By now, it's well known that opioids are addictive and potentially deadly.

But why is that?

John Williams, a senior scientist at the Vollum Institute, a research center at Oregon Health & Science University, has been studying this issue for about four decades. When he started, no one knew that opioids effected neurons or nerve cells in the brain. Then he looked into what happens to the brain, discovering that opioids rewire the brain.

So, we asked him about that. The interview has been edited for conciseness and clarity.

Q. How do opioids work?

Pain causes an increase in activity in some circuits in the brain and opioids inhibit those circuits. They decrease the activity of neurons in the brain and periphery. They do that by acting on receptors – the sensors that are on the membrane of neurons. Once the opioid binds to that sensor, it causes an inhibition of activity. Brain cells rely on electrical activity to communicate between each other and opioids decrease that electrical activity.

Q. Why do they lose their effectiveness?

A. That's a question that we've been working on for 30 years. We're discovering at least the super basics. Once an opioid binds to the sensor that we call receptors, the receptor becomes less sensitive over time. That has to do with the biochemical change in the receptor itself. Initial effects happen very rapidly – within five or 10 minutes. Then there's much more prolonged things that happen over days or weeks.

Q. Anything else happen?

A. The other thing that happens (is that) the body recovers from this inhibition. There's a change in other cells that don't have the opioid receptors that say, "OK, everything is quiet here, we're going to increase our activity." There's a change in other circuits in the brain that increase their activity.

Q. What other effect do they have on the brain?

A. There are a lot of different circuits that are affected. The pain circuit is one. Opioids (also) inhibit respiration. The problem with that is the respiratory system doesn't adapt in the same way as the pain pathway system. It adapts very slowly. So there's not much tolerance.

Q. Are there emotional effects?

A. Opioids have very strong effect on emotional aspects of pain. People will say, "Yeah, I feel the pain but it doesn't bother me." That's the emotional side of the effects of opioids. A lot of that has to do with the reward system, the system that tells people that things are going well.

Q. Then we have addiction?

A. That's the big problem. Opioids have this big effect on the reward system so people look more and more for this rewarding aspect of opioids. You become tolerant to that.

People have to take more opioids to feel the same sort of pleasure they once felt. That results in respiratory depression.

That's why we see so many deaths.

Q. So, they rewire the brain?

A. Yes. The junction between different cells, different neurons can become more or less effective with chronic treatment with opioids. Some connections are very much strengthened. Those might be the ones that are involved in the reward pathway. Other connections are weakened. Even cells that don't have the opioid receptors are affected because a neuron that has the opioid receptor has changed so much that there's an adaptive process in the non-opioid sensitive cells.

Q. What is the effect of that?

A. Overall, if people don't get the opioids they'll crave the opioids. That's one of the hallmarks of addiction. You're always looking for the drug.

Q. These changes in the brain – are they permanent?

A. They're very, very long lasting in some people. Some people have a propensity to become addictive and those changes can be very long lasting.

Q. How long?

A. Years. It applies to all drugs of abuse. You might know people who haven't been able to quit smoking. Drinking. All drugs of abuse change the brain.

Q. What happens when they stop?

A. When you remove the opioids very quickly, the cells that adapted to having the inhibitory effects now are super excitable. You get this rebound effect. That's called withdrawal. People feel terrible. They'll have diarrhea. There's all sorts of complications when you remove the opioid very quickly.

Q. How long does that last?

It's something that people recovery from in days or weeks.

But then there is this long-lasting chronic effect where people will crave the drug. They'll want to get back on the drug because it made them feel good.

Q. Are there differences among opioids?

A. Yes. Mostly it has to do with the strength of the opioid and the way that they get into the brain and out of the brain. Heroin is a lipid soluble compound that goes into the brain rapidly and there it's metabolized to morphine. That gives people a big rush. That's why it's so addictive. Drugs like buprenorphine – that's one of the drugs that's used to help opioid addicts out – it's not very potent and it sticks around for a while. People can function on buprenorphine and basically have a normal life.

Q. Why use opioids to treat opioid addiction?

A. Methadone and buprenorphine are both used because they stay in the body for a long, long time. You can function normally as long as you stick with the program.

Q. Do they relieve the pain?

A. No. This is really more for the addictive side of things.

Q. Are some opioids better than others?

A. They all have the same problem. Drug companies have spent decades developing opioids that will treat pain that don't have this addiction liability. One of the first drugs in England was heroin. Heroin was supposed to treat addiction. Look at how that turned out.

Q. Do you see another avenue for treating pain?

A. I don't study pain. But everyone who's given opioids for pain will require more and more opioids for the treatment of the pain. A certain percentage of people who are given opioids for pain will develop this addiction to it.

Q. Why do some people get addicted and not others?

A. In large part, it's genetic. These people are normal in every other way but there is a trigger that opioids and other drugs of abuse (cause) to take off. It's not just one gene but many, many genes.

-- Lynne Terry