What Causes Opioid Addiction, and Why is it So Tough to Combat?

More than 3,000 years ago, a flower began to appear in remedies in Ancient Egyptian medical texts. Across the Mediterranean, the ancient Minoans likely found ways to use the same plant for its high. Both ancient civilizations were on to something— opium, an extract of the poppy in question, can both induce pleasure and reduce pain. Though opium has remained in use ever since, it wasn’t until the 19th century that one of its chemical compounds, morphine, was identified and isolated for medical use. Morphine, codeine, and other substances made directly from the poppy are called opiates. In the 20th century, drug companies created a slew of synthetic substances similar to these opiates, including heroin, hydrocodone, oxycodone, and fentanyl.

Whether synthetic or derived from opium, these compounds are collectively known as opioids. Synthetic or natural, legal or illicit, opioid drugs are very effective painkillers, but they are also highly addictive. In the 1980s and 90s, pharmaceutical companies began to market opioid painkillers aggressively, actively downplaying their addictive potential to both the medical community and the public. The number of opioid painkillers prescriptions skyrocketed, and so did cases of opioid addiction, beginning a crisis that continues today. To understand why opioids are so addictive, it helps to trace how these drugs affect the human body from the first dose, through repeated use, to what happens when long-term use stops. Each of these drugs has slightly different chemistry, but all act on the body’s opioid system by binding to opioid receptors in the brain.

The body’s endorphins temper pain signals by binding to these receptors, and opioid drugs bind much more strongly, for longer. So opioid drugs can manage much more severe pain than endorphins can. Opioid receptors also influence everything from mood to normal bodily functions. With these functions, too, opioids’ binding strength and durability mean their effects are more pronounced and widespread than those of the body’s natural signaling molecules. When a drug binds to opioid receptors, it triggers the release of dopamine, which is linked to feelings of pleasure and may be responsible for the sense of euphoria that characterizes an opioid high. At the same time, opioids suppress the release of noradrenaline, which influences wakefulness, breathing, digestion, and blood pressure. A therapeutic dose decreases noradrenaline enough to cause side effects like constipation.

At higher doses opioids can decrease heart and breathing rates to dangerous levels, causing loss of consciousness and even death. Over time, the body starts to develop a tolerance for opioids. It may decrease its number of opioid receptors, or the receptors may become less responsive. To experience the same release of dopamine and resulting mood effects as before, people have to take larger and larger doses— a cycle that leads to physical dependence and addiction. As people take more opioids to compensate for tolerance, noradrenaline levels become lower and lower, to a point that could impact basic bodily functions. The body compensates by increasing its number of noradrenaline receptors so it can detect much smaller amounts of noradrenaline.

This increased sensitivity to noradrenaline allows the body to continue functioning normally— in fact, it becomes dependent on opioids to maintain the new balance. When someone who is physically dependent on opioids stops taking them abruptly, that balance is disrupted. Noradrenaline levels can increase within a day of ceasing opioid use. But the body takes much longer to get rid of all the extra noradrenaline receptors it made. That means there’s a period of time when the body is too sensitive to noradrenaline. This oversensitivity causes withdrawal symptoms, including muscle aches, stomach pains, fever, and vomiting. Though temporary, opioid withdrawal can be incredibly debilitating. In serious cases, someone in withdrawal can be violently ill for days or even weeks.

People who are addicted to opioids aren't necessarily using the drugs to get high anymore, but rather to avoid being sick. Many risk losing wages or even jobs while in withdrawal, or may not have anyone to take care of them during withdrawal. If someone goes back to using opioids later, they can be at particularly high risk for overdose, because what would have been a standard dose while their tolerance was high, can now be lethal. Since 1980, accidental deaths from opioid overdose have grown exponentially in the United States, and opioid addictions have also exploded around the world. While opioid painkiller prescriptions are becoming more closely regulated, cases of overdose and addiction are still increasing, especially among younger people.

Many of the early cases of addiction were middle-aged people who became addicted to painkillers they had been prescribed, or received from friends and family members with prescriptions. Today, young people are often introduced to prescription opioid drugs in those ways but move on to heroin or illicit synthetic opioids that are cheaper and easier to come by. Beyond tighter regulation of opioid painkillers, what can we do to reverse the growing rates of addiction and overdose? A drug called naloxone is currently our best defense against overdose. Naloxone binds to opioid receptors but doesn’t activate them. It blocks other opioids from binding to the receptors, and even knocks them off the receptors to reverse an overdose.

Opioid addiction is rarely a stand-alone illness; frequently, people with opioid dependence are also struggling with a mental health condition. There are both inpatient and outpatient programs that combine medication, health services, and psychotherapy. But many of these programs are very expensive, and the more affordable options can have long waiting lists. They also often require complete detoxification from opioids before beginning treatment. Both the withdrawal period and the common months-long stay in a facility can be impossible for people who risk losing jobs and housing in that timeframe. Opioid maintenance programs aim to address some of these obstacles and eliminate opioid abuse using a combination of medication and behavior therapy. These programs avoid withdrawal symptoms with drugs that bind to opioid receptors but don’t have the psychoactive effects of painkillers, heroin, and other commonly abused opioids. Methadone and buprenorphine are the primary opioid maintenance drugs available today, but doctors need a special waiver to prescribe them— even though no specific training or certification is required to prescribe opioid painkillers. Buprenorphine can be so scarce that there’s even a growing black market for it. There’s still a long way to go with combating opioid addiction, but there are great resources for making sense of the treatment options.