranial magnetic stimulation, whatever, if it does not decrease, if it does not cause... if it does not inhibit relapse significantly, it’s considered a failure. It can reduce use, that doesn’t count. Now it does for alcohol and I believe smoking as well, so those are two legal substances, but we’re very hung up when it comes to the illegal drugs on somebody going absolutely abstinent, because the drugs are illegal and so abstinence is the only clinical outcome that is acceptable and there are a lot of treatments out there that reduce use. We already discussed just a second ago reducing use reduces harm and allows the person to develop alternate behaviors, allows the person to seek help and actually develop the cognitive control to remove themselves from the environment that is allowing them such ready access to the drugs.

So it gives, it allows the less a person uses a drug, the more opportunity they have to control their drug use. So I think that’s one big mistake that the FDA is really responsible for that and so there are so many failed trials in the psychiatric diseases in general, but in particular in substance use because of this criterion when there probably are compounds that have almost no side effects, if any, that would be helpful and they’ve been shown to be helpful. They’ve reduced cocaine use just not significantly prevented people from using it at all, they didn’t create abstinence, so that’s one side.

The other side is to really realize that you’re dealing with substance use disorder, and I mentioned this earlier, to realize that you’re dealing with a complex set of symptoms and in some people one set of symptoms is really the driving force and in other people, other sets of symptoms, with some drugs one set of symptoms is more of a driving force than others. For the latter, you can think of opioids. So a major driving force of opioid abuse is the withdrawal symptoms are so profound that people, they’ll drive people to seek the drug. That’s not as prominent with other drugs like cannabis or even the psychostimulants – there is a withdrawal symptom, but it’s not as profound so people can regulate it a little bit better. So you want to really, with opioids in particular, a therapy that targeted the withdrawal symptom would be very useful and in fact, that’s what therapies are. You basically take compounds that blunt the withdrawal symptom, they happen to be opioids as well, they’re just opioids that are easier to manage, like methadone, buprenorphine. So that’s one line of treatment that is not, you can’t necessarily translate that to other addictive drugs.

We mentioned the endophenotype, as we call it, the symptom of intrusive thinking so targeting intrusive thinking will work for some people – it looks like it works well with adolescents. It doesn’t work with people that have been abusing cannabis for 20 years. So realizing that you have these sub-populations where different characteristics of substance use disorder are dominant forces in driving their relapse will allow you to shape the therapies more effectively and of course to do that, you need a better infra structure for therapy. And that’s...

[00:36:46] Lynch-Reichert: Can I...

[00:36:47] Kalivas: That’s something that’s not very prevalent. For us to set up a halfway house for us to do trials on abstinent people is very difficult to find that.

[00:36:59] Lynch-Reichert: There are countries, as we’ve known previously, that... that allow addicted persons to get into a methadone clinic or to get clean needles or to get those drugs that will maybe dampen their craving somewhat. So is that an American issue, public health issue? Or... who’s doing it well across the world, I guess is my question.

[00:37:30] Kalivas: I don’t think any country on the planet feels that it has substance use disorder under control, that they have it worked out entirely. Yes, there are countries that are more open about substance use disorder and so they can do things like needle exchange programs without a lot of negative social feedback on that particular mechanism. So the United States has issues along those lines. The United States is more wealthy and it takes money to buy addictive drugs, whether it’s alcohol or heroin and that contributes greatly to why Americans turn to addictive substances, it’s because they can afford it. That’s not to say that poor countries don’t have substance use disorder as well, they definitely do, but that’s part of our problem as well and we aren’t mitigating it with the proper education and therapy infrastructure.

[00:38:49] Lynch-Reichert: Understood. Do you see a difference regarding gender as it relates to addiction? I know that’s not quite your forte but there are so many differences between men and women when it comes to healthcare, how about addiction?

[00:39:09] Kalivas: Yeah, you’re right, it’s not 100... we don’t study that in great detail – I don’t at a human level. We look for sex differences in our rodent models and to be honest, most of the things that we find are extremely subtle. However, there are some remarkable differences but if we back up, men and women develop substance use disorder. So the fundamental... the fundamental outcome of using drugs is the same, they become addicted, the brains change. What people are finding is there’s possibly different interactions with stress, in other words the biology of stress is different in men and women and that could lead to differences in how the drugs are used, in what kind of susceptibilities they might have to different drugs.

But that’s really... there's still to my mind, still a lot of hand waving along those lines. The exciting part, I think, is that you’re finding at least at the basic level, the outcomes look the same behaviorally, but sometimes the pathways, in other words the cellular pathways, that females take is different form the way males take. By the time it integrates into a behavior, yes, they’re still going to go get the drug, but there’s different molecular structure as to how they get there and as a result, once we know more about it – we're kind of shooting in the dark right now therapeutically on that, at least that’s my observation in terms of sex differences – but once we understand how the biology is different even though you’re getting a similar output where both the man and the woman have substance use disorder, we might find that different pharmacological interventions would be appropriate for men and women.

