Revolutionizing Opioid and Trauma Treatment with Neurostimulation

Hey there everybody, and welcome to today's presentation on neurostimulation in recovery. I'm your host, Dr. Donnelly Snipes. And today we are being joined by Dr. Navid Kodaparest, who received his PhD in neurophysiology that focused on using the vagus nerve stimulation to promote restorative brain plasticity and treat neurological disease. Now, I know we've talked about that a lot, so I know that's one of those areas you're y' all are interested in. His research is considered foundational for the principle of targeted neuroplasticity training and has led to multiple VNS clinical trials for stroke rehabilitation. Dr. Kodaporest has nearly 15 years experience in translating neuromodulatory therapies to treat neurological and psychiatric disorders. He is scientific. He is a scientifically driven entrepreneur and has led clinical research at multiple early stage medical device companies involved in Parkinson's, cardiac disease and opioid use disorder. Currently, Dr. Kadavarest serves as Chief Science Officer for Spark Biomedical where he's responsible for overseeing the company's clinical research initiatives to develop treatments for opioid withdrawal, chronic pain management and acute stress reaction. He continues to explore opportunities to advance the technology to address other clinical issues. So welcome Dr. Koda Perest. How are you doing?

Well, thank you for having me, Dr. Snipes.

I am so happy that you are able to join us today because I know my audience is really interested in vagus nerve and what we'll talk about is the autonomic nervous system because, you know, we can't just pluck one thing out and talk about the vagus nerve and not think it impacts everything else. We need to look at how what I in my videos refer to as the body factory, how that all works together. And so I'm really excited about talking about this and about talking about the new treatments that you're developing that are involved in non invasive treatment. So we're not doing surgery and implanting, you know, electrodes or whatever. So let's go ahead and get started. Tell me a little bit about what the autonomic nervous system is and how it's related to the stress response.

Yeah, you know, the autonomic nervous system is a widely studied area right now. I think there's so many different applications that have been attached to it, whether that's from pharma to medical device or what have you. But when you think about the autonomic nervous system, I think people think of like two different camps. There's like the fight or flight, which is known as the sympathetic, you know, autonomic nervous system. But then there's also the rest and digest, which is the parasympathetic. And they think of a separate. They're not. It's like either one is up and one is down or one is up and one is down. Right. The thing is, is they actually work in really nice concert. They're working together consistently. And so as in a scenario where someone is, you know, anticipating going, like, I've been watching the Olympics, and you can actually see autonomics on the face as the runners are about to start the race. You can see that high sympathetic drive right before they. They start the race. And sometimes that's really good. That's. High state of anxiety at a high state of stress can be very beneficial for them in a state of. In. In the Olympics. But in the case of others, you know, unfortunately, if it's chronic states of stress due to autonomics, this can lead to other types of comorbidities, and it can lead to anxiety, some depression, ptsd, which we'll get into further, I'm sure, today.

Cool. And how are the vagus nerve and the trigeminal branch involved in the autonomic nervous system and its regulation? I mean, we. We hear those terms thrown out a lot. But what do they mean in terms of the autonomic nervous system in general?

Yeah, the vagus nerve is. Is widely known as the kind of a parasympathetic driver. Right. This is A. So Dr. Snipes, you probably notice. Very well. But the vagus nerve is one of 12 cranial nerves that you have in your body. Right. There's. But the really unique attribute to the vagus nerve is that it's the only cranial nerve that leaves your head. And in fact, it's the only cranial nerve. It's. In Latin, the vagus nerve means the wandering nerve. And so if you actually kind of look at how it wanders its way to the different organs in your body, it's pretty apparent why they call it the wandering nerve. As you said, the organ factory. Right. And some of your other podcasts. And so the vagus nerve is its primary component, when you study about it in medical school or even biology, it controls your heart rate. Right. So if you activate the vagus nerve, it can lower your heart rate and give you a sense of calm and relaxation. But since it has connections to many different organ systems, like, for example, breathing and digestion and even your brain, it has the ability to control these different systems. In different ways, mainly by promoting parasympathetic activity, kind of this relaxing sensation.

Okay. And how are stress and dysregulation of that autonomic nervous system involved in addiction detox post acute withdrawal syndrome symptoms?

