Sue Grigson’s research could help change the way we treat addiction

Neuroscientist Patricia “Sue” Grigson, PhD, has helped shift the addiction paradigm. Her research has demonstrated that addiction is more than a psychological state—it’s a physiological need.

Grigson’s research explores how drugs of abuse hijack the brain’s learning, memory, and motivation systems. Over the course of her decades-long career, she has published more than 90 peer-reviewed studies, including groundbreaking research on reward comparison—a hypothesis that suggests stimuli become less pleasurable when something better (like a drug) is anticipated.

Now, Grigson, the chair of neuroscience and experimental therapeutics at Pennsylvania State University College of Medicine, is among the first group of researchers investigating a potential new addiction therapy: GLP-1s.

In recent years, GLP-1s—shorthand for GLP-1 receptor agonist—have exploded in popularity as a treatment for diabetes and obesity. One in eight Americansopens in new window report having used one. These medications don’t just curb hunger and lower blood sugar; they also dampen “food noise.” People taking them find that their background chatter about food dies down. They don’t feel such a strong need for it. Grigson’s work, which has received several million dollars in funding from the National Institutes of Health, suggests that GLP-1s could do something similar for people struggling with substance use disorder. “If we think of addiction as a state of needing, well, maybe GLP-1s can reduce that need state like it has for food,” Grigson says.

For many years, it was assumed that people develop addictions simply because taking substances feels good, Grigson says. Then, in the late 1980s, scientists identified two separate waysopens in new window that the brain responds to rewards. They found that “liking,” the feeling of pleasure elicited by a substance, and “wanting,” the urge to consume that substance, were associated with totally different patterns of activityopens in new window in the brain. While “liking” showed up as isolated activity in small hotspots throughout the brain, “wanting” was associated with much more widely spread dopamine signaling in the brain’s reward center. The implication: it was possible to want a drug without liking it, and vice versa.

Grigson began her career in neuroscience around the same time that researchers were developing the “liking” vs. “wanting” paradigm. Early research of hers demonstrated that rats cued to expect cocaine with saccharin, a sweetener, entered a state of extreme stress in anticipation of the drug. In response to the sugary substance, dopamine levels plummeted and they began exhibiting grimaces of discomfort and disgust, as though they’d been presented with a poison. Only cocaine could bring these rats relief. “The more bad faces they made in reaction to the cue, the more cocaine they took and the faster they were to run to the cocaine,” Grigson says.

This extreme response led Grigson to believe in a third pillar to the brain’s response to rewards: needing. “Needing, we think of as a step beyond wanting,” Grigson says. Recent unpublished data from Grigson’s lab suggests that this state involves yet another pattern of brain activity, which engages fight-or-flight neurons in the brain stem.

Grigson defines “needing” as a physiologically painful state that goes beyond an urge or craving, similar to thirst or hunger. “When one is in desperate need of water, for example, food or salt will not satisfy this need—only water,” Grigson says. Similarly, “the need for the drug can be satisfied only by the drug.”

About 10 years ago, Grigson started looking for a satiety agent—a drug that satiates hunger—to study in relation to drug addiction. Because she saw addiction as a need similar to hunger, she hypothesized that such a medication would also blunt the need for drugs of abuse. 

She first learned of GLP-1s at a meeting of the Society for the Study of Ingestive Behavior. At that point, some scientists were already noticing the effects of GLP-1s on substance use. One report, presented at the 2011 meeting of the American Diabetes Association, noted that patients taking these drugs for diabetes tended to reduce their alcohol consumption. Meanwhile, the hallmarks of alcohol’s rewarding effects—like spikes in dopamine opens in new windowand increased physical activityopens in new window—appeared blunted in mice given GLP-1s, suggesting that the drug had altered the way the brain’s reward system responded to alcohol. 

Grigson and her lab were able to secure funding from the National Institute on Drug Abuse to investigate GLP-1s as a potential therapy for opioid addiction. The results of the team’s first study, published in Behavioral Pharmacologyopens in new window, were promising. The researchers cued rats to expect heroin after being fed saccharin. Soon, the rodents started avoiding the saccharin in anticipation of a heroin reward. The scientists then started the rodents on a GLP-1. After 16 days, the rats didn’t run to the heroin as quickly when it was presented to them. After another nine days, they returned to eating the saccharin. 

Subsequent animal research has shown that GLP-1s block what Grigson calls “the three roads to relapse”—environmental cues (like the saccharin in that first study), the drug itself, and stress. “These drugs are very, very protective,” Grigson says. 

In recent years, Grigson’s lab has expanded its research to include clinical trials in humans. In one small study, supported by a UG3 grant from the National Institute on Drug Abuse, 20 patients in treatment for opioid use disorder at a Pennsylvania residential treatment center took the GLP-1 injectable liraglutideopens in new window or a placebo. The results of the double-blind, fully randomized study, which Grigson conducted alongside Penn State College of Medicine’s Scott Bunce, PhD, was presented at a 2024 meeting of the Association for the Advancement of Science. It found that after three weeks, cravings dropped by 40%. But it didn’t take long for the drugs to kick in, Grigson says. Some participants noticed their cravings disappear within a day. To Grigson, that indicates it may be possible to take GLP-1s as needed to protect against relapse in triggering situations. 

Currently, Grigson’s team of coinvestigators at Penn State College of Medicine, including Tim Brick, PhD, Scott Bunce, PhD, and Jen Nyland, PhD, is one year into a larger clinical trial, in which 200 patients at an outpatient treatment facility are taking either a semaglutide (Ozempic) or placebo alongside methadone or buprenorphine. The hope is that the additional medication will keep patients safe from relapse in case they have to stop taking GLP-1s or develop a tolerance to them—which Grigson has found to be a risk of long-term use. “We do worry what happens when you stop these things. How are people going to feel?” Grigson says. “But we worry a little less when they’re taking methadone or buprenorphine. They’ll have backup protection.”

GLP-1s aren’t yet FDA-approved to treat addiction. But already, Grigson has received letters from people whose lives have been changed by these drugs. One person wrote that he had tried for years to taper off the buprenorphine and naloxone prescription medication Suboxoneopens in new window—he’d get down to just a milligram or two before developing debilitating withdrawal symptoms. Since starting a GLP-1, he’d been able to come off Suboxone completely with no symptoms whatsoever. “I kept waiting for them to start, but they never did,” he wrote.

Grigson hopes that in the future, these drugs won’t just change lives, but also reduce the stigma around addiction by demonstrating that it’s a brain disorder with a physiological basis, not a matter of willpower. “In my mind, there’s no teasing psychology from physiology,” Grigson says. “These drugs show that it’s all intertwined.”