syringes and vials

Preventing opioid addiction in pain management with dopamine co-treatment

 

What if there was a way to deliver on the painkilling potential of opioids while reducing the likelihood of addiction?

 

Dr Stefan Clemens and Dr Kori Brewers’ work at East Carolina University could mark a turning point in pain management and drug addiction.

 

Read the original article: https://doi.org/10.1016/j.pbb.2020.172935

 

Image credit: panpilia paipa/Shutterstock

 

Transcript

 

The following is an automatically generated transcript.

 

00:00:10 Will

Hello this is Will. Welcome to researchpod.

 

00:00:14 Will

Opium has been used as pain relief for somewhere in the region of 5000 years.

 

00:00:19 Will

The current crisis facing global health systems has its roots in only the last 100 years, with the development, prescription and highly habit forming tendencies of synthetic opioids such as heroin, codeine and fentanyl.

 

00:00:32 Will

Nonetheless, the usefulness of opioids in treating severe pain has yet to be matched. So what if there were a way to deliver on their painkilling potential while reducing the likelihood of addiction?

 

00:00:44 Will

This is the work of Doctor Stefan Clemens and Kori Brewer at East Carolina University, whose separate research powers converged 10 years ago and today could mark a turning point in pain management and drug addiction.

 

00:01:02 Will

Kori, Stefan hello.

 

00:01:04 Dr Brewer

Hey well, how are you?

 

00:01:05 Will

I’m keeping well and thank you both for joining.

 

00:01:07 Will

Us today by way of introduction for everyone listening at home.

 

00:01:11 Will

As wondering if we could hear a little bit about yourselves and how you’ve taken different paths to end up working on this project together. Kori, if we could start with you.

 

00:01:20 Dr Brewer

I have a PhD in Physiology. Actually got it here at East Carolina University, where I’m currently on faculty.

 

00:01:27 Dr Brewer

So I had a a close friend in college.

 

00:01:31 Dr Brewer

Who had suffered a spinal cord injury, and.

 

00:01:35 Dr Brewer

I think the thing most people think about when they think about spinal cord injury is the paralysis and the loss of mobility.

 

00:01:41 Dr Brewer

But one of the things that he complained about most frequently was this pain from parts of the body where he quote couldn’t feel anything, right?

 

00:01:49 Dr Brewer

So if you touched his legs, he couldn’t feel you touch them, but he would tell you my legs are on fire. It feels like.

 

00:01:55 Dr Brewer

Someone squeezing my legs. This is what’s keeping me up.

 

00:01:57 Dr Brewer

At night I would.

 

00:01:58 Dr Brewer

Rather trade my mobility permanently if I could get rid of these sensations.

 

00:02:04 Dr Brewer

So when I started Graduate School, I focused on neuroscience with that idea of kind of sensory systems, and how sensory systems respond to injury.

 

00:02:15 Dr Brewer

I did a.

 

00:02:15 Dr Brewer

Concentration, neuroscience and after that I went to do postdoctoral training down at the Miami project, which is a paralysis research centre at University of Miami.

 

00:02:27 Dr Brewer

Down there I started working on the problem of neuropathic pain after spinal cord injury and did all my training in trying to identify mechanisms by which people develop pain after spinal cord injury and potential interventions for those conditions, and so that kind of focused my pre faculty.

 

00:02:48 Dr Brewer

And so luckily, when I came back to EC with faculty likes a few years later, Steven came on, and while I had continued working on kind of mechanisms of pain after spinal cord injury and potential ways to intervene using animal models, when Steven came on, I had started looking at the role of opioids in managing.

 

00:03:08 Dr Brewer

Spinal cord injury, pain and the fact that they didn’t work well.

 

00:03:12 Dr Brewer

That there are a lot of problems even back then with them. And so when Steven came on with his knowledge of the dopamine system, we started recognising the overlap between the opioid system and the dopamine system and how we might be able to exploit one versus the other to get the end result that I was interested in, which was analgesia.

