The Science of Opioid Addiction and Treatments

A Professor's Perspective on Current Events

If we are to treat the growing number of opioid addicts in America, we first need to understand the basic science behind opioid addiction, and some of the treatment methods currently in use. Beyond simply avoiding social triggers or the use of naloxone and methadone, scientists are busier than ever looking into new ways to stem the tide of the growing opioid crisis.

This is the third article in a series about opioid addiction and the opioid crisis in America. You can read the previous article here.
image of an addict with opioid addiction and bottles of pills like oxycodone

Why Your Surroundings Can Trigger Cravings

When an opioid drug binds to opioid receptors in the reward circuit, it artificially triggers a big burst of dopamine. But the brain doesn’t know that the dopamine burst was triggered artificially by a drug. So it treats it as if it had been triggered by an unexpected natural reward like food or praise.

And then the brain does the two things it always does in response to a dopamine burst. First, it learns associations between the current situation and the likelihood of future reward. And in the case of a drug user, that means learning strong associations between the environmental cues associated with drug taking and drug taking itself.

For example, the people the user is with get associated with drug taking. The room where the user takes the drug gets associated with drug taking. The needle or pill bottle or other paraphernalia that are present get strongly associated with drug taking. And so on. Any and all environmental features that are associated with drug use get burned into the user’s memory.

The second thing that the burst of dopamine does is to trigger craving. And because opioids and other drugs of abuse produce abnormally large bursts of dopamine, the cravings are also abnormally strong.

And remember, over time the dopamine neurons start firing in response to the cues that PREDICT that the reward is coming, not just in response to the reward itself. For the drug user, that means that all the cues that are now strongly associated with drug taking also trigger craving themselves.

Learn more: Addiction 101

Just seeing the people with whom you’ve taken drugs in the past triggers a dopamine burst and a strong craving to take the drugs again. Likewise, walking by a location where you once used the drug also triggers craving.

So does seeing drug paraphernalia or encountering any of the other hundreds of other cues in the environment that have become strongly associated with drug taking.

With repeated drug use, those associations get stronger and stronger and the cravings become so powerful that they’re virtually impossible to ignore. And pretty soon a full-blown addiction is born.

In a very real sense, opioids and other drugs of abuse fool the brain into behaving as if there’s no more rewarding behavior in the world than taking that drug.

In a very real sense, opioids and other drugs of abuse fool the brain into behaving as if there’s no more rewarding behavior in the world than taking that drug. And over time, that’s exactly how addicts act. They become obsessed with obtaining and taking the drug and everything else in their lives becomes a lower priority.

And that’s when you see the tragic downward spiral of neglected responsibilities, broken relationships, and even criminal behavior that is associated with drug addiction.

Helping the Country’s Opioid Addicts

Finally, let’s turn to perhaps the most important question of all: Is there anything we can do to help these people and ultimately stem the tide of the opioid epidemic?

Well, yes and no. There are some very effective treatment options and promising research directions, but we still have a long way to go if we want to really address the crisis.

Let’s begin by talking about treatment options. And when we talk about treatment, it’s important to distinguish between treatment for an overdose and treatment for the addiction.

In the case of overdoses, a medication named naloxone can be used to quickly and effectively counteract the effects of opioid drugs.

The Role of Naloxone in Overdose Treatments

Naloxone is what is known as an opioid receptor antagonist. What that means is that it binds to opioid receptors just like opioid drugs do. But it doesn’t turn the receptor on. It just blocks the receptor and prevents opioid drugs from turning it on.

If you think of our key and ignition analogy, naloxone is like a fake key that you can slide into your car’s ignition but that you can’t turn. Furthermore, while it’s in the ignition it prevents you from putting the real car key in the ignition. There’s no way to start the car while the fake key is in the ignition.

Image of A naloxone kit as distributed in British Columbia, Canada
A naloxone kit as distributed in British Columbia, Canada

Learn more: Your Brain on Drugs

Likewise, naloxone binds to opioid receptors but it doesn’t turn them on. It also prevents opioid drugs from turning the receptors on and replaces drug molecules that were previously bound to the receptors.

In particular, it prevents the drugs from activating receptors in the brain stem that suppress breathing and could lead to asphyxiation and death. In fact, administering an appropriate dose of naloxone to a victim of an opioid overdose can often reverse the effects of the drug in just a minute or two and save their life.

Now that’s obviously great news, but there are at least three significant problems. First and foremost, not everyone who overdoses on an opioid drug gets treated with naloxone in time. If no one is around or if those who are around don’t call for medical help right away, then it may be too late.

In response to this concern, first responders like paramedics and policemen now often carry naloxone with them at all times so that if they encounter someone who has overdosed on an opioid, they can treat them right away. Opioid users themselves, as well as their friends and family, can often get a naloxone prescription to keep in case of emergency.

