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The opioid crisis in America killed more people in a year than the number of soldiers who died over the course of the Vietnam War. In that same year, 2016, there were more fatal overdoses than there were deaths from traffic accidents. But what are the opioids causing this epidemic? This guide to opioids will explain how opioids work and how they have driven the greatest public health threat in modern American history.
The term opioids refers to drugs derived from the opium in poppy seeds. For millennia, the poppy plant has been cultivated for its painkilling and mildly euphoric effects. The seeds work because of how the opioid molecules in them resemble chemicals in the brain called endorphins, which communicate messages between nerve cells. This function makes endorphins a kind of neurotransmitter, what the University of Queensland calls “the body’s chemical messengers.”
When a brain cell releases endorphin molecules, the molecules float between the gap between the first cell and the destination cell. On the destination cell, they bind to receptor molecules, like a key fitting into a lock. With the molecule sitting in its receptor, it can activate or deactivate the function of its new host.
The nucleus accumbens is the region of the brain responsible for controlling and regulating feelings of pleasure, reward, and anticipation, and it is home to receptors for endorphins. Such receptors are also located on nerve cells that relay pain signals. When the body produces its own natural endorphins, the messengers fight incoming pain signals and output pleasure signals to assist the painkilling process. The mechanism is similar to why runners experience “runner’s high,” even as they feel some level of physical stress because of their exertions.
This is what happens under normal circumstances, but when opioids enter the mix, everything changes. Opioids are thousands of times more powerful than endorphins; they are much better at fighting pain than the body’s chemicals (so much so that people feel a sort of disconnection from the very concept of pain). While endorphins boost feelings of pleasure, opioids unlock waves of joy that are impossible to resist.
In fact, opioids create such imaginable pleasure that people are chemically compelled to want more. This happens because when an opioid binds to an opioid receptor in the brain or the central nervous system, the brain produces dopamine – another neurotransmitter that also communicates signals of reward and desire for more. Dopamine is easily released when a person does a naturally pleasurable activity, anything from enjoying a good meal to gambling. As with endorphins, however, nothing can compare to the dopamine release caused by chemical substances. The flood of dopamine creates such an impression that every other kind of pleasurable activity (from hobbies to sex) cannot compare to the feeling of being on opioids.
As more opioids are taken to try and recapture that feeling, the brain grows increasingly tolerant of the wave of opioid molecules assaulting its receptors. Opioid tolerance is a real process that refers to the threshold for adaptability constantly being forced upward; more and more opioids (or stronger opioids) are needed to produce the same amount of dopamine. The Pain Management Secrets journal notes that the drug’s effects are even diminished with the repeated exposure, but patients become so desperate to feel that high again that they take more (or stronger) opioids, continuing the cycle.
The cycle leads to the point where trying to go without opioids (either out of a desire to quit or because supplies are exhausted) throws the brain into disarray. The body has gotten so used to the opioid molecules controlling everything from pain to sleep, from pleasure to energy levels, that the brain cannot immediately start producing its own neurotransmitters to take over. When opioids are taken away, the delicate balances in the body swing wildly as various systems try to cope with the loss of the powerful agent that was dictating terms for so long. People go through episodes of anxiety and depression; they feel like they have the flu; they experience insomnia; their muscles and their bones ache; they vomit and have diarrhea; and they have an intense desire for more opioids, convinced that just one hit will settle their problems.
This process is known as withdrawal, and it can be very dangerous for a person addi
cted to opioids. Opioid withdrawal symptoms are not life-threatening, but they can compel a person to do risky and dangerous things to alleviate their distress. One such example is if a person goes back on opioids during the process. Withdrawal is a complicated medical process of the brain unlearning its dependence on opioids to function. If opioids are reintroduced during this vulnerable time, it might deepen the connection between the perception of basic survival and the need for opioids. This reaches the point where a person is not able to control their use of opioids.
In addition to developing this psychological dependence on opioids, there are significant health problems that arise from having this problem. Opioids slow down all vital functioning in the body. That sense of disassociation is very pleasurable and alluring on a superficial level, but it means that basic systems are impacted by the abuse. This can range from the embarrassing and painful (opioid-induced constipation, which arises when the intestines cannot push stool through the bowels) to the legitimately dangerous (respiratory depression, where the breathing mechanisms are slowed down so much that the body does not get the oxygen it needs to survive, and people are so heavily sedated that they cannot draw breath).
The British Journal of Anesthesia notes that respiratory depression is even a concern when opioids are used in controlled medical environments. For those using opioids recreationally and without medical supervision, there is a genuine danger of respiratory failure, which can culminate in a coma or death.
Opioid addiction treatment is a long and involved process. It does require a person to stop using opioids, which will induce the withdrawal symptoms mentioned above; however, if the withdrawal takes place in a secure medical facility (a hospital or an opioid treatment center), the person will be given medications like methadone or buprenorphine to mitigate the worst of the effects. Both methadone and buprenorphine are opioids themselves, but they are designed to not be as powerful as heroin or prescription opioids. Methadone and buprenorphine work much slower, which helps drug users avoid the full extent of withdrawal effects while not causing the same kind of euphoric high that comes from more powerful opioids.
