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Week: 564.7 Guest: Dr., John Baron, Prof. Med. Dartmouth Med. School Topic: Positive effects of nicotine Producer/Host: Steve Girard

NEMA: There are some benefits from smoking. I know I probably snapped your head around with that statement, but it's true. Many researchers are investigating reported benefits from at least one element of smoking that can be used without inhaling burning tobacco...nicotine. Our guest today is Dr. John Baron, Professor of Medicine at Dartmouth Medical School, who has done quite a bit of epidemiology on the subject...

BARON: It really is a paradox that something as bad as cigarette smoking could have beneficial effects. But it really appears that that is the case. Clearly though, the net effect of smoking is negative..it's very harmful. But there are some benefits that have been observed.

NEMA: I know that you've been looking into the way smoking and Parkinson's disease seem to be related...tell me more about nicotine and it's role...

BARON: Nicotine is a real drug....it can kill you, it can cause seizures in very large overdoses, and this gives us a clue that it has effects on the nervous system and the brain. Nicotine is almost certainly what makes cigarette smoking addictive, and also smokeless tobacco use, by the way. Nicotine also has behavioral and nervous system benefits, because of this activity in the nervous system. All of the neurological and behavioral effects of smoking, I believe, are at least partially due to nicotine. In the brain, there are receptors for acetylcholine, which is a neurotransmitter, a chemical that is released by the neurons and that stimulates other neurons. And nicotine, it turns out, binds to a certain kind of acetylcholine receptor. And those, that type of receptors are called nicotinic receptors. By the way, the nicotinic receptors are naturally there, even if the brain has never been exposed to nicotine...and they respond to the natural neurotransmitter, acetylcholine. It's not just some aberration that's generated because people use tobacco.

NEMA: ...and I understand the nicotine then stimulates the production of substances like acetylcholine or dopamine, another neurotransmitter, that helps Parkinson's patients. Nicotine's been tested for years...you told me earlier that tests were documented as early as 1926....

BARON: So it's very clear, it's been known for a long time that nicotine can do a lot in the nervous system, and one of the things it does do, and does very, very well is alleviate nicotine withdrawal. So that's easy and obvious. But even in smokers that are not withdrawing, it looks like nicotine will slightly improve some mental tasks. So it will increase alertness and slightly increase memory in experimental settings. But the effects on Parkinson's disease are more pronounced, and over the last 30 to 35 years, over 30 or 35 epidemiological studies have shown that smokers don't get as much Parkinson's disease as non-smokers. They get about half as much Parkinson's disease. So 50% reduction in Parkinson's disease is a pretty significant reduction. In fact, smoking is the strongest environmental factor that's been related to Parkinson's disease except for some designer drugs, that cause a Parkinson's disease like-disorder. And the very consistency of the finding suggests that there is something about tobacco smoke that is protective...or it's a very potent artifact that is really very difficult to explain. There have been animal studies that have looked at experimental Parkinson's disease, and in several of them, exposure to nicotine or cigarette smoke seems to provide the same protection to the animals. So it looks like it's a real association, and the neurophysiologists have begun designing drugs other than nicotine which may have a better safety profile, and may have even a more potent effect.

NEMA: What about some of the other effects nicotine is proposed to have on other diseases...like Alzheimer's?

BARON: I think we have to separate Parkinson's disease and Alzheimer's...because the epidemiological data are very, very consistent for Parkinson's disease, but they're not as solid for Alzheimer's. And I think it's much more uncertain what the effect of smoking on Alzheimer's is, and I don't want anybody to hear your show and think that by smoking, they're going to avoid Alzheimer's. That would be, I think, not a good message to take from listening to all this.

NEMA: In your experience, have you seen a bias against your interest in nicotine, or the possible benefit of smoking?

BARON: I have experienced some hostility when I present results, because of the findings can be interpreted to mean that smoking has a beneficial side. I have never been turned down for funding because of the topic of my research, but I haven't relied on this topic for the source of most of my academic support either. I'm just aware that the reaction of many of my colleagues is one of surprise, dismissal and suspicion that the tobacco companies must have manipulated my findings or something along those lines....it's often not clear exactly what the worry is. And let's face it...this is clearly an uncomfortable set of findings. But uncomfortable or not, they may be very valuable in helping us understand the disorders that we're talking about.

NEMA: In your view, what lies ahead for the use of nicotine against Parkinson's disease...?

BARON: Well, I think it's very clear what has to be done...there's been enough epidemiology now...enough comparison of what happens to smokers and what happens to non-smokers. Those comparisons are very informative and valuable, but the problem is that smokers and non-smokers differ in all sorts of ways...and conceivably, those differences could explain what happens with regard to Parkinson's disease, or Alzheimer's...or anything else. So what's needed now, especially for Parkinson's disease, are clinical trials. Now, what's being investigated is not cigarette smoking in trials...but nicotine patch or nicotine chewing gum....

NEMA: Anything with nicotine and Parkinson's directly?

BARON: I don't know...I'm not aware of nicotine trials in Parkinson's disease. And this is sort of a sociological issue, in a way. The clinical community is very suspicious of this neurological association... the association between smoking and protection from Parkinson's disease, and it may be difficult to get such a trial going...because nicotine has a bad reputation overall. In Europe, it seems to be a little less...people I noticed are somewhat more receptive to this idea. It's been the neurochemists, the neurophysiologists and the animal experimenters that have carried this forward, largely. I did a small, sort of preliminary clinical trial of nicotine chewing gum and Parkinson's patients...in patients who already had Parkinson's disease, so this is sort of secondary prevention that I had in mind. But the study I did was just to see if Parkinson's patients could chew gum, and what would happen over the short term. There was really no realistic hope that in three hours, the gum would provide much benefit. And I found that, in fact, most patients could chew the gum, but you know patients with Parkinson's disease have a motor slowness, a retardation. And something like chewing gum in an elderly population, with dentures and so on...and with these motor deficits, is a physical challenge. There were some difficult aspects to it. And, but in another small trial, the mixture of a patch, a nicotine patch and nicotine gum was used, and there actually was a benefit shown.

NEMA: So, is there a future for nicotine to be used as a treatment as is?

BARON: ...you know, I talked to some colleagues who work for drug companies that make nicotine patches, and there's at least polite interest, but it's not clear that this is going to be something that the drug companies will pursue...and the designer drugs may have more promise. And I'm not sure of all the considerations that have gone into their thinking about this, but it may relate to the bad reputation that nicotine has.

NEMA: Dr. Baron says the nicotine-like compounds that have been developed specifically for Parkinson's and Alzheimer's diseases have to get the approval of the Food and Drug Administration before limited human clinical trials can begin. Nicotine continues to be tested on ulcerative colitis, schizophrenia, and Tourette Syndrome...with generally positive results. The National Institutes of Health puts several million dollars a year into research into the effects of nicotine, but no studies are being conducted on the drug as a treatment tool. Thanks to Dr. John Baron of Dartmouth Medical School for joining us.

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