For centuries, societies have coveted opioids for the euphoria and the pain relief they provide. In the 1800s, when chemists extracted morphine from opium poppies, it became the go-to treatment for the American Civil War. After morphine caused widespread addiction, drug companies invented what they thought was a “non-addictive” substitute: a cough syrup called heroin. That turned out poorly for the 20th century. Today, prescription opioids, like fentanyl and oxycodone, crowd America's medicine cabinets and its streets. Opioid overdoses now kill more Americans every year than car accidents But to understand how we arrived here, you’ll need to venture deep into the mind. Here’s why our brains love opioids. When opioids enter the brain, they land on tiny docking stations at the ends of your nerves called receptors. Typically, the receptors catch chemical messengers, called neurotransmitters, to activate your nerve cells. Opioid receptors do just the opposite. They stop electric pulses from traveling through your nerve cells, also known as neurons. This dampening is handy with pain relief. Say you have chronic back pain. Your inflamed muscles are constantly sending pain signals to your brain via neurons in your spine. Opioids quiet those nerves, relieving your pain. Opioids have three major receptors: Mu, Kappa and Delta. But the Mu receptor is the one to remember. The Mu receptor is responsible for the consequences of almost all opiates. It slows breathing, eliminates pain and fills the mind with warm euphoria. But too much of this opioid off-switch becomes addictive. Opioid addiction starts in the midbrain, where Mu-opioid receptors turn off a batch of nerve cells called GABAergic neurons. GABAergic neurons are themselves an off-switch for pleasure. They prevent other midbrain neurons from flooding the brain’s pleasure circuits with another transmitter, dopamine. It was definitely a party at first and it felt...it was fun, you know. No consequences right away. At one stop along these pleasure circuits, the nucleus accumbens, the dopamine triggers a surge of happiness that reinforces the idea that opioid drugs are rewarding. And in our brain’s fear center, the amygdala, the dopamine relieves anxiety and stress. It’s just an overall sense of well-being. No problems, just warm. Decision-making brain areas become overwhelmed and cravings set in. All drugs come with a dark side as they clear the body. This is known as withdrawal. Too much beer causes a hangover the next day. ALL: Cheers Ugh... ...what the hell? A cocaine high is followed by a crash. But opioids, especially long-lasting ones like methadone, don’t change a person’s outward behaviors. You can still drive and go to work. I was a functioning addict. I worked at a real estate company. I was a broker with over 900 agents. However, opioids cause brain circuits to slowly adopt a new state of normal. Soon, without opioids in the body, addicts feel constantly anxious and their stress hormones stay elevated. I just remember waking up and everything was blurry and I felt really bad. Opioids typically trigger constipation and tweak body temperature. Remove them, and a person with opioid dependence has persistent diarrhea, hot and cold sweats and goosebumps. Some describe opioid withdrawal as the sickest feeling they’ve ever had, and the desperate hunger for relief drives addiction. I had an Oxycontin in my jeans pocket and I couldn't find it and I remember just crawling all around on the ground and I didn't know what was happening to me. Here’s the dangerous kicker. The potency of opioids diminishes over time if you abuse them. Eventually, rather than remedy your chronic back problem, your pain becomes linked with the emotional and physical toil of opioid withdrawal. It becomes a vicious cycle. Popping more painkillers or injecting heroin more frequently becomes the way to keep all those bad feelings at bay. Or if you started recreationally, the struggle against withdrawal becomes all consuming. You keep chasing that high and you never get that original feeling again. You kind of get immune to it. You’re just maintaining... and then without it, you're sick.