Withdrawal address the physical need for opioids. When the process is complete (the length of which depends on a number of factors, such as individual physiology and lifestyle as well as the nature of the opioid abuse itself), the person can begin counseling and therapy, which will address the psychological aspects of opioid addiction and dependence. This process will look at any underlying mental health issues that caused or resulted from the opioid abuse, as well as how the person can cope with the temptation and stress to use opioids again in the future. Finally, the person will likely be put in touch with a peer-led aftercare support group, one that likely uses the 12-Step model to stay accountable and abstinent.
Opioid abuse is often devastating, but it does not have to end that way. There are many stories of people turning their lives around and living in health and happiness after successfully completing their stay at an opioid treatment center.
Heroin is perhaps the most infamous and well-known of the opioid family (KUOW calls it “one of the most potent and addictive substances that exists”), but its start is innocuous. It begins with farmers planting poppy seeds, then waiting three months for the poppies, rich with opium, to bloom. The opium itself is found in the pod of the poppy flower, where it produces a milky fluid. The pod is split to harvest the opium, which turns into a brownish-black sap. The sap can be made into bricks or other shapes, which are then sold to merchants who then take the solid sap to a refinery. The workers at the refinery add the opium bricks to barrels of boiling water and add lime to the mixture. The lime sinks to the bottom of the barrel as a waste product; at the top is a film of white morphine, which is harvested and reheated with ammonia. After more filtering and boiling, a brown paste forms; morphine is pasted into molds and left to dry in the sun.
Workers will add chemicals and boil and drain the mixture until the product is solidified. It will be filtered with activated charcoal, then treated with alcohol for purification. The mixture is heated again to boil the alcohol and leave heroin, which finally emerges as a fluffy white powder.
In the past, heroin was impure and often mixed (or cut) with many other substances. In the 1990s, however, black marketers were able to formulate a purer form of heroin that was easier (and safer, ironically) to smoke and snort, which led to an increase in heroin use. With the reduced risk of HIV or bloodborne diseases as a result of intravenous use, the drug enjoyed a small boom period.
Health concerns aside, injectable heroin remains one of the most popular ways of consuming the drug. Other forms of heroin are used in other ways. White heroin, for example, is the most chemically pure form of the drug, and it is typically snorted or injected. It cannot be smoked because it has a high melting point. Black tar heroin is commonly found on the West Coast of the United States and in neighboring states. Despite the name, it is usually dark brown, even dark orange. It is melted or dissolved into a solution and then injected. Brown powder heroin does not dissolve easily in water, so it is rarely injected and is instead smoked.
Heroin dealers often add other substances to the product, a process known as cutting. Cutting is done so they can artificially increase their products or to increase the effects of the heroin they sell. Common cutting agents include:
Users tend to not know what they are buying when they purchase heroin, often because they are so desperate to get high again that they will merely trust that their dealer is giving them pure heroin. While injecting heroin is threatening enough on its own, injecting other substances, such as cocaine, can be unfathomably riskier and cause additional health problems.
Heroin has become the household name of the opioid epidemic, but one of the troubling problems that has evolved from the crisis has been the spread and use of fentanyl. Fentanyl is a synthetic opioid (completely laboratory manufactured) that is 80 times stronger than morphine and hundreds of times more so than heroin. Unlike heroin, fentanyl has legitimate medical applications – it is prescribed for post-operative pain management – but it is a Schedule II substance in the United States, meaning that it is subject to some of the tightest production and distribution controls in the country. Heroin, on the other hand, is a Schedule I substance, which means that it has no accepted medical use, and it is not legal to make or distribute under any circumstances.
Fentanyl was originally synthesized in 1960, and it became a drug of abuse shortly after that. During the 1970s, it was one of many controlled substances that did the rounds, but it was only after the explosion of opioid-based painkillers in the 1990s and 2000s, and the heroin boom that followed, that fentanyl has driven what MedScape calls “the third wave” of the American opioid crisis.
Like heroin, fentanyl is a full opioid agonist. This means that when its molecules bind to an opioid receptor in the central nervous system, they activate it to its fullest possible degree. This creates painkilling and euphoric sensations unlike any other, and also gravely increases physical and psychological dependence on fentanyl.
Between 2005 and 2007, there were 1,013 fentanyl-related deaths in America, according to the Centers for Disease Control and Prevention. In many parts of the country, fentanyl has been implicated in more opioid overdose deaths than heroin; Northern California experienced 50 overdoses in three weeks, and two counties in Long Island lost more people to fentanyl than heroin. In New Hampshire, heroin killed 32 people in 2015; fentanyl killed 158, to the point where law enforcement and public health officials now refer to the opioid epidemic as “a fentanyl epidemic.”
