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. If you or someone you know is struggling  with opioid use in the United States, the Department of Health  and Human Services operates a helpline: 800-662-4357 and a database of more than 14,000  substance abuse facilities in the US: www.hhs.gov/opioids