And so I think that’s where we’re at right now. I don’t think that you can definitely go in and say ‘yes women do this, and men do that,’ there are sociological differences, and so there are tendencies for how women might become addicted versus how men might become addictive. Certain things will be more stressful for women, other things will be more stressful for men, and stress and substance use disorder go hand in hand just like we talked about with PTSD and substance use disorder. So those differences are being studied and those are very useful for cognitive behavioral therapy, that you might treat a man and a women differently in terms of the way you’re going to teach them to approach their substance use disorder and try to get a handle on it but pharmacologically and getting drugs to assist in that process, I think we're still in the early stages.

[00:42:32] Lynch-Reichert: Okay. Promising though. Promising opportunities.

[00:42:35] Kalivas: Yeah, no, no! It’s all promising, as I started off this whole podcast, the brain is so much more complicated than anybody ever imagined it ever was. The deeper we dig into it – I've spent almost 40 years as a neuroscientist thinking when I started that I would’ve solved these things by now and as we develop better tools to try to understand a problem that we have, our ideas about the brain aren’t correct, we discovered that they’re definitely not correct and there’s a whole world of the way the brain is working, the interactions between molecules, between circuits, that we hadn’t imagined and that we weren’t actually looking at it correctly.

And so this is... I like to think of it as you wouldn’t jump in the space shuttle and go colonize the moons of Saturn. That’s not the right technology, we don’t have the knowledge to do it. We’re just not there yet and understanding how the brain creates complicated behavior and understanding then how those behaviors can then go awry and create what we call psychiatric disorders, is you know... the full understanding is kind of like colonizing the moons of Saturn. It will take time. A full cure I believe will take decades. Will we be able to ameliorate with better and better and closer proximations of what’s actually going on and how we would intervene? Absolutely. And can we build a better infrastructure until such time as we have good biological tools with strong biological rationales? Absolutely, we could have a better treatment infrastructure, there’s no question about it, it’s just what we choose to do. And those can be incorporating these new approaches as they come out but it's... you can see it with all brain disorders really – there are advances and then there are cures and cures are very hard to come by when it comes to the brain. Advances in treatment are coming up all the time and it’s very promising and nobody should lose hope and I do believe that we’ll get better and better handles, but the absolute snap your fingers cure is, I’m afraid, a little ways off.

[00:45:20] Lynch-Reichert: I actually think there’s no more powerful statement than what you just made. It puts us in a realistic place. It offers us opportunities and tools for the future and that’s why you do the research you do, and you’ve been doing it for 40 years. I applaud your passion and your commitment to this. It is a human issue that may not have a cure as you say, but definitely has some problem solving as part of it and I think the whole reason we do these podcasts is because we understand how important the research is, the basic research translated into clinical research that can make a difference in a person, in a community, in world, and I really can’t tank you enough.

You have all these honors and accolades and there’s a reason for it and it’s because you’ve given your heart and soul to this problem and, you know, we’re the luckier for it at the Medical University of South Carolina which is why neurosciences is one of the top departments in the country, because of the work you do, Dr. Kalivas. Can you tell me just one more hopeful thought to leave us with as we move forward in this world?

[00:46:38] Kalivas: We’re at a very odd place right now with our nation and with the world, with the pandemic. And it’s... I think a lot of people have lost the sense of flow that we have as a culture, that we actually are still evolving, we’re actually still learning about the world around us and it’s the science that is still going on and the science that will continue going on and the new treatments that are going to come out, haven’t stopped, and there is a very bright future, it’s just not as easy as we thought it would be but I, I firmly – when I see the progress we’ve had over the last 40 years, it’s phenomenal what we know now that we didn’t know before and there’s no question in my mind that these psychiatric disorders, substance use disorder, in particular, will be highly treatable disorder over the coming decade or so.

We’re just, we’re at a place where we’re at a threshold really. I described some of the new technologies that a basic level, I’ve described some of the new perspectives that have come out of knowledge in terms of how we might deal with substance use disorder, that’s all new. That’s going to change the way we do things over the course of the next five years and in the process of that change taking place, there will be new observations and new discoveries and we’ll, slowly but surely, pick away at this horrible, this very tragic psychiatric disorder until it doesn’t exist anymore. And that’s what the new knowledge will do and a society that is willing to use the new knowledge to change a little bit, the way it thinks about things so that it can actually apply it and improve itself.

[00:48:59] Lynch-Reichert: That is a wonderful hopeful thought. And we’re going to hold you to it [laughter]. Thank you to our guest, the distinguished university professor Dr. Peter Kalivas from the department of neurosciences here at the Medical University of South Carolian. Join us again next month, we’re going to continue the discussion on the brain when we talk to some folks in neuroscience on Alzheimer’s disease and from one of our institutes, the ZIAN Institute. You'll hear more about that in our future podcasts. Dr. Kalivas, our very best thanks to you for today and for your time and our hope for continued success in the future.
[00:49:41] Kalivas: Thank you, Loretta. It’s been a pleasure to be here.