A Cigarette Chemical Packed With Helpful Effects? By John Schwartz- Washington Post Staff Writer Monday, November 9, 1998 Everyone knows that smoking is bad for you. But not every component of a cigarette is harmful. Take nicotine, the chemical that makes smoking satisfying -- and addictive. Nicotine serves as a natural insecticide in tobacco leaves. But the drug is relatively benign to humans in normal doses, especially when compared with the thousands of toxins in tobacco smoke. In fact, nicotine has a wide array of potentially beneficial effects. As a result, today nicotine is being studied as a possible therapy for a broad range of ailments that includes Alzheimer's and Parkinson's diseases, schizophrenia, depression, adult attention deficit disorder, Tourette's syndrome and ulcerative colitis. A second wave of research, meanwhile, is aimed at developing drugs that mimic nicotine's positive effects but don't produce its negative side effects. (Nicotine not only can cause nausea and rapid heartbeat, it actually tends to burn out the very receptors in the brain that it excites, forcing the brain to create more receptors to keep up.) "There is a tremendous growth of interest in the nicotine field," said Jed Rose, a Duke University researcher who co-hosts an annual scientific conference devoted to the drug. "There's been a virtual explosion of new findings on every level." This trend was on display yesterday, when several groups of researchers presented their latest work on nicotine and nicotine-like drugs at the annual Society for Neuroscience conference in Los Angeles. The presentations even included work by scientists at R.J. Reynolds Tobacco Co. on a drug designed to mimic nicotine's ability to improve memory and learning. Research on nicotine as a possible treatment for disease got its start a decade ago, as researchers began to notice that smokers suffered less from certain diseases. Nicotine, however, is not selective. It has many different, often contradictory, effects on the body -- for example, it simultaneously calms smokers and speeds up their heartbeat. "It's just what we would call a 'dirty drug,' " said Phyllis C. Pugh, a nicotine researcher at the Medical College of Ohio. "It has too many effects." So researchers are looking beyond nicotine to try to come up with compounds that will act more specifically. Neuroscientist Edward Levin and colleagues at Duke University are working with a nicotine-like compound, AR-R 17779, that appears to improve learning and memory in rats. Levin focuses on what are known as "alpha-7 nicotinic receptors," which are found in great concentrations in the hippocampus, part of the brain important to memory and learning. Receptors are cellular locks that wait for a chemical with a specific shape to act like a key and trigger functions within the cell. In nicotinic receptors, nicotine fits the locks meant for acetylcholine (ACh), one of the body's natural receptor keys. When Levin and his colleagues injected rats with the chemical, the rats were able to run mazes more effectively. The researchers then took the study a step further by giving the drug to rats whose memories had been impaired by damaging pathways to the hippocampus. Those rats improved as well -- a hopeful sign for Alzheimer's research because the connection to the hippocampus is often damaged in victims of that disease. Researchers at R.J. Reynolds have also been working with nicotine mimics, and have found similarly encouraging results. Two compounds, known as RJR-2557 and RJR-1734, also trigger the brain's ACh receptors. R.J. Reynolds researcher Patrick Lippiello gave the drugs to rats and found that the compounds boosted short-term and long-term memory. The effects last about 18 hours in rats, and the drugs can be taken orally. The chemicals also seemed to protect rat brain cells from being destroyed by some toxins, which could point the way to a therapy that not only alleviates the symptoms of Alzheimer's but also prevents brain cell degeneration. Of course, a drug that triggers receptors can work only if there are receptors to be triggered, and so the R.J. Reynolds researchers believe their drug, if effective in humans, will best be used if the disease can be caught in the early stages. "Early intervention in the disease would be a must," Lippiello said. Any human therapies based on these drugs would be years away, Lippiello warned. Seth Moskowitz, an R.J. Reynolds spokesman, said the company's venture into the drug business should not be taken as an admission that it is in the drug trade. "The work that we're doing in this area is totally separate and apart from our cigarette business," Moskowitz said. "It started about nine or 10 years ago with the realization that we have a lot of expertise and knowledge about nicotine." R.J. Reynolds is now planning to begin clinical trials on the drugs through a partner in the pharmaceutical industry. Aong with the new nicotine mimics, many researchers believe that old-fashioned nicotine still has a role to play. Paul R. Sanberg, professor and chair of neuroscience at the University of South Florida, said about 80 percent of his patients in a study of nicotine patches for Tourette's syndrome, a neurological disorder marked by uncontrollable tics, have "shown improvement in both decreasing the frequency and the intensity of the tics" with long-term effects. In a seeming paradox, giving patients drugs that block the action of nicotine also seems to lessen their Tourette's symptoms. No one yet knows why, but it may be because nicotine desensitizes receptors it works on -- in effect making it its own blocker. Other medical mysteries await researchers. The exceptionally high rates of smoking among people afflicted with Attention Deficit Hyperactivity Disorder (ADHD), depression and schizophrenia suggest that nicotine and similar chemicals might provide some relief. Studies have already shown an improvement in cognitive ability among schizophrenics and a greater ability to focus among ADHD patients who wear a nicotine patch. Abbott Laboratories is working with researchers at the National Institutes of Health to study a nicotine-like drug from the skin of Amazonian frogs used for poison darts that is, in smaller doses, a highly effective painkiller. And Esther Sabban at New York University Medical College is exploring the role of nicotine in relieving the ill effects of stress on the body. But what about addiction? Sanberg said he has given nicotine in patch form to children as young as 8 who suffer from Tourette's. "There were clearly people that didn't like the idea of giving their children nicotine and the thought that maybe they could get addicted or start smoking," he said. Nicotine in patch and gum form does not appear to carry the risk of addiction that smoking does, Sanberg said: In cigarettes, the first puff sends a potent jolt of the drug directly to the brain in about eight seconds, while patches and gum work far more slowly and consistently. "We haven't seen any addiction," Sanberg said. Compared with the usual treatments for the disease, including potent antipsychotic drugs with side effects that can be severe, parents generally opt for the nicotine treatment, Sanberg said. Scientists studying nicotine say that even if the drug can be addicting, that side effect is something that society will tolerate if the benefits outweigh the risks. Opiates, Levin noted, "can produce an awful addiction -- but if you're in severe pain, it's a godsend." Nicotine: The Benefits and the Detriments POSITIVE EFFECTS * Analgesic: Relieves pain without diminishing the sense of touch. * Cognitive enhancement: Increases process involved in thinking and knowing. * Cerebrovasodilation: Dilates the blood vessels of the brain. * Neuroprotection: Protects cells of nervous system from certain degenerative diseases. Appears to protect some neurons from Alzheimer's disease. * Anxiolysis: Lowers anxiety levels. * Antipsychotic: Helps maintain connection with reality. Untreated psychotic people are more likely to smoke than are non-psychotics. NEGATIVE EFFECTS * Gastrointestinal distress: Digestive problems; stomach upset, bowel cramping, constipation, etc. * Hypothermia: Lowers body temperature to below-normal levels. * Emesis: Vomiting. * Hypertension: Blood vessels constrict to create high blood pressure in some people, increasing potential for aneurysms. * Seizures: Uncontrolled electrical activity in the brain, resulting in tremors and other abnormal responses. * Respiratory distress: Nodules, de generation and vasoconstriction in the lungs. Increases the potential for development of small cell lung carcinomas by several hundred percent. SOURCE: Phyllis C. Pugh © Copyright 1998 The Washington Post -- Judith Richards, London, Ontario, Canada <[log in to unmask]> ^^^ \ / \ | / Today’s Research \\ | // ...Tomorrow’s Cure \ | / \|/ ```````