(CNN) -- Obesity can't be cured by pills, shots or even surgery.
If only it were that easy.
Despite centuries of supposed weight-loss remedies from anti-obesity soaps, crash diets based on vinegar to even amphetamines, fads have failed.
Over the years, Americans have become more obsessed with weight loss, but not much healthier as more than one-third of U.S. adults are obese.
Drugs have not effectively answered the problem, despite billions of dollars spent in research.
Obesity has more factors than just eating too much, according to research. The reasons why people gain excess weight vary -- and one drug isn't likely to address all these factors including lifestyle, food access and environment.
Our brains have a natural tendency to desire eating beyond need, to store in case of scarcity and famine, scientists say. That doesn't work well in the modern day when calorie-dense foods are readily available.
"We might not have any magic bullet," for obesity said Dr. Gene-Jack Wang, chair of medical research at Brookhaven National Laboratory. "We might have to use a bomb. You have to be very comprehensive."
Dr. Sidney Wolfe, director of the Health Research Group -- part of the nonprofit consumer advocacy organization Public Citizen -- isn't hopeful about the development of an effective and safe weight-loss drug.
"The possibility that the drug will only do the good things like lose weight and not have myriad effects on the body -- is zero," he said.
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Weight-loss stimulants speed up metabolism but can cause strokes, heart attacks and cardiovascular problems. Medications that block the body from absorbing fat cause really unpleasant side effects like diarrhea, oily spotting and the notorious anal leakage.
On Thursday, the Public Citizen Health Research Group petitioned the U.S. Food and Drug Administration to ban the only approved long-term weight-loss drug, orlistat.
The group said that orlistat, sold in prescription form as Xenical and over-the-counter as Alli, causes serious side effects such as liver injury and kidney failure.
Genentech, maker of Xenical, said it had not yet thoroughly reviewed the petition. The company said the efficacy and safety of the drug "is based on more than 10 years of clinical experience and more than 38.7 million patients worldwide have received Xenical."
GlaxoSmithKline which owns Alli announced on Thursday that it would put the weight-loss drug for sale along with other products, because these "lacked sufficient critical mass."
Obesity treatment "is high priority" among drug research, said Dr. Mark Gold, chair of psychiatry at University of Florida who focuses on addiction and eating habits. "They've failed most of the time before."
The weight-loss busts are plenty: Meridia (heart attacks, strokes), Fen-phen (heart risk), Rimonabant (suicidal thoughts), ephedra (heart attacks, strokes).
Last year, the FDA rejected three proposed weight-loss drugs, Qnexa, lorcaserin and Contrave because of safety concerns ranging from heart to psychiatric issues.
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"Losing weight doesn't mean anything if the drug is counteracting with adverse things," said Wolfe, who is a member of a safety advisory committee at the FDA.
He was not involved in the rulings regarding the three weight-loss drugs.
"Diet drugs should not be approved unless they're safe, because people who are overweight already have increased cardiovascular risk and risk of stroke. If you're going to add to it with a drug -- that doesn't make any sense."
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So why can't an effective weight-loss drug be made without awful side effects?
The causes of weight gain can be emotional, biological, social, psychological, environmental -- and these multiple factors don't fit into a neat capsule.
While lifestyle, diet and exercise matter, our biological wiring combined with the modern environment make it difficult, researchers said.
"A lot of people say the reason for obesity is because of personal responsibility," said Wang, a senior scientist. "As a physician, I don't think it's necessarily true."
Researchers are rethinking how to tackle weight loss because the traditional approach of blaming the patient isn't working, he said.
Our brains crave calories to store for hard times, said Gold, an obesity researcher.
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"Unfortunately for us, that worked very well when we had little food and we needed incentive to hunt. Right now, with abundant food, it's very easy to get food and fast food," he said.
Today, calorie-dense food loaded with salt, sugar and fat is everywhere. Advertisements and social cues bombard consumers to eat.
"The global obesity epidemic is due to food being widely available," Gold said. "The food has evolved, but our brains haven't really changed from the time that we had to hunt and grow our own food."
Many of our brains' pathways are linked to appetite, he said. It's hard to create a drug to suppress appetite when there could be many unknown factors involved in this instinct.
Drugs given to suppress appetites have had disastrous results such as psychotic episodes, depression and suicidal thoughts, according to experts.
Dr. Patricia Powell, clinical assistant professor for the clinical pharmacy at the University of South Carolina said "the problem with those stimulants are side effects -- cardiovascular risk, stroke, heart attack, high blood pressure. They're causing you extra work on the heart."
The risk of a heart attack or stroke "outweighs any small benefit of weight loss," she said.
Another side effect is that some people turn to new addictions such as drugs or alcohol, after their appetites have been suppressed, said experts. That's why overeating has been likened to drug addiction.
"There can be no more basic drive for people than to eat," said Wolfe, who is critical of weight-loss drugs. "It is embedded in the whole body and whether you're suppressing appetite or affecting absorption of fat, there are going to be other systems affected."
He added flatly: "The point is there is no magic."