Could tobacco save your life? - August 05, 2003 - 01:08
We all know that smoking endangers our health. But has nicotine's image problem led scientists to overlook the drug's potential health benefits? Geoff Watts investigates
05 August 2003
Light a cigarette and inhale lungfuls of smoke. Good for you? Hardly. But spend time with people suffering from schizophrenia or other forms of severe mental illness, and you'll find many of them going at it like chimneys. Why? Poor judgement about the consequences, perhaps. Or the need for anything to soothe their distress. But there's a third possibility that is much more intriguing. For them, and others with psychiatric and even physical illnesses, smoking amounts to an oddly neglected form of self-medication.
Of course, tobacco smoke - an airborne cocktail of nasty chemicals - is harmful. What's at issue is a single non-carcinogenic ingredient: nicotine. This already has one medically approved application: taken by mouth in the form of gum, or through the skin from an impregnated patch, would-be ex-smokers aim to absorb a dose sufficient to dampen their cravings. And for many trying to kick the habit, particularly when used as part of a complete programme, it works. But though we hear occasional whisperings of other possible benefits of nicotine, they never seem to get taken seriously.
In ulcerative colitis, for example, the symptoms - pain in the lower abdomen, and diarrhoea - result from an inflammation of the colon and rectum. The cause of this inflammation still isn't known, but it's now 20 years since doctors first noticed that ulcerative colitis is found mainly among non-smokers. And intermittent smokers may find that their symptoms improve when they return to tobacco. Nicotine is the ingredient most likely to have the beneficial effect, and doctors have tested its effects using nicotine patches. Surprisingly, though, only a handful of properly controlled trials have been carried out, and medical advice seems to be to use patches only with caution.
No one is yet certain how nicotine might work in ulcerative colitis. One of the leading researchers in the field, the gastroenterologist Professor John Rhodes of the University Hospital of Wales, has shown that receptors of the kind that respond to nicotine are present in the lining of the large bowel. But ideas on what effect nicotine might actually be having range from damping down an overactive immune system to reducing the amount of blood reaching the surface regions of the bowel. And, adding to the confusion, nicotine seems to worsen the symptoms of Crohn's disease, another inflammatory bowel disorder.
Schizophrenia, too, has attracted interest. Surveys have suggested that up to 90 per cent of people with the disorder smoke. There are at least two possible reasons: to calm the effects of the illness itself, or to mitigate those of some of the drugs used to control it. On this second point, there have been indications that nicotine can reverse the memory problems and slowness of thought induced by a commonly used medicine, haloperidol. But it does seem more likely that the urge to smoke is driven by its effects on the disease itself. One possibility is that nicotine suppresses inconsequential or distracting information coming into the brain. A radio playing in the next room may be irritating, but most of us learn to ignore it. People with schizophrenia find this much harder. Nicotine may help, but the evidence is mostly inferential.
Nicotine has been studied in the context of two neurological disorders: Alzheimer's and Parkinson's. A 1992 survey of Alzheimer's reported that, in 13 out of 17 published studies on the topic, smokers had shown a reduced risk of the illness. And some (though not all) researchers have shown that nicotine or nicotine-like compounds improve patients' speed at completing information-processing tasks.
When Professor David Balfour of the University of Dundee Medical School and Karl Fagerstrom, then of the drug company Parmacia and Upjohn, reviewed the effects of nicotine in 1996, they were encouraging about its clinical potential. But, they added: "In our view, the beneficial effects of nicotine in Alzheimer's disease have not been investigated in a thorough way yet." Besides testing it on more patients, what was needed were longer trials of several months. Only then would it be possible to detect real improvement in symptoms, never mind any change in the progress of the disease.
Attempts to use nicotine in Parkinson's date back to the 1920s when one clinician injected it intravenously into a dozen patients. Although benefits were immediately apparent, little more happened for 50 years. Interest picked up again in the Eighties, but virtually all studies used small numbers of patients, and results were mixed. Even so, to quote Balfour and Fagerstrom, "the experience from these few cases, although mostly uncontrolled and preliminary... warrants further investigation". For one thing, they say, nicotine may improve only certain symptoms, so may be more valuable to some patients than others.
