The Science of Addiction: Why Are Opioids So Addictive?

From the lecture series: The Addictive Brain

By Thad Polk, Ph.D., University of Michigan

The opioid crisis is very real, and very deadly. And if we want to stop it, or at least reduce the damage, we need to understand how these drugs work at a biological and neural level. Why are opioids so addictive? And is there anything we can do to counteract their effects?

This is the second article in a series about opioid addiction. You can read the first article here.
image of cutting into a poppy plant for article on what are opioids
An opium poppy seed excretes latex “milk” after being scratched by a farmer

What Are Opioids?

Opioids get their name because they are related to opium, the dried form of the milky latex that is secreted by an opium poppy’s seed pod when it is scratched.

Opium contains both morphine and codeine. These are so-called opiate drugs, which just means that they’re natural ingredients of opium itself.

The more general term OPIOID refers to drugs that have biological effects similar to the natural opiates, whether they’re found in opium or not. For example, heroin is an opioid drug that is very similar to morphine but about 3 times more potent.

This is a transcript from the video series The Addictive Brain. Watch it now, on The Great Courses Plus.

Although heroin isn’t found in opium itself, its biological effects are very similar to those of the natural opiates, and so it would be classified as an opioid drug.

Likewise, prescription painkillers like Vicodin and Percoset contain opioid drugs that are derived from chemicals in opium, but that aren’t found in opium themselves.

Some of the most powerful opioid drugs, like fentanyl and carfentanil, are completely artificial and man-made, and aren’t even derived from opium or its contents. But because their biological effects are similar to the biological effects of the opiates, they’re also classified as opioids.

Learn more about opium and its derivatives, from regularly prescribed painkillers like codeine and morphine to heroin

The Biological Effects of Opioids

All opioid drugs interact with the same receptor molecules in the brain and body. In fact, these molecules are called opioid receptors, precisely because they interact with opioid drugs.

Receptors are kind of like the ignition in your car and opioid drugs are kind of like your car key. Your car key fits the ignition of your car, but it doesn’t fit your front door or the ignition of your neighbor’s car. And when you put your key in the ignition of your car, it causes a chain reaction of events that can start the car.

Likewise, opioid drugs fit into opioid receptors, but they don’t fit any of the countless other receptors throughout your body. And when an opioid drug connects with an opioid receptor, it triggers a chain reaction of cellular events that ultimately produce the effects associated with opioid drugs.

For example, the deadly effects of opioid drugs are caused by their interaction with opioid receptors in the brain stem that affect breathing. In particular, activation of these receptors can significantly suppress the breathing reflex. And an opioid overdose can suppress breathing so much that the user suffocates and dies from a lack of oxygen.

The pain-relieving properties of opioids depend on a different set of opioid receptors on cells in the body’s pain pathways. When these receptors are activated they block pain signals from reaching the brain, thereby providing significant pain relief.

Learn more about the ways addiction alters the brain

You also have opioid receptors in your digestive system. And activation of those receptors can lead to constipation and nausea, both of which are commonly associated with the use of opioid drugs.

image of an opioid addict dealing with craving and addiction
There are a lot of opioid receptors in the brain’s reward circuit, and when those receptors are activated the user experiences a feeling of peaceful euphoria. And that’s why opioid drugs like heroin produce what users describe as a warm, euphoric high.

The Role of Dopamine in Addiction

The activation of these opioid receptors in the reward circuit also leads to the release of unusually large bursts of the neurotransmitter dopamine. And those bursts of dopamine are what makes opioids, and all other drugs of abuse, so addictive.

To understand why, we need to understand how the brain interprets the release of dopamine in the reward circuit. And there are two important parts of the puzzle that together help to explain the neural mechanisms of addiction. The first is dopamine’s role in CRAVING. And the second is dopamine’s role in reward prediction.

Learn more about the history of drug use, from ancient history through the development of synthetics in the 19th and 20th centuries

First, Consider Craving

For a long time, scientists thought that the release of dopamine reflected pleasure or liking. But a number of studies now suggest that dopamine release is really more about wanting. And not normal, run-of-the-mill wanting, but intense craving.