Right. And so, you know, as patients unfortunately become dependent on opioids or other substances of abuse, a lot of times this is stemmed from trauma. You know, there's something, either they're living in a very high stress environment or they've been succumbed to some really stressful situations in life where they can then become more predisposed, they become more open to trying different self medications, whether that's alcohol, opioids, methamphetamine, cocaine, whatever it may be. And so as they become dependent on these medications or drugs, they're living a much stressful life. Because specifically for someone that is taking heroin or fentanyl, I heard once that they don't eventually the thrill and the nirvana goes away. They're really just running away from the withdrawal that can eventually occur. So every six to eight hours or 12 hours, they may get this sense of I'm going to go through withdrawal, so I need another hit, I need to take my medication again. And this can lead to stress and anxiety. And so as patients unfortunately experience this as they run away from withdrawal, this is where there's a kind of this cycle that develops. Right. As they continue to see the drug in different situations.

Okay, what does it mean when somebody is told they have poor vagal tone? That's one of those buzzwords that has been sort of taking over the Internet and YouTube for about two years now. And a lot of people, you know, a nerve is not like a muscle. You can't go to the gym and get better vagal tone. So what does poor vagal tone actually mean?

Yeah, this, this has actually been defined many different ways as, you know, and the way that I view poor vagal tone is in the sense that they're having less parasympathetic activity than they normally should. Right. So the, these are people that are kind of more on high stress or high anxiety. They're living more of this, this fight or flight type of mentality and lifestyle. So they're high sympathetic drive. And so there are certain factors that are leading to that. I do think that you can improve vagal tone. And when I say that, what I mean is that you can actually increase your parasympathetic activity. There's a lot of different ways of doing this. There's like breathing exercises can increase vagal tone, even doing what they Call is a carotid massage where you actually kind of vigorously massage on your neck, which can activate your vagus nerve. Some people even do it via the ear, which is something I'm very much focused on is, you know, you can actually stimulate the vagus nerve via your ear, which we can talk more about. There's many different ways that you can increase vagal tone and I think by, by doing that in a repetitive motion, Right. Over days or even weeks, you can actually have a, a new baseline for your vagal tone and then maintain that, which will kind of restore some of that autonomic balance that patient that we're all looking to achieve.

Right, right. And I know in a previous meeting we had talked about how my daughter is diagnosed with hyper adrenergic pots. So when she stands up, her blood pressure goes way high and her heart rate just increases incredible amounts. And one of the things she was told was she had poor vagal tone. And it took a while of trying to figure out what that meant and how to help her improve that. So her body didn't have such extremes. The use of auricular vagus nerve stimulation has gained a lot of traction in research as well as online. Tell me a little bit about auricular vagus nerve stimulation and we started to talk about that earlier and how is it useful for, for treating stress related disorders, trauma and addiction.

Yeah. And so you're exactly right. I would say in the last five to 10 years, maybe even longer than that, the term auricular vagus nerve stimulation has become really a kind of a buzzword in the science field. Right. And what and why that is is because even 30 years ago, 40 years ago, implantable vagus nerve stimulation. And what I mean by that is there are devices that are surgically implanted in people that can put an electrode directly on the vagus nerve, which is in your neck. Right. And it sits right next to your carotid artery. It's very safe procedure. Now you do have to receive surgery in order to receive this technology. These are FDA approved treatments for epilepsy, depression, now stroke. But again, the issue with it is there is some invasiveness to it. And so researchers have really been focused on how to apply vagus nerve stimulation or something very similar to that. Non invasively using wearable stimulation, wearable devices. You know, the Apple Watch has made everyone really interested in wearable treatments and diagnosis and understanding what is going on in my body. And so from a neurostimulation standpoint, this really intrigued me. I really wanted to understand can you activate the vagus nerve via, in this case, your ear? And the answer is yes, you can do it very effectively, and you can do it very safely. The way that we activate the vagus nerve is by essentially using an ECG pad. So if you're ever gone to the hospital, they put those pads on you, they can listen to your heart, it can record activity of your heart. And, well, we deliver it via hydrogels, which can deliver mild stimulation to the auricular branch of the vagus nerve in your ear. And this is a very effective treatment. So, and as you mentioned, how does it help with anxiety? How does it help with stress? Again, these are autonomic imbalances. Stress and anxiety is when you kind of push the scale more towards sympathetic drive. And so by activating these vagal nerve fibers, by activating the vagal network, you are able to push yourself from a high stressful drive, sympathetic drive, to a more relaxed state. By activating the vagus, you're activating their sympathetic nervous system. And this really can be quite effective for people, especially in acute settings where it's just like, I'm feeling this anxious moment, or it can be very effective long term. That can actually reduce the chances of you experiencing stressful events.