Heroin and fentanyl are both lethal drugs, but while it takes 30 milligrams of heroin to cause a fatal overdose, it takes only 3 milligrams of fentanyl to cause the kind of respiratory failure to induce a coma or death. Unfortunately, explains Stat News, drug users tend to be unaware when their heroin has been cut with fentanyl. Dealers do this to cut down on their costs and to get a reputation for selling the most potent product. Addicted users, however, are usually so desperate for a fix and undiscerning about how it comes that many buy what they think is heroin and end up unwittingly injecting themselves with an opioid that needs only 3 milligrams to kill them. Additionally, fentanyl sold illegally is almost always made in an underground lab in China or Eastern Europe, and not as pure as the pharmaceutical version used in hospitals; therefore, there will likely be additional side effects as a result of the adulterants with which it was cut. The director of the New Hampshire State Police compared it to “injecting yourself with a loaded gun.”
The opioid epidemic has led to unprecedented uses of heroin and fentanyl, but it is likely that neither drug would have taken such a hold if not for oxycodone. Oxycodone is the generic name for the brand-name drug OxyContin, which is an opioid medication used in the treatment of moderate to severe levels of pain. The drug is manufactured by Purdue Pharma and approved by the Food and Drug Administration in 1976.
In the mid-1980s, Purdue Pharma embarked on a promotional blitz to market OxyContin not just to doctors, but also directly to patients, with the message that pain did not have to be acceptable. Doctors were lavishly compensated for every OxyContin prescription they wrote and every other physician they got to prescribe OxyContin to their own patients. Patients themselves were subjected to glossy advertising campaigns that espoused the safety and benefits of opioid medications with barely a word on the potential for addiction.
By 2000, Purdue Pharma had to double the size of its salesforce to keep up with the incessant demand for more pain pills, and representatives from the manufacturer were paid upwards of hundreds of thousands of dollars a year. Such was the pressure from the pharmaceutical industry that the Joint Commission, the accrediting organization for over 20,000 healthcare organizations and programs in America, declared pain to be one of the vital signs of medicine, officially adding it to the evaluation criteria of respiration, core temperature, pulse, and blood pressure. This meant that all hospitals and healthcare facilities in America had to monitor pain, even though it is unquantifiable and subjective, and provide appropriate treatment. In 2001, the Joint Commission wrote that “in general, patients in pain do not become addicted to opioids.”
Even the Drug Enforcement Administration agreed to allow doctors to prescribe opioids without fear of prosecution for overprescribing. When stories emerged of addiction, the problem was attributed solely to misuse or abuse of OxyContin, and not because of doctors prescribing wildly unnecessary amounts of the drug. A pain physician and spokesman for Purdue Pharma told the press that “the vast majority of people who are given these medications by doctors will not become addicted.”
In 2009, the American Journal of Public Health wrote that prescriptions for OxyContin for non-cancer-related pain skyrocketed from 670,000 in 1997 to 6.2 million in 2002. That same year, sales of OxyContin passed $1.5 billion. It was a “commercial triumph,” wrote the journal, but a “public health tragedy.” In 2012, OxyContin alone accounted for 30 percent of the painkiller market. From 1991 to 2013, the number of annual opioid prescriptions went from 76 million to 207 million, but it became evident that as Purdue Pharma’s stock went through the roof, more and more patients who were prescribed OxyContin for their chronic pain and work-related injuries were falling prey to abusing the drug.
With rising numbers of overdoses, the Department of Justice charged Purdue Pharma with being misleading about the addictive nature of the drug. In 2007, Purdue pleaded guilty and paid $600 million in fines, with three company executives admitting to misbranding OxyContin’s risk of abuse and addiction.
To address the misuse of OxyContin, Purdue reformulated the medication in 2010 and withdrew the original version from sale. The new formulation was designed to be harder to abuse, and this was moderately successful in that goal. Unfortunately, this also had the effect of driving desperate users to heroin, which provided a stronger and cheaper narcotic experience than the new OxyContin. Researchers discovered that the death rates from OxyContin peaked in August 2010 and then flattened; heroin deaths rose literally the next month.
By the 2010s, OxyContin had fallen out of favor so drastically that the FDA refused to approve generic oxycodone, leaving Purdue Pharma as the only authorized manufacturer of oxycodone products in the US. However, the victory was bittersweet; in 2018, Purdue announced that it would no longer market OxyContin and other opioid medications to doctors and slashed its sales force by half.
Between 1999 and 2014, more than 165,000 people died from overdoses from prescription opioids alone and thousands more from illegal opioid use that likely started with prescription drugs. The former commissioner of the Food and Drug Administration wrote in The New York Times that the belief that opioids were safe to use was “one of the biggest mistakes in modern medicine.” The difficulty now is that many people fear they will be denied access to the opioids they need to manage their chronic pain – everything from HIV/AIDS or surgery to cancer – because of the national stigma surrounding everything to do with opioids. Walmart, for example, is restricting initial acute opioid prescriptions. Similar moves have been opposed by patient advocacy groups and doctors, who claim patients with legitimate medical needs are being harmed by the heavy-handedness of prescription control. The debate suggests that although much has been done to right the wrongs that started the opioid epidemic, the way forward with opioids remains unclear.