*** ANALYSIS and INSIGHT ***
*** ORIGINAL ESSAYS by JONATHAN MARIN ***
The government's decision to file criminal charges against companies for "plotting" to develop high-nicotine tobacco (1) is truly bizarre. In light of the prospective public health benefits of a high nicotine cigarette, prosecuting the developers of a variety of tobacco which would provide smokers with twice the nicotine, for a given load of tar and particulate, seems tantamount to prosecuting Jonas Salk for working on his polio vaccine.
The hazard presented by a given nicotine load, alone, must necessarily be less than the hazard posed by that same nicotine load _plus_ a load of tars and particulates. The amount present in cigarette smoke of these constituents - which are the cause of smoking-related bronchitis, emphysema, and cancer - currently exceeds the amount of nicotine by a factor of ten. The risk of pulmonary disease is a linear function of the exposure to these substances. Given what is known about the behavior of smokers in general, and of smokers who use the chewing gum and patches to "cut down", doubling the nicotine to tar-and-particulate ratio of cigarettes would reduce smokers' risk of pulmonary disease by half.
Numerous studies have established that blood nicotine level determines how much cigarette smokers smoke. These studies are the basis for the NIH decision to declare cigarette smoking "addictive". Nicotine is the substance that smokers crave; they smoke to satisfy the craving. Nicotine is the active ingredient of legally available chewing gum and skin patch products. Their nicotine enables users of these products to smoke fewer cigarettes, thus satisfying their craving with a reduced load of tars, particulates, and other dangerous constituents of tobacco smoke. High-nicotine cigarettes would similarly enable smokers to satisfy their craving with fewer cigarettes, reducing their exposure to the harmful substances at lower cost, and with less disruption of well-established personal routine, than the gum or the patches.
While nicotine can be poisonous, and even lethal, it is not ordinarily dangerous at the modest dosage self-administered by cigarette smokers. This is why people are able to safely use the gum and the patches. The hazards posed by nicotine poisoning - occlusions due to vascular constriction, and cardiac cramping and arhythmia - last only while blood nicotine level is above a "red line" threshhold, and passes when it falls below the "red line". Smokers smoke to maintain their blood nicotine level within a "comfort zone" whose upper limit is ordinarily safely below the "red line". Smokers who develop occlusive vascular disease may be endangered by nicotine levels within their previously established comfort zone, but it is other components of cigarette smoke - tars and particulates - which initiate and aggravate vascular disease and create the vulnerability.
Smokers are further protected from nicotine poisoning by their acquired tolerance; their "red-line" threshhold has risen to a higher level. Several of the mechanisms of tolerance and addiction are well characterized and understood.Some nicotine receptors, normally present on the membrane surface of neurons, proliferate as an adaptation to recurring high nicotine levels. When not "satisfied", the receptors initiate a chain of chemical and electrical events, in effect crying out "Feed me! Feed me!".
Acerylcholine receptors are also important to nicotine addiction. Nicotine affects the cholinergic (post-synaptic) pathways not by affecting the density or count of receptors, but by making them less sensitive. Nicotine causes the firing neurons to produce more neurotransmitter, which compensates for the receptors' reduced sensitivity, enabling the smoker's brain to function properly when enough is present.(2) When nicotine deprivation causes the quantity produced to return to "normal", however, that "normal" amount of neurotransmitter isn't enough to make the deadened receptors work properly. This probably at least partly explains tolerance (e.g. reduced vascular constriction), and the memory problems and reduced mental acuity of smokers in withdrawal and people who have quit, but is probably not the primary source of cravings they experience.
The cravings are apparently primarily due to pathways involving pre-synaptic glutamate receptors. These pathways' addictive and tolerance mechanism is the mirror image of the cholinergic pathways' - i.e., nicotine increases the receptors sensitivity to glutamate.(3)
Cigarette smoking is the leading cause of preventable serious
disease and death in the USA. No practical achievable advance would lower
the cigarette-related health toll as effectively as the commercial availability
of high-nicotine cigarettes. The number of lives that would be saved by the
commercial availability of such a product probably exceeds the number that
would be saved by a cure for AIDS. That the government has chosen to prosecute
companies for "plotting" to do this is beyond grotesque.
(1) Biotech Company Charged With Plot to Develop High-Nicotine
(New York Times Jan 7, 1998)
(2)Lester, R.A.J., and Dani, J.A. Acetylcholine receptor desensitization induced by nicotine in rat medial habenula neurons. J.Neurophysiol. 74:195--206, 1995.)
(3) A summary of research on the involvement of pre-synaptic receptors in nicotine addiction is on the web at URL: http://www.columbia.edu/cu/record21/record2104.14.html
Copyright(C) 1998 by Jonathan Marin
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