 

00:03:32 Dr Brewer

Or pain relief.

 

00:03:35 Dr Clemens

Yeah so hi, my name is Stefan Clemens and I’ve had a bit of more circuitous route to get to East Carolina.

 

00:03:43 Dr Clemens

I have a masters in biology from the University of Minister in Germany, a pH D from the University of Bordeaux in France.

 

00:03:51 Dr Clemens

And in both cases I was working on understanding modulation of neural circuits and how it comes at a fixed wired circuit can produce multiple behaviours.

 

00:04:03 Dr Clemens

I was always challenged in understanding how this behaviour occurs and when I got into my post docs in particular, I was looking at individual entities in the nervous system that could control locomotion or locomotor aspects, and we could identify individual neurons on how they behave and change as a function.

 

00:04:23 Dr Clemens

Of something being added to that in terms of dopaminergic or other neuromodulators, and they’re called. I did. Then two postdocs in Atlanta, one at Georgia State University.

 

00:04:36 Dr Clemens

And one at Emory University School of Medicine, where then finally came from an invertebrate background to start working on rodents and mice.

 

00:04:46 Dr Clemens

Spinal cord function and the role of dopamine in particular, and I was looking at how doubling shapes modulates spinal reflexes from there on with the work of advisor there, I developed a model of restless leg syndrome that was based on a dysfunction of programming in the spinal cord.

 

00:05:05 Dr Clemens

And when I joined East Carolina University in 2008, about 10 years later than Kori did, I came then from this angle of trying to understand dopamine function in the spinal cord and when we sat together and talked in hallway conversations core and I chatted about how her.

 

00:05:25 Dr Clemens

Animals after spinal cord injury showed similar responses to the animals I had brought with me from Emory University.

 

00:05:34 Dr Clemens

And so she had this well established line with spinal cord injury and the chronic pain, and the opioids not working.

 

00:05:41 Dr Clemens

And she at some point simply asked, well, why don’t you test the opioids that we use on your dopamine model and it turned out they didn’t work?

 

00:05:53 Dr Clemens

And so that was kind of wow. This is the the moment where we found.

 

00:05:58 Dr Clemens

Perhaps we have now an angle if we compliment rather than destroyed and stop him. And partly if you enhance it.

 

00:06:07 Dr Clemens

Improve pain outcomes overall and perhaps even in chronic pain condition.

 

00:06:17 Will

What is pain? That’s probably a pretty big question. There’s lots of different types of pain, different sources, but how do we on a physical and neurochemical basis, experience pain?

 

00:06:30 Dr Brewer

So there is an official definition of pain that’s put out by the International Association for the Study of Pain, which I probably get wrong.

 

00:06:37 Dr Brewer

They don’t have written down in front of me, but it basically says it’s a complex sensory and emotional event that is associated with tissue damage.

 

00:06:47 Dr Brewer

Or potential tissue damage, or anything that is described by a patient in those terms. And so when they try to put that in lay terms, what they say is pain is whatever the person experiencing says it is when they say it’s happening, and I think that what that underscores is the fact that it is an extremely complex.

 

00:07:07 Dr Brewer

Event, and because it’s difficult to separate.

 

00:07:10 Dr Brewer

Actually, the the physical biochemical part of pain from the emotional and affective part of pain makes it a really challenging problem.

 

00:07:23 Dr Brewer

And so two different people having the exact same experience will describe the pain completely differently. One person may say it is painful.

 

00:07:32 Dr Brewer

Another person may not because it’s influenced by your history with pain by your background, by your personality. So it is a difficult, complex problem.

 

00:07:43 Dr Brewer

Now there are some underlying.

 

00:07:46 Dr Brewer

Biological processes that we know contribute to the perception or generation of pain in all people, and so that’s where we try to target 1st. And then you can have to layer on kind of considering the harder to define aspects of pain. Like someone experience someone emotional.

