For millennia, human survival depended on the drive to seek out pleasure and avoid pain. When we do something beneficial — like eating when hungry or seeking shelter when cold — our brain releases dopamine, a chemical messenger that makes us feel good and reinforces the behavior.

“The reward pathways in our brains have actually been conserved over millions of years of evolution and across species,” said Stanford Medicine’s Anna Lembke, MD, a professor of psychiatry and behavioral sciences and author of the bestselling book Dopamine Nation. “Even the most primitive worm will be driven by this reward system to move toward food.”

This system worked beautifully in environments of scarcity. Pursuing things that released dopamine was, indeed, more important than anything else.

In modern times, however, humans have become inundated with easy access to things that light up this reward pathway in the brain: sugary and salty food, nicotine, alcohol, drugs, slot machines, and digital media, among others. All are engineered to deliver a faster, more intense dopamine spike than anything in nature.

“In the 19th century, this reward mechanism went from being a minor concern to a significant liability,” said Humphreys, the Esther Ting Memorial Professor. “People’s brains are treating harmful substances and behaviors as if they literally need them to stay alive.”

It’s about that dopamine rush

When addictive substances and behaviors repeatedly cause an exaggerated surge of dopamine, the brain compensates by reducing the number and sensitivity of dopamine receptors — the molecules that detect dopamine. As a result, it becomes harder to feel pleasure, not just from the drug but also from everyday life.

“People use more just to feel normal,” Lembke said.

Nicotine offers an example of how this works. When someone smokes or vapes nicotine, the chemical binds to receptors in the brain, causing a cascade that releases dopamine and other signaling molecules.

“That combination can improve focus, elevate mood and even suppress appetite, but the effects are short-lived,” explained Jodi Prochaska, PhD, a Stanford Medicine clinical psychologist who studies tobacco addiction.

To maintain the desired effect, users end up dosing frequently — about 200 puffs per day for someone who smokes the equivalent of a pack. Over time, the brain creates more receptors to accommodate the constant input.

“You’re no longer smoking to get high. You’re smoking to avoid withdrawal,” said Prochaska.

Humphreys described this process — which also occurs with addictions to substances such as alcohol and opioids — as “maladaptive learning.” The brain starts treating the substance as more important than basic needs like food, safety or connection.

“Although someone might begin using a substance or behavior to have fun or solve a problem, our brains adapt and we stop getting the same effect,” Lembke said. “Now they need more of the substance, or a more potent form, to get the same effect and prevent withdrawal.”

Straddling the impulse-action line

Some people are more vulnerable to addiction than others. Genetics account for roughly 50% to 60% of the risk, according to family and twin studies. Traits like impulsivity, emotional dysregulation and certain mental health conditions — including attention deficit/hyperactivity disorder and bipolar disorder — also increase susceptibility.

“People who have a harder time pausing between impulse and action are more at risk,” Lembke said.

Age plays a key role, too. Studies have shown that the younger someone is when they start using a substance, the more likely they are to become addicted — and the more quickly they become addicted.

“The brain is still developing until about age 25,” Prochaska noted. “That’s why delaying the start of substance use is so important.”

Researchers have found a handful of genetic markers that explain individual differences in addiction vulnerability, but some of the most useful clues are easy to spot.

“You can do a million genetic analyses,” Humphreys said, “but nothing beats asking: ‘Were your parents addicted?’”

That said, people not classically at risk for addiction are now being diagnosed with opioid, gambling, social media, sex, pornography and other addictions that all affect the same dopamine pathways in the brain.

“We have so many more drugs than we used to, and they are so much more potent than older drugs, that even people who thought of themselves as immune to addiction are now experiencing problems with compulsive overconsumption,” Lembke said.

The struggle to quit is real

A better understanding of what occurs in brain cells during addiction is beginning to reshape how clinicians treat addictions.

“The science informs our treatment because we now know that people who are addicted have gone outside of our normal homeostatic boundaries in the brain,” Lembke said. “A major goal of addiction treatment is to return patients to that healthy balance, and there are a number of ways to achieve that, depending on the substance.”

The number one way, Lembke said, is abstinence. She recommends a 30-day “reset” as a way to challenge one’s own relationship with a behavior or substance.

“During those 30 days, people will generally feel worse before they get better, but if they can make it to 30 days, they’ll have gathered their own data on how difficult it was and how they feel when they’re not engaging. They’ll be able to make their own informed decisions about how they want to use a behavior or substance in the future.”

If a 30-day abstinence period seems impossible, it is time to speak with a medical professional, Prochaska said. For nicotine addiction, she said, the go-to treatments include a patch for steady delivery, paired with fast-acting gum or lozenges for cravings. Medications like varenicline (formerly known by the brand name Chantix) reduce withdrawal and make smoking less satisfying. A plant-derived drug called cytisine (branded as Cytisinicline) is in development and shows promise, Prochaska said. Psilocybin is also being studied.

“Nothing new has been FDA-approved since 2006,” Prochaska noted, “but that may be about to change.”

Meanwhile, medications developed for diabetes and weight loss — GLP-1 receptor agonists like Ozempic — have shown unexpected benefits for people struggling with alcohol, food and nicotine use.

“These drugs weren’t designed to treat addiction,” Humphreys said. “But people started reporting that they just didn’t want to drink as much. If it holds up in trials, that’s a big deal.”

Ultimately, these drugs all have different (in some cases unknown) mechanisms to help people through the initial period of abstinence, during which withdrawal symptoms and cravings can make it difficult to refrain. But if abstinence sticks, brain receptors slowly return to a healthy homeostasis.

Trying to rewire addiction pathways

Recovery is possible, but it takes time, and the brain may not return fully to its pre-addiction state.

In the early stages of abstinence, people experience the effects of withdrawal: irritability, poor sleep, low mood, difficulty concentrating. These symptoms typically peak within three days and improve by week four. But that’s not the end of the story.

“Craving can persist for months, even years,” Prochaska said. “That’s partly due to ‘addiction memory’ — the way your brain links the drug to daily routines like coffee or stress or driving.”

Even after brain receptors normalize, environmental triggers can reignite the urge. That’s because the brain — separately from addiction pathways — has learned to associate a behavior with other routines.

“It’s not about willpower,” Lembke emphasized. “It’s about the brain adapting — and sometimes those changes are deep and persistent.”

Still, the brain is remarkably resilient. “With the right support, people can rebuild their natural reward systems,” Humphreys said. “It starts to feel good again to play with your kids, to eat a good meal, to feel connected.”

LISTEN: Keith Humphreys explains how neuroscience is reshaping our understanding of substance abuse—and why policy still hasn’t caught up — on the From Our Neurons to Yours podcast.