Excellent. And I will do a little segue here for some people who are not familiar with transcutaneous nerve stimulation. They do have a lot of devices out there that have been used for decades to help with pain and recovery from injury illnesses. A little bit in some training back, Russian training back, you know, decades ago, I don't know if they still do it or not. But what, what Dr. Kota Perest was talking about was the pads that you put on. And it's just, it has a little gel on it. It's not inserted in any way. It's a little pad that just like when you use one of those for muscle stimulation, it's a similar thing al, albeit much smaller pads than you're using. So the other question that kind of follows on with that is over the past again. Well, I guess around the time Haley was diagnosed, so about the past four or five years, using these clips with a tens unit that you can get offline, I won't say any particular place has been the big thing. And people are promoting it, but they're not talking about, is it safe? Does it actually work? Why would it work or why would it not work? They're just like, hey, go ahead and clip this to your ear and go for it. So what are your thoughts on all that?

Yeah, as you can move away from the surgical setting and move into wearables. The unfortunate thing is, once people start seeing that this is effective, you're actually able to help with various forms of disease. There are companies out there that are essentially trying to copy that and they look for faster routes to market. In most cases, if not all cases, these types of products are not regulated. They're not going through the FDA approval pathways. And so the device that I'm describing today is an FDA cleared device. So it has gone through clinical trials, it's developed the level of evidence to support that this is safe and effective. And it's gone through the review of the FDA to ensure that we can provide technology that's safe for the American people. So there is a big risk for people that are buying technology that is essentially stimulating your nervous system and treating disease. Because although it may be effective on top of that, it could actually alter your nervous system in ways that, that could be harmful for them. And additionally, you don't know what types of products they're putting in them. And could they cause skin irritation? Could they cause allergic reactions? Can they burn you? There's a lot of different areas that medical device companies have to be very careful about. And we spend a lot of time thinking on how to ensure our products are safe.

I know in some of the studies I read, and I remember back in the day when I had a tens unit for muscular issues, but again, in some of the current studies that I've read, they actually adjust and you're going to have to correct me on the terms the, the height of the wave as well as the frequency of the wave in order to tune in and specifically address issues. And these OTC machines don't do that. It's just kind of a one size fits all.

Yeah, that's exactly right. And there are a lot of different ways that you can change the waveform as you're describing. So electrical waveforms, you know, the frequency is how often it is firing, there's the duration, which is as you, as it sounds like how long you're going to be delivering something. There's even pulse width, right? Like, so each individual wave has a width to it, right? How wide is that wave? And that, that can actually have a lot of different attributes to the nervous system. And so we all, everybody that understands nerves and how they fire, they, they know they, they listen to frequencies, right? So some nerves will stimulate at lower frequencies, some nerves will stimulate, it will activate at higher frequencies. And then these different firing patterns can lead to different events in the, the brain. And so to your point, it's definitely not a one size fit all. You know, you may there, you know, there's always a hammer. A hammer is a great tool, but that doesn't necessarily mean it's going to, you know, fix all of your problems, not the tool for all projects. Right.

And going along with that, in some of your research you've talked about how the stimulation can also improve neuroplasticity. Do you want to touch on that real quick? What is neuroplasticity? And we're going to get into the neonatal thing in a study in a minute, which is just absolutely amazing. But with your stroke patients, you know, tell me a little bit about how, how it stimulating the autonomic nervous system can help with neuro. Neuroplasticity.

Sure, of course. So neuroplasticity is a. Another term that's actually widely used now. And boiling it down, just, you know, neuroplasticity is just your brain's ability to change. Right. And your brain is changing every day. You know, the second you drink your cup of coffee in the morning to the second that you go to bed, it's consistently changing. And even while you're sleeping, actually a lot of changes occurring. But, you know, the vagus nerve has been shown to be very effective at changing brain function in ways that can be very beneficial to people. In one area, which is this is research that I was doing earlier on when I was back at the university, this type of research was used to focus on using the vagus nerve to make your brain more aware of certain things that are happening. And so in the case of someone that is having, that had a stroke, they lost the ability to use their hand or they lost the move their arm and they go through physical rehab. And rehab is essentially a way of retraining your brain to use your arm again. But what we did with vagus nerve stimulation was quite unique in the sense that every time that they would use their arm, we would stimulate the vagus nerve to help the brain say, this is really important, you should focus on this. And the more times you did that, the brain would reorganize itself and put more brain cells, more neurons to pay attention to that task and essentially help rewire and regain function. And so you could take someone that has lost complete function and restore function to the arm over a few weeks to a few months now, in the sense of opioid withdrawal and addiction. I think it's a similar scenario, Dr. Snipes, in the sense that as patients Use opioids and substance of abuse for periods of time. The brain does change. They get less and less amount of dopamine. And so that means there's less of these neurons that are firing to help promote dopamine. And this is not good. Right. You want to have a good amount of dopamine. So, again, using neurostimulation, and we can talk more about this when we speak about the neonatal and some of the adult trials, Using neurostimulation to help your brain create more dopamine, again, is also a sense of neuroplasticity because you're changing the brain from what it was doing prior to trying it to say, no, you should develop more dopamine to help overcome these symptoms and hopefully overcome the disease over time.

