January 14, 1997
Researchers Investigate (Horrors!)
Nicotine's Potential Benefits
http://www.nytimes.com/yr/mo/day/news/national/nicotine-benefits-sci.h
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By WARREN E. LEARY
n work that sounds a little like scientific blasphemy,
medical researchers have begun paying increasing
attention to some
beneficial effects of nicotine that were first noticed in
cigarette smokers.
After years of quiet discussion among scientists, hints that
cigarettes can protect against some diseases or improve the
outcome of others have led to growing interest in finding
out why. This has focused attention on nicotine, tobacco's
most active ingredient, as a potential treatment for several
major health problems, including Parkinson's and Alzheimer's
diseases.
Without question, researchers say, cigarette smoking does
far more harm than any potential good and should be strongly
discouraged. Smoking is a major cause of cancer and a host
of cardiovascular and other diseases that cause millions of
deaths each year, they say, while draining the world's
health care systems of billions of dollars.
But some researchers say efforts to stop smoking have
discouraged research into the possible benefits of nicotine
and related compounds in treating conditions like attention
deficit disorders, an inflammatory bowel disease and a
neurological condition called Tourette's syndrome.
"The problem with nicotine is that it is tied to cigarettes
and therefore seen as 'bad,' " said Dr. Paul Newhouse of the
University of Vermont College of Medicine. "Clearly, this
affects getting funding and it makes life difficult for
those of us interested in nicotine as a drug. A lot of
people have difficulty in being convinced that nicotine is
potentially valuable."
Dr. John A. Baron, a professor of medicine at Dartmouth
Medical School who has studied the epidemiological link
between smoking and Parkinson's disease for more than a
decade, also says there has been resistance to doing
research on nicotine and possible benefits.
"The link between smoking and possible benefits is
uncomfortable for many people," Baron said. "It's hard to
accept, in an emotional sense, that an exposure so harmful
in so many ways can have benefit. I detest smoking, but I
also see evidence that research on nicotine could prove
valuable and should be done."
Dr. Zach W. Hall, director of the National Institute of
Neurological Disorders and Stroke, said the federal
government spent several million dollars a year on research
related to nicotine. This work is mainly focused on looking
at how the chemical acts on the brain and why there are
receptors in the central nervous system that bind so
strongly to nicotine, he said.
"We have supported a program of basic research, which has
been very fruitful," Hall said. "But we are not currently
funding research on using nicotine as a treatment."
Part of the renewed interest in testing nicotine as
potential therapy for a number of conditions is that the
chemical has recently become available in numerous
nontobacco forms that allow it to be readily administered to
people in different doses without the risks of smoking.
Nicotine is available to help people stop smoking in
delivery systems that include patches that allow the
chemical to be absorbed through the skin, chewing gum, a
nose spray and an oral inhaler.
Another advance encouraging nicotine research is a better
understanding of how the chemical works in the body,
particularly in the brain. Throughout the body, there are
protein units called nicotinic cholinergic receptors on the
surface of many types of cells. Nicotine attaches to the
receptors and stimulates activity in the cell. In
particular, it stimulates the release of many types of
neurotransmitters, chemical messengers that carry signals
from cell to cell, including dopamine, acetylcholine and
glutamate.
Dr. Lorna W. Role, a professor of cell biology and anatomy
at the Columbia University College of Physicians and
Surgeons, said work by her group and others showed that
nicotine binds to brain cells in a way that causes them to
release a flood of neurotransmitters. This action by
nicotine amplifies the signals of these neurotransmitters,
helping to explain the broad spectrum of behavioral and
cognitive effects that have been attributed to nicotine, she
said. "This activity primarily affects the limbic system,
which is the reward center of the brain, which encourages
people to repeat whatever behavior that stimulated it," she
said.
For more than 20 years, evidence has been accumulating that
cigarette smokers have a reduced risk of developing
Parkinson's disease. A similar effect has also been noticed
in epidemiological studies of Alzheimer's disease and
ulcerative colitis, an inflammatory bowel disease.