 

00:08:06 Dr Brewer

Another thing.

 

00:08:08 Dr Clemens

I think pain is from my background to be too complex and So what I’m trying to get to all those.

 

00:08:16 Dr Clemens

I gotta call nociceptive pathways that leads to pain so you have pathways rising that say when they arrive at the brain level or this is painful.

 

00:08:28 Dr Clemens

But they are already controlled at different levels of the nervous system, in particular, the spinal cord in our studies where we can look at identified neuron populations, how they talk to each.

 

00:08:40 Dr Clemens

Pain is extremely complex with Toy pointed out.

 

00:08:44 Dr Clemens

Then we try to access that pain.

 

00:08:49 Dr Clemens

Pathways prior to even becoming pain and looking at these paths with it lead to the emotional aspect of pain, and that’s where our models have strengthened showed promise.

 

00:09:03 Dr Brewer

I like that.

 

00:09:03 Dr Brewer

Distinction, actually, you can think of pain as how the brain interprets a particular type of sensory input.

 

00:09:11 Dr Brewer

So we know the neurons involved and the circuits involved in transmitting pain. So the experience of pain is how an individual interprets the activity through those systems.

 

00:09:22 Dr Brewer

So if we can control those systems that transmit the pain we hope to intervene before those signals get to the point of being to the brain where they can be interpreted as pain.

 

00:09:32 Dr Brewer

You hope that any pain treatment is directed towards the mechanism of that pain, so we know that if someone sprains their ankle.

 

00:09:42 Dr Brewer

It’s very painful and that pain is generated from an inflammatory reaction that is started in the injured tissue. So drugs that target that inflammation should effectively combat pain under those conditions.

 

00:09:57 Dr Brewer

I would say the broadest class of drugs are targeted inflammation so the non steroidal anti inflammatories steroids themselves are great pain medications because they reduce inflammation.

 

00:10:09 Dr Brewer

Several years ago there were the Cox 2 inhibitors that came out.

 

00:10:13 Dr Brewer

For a while.

 

00:10:14 Dr Brewer

But again, they targeted a specific enzyme in that inflammatory pathway.

 

00:10:19 Dr Brewer

So all these had kind of a similar mechanism of action, just targeting different parts of that inflammatory pathway. So that’s probably the biggest class of pain drugs.

 

00:10:28 Dr Brewer

That are commonly used.

 

00:10:31 Dr Brewer

So opioids are a little bit different than the NSAIDS typically would only see them use with the moderate to severe pain, and they’re not necessarily targeted towards the underlying mechanism of the pain, but what they do is prevent the neurons that carry the pain information to the brain from being activated.

 

00:10:52 Dr Brewer

So if you would have an acute injury or surgery, opioids might be given.

 

00:10:57 Dr Brewer

During that recovery period, to prevent the person from experiencing the pain, the problem comes in in that those same drugs also activate areas of the brain associated with pleasure or reward.

 

00:11:10 Dr Brewer

So you might you know a side effect is that even when the injury has healed, the pain should have subsided.

 

00:11:18 Dr Brewer

A patient might want to continue to take those drugs for that pleasure, or that kind of euphoria that they got when they.

 

00:11:24 Dr Brewer

Were taking them for.

 

00:11:26 Dr Brewer

The pain.

 

00:11:27 Dr Brewer

And so clearly, that’s when we transition into a side effect that we don’t want to see.

 

00:11:31 Dr Brewer

With these drugs.

 

00:11:33 Will

So when it comes to opioids and their prescription for severe and intense and long lasting pain.

 

00:11:41 Will

At what point does that change from being a treatment to a problem?

 

00:11:46 Will

Thinking of some of the opioid problems that society is facing broadly and then how that is leading, perhaps even challenging treatment options for pain management. Coming at things from your angle.

 

00:12:01 Dr Brewer

Well, I think the problem comes in the fact that.