Awesome. And, you know, I'm just thinking, as I hear you talking about people who have trauma and how is the vagus nerve and the autonomic nervous system involved with the amygdala? And a lot of people out there are familiar with the amygdala being sort of your fear processing place.

Yeah, it plays a big role. It definitely plays a big role. This, and this, this whole network in the brain, as you know, you know, especially the reward network. Right, Reward. I always call it the sixth sense. Right. In the sense that you have to have a very strong reward network to stay alive and to essentially keep yourself, you know, propagate, keep your species alive even. But when you're talking about the amygdala, you're right. The amygdala is an area in your brain that is responsible for fear. It's also very responsible for learning and memory. And so it plays a big factor in those components. But when you're talking about the vagus nerve and how it can play a role here, the vagus nerve has been shown to modulate. When I say modulate, that word means essentially change the activity of a certain structure in your body. In this case the amygdala, the vagus nerve has connections that can potentially help change the function of the amygdala. When someone is experiencing fear, and especially during opioid withdrawal, there's a lot of fear involved with that. The amygdala is firing at a very high rate. And so the vagus nerve has the ability, through autonomics, to help reduce that fear, reduce the firing rate in the brain that can essentially alleviate some of that fear. And that's when you start seeing your heart rate comes down, you start breathing a little bit slower, and then you come to a more calm State. And so, again, the autonomic nervous system is very powerful in the sense that it can help regulate a lot of these, you know, these symptoms that we experience.

Right, right. And like you were saying earlier, it's not one off and one on. It's more like. In my day, we called it a teeter totter, where you want to have this balance. And. And that's what we're really striving for. So let's move into one of my favorite studies that I read, the one that talked about neonatal opioid withdrawal syndrome and the use of. Well, I guess start out by telling me a little bit about Sparrow and how it's different than the OTC things and, you know, a little bit about that trigeminal activity, and then we'll talk about the neonatal opioid withdrawal.

Sure, yeah. So the Sparrow Ascent device is something. Is. Is a wearable neurostimulation device that has an FDA clearance. And. And this device has a unique capability in the sense that one, it's completely non, invasive, as you noted. It has hydrogels, these little pads that essentially are placed on and around your ear. And two of these pads are specifically targeting the auricular branch of the vagus nerve, which is exactly what it sounds like. It's a branch of your vagus nerve, and it's also targeting right in front of your ear. So next to your tragus, that little flap and your sideburn, there's a nerve under there called the auricular temporal nerve. And that's a big name, but that's essentially a branch of your trigeminal nerve. And it. The Sparrow is very unique in the sense that it's the only device that stimulates two cranial nerves simultaneously. And so the vagus is a trigeminal, is a cranial nerve, and the trigeminal is also a cranial nerve. And it can stimulate both of them at the same time. And why we're doing that is that, as my CEO and co founder says at Spark, this is a one plus one equals three scenario. Right. And we believe that by stimulating both nerves, this is synergistic, they're working together to help alleviate whether it's stress, help alleviate fear, help alleviate symptoms of withdrawal, which is what the device is indicated for.

And when people experience pain, like in opioid withdrawal or some of those others, that triggers that autonomic nervous system, that triggers that sympathetic response, because our body says pain means something ain't right. And so even if somebody's not Identifying necessarily as fear, we recognize that during the withdrawal period, it is a highly stressful event for the entire body and it's going to be triggering that system. So with, with Sparrow and using the stimulation of the vagus nerve and the trigeminal nerve, what did you find when you were working with, did the trial with the neonatal opioid withdrawal syndrome babies?

