Pain and pleasure rank among nature\u2019s strongest motivators, but when mixed, the two can become irresistible. This is how opioids brew a potent and deadly addiction in the brain. Societies have coveted the euphoria and pain relief provided by opioids since Ancient Sumerians referred to opium poppies as the \u201cjoy plant\u201d circa 3400 B.C. But the repercussions of using the drugs were ever present, too. For centuries, Chinese patients swallowed opium cocktails before major surgeries, but by 1500, they described the recreational use of opium pipes as subversive. The Chinese emperor Yung Cheng eventually restricted the use of opium for medical purposes in 1729. Less than 100 years later, a German chemist purified morphine from poppies, creating the go-to pain reliever for anxiety and respiratory conditions. But the Civil War and its many wounds spawned mass addiction to the drugs, a syndrome dubbed Soldier\u2019s Disease. A cough syrup was concocted in the late 1800s \u2014 called heroin \u2014 to remedy these morphine addictions. Doctors thought the syrup would be \u201cnon-addictive.\u201d Instead, it turned into a low-cost habit that spread internationally. More than 70 percent of the world\u2019s opium \u2014 3,410 tons \u2014 goes to heroin production, a number that has more than doubled since 1985. Approximately 17 million people around the globe used heroin, opium or morphine in 2016.<\/p>\n
Today, prescription and synthetic opioids crowd America\u2019s medicine cabinets and streets, driving a modern crisis that may kill half a million people over the next decade. Opioids claimed 53,000 lives in the U.S. last year, according to preliminary estimates from the Centers for Disease Control and Prevention \u2014 more than those killed in motor vehicle accidents.<\/p>\n
How did we arrive here? Here\u2019s a look at why our brains get hooked on opioids.<\/p>\n
The pain divide <\/strong><\/p>\n Let\u2019s start with the two types of pain. They go by different names depending on which scientist you ask. Peripheral versus central pain. Nociceptive versus neuropathic pain.<\/p>\n The distinction is the sensation of actual damage to your body versus your mind\u2019s perception of this injury.<\/p>\n Your body quiets your pain nerves through the production of natural opioids called endorphins. Pain fibers sense these injuries and pass the signal onto nerve cells \u2014 or neurons \u2014 in your spine and brain, the duo that makes up your central nervous system.<\/p>\n In a normal situation, your pain fibers work in concert with your central nervous system. Someone punches you, and your brain thinks \u201cow\u201d and tells your body how to react.<\/p>\n Stress-relieving hormones get released. Your immune system counteracts the inflammation in your wounded arm.<\/p>\n Your body quiets your pain nerves through the production of natural opioids called endorphins. The trouble is when these pain pathways become overloaded or uncoupled.<\/p>\n One receptor to rule them all <\/strong><\/p>\n Say you have chronic back pain. Your muscles are inflamed, constantly beaming pain signals to your brain. Your natural endorphins aren\u2019t enough and your back won\u2019t let up, so your doctor prescribes an opioid painkiller like oxycodone.<\/p>\n Prescription opioids and natural endorphins both land on tiny docking stations \u2014 called receptors \u2014 at the ends of your nerves. Most receptors catch chemical messengers \u2014 called neurotransmitters \u2014 to activate your nerve cells, triggering electric pulses that carry the signal forward.<\/p>\n But opioid receptors do the opposite. They stop electric pulses from traveling through your nerve cells in the first place. To do this, opioids bind to three major receptors, called Mu, Kappa and Delta. But the Mu receptor is the one that really sets everything in motion.<\/p>\n The Mu-opiate receptor is responsible for the major effects of all opiates, whether it\u2019s heroin, prescription pills like oxycodone or synthetic opioids like fentanyl, said Chris Evans, director of Brain Research Institute at UCLA. \u201cThe depression, the analgesia [pain numbing], the constipation and the euphoria \u2014 if you take away the Mu-opioid receptor, and you give morphine, then you don\u2019t have any of those effects,\u201d Evans said.<\/p>\n Opioids receptors trigger such widespread effects because they govern more than just pain pathways. When opioid drugs infiltrate a part of the brain stem called the locus ceruleus, their receptors slow respiration, cause constipation, lower blood pressure and decrease alertness. Addiction begins in the midbrain, where opioids receptors switch off a batch of nerve cells called GABAergic neurons.<\/p>\n GABAergic neurons are themselves an off-switch for the brain\u2019s euphoria and pleasure networks.<\/p>\n When it comes to addiction, opioids are an off-switch for an off-switch. Opioids hold back GABAergic neurons in the midbrain, which in turn keep another neurotransmitter called dopamine from flooding a brain\u2019s pleasure circuits. Image by Adam Sarraf<\/p>\n Once opioids shut off GABAergic neurons, the pleasure circuits fill with another neurotransmitter called dopamine. At one stop on this pleasure highway \u2014 the nucleus accumbens \u2014 dopamine triggers a surge of happiness. When the dopamine rolls into amygdala, the brain\u2019s fear center, it relieves anxiety and stress. Both of these events reinforce the idea that opioids are rewarding.<\/p>\n These areas of the brain are constantly communicating with decision-making hubs in the prefrontal cortex, which make value judgments about good and bad. When it hears \u201cThis pill feels good. Let\u2019s do more,\u201d the mind begins to develop habits and cravings.