Opioids mimic naturally produced endorphins to dull pain.

The body produces its own opioids that act on several receptor types throughout the body, triggering the release of dopamine and suppression of noradrenaline, neurotransmitters associated with reward and alertness, respectively.

Overuse of opioids can lead to hypersensitivity to pain.

Why the human brain loves opioids

When opioids enter the brain, they dock in receptors, blocking electrical pulses such as those that communicate pain. They also trigger the release of dopamine, a neurotransmitter tied to motivation and associated with stress relief.

Opioids are a class of drugs including fentanyl, heroin, oxycodone, and more.

Methadone binds to the same receptors as heroin and other opioids

Methadone is a long-acting opioid agonist that works by binding to the same brain receptors as other opioids (like heroin or morphine), but without producing intense euphoria. It reduces withdrawal symptoms and cravings, helping people stabilize and avoid illicit opioid use.

Synthetic opioids: a historical and clinical review

In the 19th century, researchers began synthesizing and isolating poppy plant alkaloids, leading to the invention of morphine, codeine, heroin, oxycodone, and others. These highly addictive variants eventually gave rise to illicit use and a widespread underground market, laying the foundation for the current opioid crisis.

Opium is a milky liquid substance extracted from unripe poppy plant seeds

It's been used for ages to reduce pain and induce euphoria, both of which are side effects of the plant's alkaloids—nitrogen-based compounds with pronounced physical effects. Isolating and synthesizing derivatives of these naturally occurring chemicals enabled the invention of morphine, heroin, and other opioids.

Narcan is an opioid antagonist that can rapidly reverse overdoses

Naloxone, also known by the brand name Narcan, is an opioid-overdose reversal medication that typically begins working within a few minutes. An opioid antagonist, the treatment attaches to opioid receptors without activating them, forcing opioid molecules out of their respective receptors and allowing users' breathing rates to normalize.

Fentanyl can be up to 100 times more potent than morphine

A synthetic opioid, fentanyl is highly addictive and incredibly fast-acting—a fatal dose is equal to a few grains of table salt. Once it enters the body, fentanyl floods naturally occurring opioid receptors, which can cause the body to shut down its breathing reflex, leading to a fatal overdose.

Addictive drugs can cause dopamine levels to become ten times higher than normal.

Naltrexone blocks the reward effects of alcohol and opioids

Naltrexone is used to treat alcohol and opioid dependence, blocking opioid receptors in the brain, reducing cravings, and preventing the euphoric effects of alcohol or opioids. It is nonaddictive and works best as part of a comprehensive treatment plan, including counseling or therapy, to support long-term recovery.

Fentanyl is better at crossing the blood-brain barrier than other opioids

Among opioids, fentanyl is uniquely adept at crossing the blood-brain barrier—the brain's security fence against harmful substances. This enables a lightning-fast high. It ends just as quickly, sometimes within minutes (where a heroin high lasts hours), and still results in the same withdrawal symptoms.

Anesthetics slow brain activity by promoting inhibitory neurotransmitters

Drugs like propofol and isoflurane increase activity at the GABA receptor, which opens chloride channels. These ions enter neurons and hyperpolarize them, making them less likely to fire. Dexmedetomidine instead blocks norepinephrine receptors in the brainstem to sedate patients.

Why are drug dealers putting fentanyl in everything?

A few grains of fentanyl, a synthetic opioid far more potent than heroin or morphine, are enough to kill a typical adult human. It's made its way into other, less lethal street drugs, where it may be used to increase the highs experienced by unknowing users, increasing their likelihood of addiction and overdose.

Drug tolerance and withdrawals are consequences of overloading dopamine circuits

Addictive substances or behaviors will typically flood our brains with more dopamine than usual. In response to the overstimulation, our brains will decrease the number of available dopamine receptors. This results in the need for more stimulus for the same response (tolerance) and a rise in negative feelings when the stimulus is absent (withdrawal).

Why is fentanyl poisoning street drugs?

A few grains of fentanyl, a synthetic opioid far more potent than heroin or morphine, is enough to kill a typical adult human. It's made its way into other, less lethal street drugs, where it may be used to increase the highs experienced by unknowing users, increasing their likelihood of addiction and overdose. This 39-minute podcast episode is the first half of a two-part series exploring fentanyl's rise.

Morphine, heroin, codeine, and more were derived from opium

Opium reached the US at about the time early colonists were itching for ways to soothe aches and pains. The active ingredient in the substance was isolated in the early 19th century, eventually leading to the manufacture and commercial sale of morphine, heroin, and other opium-based drugs.