A second problem is that the new synthetic opioid drugs like fentanyl and fentanyl analogs are so potent that the usual doses of naloxone may not be strong enough to counteract the effects of the drug.

In such cases, it may be necessary to repeatedly administer multiple doses of naloxone every couple of minutes until the victim finally responds. Of course, that’s a problem if you don’t have enough naloxone or if the person administering the naloxone doesn’t recognize the need for multiple doses.

…the effects of naloxone only last about 30 to 90 minutes, while the opioid drug may stay in the system significantly longer.

Furthermore, the effects of naloxone only last about 30 to 90 minutes, while the opioid drug may stay in the system significantly longer. So an overdose victim who initially responds to naloxone and recovers could still overdose an hour or two later, even if they don’t take any more of the drug.

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It’s therefore critical for any overdose victim to get immediate professional care and to be closely monitored for an extended period of time.

But the third, and perhaps most serious problem, is that naloxone only treats the overdose, not the underlying addiction. As a result, it’s quite likely that an overdose victim who is saved by naloxone will overdose again in the not too distant future.

In fact, a study that tracked emergency room patients who had been successfully treated with naloxone for an opioid overdose, found that about 10% of them had died within a year from another opioid overdose. And 5% of them had died within a month. Clearly, naloxone alone is not the entire solution. We need to find ways to help people escape the addiction itself.

The Role of Methadone in Addiction Treatment

The most common approach is to replace the use of illegal opioids with the controlled administration of safer, legal opioids. That’s the idea behind what’s called methadone maintenance therapy.

Methadone is another opioid drug, and so administering it to an opioid addict will significantly reduce their cravings. It will also prevent them from experiencing the extremely unpleasant withdrawal symptoms like anxiety and muscle aches that quitting cold turkey would produce.

40 mg of methadone pills for opioid addiction
40 mg of methadone in pill form

When administered by a professional in a clinic, methadone is much safer than a street opioid like heroin. For one thing, the dosage is controlled and so there’s virtually no chance of an overdose.

For another, the methadone from the clinic is pure, while street drugs are often contaminated by other substances, including potentially very dangerous synthetic opioids like fentanyl or carfentanil.

Methadone also doesn’t produce the strong, euphoric high associated with other opioids like heroin and fentanyl. And perhaps for that reason, once an addict has switched to methadone, they may find it easier to slowly reduce their dose and ultimately kick the habit entirely.

But other opioid addicts stay on methadone maintenance therapy for years on end. And although they’re still addicted to an opioid, many of these addicts can return to a relatively normal life. They can hold down a job and develop relatively normal relationships.

So although methadone maintenance may not be as desirable as complete abstinence, it’s a lot better than living from hit to hit on the street.

The Future of Opioid Addiction Treatment

Where do we go from here in our fight against the Opioid Crisis? Well in May of 2017, the director of the National Institutes of Health and the director of the National Institute on Drug Abuse suggested 3 major research directions that scientists could pursue in order to address the issue.

The first idea is to try to develop new overdose-reversal interventions that are better than the current approaches. For example, scientists could develop new drugs that are strong enough and long-lasting enough to counteract the effects of the powerful synthetic opioids more effectively than naloxone can.

Scientists could also develop technologies that detect overdose and automatically intervene, by signaling for help or administering an opioid antagonist like naloxone even if no one else is around.

The second idea is to develop new approaches to treating opioid addiction itself. As we discussed, addiction leads to neural changes that lead to craving and compulsive drug use. If those neural changes could be counteracted in some way, then we could potentially treat the disease rather than just the symptom.

One promising possibility is to develop vaccines that cause the body’s own immune system to attack opioid drugs and prevent them from entering the brain.

A third idea is to improve the way we treat pain. It’s important to remember that opioid drugs still play a crucial role in relieving the suffering of countless patients with chronic pain. But unfortunately, when the current drugs are used long-term, they can be habit forming.

Learn more: The Science of Poppies, Pleasure, and Pain

What’s needed are new ways to treat chronic pain that are safe and effective, but that are not addictive. And there are a few promising candidates on the horizon.

For example, drugs called biased agonists seem to be able to bind to opioid receptors in the pain pathways, without producing the undesirable effects on breathing and the reward circuit. Non-opioid approaches like medical marijuana and brain stimulation have also shown some promise.

So although the current crisis is very serious, there’s light on the horizon and reason to be cautiously optimistic about the future.

For more with Professor Polk, check The Addictive Brain Wondrium.

Keep Reading:
The Opioid Crisis: Fentanyl and The Dangers of Synthetic Opioids
The Science of Addiction: Why Are Opioids So Addictive?
How to Reduce Anxious Thoughts: Stop Thinking Ahead

Image credits:
By James Heilman, MD (Own work) [CC BY-SA 4.0 (], via Wikimedia Commons