For example, mice that have been genetically engineered to release more dopamine than normal, seem to crave food in a way that normal mice don’t. For one thing, they will run much faster and farther to get it compared with normal mice.

Conversely, mice that have been engineered NOT to produce dopamine exhibit the opposite symptoms. They don’t show any signs of wanting food at all. In fact, they won’t bother to walk across their cage to eat even if they’re starving to death.

On the other hand, these genetic alterations in dopamine levels don’t seem to influence how much the mice LIKE food. For example, mice typically exhibit characteristic facial expressions and mouth movements when they eat something they particularly like.

But mice that produce more dopamine than normal don’t produce any more of these characteristic expressions when they eat than other mice do. And mice that produce less dopamine don’t produce fewer such expressions.

The bottom line is that a burst of dopamine in the reward circuit is associated with wanting or craving more than liking. And we’re not talking about thoughtful, planned wanting, like the long-term goal of wanting to be an engineer or a lawyer.

We’re talking about short-term cravings like wanting to eat some chocolate even though you’re going to eat dinner soon. Or wanting to watch the next episode of a TV show that you’re binging, even though it’s late and you need to get up early.

Learn more about the process of neurochemical transmission and see how drugs mimic this activity

Reward Prediction Error

The release of dopamine signals what’s sometimes called a reward prediction error. Some of the most important studies on this topic were conducted by Dr. Wolfram Shultz, who was at the University of Fribourg at the time.

Dr. Schultz trained monkeys to perform a task in which they received fruit juice as a reward at relatively predictable times. While they were doing this task, he recorded from neurons in the reward circuit of their brains. And he found that these neurons fired and released dopamine when a reward occurred, but only if that reward was unexpected.

If the monkeys got some juice when they weren’t expecting it, then these dopamine neurons fired and produced a burst of dopamine. But if the monkeys were expecting the juice, then the neurons didn’t release dopamine.

…dopamine is released not when you get a reward, but rather when you get more reward than you were expecting to get.

Schultz interpreted these results to mean that the release of dopamine in the reward circuit signals a reward prediction error. In other words, dopamine is released not when you get a reward, but rather when you get more reward than you were expecting to get. In other words, when your prediction about the amount of reward was wrong.

A long line of research in psychology had previously shown that errors in reward prediction trigger new learning. And that makes a lot of sense.

After all, if your predictions are correct, there’s no real need for new learning. It’s when your predictions are wrong that you really need to learn, because that’s when it’s clear that your model of the world isn’t quite right and needs to be updated.

And what do you learn? Well, you learn associations between the current situation and the arrival of a reward. So then the next time you’re in a similar situation, you’ll be able to make a better prediction about what’s going to happen.

Dr. Schultz also found that over time the dopamine neurons started firing in response to the environmental cues that PRECEDED the reward. In one of his experiments, a light flashed a second or two before the juice arrived. And he found that once the monkeys had learned that the juice was associated with the light, then their dopamine neurons would fire in response to the light, rather than the juice.

Learn more about how our DNA can significantly influence whether we become addicts

OK, dopamine release is associated with craving. And it also signals reward prediction error and triggers learning associations between the current situation and the future appearance of a reward.

Common Questions About Opioid Addiction

Q: What exactly are opioids?

Opioids are a class of drugs that are prescribed as pain relievers but also include illegal drugs that function in the same manner such as heroin.

Q: Do opioids cause endorphins to be released?

No. Opioids do not cause endorphin release. Opioids mimic endorphins with a much stronger version, leading the body to stop producing endorphins.

Q: Does the body have natural opioids?

Yes. The brain makes endogenous opioids that perform a myriad of functions such as making you vomit or feel better after a broken bone.

Q: Do opioids harm the body?

Opioids can harm more than the brain; they can also cause respiratory arrest or even deprive the body of oxygen—enough to cause organ damage. They cause constipation from the slowing of the intestinal system as well as a reduced immune response.

This article was updated on 9/14/2019

Keep Reading
The Opioid Crisis: Fentanyl and The Dangers of Synthetic Opioids
Understanding Opioid Addiction: The Science of Addiction and Treatment
How to Reduce Anxious Thoughts: Stop Thinking Ahead