From prescriptions to street drugs: Opioids trajectory across America

Exclusive data obtained by The Washington Post from the Centers for Disease Control and Prevention shows how individual counties moved through three waves of the opioid crisis, each wave paving the way for the next. Between 2011 and 2017, the drug responsible for the majority of overdose deaths shifted from prescription pills to heroin to fentanyl. Together, oxycodone, hydrocodone, heroin, and fentanyl have been major drivers in declining life expectancy in the US.

Love and heartbreak trigger powerful, neurochemical-driven changes in the body

The feeling of falling in love floods the brain with dopamine, oxytocin and serotonin, which collectively dull pain and boost immunity. However, the loss of these chemicals during a break-up produces withdrawal-like symptoms and heart issues, such as high blood pressure.

Opioid prescription rates by states and counties

The origins of the US' ongoing opioid crisis are typically traced to the more than 1 billion prescription pain pills that flooded medicine cabinets between 2005 and 2019. This prescription opioid epidemic resulted in more than 210,000 fatal overdoses and set the stage for the ongoing crisis fueled by heroin and fentanyl.

One person dies from opioids every 7 to 8 minutes

This collection of infographics by the National Institute for Health Care Management helps put the crisis into perspective. The opioid epidemic has had three waves. Opioid-related deaths increasingly involve synthetic versions of the drug class, contributing to 83 percent of all opioid-related deaths in 2020. Use these infographics to learn more about the crisis.

The three waves of the opioid crisis: overprescription, heroin, and fentanyl

The US opioid crisis has unfurled in three distinct waves, each spiraling into an epidemic that's killed millions. The first crested in the 1990s with the overprescription of opioids for pain relief. The second manifested as heroin overdoses in the 2010s. The third began in 2013 with the rise of deaths related to tramadol and fentanyl.

Addiction develops when the pleasure circuits in the brain get overwhelmed

Normal pleasure circuits become overwhelmed by addictive substances, triggering dopamine floods many times stronger than those induced by everyday reward experiences. The understanding of addiction as a brain disease has led to treatments pairing medication and counseling.

Drugs 101: An interactive guide

What's the difference between opioids and psychedelics? This guide details specific drugs and their various associated effects. Drugs in this wheel fall into seven categories: stimulants, depressants, empathogens, psychedelics, dissociatives, cannabinoids, and opioids.

What exactly is dopamine?

Dopamine is a neurotransmitter—a chemical released by neurons that enables neural communication—that makes people want things with an "almost animalistic desire," compelling them to snack or check phone notifications. Often misrepresented as a "pleasure" chemical, dopamine is involved in motivation, learning, attention, habit formation, and more. Trends like dopamine fasting overinflate its role in mental health and often use it as part of "straw man" biohacking claims.

Fast, cheap, and deadly: How fentanyl replaced heroin and hooked America

This interactive article details how fentanyl has largely replaced heroin in the drug trade, with fatal results. Fentanyl was first developed in 1959 as an anesthetic for pain relief, but the drug took hold in the US black market in 2014 and has since exploded in the intervening decade.

Evidence of opium use dates to as early as 5000 BCE

Archaeological evidence shows the use of the poppy plant for its pain-killing properties likely originated in the Mediterranean before making its way to the East and West via trade. It has since inspired two eponymous wars, and highly addictive derivatives of the naturally occurring substance have led to an ongoing overdose crisis.

Opioid epidemic 101: lawsuits and settlements

State and local governments trying to address the opioid epidemic have sued organizations they believe started and supported the crisis. Companies that made, distributed, or contributed to sales of the highly addictive painkillers are expected to pay more than $50B in settlements. These settlements specifically state that at least 85% of settlement funds must be spent on addressing the epidemic, though where exactly the money is going is unclear.

The story of the Sackler empire behind highly addictive OxyContin

This investigative report examines how the Sackler family built its fortune through Purdue Pharma’s aggressive marketing of OxyContin, a highly addictive painkiller. Through 2017, the drug had generated more than $30B in sales for Purdue Pharma, controlled by the Sacklers.

Your favorite music can minimize physical pain, according to a 2025 study on how music can bring solace and address pain.

Learn about the point of the physical and emotional experience of pain, which has three broad categories that help determine treatment approaches.

The Cincinnati Enquirer's Pulitzer-winning look at the opioid epidemic

Synthetic opioids kill someone in the US every 16 minutes. Communities across the country have been ravaged by deaths, overdoses, jail time, and babies born with drug-related medical problems as opioid abuse became a typical feature of many American towns. This seven-part exposé provides an inside look at the effect in southern Ohio and northern Kentucky.