 

00:12:05 Dr Brewer

Really, there have been no studies of long term effectiveness of opioids, so there’s lots of studies acutely, and they know that they’re great.

 

00:12:15 Dr Brewer

So I think if you’re in a controlled setting, someone comes the emergency department and they need.

 

00:12:20 Dr Brewer

Severe pain control. You know they’re they’re great there.

 

00:12:24 Dr Brewer

But there really has not been any controlled scientific studies of their effectiveness when used chronically, but because they were so effective acutely.

 

00:12:34 Dr Brewer

They said, Oh well, you know we’ll lay them out for people to use for chronic long term pain and what’s developed because of that is what everyone talks about currently as the as the.

 

00:12:45 Dr Brewer

Right?

 

00:12:46 Dr Brewer

They have severe side effects which include propensity to create addiction pretty readily. The need to escalate doses over time when people become tolerant to the effects of the drug respiratory depression. So all types of things that can put people at risk and then of course accidental overdoses.

 

00:13:06 Dr Brewer

Those people try to increase that dose to a dose that provides effective analgesia for pain. So I guess what we’ve learned is even opioids may not control.

 

00:13:17 Dr Brewer

Chronic pain over time.

 

00:13:20 Dr Brewer

When they’re used that way, they can create a host of these unwanted side effects.

 

00:13:27 Dr Brewer

Now I want to temper that by saying I am not a clinician right. I’m not a physician, so I’m not prescribing opioids or that type of thing.

 

00:13:33 Dr Brewer

I’m talking about this in terms of the research behind them and what we know on a policy level.

 

00:13:40 Dr Clemens

And to come back to the point well about the when do we think it might actually go loses efficacy?

 

00:13:48 Dr Clemens

I think what Kori just said is the key point is, as soon as there is a need to increase the dose.

 

00:13:55 Dr Clemens

That might be the trigger point. When the alarm bells should go off.

 

00:14:00 Dr Clemens

That it’s no longer a chronic treatment, and this is now on the verge of becoming or something that is no longer effective. So we increase the dose and then comes all the subsequent problems that caused this.

 

00:14:14 Dr Clemens

So I would probably start again with the clinical trial that we have initiated.

 

00:14:19 Dr Clemens

We were working on two parallel systems, Kori and I. She was working on the spinal cord pathways that are affected by spinal cord injury and I was looking at possible spinal cord mechanisms that could explain the symptomatology in restless leg syndrome and.

 

00:14:40 Dr Clemens

Restless Leg syndrome is commonly treated with a certain set of dopaminergic synapse lately, and the efficacy is layer and works well.

 

00:14:48 Dr Clemens

And we have based this genetically modified animal model as the result out of that that was missing this particular.

 

00:14:57 Dr Clemens

Molecule to process the dopamine or the dopaminergic. Kori had been using opioids with

 

00:15:06 Dr Clemens

Success in her injury animals. The restless Leg syndrome model that we had at the time and the spinal cord injury model showed.

 

00:15:16 Dr Clemens

Changes in the spinal cord behaviour span got immediate behaviour in reflexes, So what we were doing with the testing essentially how sensitive are the animals to a painful stimulus?

 

00:15:29 Dr Clemens

In spinal cord, injured animals showed increased excitability, as did our restless leg syndrome animals, so they showed philanthropically a similar effect.

 

00:15:42 Dr Clemens

And then it was simply really OK calling you a weakness. Opioids, we have this programming model.

 

00:15:49 Dr Clemens

Let’s try if the opioids work. Actually in our model or not. That was simply the curiosity question and it turned out that in this animal model for restless leg syndrome.

 

00:16:02 Dr Clemens

They were not working.

 

00:16:03 Dr Clemens

And that’s part. That’s the thought. Well, so if the dopamine pathway is compromised at the spinal cord level, again we were looking at the system.

