First, Edward Levin gives his disclaimer. "I'm not recommending that anyone take up smoking," he says. "Also, the use of nicotine aside from tobacco is only at the experimental stage. The risk-benefit relationship hasn't been worked out."
Prof. Levin, chief of the neurobehavioural research lab at Duke University Medical Center, researches nicotine's effects on the brain. Evidence for its beneficial effects is mounting, but he knows his work can be misconstrued and misrepresented. The fight against cigarettes has made smokers pariahs, and by association researchers such as him risk their reputation.
Yet science is on Prof. Levin's side. Studies suggest that nicotine can enhance cognitive functioning. They also suggest that it can help with such brain disorders as Parkinson's disease and schizophrenia. And then there's nicotine's ability to prevent or ameliorate Alzheimer's symptoms, an area on which Prof. Levin focuses.
"Nicotine does a lot of different things. Some are adverse, such as addiction, and others might be beneficial," he says. "I think that it's a pretty promising treatment."
Despite this promise, however, it is possible that doctors may never prescribe nicotine for anything but smoking cessation. Besides the stigma of its association with cigarettes, nicotine cannot be patented, which means that pharmaceutical companies are not investing in or promoting it. They cannot make back what they would need to spend on such things as clinical trials.
Instead, they are working on nicotine analogues and derivatives that can be patented. Studies on these compounds, as well as the curiosity of a handful of scientists, are driving research into nicotine's possible medical uses. And with larger trials likely in the next few years, Prof. Levin and colleagues may soon worry less about the stigma of their work.
The evidence for nicotine's beneficial effects stretches back to the mid-1900s. Prof. Levin says research in the 1960s showed that nicotine improves learning in rats. There has also been evidence that smokers are protected from some cognitive disorders.
But establishing a connection between smoking and brain functioning is complicated. "Part of the problem is that people who smoke naturally have other problems, such as heart disease," Prof. Levin says. "That actually might cloud the picture."
Nicotine's beneficial effects are partly attributed to how it mimics an important neurotransmitter. Quickly distributed through the bloodstream, nicotine can cross the blood-brain barrier in seconds. In the brain, it impersonates the neurotransmitter acetylcholine and binds with a subtype of acetylcholine receptor called the nicotinic receptor. Nicotinic receptors control the release of other neurotransmitters that have an influence on emotion and cognition.
One of nicotine's proven beneficial effects is enhancing cognitive performance. Recording electrical impulses in rat neurons, researchers at the National Institute of Environmental Health Sciences in 1997 found that nicotine has a stimulating effect on the hippocampus, which is important for learning and memory.
Advancements in brain-imaging technology have allowed researchers to probe deeper into the connection between nicotine and cognitive performance.
In October, 2002, researchers from the U.S. National Institute on Drug Abuse, the Medical College of Wisconsin and the Institute of Psychiatry in London reported using magnetic-resonance imaging to watch brains in action under the influence of nicotine. They gave 15 smokers either a nicotine patch or a placebo and asked them to perform a visual task. Parts of the brain associated with visual attention, arousal and motor activation lit up.
Findings from the study suggest that nicotine helps to focus attention by shifting resources from less-used parts of the brain to parts required for task performance.
But enhancing cognitive performance isn't all that nicotine is good for. Evidence also suggests that by affecting neurotransmitters, nicotine can treat a number of brain disorders.
Among schizophrenics, for example, the prevalence of smoking is about three times as high as in the general population -- about 70 to 90 per cent of schizophrenics are smokers, compared with 25 per cent of non-schizophrenics. Studies have also found that schizophrenics have fewer nicotinic receptors in the hippocampus.
All of this suggests that by smoking they are unconsciously self-medicating.
People with Parkinson's disease could also benefit from nicotine treatment. Smokers have lower rates of Parkinson's disease, and Paul Newhouse of the clinical neuroscience research unit at the University of Vermont has conducted preliminary experiments showing that nicotine patches reduce Parkinson's symptoms.
"There may be some toxin that's responsible for neural damage in Parkinson's that's protected against by nicotine," Prof. Levin says.
Nicotine has also received much attention as a potential treatment for Alzheimer's disease.
In November, 1998, Prof. Levin presented data at a Society of Neuroscience annual meeting showing that nicotine-like compounds can restore learning and memory ability to rats that have brain lesions similar to those in people with Alzheimer's.
He has also been involved in small studies testing the impact of nicotine patches on cognitive impairment.
In one study, eight people with mild-to-moderate Alzheimer's disease wore nicotine patches for two four-week periods and six of them experienced 20 to 80 per cent improved performance on cognition tests.
With Alzheimer's, nicotine appears to have many beneficial effects beyond its role as a neurotransmitter mimic and cognitive enhancer.
"We believe that there are at least two and possibly three different mechanisms involved that seem to have nothing to do with the nicotinic receptors," says Daniel Sitar, head of the department of pharmacology and therapeutics at the University of Manitoba.
Conducting research into how nicotine inhibits the formation of amyloid plaque associated with Alzheimer's, Prof. Sitar and colleagues found that it interferes with the activation of two phospholipases, a class of enzymes.
Research published in June has identified another mechanism. Reporting in the Proceedings of the National Academy of Sciences, researchers from Scripps Research Institute in California say the nicotine byproduct nornicotine prevents beta-amyloid proteins from clumping together to form amyloid plaque. Nornicotine reacts with sugars and beta-amyloid in a process called glycation, which denies beta-amyloid the opportunity to clump.
Despite the evidence for nicotine's beneficial effects, it's unlikely that nicotine itself will ever be available in pharmacies for cognitive enhancement or protection.
Part of the problem is that nicotine is stigmatized. But that's not the only problem. Prof. Sitar says drug companies won't pursue work on nicotine itself because there's no patent protection and they can't recoup the millions of dollars it costs to get a drug approved for sale.
Instead, he says, drug companies are developing "sons and daughters" of nicotine.
Prof. Levin doesn't think that the development of nicotine-like drugs is a bad thing. He says such drugs can exist side by side in the market with nicotine, as they can be developed to have a more specific effect than nicotine and can better treat specific conditions.
"I compare it to morphine," he says. "Morphine's a terrible drug in terms of addiction. But it's a godsend if you're in severe pain. But also, there are many opiate analogues that have been developed to treat one or another type of pain. I see that as kind of way that nicotine would develop. There would be analogues developed for different conditions, but nicotine itself may be useful in some ways."
Simon Smith is a freelance writer based in Montreal.