Well, yeah, we, we've. Our first clinical trial that we ran. And so, so nows is, is a big problem in the United States. Right. So neonatal opioid withdrawal, short for nows. There's roughly about 40 to 50,000 babies every year that are born with an opioid dependency. And this is due to the mother essentially taking an opioid, whether that's for pain relief or that's illicit use. And unfortunately, when babies are born, they are dependent and the clock starts ticking as soon as they cut the umbilical cord. And so within 24 to 48 hours, they start developing opioid withdrawal symptoms. In some cases, this can be treated by just consoling them. There's a common method out there called eat, sleep console. A lot of NICUs use across the nation. NICUs are neonatal intensive care units. And it can be effective where they don't need to give them any medication. In certain scenarios, the withdrawal symptoms are severe enough where they require medication. And a lot of times they give them morphine, oral morphine, which is an opioid. And this makes sense. Someone that's experiencing withdrawal from an opioids, if you give them an opioid, the withdrawal symptoms go away. The problem with oral morphine is that it can be toxic to babies. Babies are young, especially now as babies. A lot of them are premature or preterm and their livers are not as developed, so it can be toxic for them. There's also neurotoxicity, so it can lead to changes in their brain that can have lifelong consequences. And so when we looked at this at Spark, we said, is there a way that we could use our FDA clear device for patients with adult opioid withdrawal, which has shown to be very effective. Can we miniaturize the earpiece? So we took an earpiece that fits an adult and we shrunk it down to fit a baby's ear, which is super tiny. That was the idea. And we got this funded by the nih, the National Institute of Health, specifically nida. And we received some money to run a first in human study. And this was the youngest population to ever receive neurostimulation and so we started testing this idea where we delivered stimulation to them four times a day right before they received their morphine dose. And what we saw was that there is a scale they use in the NICU called the Finnegan Scale. It measures how much withdrawal you have or how much withdrawal the babies have. And we saw that the numbers were going down very quickly. And that same scale is used to determine how much morphine these infants are required to have. As you would imagine, the morphine numbers were also coming down. And so that first study, the national average of babies that have nows and receiving morphine is around 20 to 25 days. In our study, where we looked at using neurostimulation as a way to reduce withdrawal for infants, it was around seven days that they were receiving morphine. So this was really eye opening to us. It wasn't a controlled trial. Everyone received the same treatment. But it led to more questions. Could this device be useful for treating babies with NAOs? And the answer was yes, very clearly. That then led to a much larger clinical trial that's happening right now, which is what's called a randomized controlled study across several different university academic hospitals across the US and that.

That's just amazing. When I was a bit younger, one of the programs that I supervised was a mother baby addiction recovery unit. And the majority of our patients at that point in time were on opioids of some sort. And as you well know, you can't just discontinue opioids in a pregnant woman. That's, that's could cause the baby to die. So they have to stay on the opioids until they give birth. And which is why, because a lot of people are like, well, why didn't the mom just quit using? Well, it ain't that easy. But we also have seen a lot of research on adverse childhood experiences and the pain that the infants experience and the stress that the infants experience when they're dead. Detoxing from the opioids can be incredible. And as you mentioned earlier, basically the more times you attend to a memory pathway or attend to a pathway, the stronger it becomes. And it's kind of like a rope. Every time you add another strand to it, it becomes stronger. And instead of allowing that rope between detox and pain to become stronger, what you're doing with the sparrow is strengthening that attachment with the paras. Parasympathetic nervous system and really decreasing the pain and the anxiety. If you believe that infants can have. Have anxiety, I do in, in the infant. And my sense is by Doing that, you're also reducing neurotransmitters like glutamate that we know in high levels can be neurotoxic. So there's just so many benefits. And when baby can go home, there's a lot less irritability and they're able to be discharged sooner, which I know insurance companies probably, probably like. So there's financial benefits, but there are so many health benefits to the infants. It was just incredible to me because you look at these babies that are just in so much pain and so uncomfortable and feels so bad and there's nothing you can do. You know how it is when, when your child is sick, even with an ear infection, no matter how much you talk to a two week old, they don't understand that you're trying to make it better. So this is, this is just fabulous. And using the Finnegan Scale, it's an objective scale, it's looking at heart rate, blood pressure, right. Respiration rate. So it's not just a caregiver or a nurse going, well, he doesn't seem to be as stressed. So we do have a lot of objective proof that hey, this works and look how much faster it works. And I wish it worked that fast on adults. But my sense is, and correct me if I'm wrong, since infants have so much more neuroplasticity going on, their brains can rework themselves easier than maybe the adult brain.

Absolutely, yes, that's, that's a great statement. You know, and you know, definitely babies brains are much more plastic than adult brains in some, in some cases, right, they're, they're being exposed to so many different stimuli, right? Sights, sounds, smells, people everywhere. Just, you know, especially in a hospital setting that can be quite, in some cases, can be quite traumatic for babies. You know, a lot of times just putting them in a more quiet, more dim lidded room can be soothing to them because they're already experiencing so much in terms of their withdrawal. You want to be able to minimize that as much as possible. But yeah, in terms of how babies are experiencing withdrawal and then also in the sense that how does that lead to lifelong consequences? To your point, that's a really interesting topic of research right now where when you look at now they think of, it's just, it's while they're in the hospital and then once they, they get rid of the withdrawal, they're good. It's not the case. It, it follows them for years. In some cases you'll see it in the reports at school where they have trouble at school. In terms of academic, their grades are there are below average. Some kids develop PTSD anxiety at higher levels because of the experience they had at such a young age. And in some cases, the research has been showing now that they're more predisposed to substance use disorder because they were experienced to a substance of abuse or substance of, in this case, an opioid at such an early age that that can change the way the brain was functioning at that time. That could lead to a higher chance that they could have a substance use disorder down the road. So it's makes sense. This is where neuroplasticity can become a slippery slope and you have to be very careful about how you view it.