 

00:16:13 Dr Clemens

Not the pain per southeast, but the neural circuits if you will, that are at the origin of the pathways that signal to the brain what’s going on in spinal cord. We found that both animal types showed a similar responsiveness or lack of responsiveness to.

 

00:16:32 Dr Clemens

The opioids

 

00:16:33 Dr Clemens

And so suddenly we had.

 

00:16:35 Dr Clemens

The injury model and we had a mechanism. A potential mechanism by which the opioids were not working properly.

 

00:16:45 Dr Clemens

And so we had stuff, I mean knockout as we call it for a specific subtype of the receptors.

 

00:16:53 Dr Clemens

Instead of knocking out this receptor, if we now use a drug that is targeting this particular pathway.

 

00:17:02 Dr Clemens

Shouldn’t that improve the outcomes even in the injured animal?

 

00:17:07 Dr Clemens

And that is what we found out. We used compounds that are clinically approved for different diseases like Parkinson’s and even for us with legs in the spinal cord. Injured model in conjunction with the opioids.

 

00:17:22 Dr Clemens

And suddenly animals that had not responded previously were responding to the analgesic effect.

 

00:17:32 Will

What is blocking what their what are the atomic details to explain why this is happening?

 

00:17:39 Dr Clemens

So morphine is supposed to be working through smoking receptor, in particular the receptor subtype, called New Oprah receptor, and Kori knows much more about that, while the dopaminergic that we have been using work through a pathway emitted by a dopamine 3 receptors.

 

00:17:59 Dr Clemens

Both of these.

 

00:18:01 Dr Clemens

A molecule sit in the membrane of the neuron and both inhibit a similar intracellular pathway that modifies the signalling.

 

00:18:13 Dr Clemens

Uh, with engineering, how molecules talk to each other and how these molecules in turn control the excitability of that neuron.

 

00:18:23 Dr Clemens

So if you have a drug like the opioid, attaching to a thread septer it reduces the excitability in this host synaptic.

 

00:18:34 Dr Clemens

And similar and the same pathway for the dopaminergic.

 

00:18:39 Dr Clemens

So we think there’s a convergence of intracellular pathways that we simply tap into that have been overlooked so far.

 

00:18:48 Dr Brewer

The point that I think is interesting about the mechanism is one thing we’ve learned in our spinal cord injury model.

 

00:18:53 Dr Brewer

Is that injury induces changes in those MU opioid receptors on the cell membrane so that they become phosphorylated and once they’re phosphorylated then they can no longer bind a ligands. So it’s basically like taking them functional receptors.

 

00:19:08 Dr Brewer

Away, so we create an injury. Those new receptors become phosphorylated but they no longer free.

 

00:19:14 Dr Brewer

But because this dopamine 3 receptor activates that same intercellular pathway, it gives us another Ave by which to stimulate the intercellular pathway that leads to all the effects Stephen described which was decreased excitability of those cells that would normally transmit pain. And so we were able to exploit that overlap.

 

00:19:34 Dr Brewer

In signalling that he described to kind of bypass that dysfunctional opioids or MU opioid receptor.

 

00:19:43 Will

There’s a certain irony to the idea that an injury will numb the receptors through phosphorylation to the painkillers you’re trying to actually admit.

 

00:19:52 Dr Brewer

That is correct. That’s that’s an irony to it, but that’s one of the reasons there there’s several types of pains that don’t respond well to opioids, neuropathic pain, or pain that occurs after nervous system injury is one of those, yeah.

 

00:20:04 Dr Clemens

In the animal model we have these two.

 

00:20:07 Dr Clemens

Models of chronic pain. One centrally induced on peripherally induced.

 

00:20:13 Dr Clemens

And they show overlapping or sponsors.

 

00:20:15 Dr Clemens

To these drugs. So I think that strengthens our approach and our hypothesis.