Nicotine has also been tested in small studies on pain, depression, attention deficit hyperactivity disorder, obesity and anxiety. In these disorders the evidence so far has been even more patchy. But serious research programmes have often been triggered by less impressive findings. So why the relative lack of interest in nicotine as a research topic with clinical payoffs?
The usual explanation is that nicotine, a natural material, cannot be patented. Few companies would be prepared to invest in testing it for disorders if, when it was licensed, anyone could make and sell it. Melatonin, thought to be good for jet lag, is similarly disadvantaged. The standard way round this is to jiggle about with the basic molecule in the hope of finding a new, patentable version that works as well or better. Some nicotine-like compounds have been tested, but with results no more conclusive than those from nicotine itself.
Of course, there is also a quite separate reason for the lack of interest: nicotine has an image problem. The reasoning seems to be that nicotine is found in cigarettes, that smoking is bad, and therefore that nicotine, too, must be bad.
Writing in Pharmacology and Experimental Therapeutics, the drug-industry researchers G Kenneth Lloyd and Michael Williams stressed the absurd consequences of nicotine's negative connotations. "An analogous situation would be if the serotonin (5-HT) receptor family, which has yielded many efficacious and widely used therapeutic agents... had been termed the LSD receptor because the latter was the first [molecule] identified to react with [it]."
Fagerstrom agrees that nicotine is tainted by association. "It's politically very difficult to give nicotine to a young person," he says. True, nicotine is addictive, but this does not of itself impress Fagerstrom. The taint, in his view, is not just unfortunate, but unfounded. "There is no such thing as a pure nicotine addiction. There is addiction to nicotine when the vehicle is tobacco. But have you heard of a culture in which people distil the nicotine out of tobacco and use it by itself? Have you heard of anyone walking into a pharmacy and buying nicotine gum or spray and then starting a primary addiction?" He doesn't wait for an answer. "Well, neither have I."
Nicotine addiction, Fagerstrom argues, arises specifically through inhaling burnt tobacco. "If you want a psychoactive effect, speed of absorption matters a lot. All addicts try to get their drugs in as fast as possible. They don't eat or chew them. They prefer to smoke, sniff or inject them."
Nicotine, after all, is only the world's second most popular drug; caffeine is still No 1. "We could take caffeine in a pill if we wanted. I don't want to. I'm sure it's much more addictive when it comes in a cup with a smell, with a look, with a taste, and combined with some social activity." Clearly there is a big difference between being given a drug to treat an illness and seeking it out for non-medical reasons. Fears of inducing nicotine addiction by giving a pill or a piece of gum are, he believes, unwarranted.
We've long since learnt that even the best drugs have side effects. We seem to find it harder to accept that "bad" drugs might also do some good.
A longer version of this article appears in the August edition of the monthly newsletter 'Medicine Today' (www.medicine-today.co.uk)
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* Nicotine is found in the dried leaves of tobacco plants.
* Chemically speaking, it's an alkaloid: one of a large family of organic compounds that are made by plants, contain nitrogen, and often have a profound effect on the body and especially its nervous system. Other alkaloids include caffeine, morphine, quinine, cocaine and even strychnine.
* With relatives such as these, it comes as no surprise to learn that nicotine can cause sickness, high blood pressure, seizures and hypothermia. It is also, of course, addictive.
* Nicotine also has some positive effects: it seems to reduce anxiety, boost the flow of blood to the brain, counteract pain, and protect nerve cells against damage.
* The explanation for nicotine's actions lies in its capacity to mimic the effects of a molecule found naturally in the body. This is acetylcholine, one of the neurotransmitters, or chemical messengers, by which signals travelling through the nervous system are relayed from one nerve cell to the next, or from nerves to the muscles they control. The activation occurs when the nicotine attaches to receptors: special sites on the surfaces of cells that act as molecular switches.
5 August 2003 01:03
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