Well, as you're talking, it makes me remember my son was a micro preemie and he was in the hospital for about six weeks and, and when he came home, you know, normally kids need quiet to sleep. And it was, if it was too quiet, he would be restless and he wouldn't sleep very long. So when he was napping was when I was vacuuming because he was so used to the beeping and the noise and the commotion in the NICU when he first came home. Now eventually we weaned him down off of that. But, you know, to your point, I'm wondering, and, and I know, you know, we're going to talk about other things right now, but for any preemie in the nicu, because when he was first born, we weren't allowed to touch him because it was over stimulating. And then once we were allowed to touch him, it was only in the, in the incubator and that's stressful to them. So I'm wondering with just any, any old premature infant, it seems like that would be a, to help them regulate their autonomic response when they are in the nicu, but that's just my mind wandering. So tell me a little bit about some of these other studies, particularly the Tandem and the Restore study.

Yeah. So Tandem and Restore are two very large clinical trials that are happening right now. The Restore clinical trial is in patients that have opioid use disorder. This is really a continuation of our first clinical trial which helped us get FDA clearance for the device. But that study was only. We only looked at a very short amount of time. It was inpatient treatment for opioid use disorder. And we were trying to see if we could reduce opioid withdrawal symptoms within five days that we published it. The data looked really nice. We were able to reduce symptoms within 30 minutes to one hour by 50% which was pretty remarkable. It actually in some cases is faster than some of the other treatments such as Suboxone and methadone in terms of withdrawal mitigation or withdrawal reduction. Restore is a more long term study. So these are patients again with opioid use disorder. They come in for inpatient treatment. We're partnered with Hazelton Betty Ford foundation in Minnesota and in California, we also have partners called Cadenzia, you may have heard of them, they're more known in the Pennsylvania northeast area. The patients come in for a seven day inpatient detox. We treat their withdrawal symptoms using neurostimulation and then they go to outpatient treatment, which is where the patients are then put on a medication called Vivitrol. And you know, Vivitrol, I'm sure very well. It's a, it's an opioid antagonist medication, blocks the opioid receptor. And so that in the case that if you wanted to use an opioid, you really wouldn't get much of the pain effect or the euphoric effect from it. And so it's very effective medication in terms of opioid cessation and opioid long term treatment. But the problem with Vivitrol is not a lot of patients adhere to it. They don't stay on it for a long period of time. And so that can lead to relapse when they come off. And so what we wanted to do is to see can the device help patients stay on Vivitrol longer so that, that way they can remain abstinent and then they can, the longer you remain abstinence, that the longer your chances or the better the improvement of the chance that you won't relapse, which is really important obviously for addiction. And so the study is really amazing. It actually will end this year. It's about, it's almost will be about three years that we've been in this study and we're hoping to share data next year showing that it can help improve cravings, it can reduce withdrawal symptoms, it can help with treatment retention, essentially keeping you in the game. Right. And hopefully we show that it can kind of stem the relapse rate. That's, that's kind of the overall drive objective of the study.

And you had mentioned earlier that you're looking, you're either doing a study now or getting ready to do a study on alcohol use. And I know Vivitrol is used in some clinics for people who are addicted to alcohol. So it seems like, yeah, it's a.

Question we get all the time. You know, your device works great for opioid withdrawal, but does it help with XYZ drug? Right. The number one question we get outside of opioids, does it help with alcohol withdrawal? And as you know, alcohol withdrawal is very different than opioid withdrawal. And the main difference is that alcohol withdrawal can be lethal. You can actually have seizures. You can die from it. It can be really catastrophic if it's not properly treated. And so we really looked at it from that perspective. We also looked at it from the side of there's just a lot more patients that have alcohol use disorder. Right. When you look at treatment facilities, usually 70 to 80% in treatment are alcohol use disorder patients or alcoholics. There are numbers there that we saw. Well, we should really be focusing on this population. So, yeah, we're starting a study later this year with the Menninger Clinic in Houston, Texas, and Baylor College of Medicine and looking at how we can help patients overcome alcohol withdrawal using neurostimulation. Also doing some brain imaging pre and post to understand what's the relationship between the orbital frontal cortex and also the striatum and dopamine, and how we're able to help rebalance that using neurostimulation, which is actually more in line with that tandem study. And I'll talk about that in a minute.

