For much of his life, 32-year-old Michael Smith had a war going on in his head.

After a big meal, he knew he should be full. But an inexplicable hunger would drive him to pick up the fork again. Cravings for fried chicken or gummy bears overwhelmed him, fueling late-night DoorDash orders that – despite their bounty of fat and sugar — never satisfied him.

He recalls waking up on the couch, half-eaten takeout in his lap, feeling sluggish and out of control. “It was like I was food drunk,” recalls Smith, who lives in Boston. “I had a moment I looked at myself in the mirror. I was around 380 pounds, and I said, ‘OK, something has got to give.’”

Smith is among the 42% of U.S. adults living with obesity, a misunderstood and stubbornly hard-to-manage condition that doctors have only recently begun to call a disease. Its root causes have been debated for decades, with studies suggesting everything from genes to lifestyle to a shifting food supply loaded with carbohydrates and ultra-processed foods. Solutions have long targeted self-discipline and a simple “eat less, move more” strategy with remarkably grim results.

Those who successfully slim down tend to gain back 50% of that weight within 2 years, and 80% within 5 years. Meanwhile, the obesity epidemic marches on. But a new frontier of brain-based therapies – from GLP-1 agonist drugs thought to act on reward and appetite centers to deep brain stimulation aimed at resetting neural circuits – has kindled hope among patients like Smith and the doctors who treat them. The treatments, and theories behind them, are not without controversy. They’re expensive, have side effects, and, critics contend, pull focus from diet and exercise. Butmost agree that in the battle against obesity, one crucial organ has been overlooked.

“Obesity, in almost all circumstances, is most likely a disorder of the brain,” said Casey Halpern, MD, an associate professor of neurosurgery at the University of Pennsylvania. “What these individuals need is not simply more willpower, but the therapeutic equivalent of an electrician that can make right these connections inside their brain.”

Throughout the day, the machine that is our brain is constantly humming in the background, taking in subtle signals from our gut, hormones, and environment to determine when we’re hungry, how food makes us feel, and whether we are taking in enough energy, or expending too much, to survive.

“We like to think that we have control over what we eat, but the brain is also integrating all of these factors that we don’t fully understand in ways that shape our decisions,” said Kevin Hall, PhD, an obesity researcher with the National Institute of Diabetes and Digestive and Kidney Diseases. “I liken it to holding your breath. I can do that for a period of time, and I have some conscious control. But eventually, physiology wins out.”