 

00:20:23 Dr Brewer

This whole idea of it being dopaminergic mediated processes just kind of coincidental or recent studies. We create a set of spinal cord animals and they kind of diverge about 1/3 of the animals are responsive to opioids after injury, and about 2/3 aren’t, and so, like what’s different about these populations of.

 

00:20:42 Dr Brewer

Animals after a pair of time drew some blood ransom metabolomics right, which is just kind of a way to get a broadview of any differences between the animals.

 

00:20:53 Dr Brewer

And we found that the big distinguishing difference between animals that responded to morphine versus those that don’t or changes.

 

00:21:02 Dr Brewer

And the dopamine system right dopamine metabolism, dopamine synthesis. So there’s some real relationship here between these two systems that seems to be controlling the response of animals to opioids.

 

00:21:16 Dr Brewer

So I don’t think it’s just kind of a mistake or a coincidence that this particular dopaminergic works. It seems like the pain conditions that don’t respond to opioids.

 

00:21:27 Dr Brewer

Also have alterations in this dopamine system, which we think we are restoring by adding this dopamine through receptor agonists.

 

00:21:36 Will

Leaves I suppose quite neatly to the IT was a renal colic trial. Is the recruitment still enrolling for that?

 

00:21:42 Will

You know, for any clinicians who are listening to this and want to get involved, or anyone else who’s clutching their kidneys and wincing in memory like I am.

 

00:21:49 Dr Brewer

Right, so we were actually very excited at the opportunity to test our.

 

00:21:55 Dr Brewer

Kind of preclinical data that we’ve generated in the lab in a human population, and the one thing that allowed us to do this is that we were using previously approved FDA drugs just repurposing so we weren’t having to get approval for new investigative device or anything like that.

 

00:22:11 Dr Brewer

Our goal is to create a good new chronic pain treatment. The first step is to just see if it provides analgesia and the acute.

 

00:22:18 Dr Brewer

Setting and so the goal was what we’d seen in our animals is that we could take a dose of morphine that on its own, provided no analgesia in animals.

 

00:22:29 Dr Brewer

And if we added the D3 receptor agonist in this case pramipexole to that, you now got better analgesia than you would get with a high.

 

00:22:38 Dr Brewer

Dose of opioid.

 

00:22:40 Dr Brewer

So the idea was can we?

 

00:22:44 Dr Brewer

Make this work in in humans, right? So we created this study using an acute pain condition. Since I’m in the.

 

00:22:50 Dr Brewer

Emergency department I.

 

00:22:51 Dr Brewer

I work in the emergency department not as a physician of the as a researcher.

 

00:22:55 Dr Brewer

I consulted with the physicians on there and they said one of the most common acute pain things we see are kidney stones, and it’s severe pain, and it’s something that we use.

 

00:23:04 Dr Brewer

Opioids for a lot.

 

00:23:06 Dr Brewer

Try the nonsteroidal first. If that doesn’t work then we go straight to the opioids.

 

00:23:11 Dr Brewer

So we set up this study where patients would get it’s suspected that they have renal colic or kidney stone pain.

 

00:23:18 Dr Brewer

They would get a standard dose of morphine or half that dose of morphine plus a low dose of the primary packs also would get randomised to one.

 

00:23:28 Dr Brewer

Of the two groups.

 

00:23:30 Dr Brewer

We started the study actually a couple years ago. We had to shut down due to COVID ’cause anybody non clinical had to be removed from the space. And so we’re about to.

 

00:23:37 Dr Brewer

Get started back up.

 

00:23:39 Dr Brewer

We were about 25% through our enrollment.

 

00:23:43 Dr Brewer

And the early data looks encouraging.

 

00:23:47 Dr Brewer

Our goal was just to show not that anything is better than morphine, but is as good as right so we can get the same degree of analgesia by cutting the dose of morphine in half, but adding the primary pacsoa as we can get with a normal dose of morphine.

 

00:24:01 Dr Brewer

To show that we can reduce people’s exposure to opioids. This is a good analgesic drug right? Morphine works, but if we.