Yeah, okay, go ahead and tell me more about that tandem study.

Yeah, so tandem is a really unique study in the fact that we're looking at the mechanism of action. And so, you know, Dr. Snyce, we've been talking a lot about the autonomic nervous system today and, and how vagus nerve stimulation can restore that balance. Well, the other mechanism that we're very interested in that, that we believe our device is able to do by stimulating the vagus and the trigeminal nerve is that it can help release what are called endogenous opioids. Right. This is your body's natural produce these on an everyday basis. They're also known as endorphins. And so endorphins are these. They're pleasure chemicals. Right. So as you release endorphins when you're happy or excited about something, or if you're playing again, and I get the Olympic analogy again, you can obviously tell how much Olympics I watched. These are really powerful chemicals that when they bind, they bind to the same receptors in the brain that opioids bind to. And the consequence of when an endorphin binds to an opioid receptor is it releases dopamine. And so the Tandem study is a brain imaging trial. We're going to have almost 300 people in this study where we're examining their brains. We're looking at their brains with what's called fmri. There's three different studies within it. One is just looking at what does the brain do when you stimulate these nerves? What areas light up? And so we look at the different brain patterns that are lighting up with vagus and trigeminal nerve stimulation. The other aspect is looking at where are these endogenous opioids binding? Are they binding to the mu receptor? So we're looking at specific receptors in the brain to understand are we changing these receptors, is that leading to more dopamine and is that beneficial for opioid withdrawal? And this is all in healthy people. But then we pivot over to patients that have chronic pain, that are constantly. That are taking opioids for very long periods of time. We look at, can we use the device to help reduce their withdrawal as they come off of the opioid, and can we reduce their pain? And then we're doing brain imaging pre and post before the taper and then after the tapering off the opioid. It's a very large study. It's going to take five years. We're in year three right now. And by the end of it, I think we'll have a really good understanding of how neurostimulation helps reduce pain and how it helps reduce opioid withdrawal, especially in patients that have chronic pain.

So, yeah, and I'm thinking, and again, correct me if I'm wrong, you're the expert with the frequency with which trauma occurs with addiction, whether it predated the addiction or it occurred during the addiction. I'm wondering if using neurostimulation might be something that somebody with cptsd, for example, might be able to continue using after they've withdrawn from their drug of abuse, their opioid or whatever it is, because we know that people with chronic CPTSD or PTSD do struggle with emotional dysregulation and, and really helping to sort of reprogram the autonomic nervous system over time in order to empower them to feel safer in their own skin.

Absolutely, yes. You know, and, you know, I think addiction is a. Is a masquerading disease in the sense that it's a mask. Right. So just because you get through opioid withdrawal. Right. Which is really the biggest hurdle to come off of an opioid and most substances, well, that trauma is still there. Right. We didn't cure the trauma that led to the drug dependency, that led to an addiction that's still present. And so what you. What you see, and as you've seen this in your patients, is that when they get through the withdrawal and even in the very short phase after that, just a few weeks, that's when the ptsd, the depression, some of these life triggers start coming back that lead to episodes. Right. And which can help. Which can enhance their ability to relapse, which is really the most crucial point. And so I do think that neurostimulator, and there's studies that have been done on this. There are studies that are focused on just stimulating the earth and helping patients with ptsd. We have a study right now where it's OUD and PTSD at the University of Cincinnati, where we're looking at using neurostimulation for three months, so 12 weeks. And understanding. Can it help patients reduce PTSD through autonomic nervous system enhancement? And also can it help them maintain, in this case, they're on Suboxone, can they stay on Suboxone, which is an opioid medication to help reduce cravings and withdrawal and to improve the chances that they don't relapse, can they maintain? So, yeah, neurostimulation has really been framed in this way of kind of like as a. A crutch. Right. It really kind of helps promote other treatments. So whether you're on certain medications, it can enhance their ability to be more effective. In some cases, it's a standalone treatment. It can reduce things that you can reduce the PTSD symptoms, it can reduce the withdrawal, and that. That can be very beneficial in both of those camps.

And again, I want to point out to the viewers that we're talking about a medical device that's specifically tuned for a particular problem. We're not talking about just getting any old TENS unit and trying to clip it to your. To your ear. I have a lot of patients who, when they go on antidepressants, for example, they'll go on one and it won't be a good fit.

And.

And they'll assume that all other antidepressants are not going to work. And so one of the dangers, aside from the fact that you could actually hurt your nervous system, one of the dangers of people just using something over the counter is that they may try it, it may not work, and then something that actually could have been a really awesome tool for them, they may have already discounted as being not helpful for them.