Researchers have investigated the benefits of extreme pain rituals, exploring how and why we engage in these events when humans generally naturally avoid pain and perceive it as a negative experience.

Touch deprivation can heighten anxiety and depression

Pacinian Corpuscles are pressure receptors just under the skin that send signals to the vagus nerve in the brain—that's the cranial nerve which regulates involuntary actions like breathing, heart rate, and the general "fight or flight" response. Activating those receptors can slow the heart, decrease blood pressure, and lead to the release of oxytocin and cortisol. The absence of touch, conversely, can promote negative feelings.

Opium's history traces from religious use to mass-market commercial products

Religious or medical use of opium was present across Europe and Asia as early as 5000 BCE. By the 16th century, humanity had come to see opium as more than medicine: It was a marketable product. This perspective also defines today's relationship with opioids, highly addictive painkillers at the heart of an ongoing drug crisis.

Explore the biology of pain and why the experience of pain may differ widely from one person to another.

Itching is caused by stimulated nerve cells in the skin

Scratching produces low-level pain signals to the brain, distracting from the itch. Scratching also releases serotonin, a neurotransmitter that creates a happy sensation, which resets the itch signal. This can cause a cyclical itch-scratch cycle.

This is the human brain on the world's strongest psychedelic

Within seconds of inhaling a high dose of vaporized synthetic 5-MeO-DMT—a lab-produced substance that otherwise is naturally derived from the glands of the Colorado River toad—it induced slow brain waves. Such waves are typically associated with unconsciousness due to a coma or anesthesia, perhaps explaining why users describe feeling like everything falls away. The compound is currently in clinical trials for treating depression.

Learn about the US opioid crisis in this free course

Where did the US opioid crisis come from, and how did it spread? Learn this and more in this free, online Harvard University course. Learn about the disease model of addiction treatment and management, and get up-to-date with public health and law enforcement's current harm reduction practices. This free resource gives users a greater understanding of opioid addiction and the epidemic still haunting the US.

See how DOJ prosecutors took down a pharmaceutical company's executives over the opioid crisis

This FRONTLINE documentary follows federal prosecutors as they used anti-racketeering laws to convict executives at Insys Therapeutics, a pharmaceutical company that bribed doctors to overprescribe a fentanyl painkiller.

Doctors ignored women's pain as a nurse replaced their fentanyl with saline

This five-part podcast series, produced by Serial Productions, focuses on the experiences of women undergoing fertility treatments at a Yale clinic where a nurse secretly replaced pain medication with saline solution. This led to women experiencing excruciating pain during procedures, but the clinic downplayed or ignored their complaints.

A 201-level at how GLP-1 drugs lead to appetite reduction

It's well-established that drugs which mimic the hormone GLP-1 can help people lose weight and control blood sugar levels, primarily through appetite reduction. This technical review provides an overview of how both natural and therapeutic GLP-1 interacts with the gut and brain to produce its effects.

Theories vary on why we love to eat spicy food—even when it hurts.

Researchers are studying roller coasters to improve mental health treatments

Scary rides stimulate our fight-or-flight response while simultaneously releasing feel-good endorphins like dopamine, serotonin, and oxytocin. Once we realize we're in a safe space, we can enjoy the ride and even feel confident and relieved by the accomplishment of overcoming a fearful feat.

Skull bone marrow may be playing a key role in chronic pain.

A major dopamine hit from social media use comes from unpredictability—not knowing if the content users post or share will get the 'like' from other users, triggering cycles of anticipation similar to those experienced with a slot machine.

Stress activates the "fight-or-flight" response when we face threats, a reaction that can help keep us alive.

Fame can trigger addictive, drug-like highs in the brain

Differences in the type of fame, such as movie stardom, sports, and internet virality, can produce varying degrees of dependence on individuals based on their age and background. Some individuals—particularly children—can develop drug-seeking behavior as they pursue continuous dopamine spikes if they lack an existing sense of fulfillment from elsewhere.

LSD-like drugs may inspire new antidepressants

LSD and psilocybin have shown promise as antidepressants. Using a virtual library of similar chemical compounds, researchers determined via animal studies that two molecules inspired by LSD have antidepressant effects without any associated hallucinogenic experience. These molecules were found to be 40 times more potent than the common antidepressant fluoxetine, also known as Prozac, with antidepressant effects lasting up to 21 days.

Certain medications that affect blood flow or mood boost the risk of heatstroke

Drugs that narrow blood vessels, beta blockers that regulate blood pressure, diuretics, antidepressants, and antipsychotics can all affect the body's ability to regulate its internal body temperature, and so individuals taking these medications need to take special care in extreme heat and when exercising in hot conditions.