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Nicotine studied as treatment for brain disorders

Scientists reported yesterday that nicotine seems to diminish mental impairment stemming from stress or an underactive thyroid -- the latest in a growing body of evidence that the long vilified substance may help people with brain disorders ranging from Alzheimer's disease to schizophrenia.

Nicotine researchers caution that the findings by no means offset the health ravages of smoking. But for years, a growing number of them have been exploring the aid nicotine may offer people with dementia, depression, attention deficit hyperactivity disorder, and more.

"Yesterday's poison can be today's therapy," said Dr. Jerry J. Buccafusco, a pharmacologist and researcher at the Medical College of Georgia.

Pharmaceutical researchers are racing to synthesize drugs that could offer the benefits of nicotine without its negative side effects, such as addiction and narrowed blood vessels.

"It's a critical moment, because we're really on the threshhold of a whole family of these new drugs coming on the market," said Dr. Ed Levin, a professor of psychiatry at Duke University who is considered a pioneer in nicotine research. Drugs based on nicotine could begin arriving within the next couple of years, he said.

Nicotine, a naturally occurring compound called an alkaloid, makes up about 5 percent of tobacco by weight, and is believed to be the chief reason smoking is both so addictive and found by some to be so pleasurable. It is such a potent poison that a child who eats a cigarette is in serious danger, but in low doses it has shown medical promise.

Researchers have reported several encouraging nicotine findings at the annual meeting for the Society for Neuroscience, now underway in New Orleans.

In one small study on non-smoking teenagers with ADHD, nicotine administered through a skin patch appeared as effective as Ritalin in helping them peform an important mental function called inhibition, which involves the patient blocking a distracting response.

The teens' improved concentration could help explain why adolescents with ADHD are much more likely to smoke, according to researcher Alexandra Potter of the University of Vermont.

A study in rats found another type of mental improvement. When the rats were given low doses of nicotine and subjected to stress -- which normally impairs memory -- they performed on a test as well as rats free of stress. And a third study found that when rats' thyroids were surgically reduced, those given nicotine made far fewer errors on a test than those without nicotine. They even did as well as rats whose thyroids were intact. The surgery was meant to mimic hypothyroidism, a condition that affects about 5 million Americans and tends to produce problems with memory and thinking.

In all, nicotine appears well on its way to joining the ranks of other poisons -- from botulinum to digitalis -- that can be converted from toxic enemies to useful medical tools. But that conversion is not a simple process, and particularly not with nicotine, researchers say.

Side effects, such as nausea and blood vessel constriction, have plagued attempts to test nicotine on patients with Alzheimer's disease, Parkinson's disease, and other maladies in which, studies indicate, nicotine could alleviate some symptoms.

Several companies are starting clinical trials in humans for drugs based on nicotine, said Dr. Paul Newhouse, director of the University of Vermont's clinical neuro-science research unit. But "the bugaboo of this field is that we have thus far, until fairly recently, not been able to get enough distance between side effects and the therapeutic dose," he said.

Nicotine works in the body by mimicking a neurotransmitter called acetylcholine, a chemical messenger that, among other things, helps the brain communicate with the muscles, and helps the brain process information.

The trouble, researchers say, is that acetylcholine is one of the most basic and widespread neurotransmitters in the human body. Since the turn of the century, pharmacologists have found that drugs that try to affect acetylcholine levels have too many side effects, Buccafusco said.

But recently, he said, researchers have found perhaps a dozen different sub-types of the acetylcholine receptors that nicotine works on, raising the possibility of more exact targeting.

He also reported yesterday that a metabolite, or breakdown product, of nicotine called cotinine appears able to reduce mental impairment in monkeys much as nicotine does, possibly with fewer side effects.

Levin said that money for the research is coming from pharmaceutical companies, federal grant-givers, charitable foundations, and tobacco companies. The tobacco money tends to be given in a "very gingerly way" -- putting no pressure on researchers for desired results -- because the companies have had so much bad publicity, he said.

The general picture emerging, Newhouse said, is that nicotine therapy may be helpful for any disorder that involves problems with attention. Whether it can help people with just mild memory impairment remains to be shown. Newhouse and colleagues just got a $1.5 million federal grant to explore whether nicotine patches help 75 people with the mild memory impairment that sometimes precedes Alzheimer's.

He warned, however, that healthy people shouldn't consider using nicotine, even in its patch form, for its mental effects.

"It has been difficult to show that anything reliably enhances normal performance," said Newhouse.

Carey Goldberg can be reached at goldberg@globe.com

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