Data from numerous studies, which take into account the
premature death of some smokers, suggest that smokers have
half the risk of developing Parkinson's disease as those who
have never smoked, researchers say, and several small
studies have indicated that there is also a reduced risk for
Alzheimer's disease, particularly with the inherited form of
the disease.
Parkinson's disease, a degenerative brain condition that
results in tremors and loss of body control, is
characterized by the death of brain cells that make the
neurotransmitter dopamine and can be treated with drugs that
replace the chemical.
"Nicotine stimulates dopamine production in the brain and
this could be a reason smoking appears to be beneficial with
Parkinson's," said Dr. Newhouse of the University of
Vermont. There are preliminary indications from small
studies that nicotine patches or intravenous infusions of
nicotine may help treat Parkinson's symptoms, he said.
The relationship between nicotine and Alzheimer's disease, a
progressive brain condition that leads to dementia and loss
of memory, is also spurring interest. Dr. Michael G.
Zagorski and his colleagues at Case Western Reserve
University have found that nicotine appears to interfere
with a major process of Alzheimer's, the formation of beta
amyloid plaque deposits that block cell-to-cell
communication. The researchers found in test-tube studies
that nicotine kept soluble, beta-peptide chemicals from
transforming into plaques that are toxic to nerve cells.
Zagorski said the finding might help explain the inverse
relationship between smoking and Alzheimer's that had been
shown in epidemiological studies, and could lead to
development of nicotine-like compounds that prevented or
slowed the formation of amyloid plaque.
Researchers are also developing artificial compounds that
are either structurally or functionally similar to nicotine,
hoping to mimic the action of the chemical without some of
its side effects.
Animal and human studies have shown that nicotine can
enhance learning, memory, cerebral blood flow and the
performance of certain repetitive tasks. Researchers have
developed a series of nicotine-like compounds to enhance
certain effects to make them more useful for particular
diseases while reducing unwanted side effects.
Newhouse recently reported on a small study he conducted
with Alzheimer's patients using a nicotine analogue
developed by Abbott Laboratories called ABT-418. After
six-hour infusions with the drug, researchers found
significant increases in short-term recall, improvements in
spatial memory and better reaction times on tests.
Dr. G. Kenneth Lloyd of Sibia Neurosciences Inc. in San
Diego said his company was testing two nicotine-like
compounds that separately targeted Parkinson's and
Alzheimer's diseases. The idea is to home in on certain
types of nicotine receptors in the brain, he said.
One compound, SIB 1508Y, works on the release of the
neurotransmitters dopamine and acetylcholine to target
cognitive dysfunction associated with Parkinson's disease,
and the other, SIB 1553A, enhances release of acetylcholine
in hope of reversing short- and long-term memory defects
associated with aging and Alzheimer's disease, Lloyd said.
The company announced last month that based on promising
results with animals, it had applied with the Food and Drug
Administration to begin preliminary safety and dosage tests
of SIB 1508Y in humans.
Researchers have long noticed that ulcerative colitis, a
chronic inflammation of the colon and rectum, is mostly a
disease of nonsmokers.
In a randomized, controlled trial with 72 patients,
researchers at University Hospital of Wales in Cardiff found
that after six weeks of using nicotine patches, patients had
significantly improved symptoms.
Digestive disease specialists note, however, that smoking
and nicotine apparently have the opposite effect on a
related inflammatory bowel condition, Crohn's disease.
Studies indicate that smoking increases the risk and
severity of Crohn's.
Dr. Edward D. Levin of Duke University Medical Center
studied the effects of nicotine patches on schizophrenic
patients who were given haloperidol, a commonly used
treatment but one with side effects harmful to memory and
alertness. He found that nicotine significantly reduced the
memory impairment caused by haloperidol.
Dr. Paul R. Sanberg, a professor of neurological surgery at
the University of South Florida in Tampa, has tested
nicotine patches and haloperidol on patients with Tourette's
syndrome, which causes them to twitch constantly and mutter
meaningless sounds or phrases.
Sanberg said the nicotine patch helped patients on whom
haloperidol did not work well. He was co-author of a letter
published in the journal Nature in October saying there was
growing evidence indicating that nicotine had therapeutic
properties.
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