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

Now recognized as a physiological brain disease, addiction rewires the brain's reward system to make drugs feel necessary and weaken self-control by dulling the relative effects of natural rewards like food and social connection.

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.

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.

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).

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.

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.

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.

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

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.

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.

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.

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.

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.

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.

The subjectivity of pain means that one person's kidney stones may be another's childbirth, but most sources of pain do have objective, underlying causes.

Diabetes is a hormonal disorder

Hormones are naturally produced in the body in concert with cell receptors, influencing how cells behave, but diseases that affect hormonal production, including those produced by the pancreas or the thyroid, can upend those processes.

Menopause hormone therapy infuses the body with estrogen after the body's natural levels drop

The treatments can treat symptoms like hot flashes and vaginal dryness at varying doses. Progestogen, another hormone, is also typically prescribed with estrogen because estrogen alone can thicken the uterus lining, which elevates the risk of developing endometrial cancer.

Anhedonia, which means 'without pleasure' in Greek, is typical in major depressive disorder

This common symptom—a flat affect—results in previously enjoyable hobbies no longer bringing pleasure. People with anhedonia may also avoid social situations because they anticipate they'll bring no joy, not because of anxiety or fear.

Prolonged stress impairs the prefrontal cortex

Burnout isn't just a feeling—it physically affects the brain. Prolonged stress impairs regions of the brain responsible for decision-making, emotional control, memory, and more. It can also lead to chemical imbalances, like reduced dopamine and norepinephrine levels, that worsen these effects.

Immunosuppressants enable organ transplants, but come with severe side effects

This drug cocktail helps to lower your body's natural response to attack a transplanted organ. Such medications usually need to be taken for a lifetime after receiving an organ and can come with serious side effects including high blood pressure, diabetes, increased risk of some cancers, and high cholesterol, among others.

Surgery before the dawn of anesthesia

The arc toward anesthetics was painfully slow, with early pain mitigation offerings ranging from analgesics—drugs that dim pain but don't block it—and numbing surgical sites with cold water to gassing patients with carbon dioxide or bashing or bleeding them unconscious. Such treatments and the torturous surgery they preceded led many to avoid even life-saving procedures, and those who survived often kept silent about the trauma.

How bitter taste receptors help guard against infection

Receptors for "bitter" tastes evolved to detect potentially harmful plant chemicals, such as nicotine. The receptors also trigger bacteria-fighting responses, including waving hairlike projections to bat away bacteria, ordering the release of bacteria-killing nitric oxide, and calling for antimicrobial protein reinforcements.

Plant hormones and growth regulators guide growth stages and responses in plants

Plants naturally produce hormones like auxin and gibberellins, while humans apply synthetic or extracted growth regulators to control plant development. These substances influence processes like flowering, root growth, dormancy, and ripening—even in very small doses.

Misophonia is a neurological disorder where sounds trigger strong emotions

The phenomenon is characterized by decreased tolerance to specific sounds, such as heavy breathing, pen clicking, and water dripping, which trigger a fight-or-flight response. The resulting emotions, which can range from irritation and disgust to anxiety and fear, can be overwhelming and uncontrollable.

Phantom limb pain may often match the pain or contortion of the injury that led to the limb loss.

Some Ozempic users lose their desire to eat

This essay follows a writer whose Ozempic journey involves a dramatic loss of appetite, leading them to stop compulsive snacking and even lose some of the joy of eating. As a result, he becomes fixated on watching food videos and eventually tries to "beat" an all-you-can-eat steak buffet. The experience leaves him feeling disappointed and lacking in desire.

Overmedication has put type 2 diabetics at risk of low blood sugar

Type 2 diabetics in the US risk dying from low blood sugar, an epidemic traced to a decades-old, multi-million-dollar drug industry campaign encouraging an average blood sugar level below 7%. Contemporary research correlated such levels with reduced risk of eye, nerve, and kidney damage and increased hypoglycemia risk.

Inhalers dilate airways and reduce inflammation

People with asthma suffer from constricted airways in their lungs, whether from muscle pressure, mucus buildup, or inflammation. Inhalers help people breathe medicine directly into their lungs to immediately relieve these symptoms.

Sleep disorders can exacerbate neurological and other health conditions

Brain regions that control sleep sit adjacent to those that regulate the autonomic nervous system, which controls involuntary bodily functions like heart and breathing rates. These neighbors influence each other, meaning poor sleep can impair or negatively impact the ANS, further disturbing sleep.

How the feared self fuels OCD

Obsessive-compulsive disorder is characterized by intrusive thoughts that prompt people to enact compulsions—behaviors intended to relieve the anxiety or stress from the obsession. A significant intrusive thought OCD sufferers endure is the fear they will become a dangerous or immoral person. Therapeutic approaches try to show patients this is just a story that can be set aside.

The body's response to cardiac arrest has been linked to near-death experiences

Most people who report near‑death experiences experience events like out‑of‑body sensations, altered cognition, emotional and spiritual shifts, or even supernatural phenomena, particularly during cardiac arrest. Research suggests many such experiences may be linked to brain-generated sensory distortions that can be experimentally replicated, suggesting a physiological rather than mystical cause.

The second phase of acute stress: the 'slow' response

The body's reaction to acute stress involves two responses: fast and slow. The first occurs immediately, with the central nervous system triggering the release of adrenaline. The second releases cortisol, which elevates blood sugar and blood pressure and restricts nonessential functions like digestion and the immune system.

Myokines are molecules that facilitate some of the benefits of exercise

When muscles contract, they release ‘hope molecules’ (myokines) such as IL-6 and irisin. These proteins then travel through the bloodstream to reduce inflammation, improve insulin sensitivity, and even support brain repair. This piece illustrates how movement triggers a systemic healing cascade throughout the human body.

The word allergy is partly derived from the Greek word 'allos' for 'other'

For people with allergies, their immune systems recognize substances as a harmful "other"—cuing an inflammatory response. This podcast explores allergy details and related topics, including how scientists are interested in if the same allergic response mechanisms could underpin other health issues, including severe, painful symptoms around the time of menstrual cycles. Since estrogen acts on white blood cells called mast cells, which leads to the release of histamines—similar to what happens during allergic responses—an understudied question is whether the same process is fueling some of the uncomfortable symptoms around menstruation. An allergist guest notes this raises questions about if antihistamine medications like Pepsid might alleviate them, something that hasn't yet been explored in clinical trials.