<\/p>\n Taking the drug soon becomes second nature or habitual, Evans said, much like when your mind zones out while driving home from work. The decision to seek out the drugs, rather than participate in other life activities, becomes automatic.<\/p>\n The opioid pendulum: When feeling good starts to feel bad<\/strong><\/p>\n Opioid addiction becomes entrenched after a person\u2019s neurons adapt to the drugs. The GABAergic neurons and other nerves in the brain still want to send messages, so they begin to adjust. They produce three to four times more cyclic AMP, a compound that primes the neuron to fire electric pulses, said Thomas Kosten, director of the division of alcohol and addiction psychiatry at the Baylor College of Medicine.<\/p>\n That means even when you take away the opioids, Kosten says, \u201cthe neurons fire extensively.\u201d<\/p>\n The pendulum swings back. Now, rather than causing constipation and slowing respiration, the brain stem triggers diarrhoea and elevates blood pressure. Instead of triggering happiness, the nucleus accumbens and amygdala reinforce feelings of dysphoria and anxiety. All of this negativity feeds into the prefrontal cortex, further pushing a desire for opioids.<\/p>\n While other drugs like cocaine and alcohol can also feed addiction through the brain\u2019s pleasure circuits, it is the surge of withdrawal from opioids that makes the drugs so inescapable.<\/p>\n Could opioid addiction be driven in part by people\u2019s moods?<\/strong><\/p>\n Cathy Cahill, a pain and addiction researcher at UCLA, said these big swings in emotions likely factor into the learned behaviors of opioid addiction, especially with those with chronic pain. A person with opioid use disorder becomes preoccupied with the search for the drugs. Certain contexts become triggers for their cravings, and those triggers start overlapping in their minds.<\/p>\n \u201cThe basic view is some people start with the pain trigger [the chronic back problem], but it gets partially substituted with the negative reinforcement of the opioid withdrawal,\u201d Cahill said.<\/p>\n That\u2019s why Cahill, Evans and other scientists think the opioid addiction epidemic might be driven, in part, by our moods.<\/p>\n Chronic pain patients have a very high risk of becoming addicted to opioids if they are also coping with a mood disorder. A 2017 study found most patients \u2014 81 percent \u2014 whose addiction started with a chronic pain problem also had a mental health disorder. Another study found patients on morphine experience 40 percent less pain relief from the drug if they have mood disorder. They need more drugs to get the same benefits.<\/p>\n People with mood disorders alone are also more likely to abuse opioids. A 2012 survey found patients with depression were twice as likely to misuse their opioid medications.<\/p>\n \u201cSo, not only does a mood disorder affect a person\u2019s addiction potential, but it also influences if the opioids will successfully treat their pain,\u201d Cahill said.<\/p>\n Meanwhile, the country is living through sad times. Some research suggests social isolation is on the rise. While the opioid epidemic started long before the recession, job loss has been linked to a higher likelihood of addiction, with every 1 percent increase in unemployment linked to a 3.6 percent rise in the opioid-death rate.<\/p>\n Can the brain swing back?<\/strong><\/p>\n As an opioid disorder progresses, a person needs a higher quantity of the drugs to keep withdrawal at bay. A person typically overdoses when they take so much of the drug that the brain stem slows breathing until it stops, Kosten said.<\/p>\n Many physicians have turned to opioid replacement therapy, a technique that swaps highly potent and addictive drugs like heroin with compounds like methadone or buprenorphine (an ingredient in Suboxone).<\/p>\n These substitutes outcompete heroin when they reach the opioid receptors, but do not activate the receptors to the same degree. By doing so, they reduce a person\u2019s chances for overdosing. These replacement medications also stick to the receptors for a longer period of time, which curtails withdrawal symptoms. Buprenorphine, for instance, binds to a receptor for 80 minutes while morphine only hangs on for a few milliseconds.<\/p>\n For some, this solution is not perfect. The patients need to remain on the replacements for the foreseeable future, and some recovery communities are divided over whether treating opioids with more opioids can solve the crisis. Plus, opioid replacement therapy does not work for fentanyl, the synthetic opioid that now kills more Americans than heroin. Kosten\u2019s lab is one of many working on a opioid vaccine that would direct a person\u2019s immune system to clear drugs like fentanyl before they can enter the brain. But those are years away from use in humans.<\/p>\n And Evans and Cahill said many clinics in Southern California are combining psychological therapy with opioid replacement prescriptions to combat the mood aspects of the epidemic.<\/p>\n \u201cI don\u2019t think there\u2019s going to be a magic bullet on this one,\u201d Evans said. \u201cIt\u2019s really an issue of looking after society and looking after of people\u2019s psyches rather than just treatment.<\/p>\n Source: http:\/\/www.pbs.org\/newshour\/updates\/brain-gets-hooked-opioids\/ <\/em><\/p>\n","protected":false},"excerpt":{"rendered":" Pain and pleasure rank among nature\u2019s strongest motivators, but when mixed, the two can become irresistible. This is how opioids brew a potent and deadly addiction in the brain. Societies have coveted the euphoria and pain relief provided by opioids since Ancient Sumerians referred to opium poppies as the \u201cjoy plant\u201d circa 3400 B.C. 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\nStuff that damages your skin and muscles \u2014 pin pricks and stove burns \u2014 is considered peripheral\/nociceptive pain.<\/p>\n