 

00:24:09 Dr Brewer

We can minimise the dose of morphine that you need to get effective analgesia by adding on this agreement. Then you have reduced people initial exposure to morphine and then if that last long term, maybe you are now working with doses of opioid that are not going to produce the side effects that we worry about.

 

00:24:29 Dr Brewer

The tolerance, the addiction, the dependence.

 

00:24:31 Will

Now something that I remember from my time working as a medical reporter, drug repurposing. That’s tough to fund and the work concerning some funders that they did not know how the drugs would interact.

 

00:24:44 Will

That even you know, the two known side effect profiles of independent drugs when combined, might have some kind of weird synergy that posed a risk.

 

00:24:53 Will

Is that something that you’re worried about in this trial, or is it something that the animal model is just completely cleared off?

 

00:25:01 Dr Clemens

I think the animal models gave us a good indication that we are likely unsafe waters at this point.

 

00:25:08 Dr Clemens

By reducing the opioid exposure to levels that are non effective on their own.

 

00:25:15 Dr Clemens

And they don’t give any euphoria on their own. These clinical studies only looking at the effects of this combination on chronic pain.

 

00:25:24 Dr Clemens

But based on the animal data that we have, we think that reduction of the opiate by half and then adding on a low dose of pramipexole does not lead to any drug seeking behaviour. Side effects that we know it does not lead to.

 

00:25:41 Dr Clemens

Tolerance that we know of.

 

00:25:43 Dr Clemens

If we ever do this study, the same drug profile we.

 

00:25:47 Dr Clemens

Gives these animals.

 

00:25:48 Dr Clemens

Repeated exposure to the opioids. They develop tolerance.

 

00:25:51 Dr Clemens

Within a week easily.

 

00:25:54 Dr Clemens

With this combination like we have not seen animals develop this tolerance.

 

00:26:00 Dr Clemens

We have not seen that these animals show any signs of what is called drug preference, so when they are tested in a teammate where they can go either left or right, they had exposed in one but not the other and we test them again after the end of the third trial. There is no indication that these animals.

 

00:26:20 Dr Clemens

Show any drive to go to the chamber that they received the Dragon.

 

00:26:26 Dr Clemens

So we we don’t know what happened in humans, of course, but we are following the very strict IRB guidelines here on this one to make sure that we stay at safe levels.

 

00:26:38 Dr Clemens

And we are actually right now in the process of developing a chronic study with the Veterans Administration. We’re trying to get this study into a chronic popule.

 

00:26:52 Dr Clemens

Patient with MD, North Carolina, and at that point, yes, we will be able to assess much better in detail if there are any additional side effects that we need to worry about, but it will be tempered as much as possible.

 

00:27:14 Will

This could have potentially societal level implications of people not being at so much a risk of opioid dependency, not just a much cheaper, effectively a half price way of treating pain and alleviate a lot of funds within a health care system.

 

00:27:31 Will

Assuming this is as effective as full dose morphine, what would?

 

00:27:36 Will

B. The potential implications for it looking maybe as a new standard of care.

 

00:27:42 Dr Brewer

I think the question always comes up about why even look at opioids. They’re bad. We know how dangerous they are. Should you even be considering something that still includes them? So I look at our CDC.

 

00:27:57 Dr Brewer

Put out an updated guideline for opioid prescribing in in 2016.

 

00:28:02 Dr Brewer

And basically their conclusions were that opioids obviously have risks.

 

00:28:09 Dr Brewer

But these effects are dose dependent, which say OK, lower the doses. You lower the risk.

 

00:28:15 Dr Brewer

It doesn’t say that clinicians should not use opioids. It says when they do use opioids they should prescribe the lowest effective dose.

 

00:28:24 Dr Brewer

So we think this is ticking that box.

 

00:28:28 Dr Brewer

I mean, if we are totally rose coloured about it and look into the future what we hope is that this provides a a total alternative or better option for clinicians who are faced with someone who’s really suffering.

