The opioid crisis

03 July 2018

Interview with

Dr Bryan Roth - University of North Carolina Chapel Hill

In the US last year, more than 50,000 people died of opioid overdose. Georgia Mills spoke to pharmacologist Bryan Roth at the university of North Carolina Chapel Hill...

Bryan - Currently in the US we’re having a crisis of really catastrophic proportions. In the last year alone more than 50,000 people died of opiate overdoses and many hundreds of thousands or millions of people are currently dependent on opioids both prescription and illegal opioids. And to sort of put that in perspective, the number of people that died last year in the United States from opioid overdoses is roughly the same as the number of Americans who died in the entire Vietnam war, and the same as the number of Americans who died in the entire Korean war. So this is a huge huge problem.

Georgia - People are prescribed these for pain. Then what happens?

Bryan - Most people actually have no problem with them at all. But there is a significant portion of individuals that even after the first time they take a prescription opioid basically have a tremendous feeling of euphoria. I was at one time a full time psychiatrist and would frequently have patients who were opioid or heroin addicts as my patients, and the story they would tell invariably was after the first or second time they took a prescription opioid they basically felt like they had found what they were looking for their entire life in terms of the feeling of wellbeing and the euphoria that was attained.

As I said, this doesn’t occur with everybody, but when you have millions and millions of people taking these compounds, even if it occurs with only 5 or 10 percent of the patients, then you have hundreds of thousands to potentially millions of people who are at very high risk of ultimately abusing the medications and becoming dependent upon them.

Georgia - How does this eventually lead to death?

Bryan - Well, what happens typically is drugs like opioids lose their effectiveness in terms of producing the euphoria, relatively quickly actually. People will increase the dose and very quickly they can get to a point where the dose that is required to induce euphoria or to stave off symptoms of withdrawal from opioids after they become dependent gets very close to the dose that suppresses respiration. And death is typically due to suppression of respiration so people basically stop breathing and then they die within a few minutes.

Georgia - What is your lab doing to try and solve this problem?

Bryan - My lab has been studying opioids and the molecules that they bind to in the brain - they’re called “opioid receptors” - since 1983. And our idea is that if we can understand how these drugs interact with their targets in the brain, which are the receptors, then we might be able to make new medications that mimic the beneficial actions of opioids, reducing pain without the side effects.

Georgia - So you get all of the good and none of the bad. Is it the fact that it’s the way that it docks onto a cell in one place or does it have - this might be simplistic - but does it have one bit that causes the pain relief, one bit that causes the addiction, and if you could just get rid of that bit it would all be fine?

Bryan - That’s what a lot of scientists think. And we’re currently in the process of testing that notion that there is sort of one confirmation of the receptor which interacts with certain proteins which is responsible for relief of pain, and another sort of set of interactions which are responsible for the side effects. We can sort of break that down into chemical reactions inside the cell and then it’s relatively straightforward - I wouldn’t say it’s simple - but a relatively straightforward way then to design medications that sort of tickle one pathway and not the other. Then, of course, once we have them then we test them in mice and through multiple irritative cycles eventually hope to get these into humans for human testing.

Georgia - These are just sitting on the table waiting to get through the system really?

Bryan - Yes. Yeah, there are lots of safety things. We want to make sure that even though the drugs hit the receptors in the brain that we want them to hit that we want to make sure they don’t hit other receptors or have serious side effects that are not related to their known actions, and these things take time.

Georgia - Have you had people suggesting this maybe could do more harm than good?

Bryan - This is always the concern that when you make something new that hits opiate receptors that it may actually be more addictive than what you started out with. Heroin actually was made I think in Germany, but was initially used in the US to stave off dependence of morphine. So at that time in the US we had a number of people who had survived the Civil War that were morphine addicts and heroin was initially used to stop morphine addiction.

Georgia - Woops!

Bryan - It turned out to be more addictive than morphine. And so, as you can imagine, the regulatory people have a number of hurdles that these drugs need to go through to assess what’s called “addiction and dependence liability” before they can be tested in humans. And then, even in early human studies it’s possible to get a really good signal as to what their abuse potential will be. So I wouldn’t say we’re 100 percent confident, but certainly all the regulatory procedures and testing is in place to help to make sure that doesn’t occur again.


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