You're exactly right. And the Device that we're talking about today, as you mentioned, is specifically tuned for opioid withdrawal. And everything we've been talking about today has been clinical trials. So this is looking at other indication, other areas that it can help with. And in that case the device is being used differently. Might be longer stimulation duration where you're stimulating for longer periods of time during the day. As you mentioned earlier, we're changing the frequency, right. We're looking at how the nerves listen to this type of stimulation. Are they more receptive to it, are they less receptive to it and does that lead to better outcomes? So yeah, we really have to be, as a scientist, you have to be, be really careful with saying that. Oh just every, every type of stimulation pattern will work for all different types of diseases. I wish it worked that way.

Right.

But in this case it's unfortunately not the case. But that's why, that's why I come to work every day. That's why I come and I, and I get to have fun thinking about this and thinking about how different parameters will help with different diseases.

Right. And it's again, it's just so mindboggling and amazing that we may have something that's non pharmacological that can help with so many different things. And we know, I mean even the CDC says that something like 80% of our physical and mental health conditions are stress related. So we know that there's something going on with a dysfunction in that autonomic nervous system. I know a lot of people watching right now are struggling with, you know, the things that we talked about, you know, the, the whole basket. How can people access Sparrow now?

Yeah, it's so it's, it's actually quite easy. You know, Sparrow is available in certain different ways. One is if you're going to a treatment facility, you know, the physician there can be able to prescribe it. We're over, we're in over two dozen treatment facilities in the whole, in the whole United States. But I would say the most readily way for readily accessible way for patients to receive Sparrow is just go to sparrowrx.com they can go there, they can fill out a few questions. It'll determine if they're a good candidate for the device. And then we have a telehealth partner that will then schedule an appointment with the patient when they meet with a physician online like a Teladoc. And if the physician believes that they'd be a great candidate, they get prescribed the device and we can ship the device directly to their home for treatment.

And if somebody is, for example, getting ready to go through addiction recovery, if they go to Sparrow Rx, will they be able to find, Will somebody there be able to tell them what treatment centers they may be able to go to in order to benefit from this?

Absolutely. And so we have all the centers listed on the website. There's also a way for them to chat with someone at Spark and if they have questions regarding where, where they can get the device. But again, with telehealth, we're available in, I think, all 50 states. We may be at 48 states, but they have the ability to get it via telehealth and they can receive the device directly at their home. And we have a lot of really great instructional videos that they can watch on how to use the system and get educated on how neurostimulation can help them.

Perfect. And just a little bit of an aside in terms of Medicaid and Medicare. Are they covering it yet or.

We do not have reimbursement yet. This is something that we are pushing on very hard right now with Medicare, with CMS and some of the private insurance companies. I do think we will have that hopefully by next year. But as of right now, the device is pretty much cash pay. We have some payment plans that are available to help patients have better accessibility to the device.

Right. And that's awesome. So even if somebody can't afford it right now, they can see that in the near future they may be able to access the device and use that. Is there any way to, for people to enroll in clinical trials?

Absolutely, yeah. Clinical trials. We have, you know, I oversee over a dozen clinical trials right now that are involved either in addiction or other forms of mental health. And they're across the U.S. they, they can find them on our website. You can also search for them just on Google, put in, you know, wearable neurostimulation and X, you know, indication or X condition and see if they pop up and then they can see if they qualify for these studies.

Okay. So for those of you who are unfamiliar with a clinical trial, the cost is covered. So during the trial period for the device, my daughter, when she was, she went through the Vanderbilt POTS program clinical trial and was able to get a lot of help and guidance through that. So I think clinical trials are wonderful not only because they help the patient, they make it more financially accessible for the patient and it contributes to our body of knowledge that can eventually help people. People in the future.

Yeah. And I'll state if anyone has opioid use disorder and is an adult listening to this, you know, and you're in the Minneapolis area or in California, near San Diego or in the Baltimore area, there's a large test of restore trial and you can see if you qualify for that and if you have chronic pain. Down in the Galveston, Houston area, we have studies down there as well if they're interested in partaking.

Perfect. Perfect. Is there anything else you would like to add?

Well, I'm just. I was just very excited to be on your podcast today. This is an amazing opportunity for me, and you gave me a great platform to be able to talk about wearable neurostimulation and how it's helping, you know, so many different Americans suffering from addiction. And so, yeah, I just want to thank you so much for this opportunity.

Well, I appreciate you being on. I know I always love talking neuroscience and. But obviously I'm not the expert on it, so I enjoyed having an expert here to educate us. So, Dr. Kota Perez, thank you for being here, and I will hopefully talk to you in the near future.

Thank you so much, Dr. Snipes.

Thank you. Bye. Bye.