 

00:28:42 Dr Brewer

Severe, either acute, severe pain or chronic long term pain that’s not responding to anything else. This will give them something to use that can be effective.

 

00:28:53 Dr Brewer

Without creating the side effects that come with opioids, use at current doses that they’re used.

 

00:29:01 Dr Brewer

I think the idea that we’ve kind of spent a few years in the lab testing things on animals that has the potential to translate like that.

 

00:29:09 Dr Brewer

I think that’s a that’s a dream for any basic scientists, and it’s fun. It’s fun to think about, and I think.

 

00:29:17 Dr Brewer

Again, all else staying equal, that’s where I think it has the potential.

 

00:29:22 Dr Brewer

To go and I think there’s some people interested in developing idea that Steven can talk about.

 

00:29:27 Dr Clemens

Yeah, so when we first presented this data, I was contacted by one of the attending physicians.

 

00:29:34 Dr Clemens

At the time and.

 

00:29:36 Dr Clemens

Who said that she had a patient who was not responsive to either of these?

 

00:29:40 Dr Clemens

Two drugs on their own.

 

00:29:42 Dr Clemens

The dopaminergics or the opioids for the treatment of and that yes was actually a combination of pain and restless leg syndrome.

 

00:29:52 Dr Clemens

And she told me two years later that she had used this combination that he had introduced.

 

00:29:59 Dr Clemens

At the time.

 

00:30:00 Dr Clemens

Again, these data have not yet been published.

 

00:30:03 Dr Clemens

She used this study in a chronic setting, so she gave his patient low doses of each.

 

00:30:09 Dr Clemens

Last time I spoke with her it was 2-3 years after the she had started the treatment and the efficacy was still there.

 

00:30:18 Dr Clemens

That gives us hope that data we get from the animals can fairly readily translate to the human.

 

00:30:27 Will

Well, if there is anyone listening to this who finds themselves in a similar prescribing circumstance, or anyone who’s maybe working locally and would like to get their clinic involved, what would be the best way for them to get in touch or find any more of your research? If they did want to just even keep track of things so they know where things are at?

 

00:30:46 Will

And how they can maybe start participating?

 

00:30:48 Dr Brewer

So currently this is just a trial in our Hospice.

 

00:30:52 Dr Brewer

Currently open to expanding it to other centres. I think that’s what eventually we’re going to need different experiences, different pain populations.

 

00:31:01 Dr Brewer

Like Steven said, our goal next is to look at veteran population with chronic pain.

 

00:31:06 Dr Clemens

For this chronic study that we are envisioning right now, one of the goals is that we may be able to identify, based on blood samples, patients who may respond who will respond to these opioids and those who will not, prior to even.

 

00:31:24 Dr Clemens

Giving them the openness.

 

00:31:26 Dr Brewer

You know ideally, because really what we’ve talked about so far is using this combination to treat pain. We have no claims to whether someone who’s already addicted to opioids or dependent on them.

 

00:31:39 Dr Brewer

If you can switch them to this, we don’t know how it feeds into the addiction side of things.

 

00:31:45 Dr Brewer

We know that this combination doesn’t create the same kind of addictive profile as the higher dose opioids do on their own.

 

00:31:53 Dr Brewer

Phone, but again, we’re not addiction specialist and we haven’t really rigorously assessed whether this combination might be used to treat addiction or as an opioid.

 

00:32:04 Dr Brewer

Replacement therapy for people who have been on opioids a long time and need to decrease that. It’s a whole new Ave that has yet to be examined, but we hope all those things will come.

 

00:32:13 Dr Brewer

Out of this First step.

 

00:32:15 Dr Clemens

We are hoping that this once it’s a an approved and patent idea that we will not find collaborators, companies, possibly willing to licence this idea and then get it out to the appropriate populations as quickly as possible and safely as possible.

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