"The interesting realization that I went through last time I tried to quit was that I do not know myself as an adult without the drug nicotine," she muses. "I started smoking when I was 13 or 14, and I've been smoking for over half my life.
"My entire adult life has been under the influence of this drug. And I don't know myself as an adult without it." What would she be like, I wonder. Would her wit have a dull edge? Would her eyes dart a little more slowly, her gestures be a little more subdued? What would be different, or would I even notice the difference?
"I find that when I quit, I need to really work on behavioral changes as well, and not just for the withdrawal period, but also after the withdrawal has ended. Without smoking, I think differently, I feel different, I feel less patient. I get deeply irritated.
"I know I'm gonna have to go through and do it all again when I quit. I'll have a better starting place next time because I'll know more what fits and what feels good and what I feel comfortable with, and how to be patient, and how to keep my mouth shut (which I have to work on).
"I'm going to have to do it again. And that's scary."
Most of us use something, sometime or another. We want that little kick in the morning, that little oomph in the afternoon, that little flight away from blah, or that little sharpening on a dull day. To get that little buzz, we drink that cola, sip that coffee, nibble on that chocolate, or smoke that cigarette. Unless we ingest caffeine in fairly high doses, we don't get as much of a jump-start from it as we would get from nicotine. The effects from the nicotine in smoked tobacco take about seven seconds to occur. Achieving the same effects from caffeine takes 10 to 20 minutes. Some researchers believe that smoked tobacco's almost immediate impact is what makes its effects so reinforcing.
It is nicotine's adaptability, as well as its addictive properties, that make it so popular. A smoker not only forestalls abstinence symptoms, or withdrawal, with the morning drag, the smoker probably also perceives that he or she is affected emotionally and mentally. This is accomplished not through using one brand with a precise level of nicotine in its cigarettes, but through a smoker's precise ways of using tobacco to achieve a desired state.
Whether the nicotine in tobacco enhances mental skills is a focus of scientific debate. On one side is the argument that nicotine enhances specific aspects of thinking skills, or cognition. On the other side is the hypothesis that the so-called enhancements are really just "medicating the deficit" that occurs when a smoker is in withdrawal. As in many efforts to study human behavior and performance, this debate hinges to some extent on questions of methodology. And as with many explorations into human behavior, it starts in animal laboratories.
Researcher Karey Elrod and colleagues at the Medical College of Georgia reported a decade ago that nicotine enhanced task performance in young adult macaques (nonhuman primates). The macaques' performance on a matching task improved when they were administered nicotine. Conversely, chemically blocking the nicotinic receptors in the animals' central nervous system inhibited performance. The researchers hoped to extend their research to humans suffering from dementia.
Nonhuman research has covered such smoking-related factors as the effects of prenatal nicotine exposure on rat pups (i.e., baby rats), a line of inquiry that allows researchers to explore the subtleties of prenatal nicotine exposure. The adverse effects of a mother's smoking during pregnancy are a health concern because about one-fourth of pregnant women in U.S. urban areas smoke. Their tobacco use affects their offspring's size, health, and behavior, often throughout the child's life. Studies also have noted long-lasting cognitive deficits that appear to result from prenatal smoking.
An animal study that examined analogous effects in rat pups was performed by Edward D. Levin and colleagues at the Duke University Medical Center. They exposed pregnant rats to nicotine infused through a tiny implanted pump, and later monitored the offspring's performance on maze tasks. The exposed rats' performance was compared with that of control rats that received no nicotine exposure. The investigators found subtle but measurable effects of prenatal nicotine exposure. The nicotine dosage was low enough not to cause any significant deficits in the mother rats' weight gain, in the litter size, or in the pups' birth weight. However, it was sufficient to affect performance.
The researchers were careful to note that although the infusion method was useful for the study question, it did not exactly parallel the nicotine effects a smoker would experience over the course of a typical day of smoking. Despite that limitation, they concluded that their studies provided evidence that prenatal nicotine exposure could increase the vulnerability of offspring to lasting deficits, and could decrease any benefits from being in an enriched environment after weaning. They also expressed concern that prenatal nicotine exposure could reduce the adaptability and development of an offspring's nervous system, which could impair chances for recovery from damage caused by the nicotine exposure.
The next step, following the lines of animal research, has been to extend the findings to humans. One of the notable efforts to analyze the effects of nicotine on human cognition and task performance was a 1993 report from Stephen J. Heishman and colleagues of the National Institute on Drug Abuse's Addiction Research Center (NIDA/ARC) in Baltimore. Rather than follow a more typical course of testing smokers who had been using tobacco for some length of time, Heishman's group used volunteers who were naïve to tobacco and thus had little or no experience using nicotine. The hazard in the study was that exposing the participants to nicotine might put them at risk for later taking up regular tobacco use. This risk was mitigated to some extent by the subjects' using exact amounts of nonsmoked nicotine, starting with a placebo (non-nicotine) dose, then a 2-mg dose 90 minutes later, then a 4-mg dose 90 minutes after that. The researchers measured physiological measures including heart rate, blood pressure, and skin temperature, as well as assessing performance on several cognitive tests. In this group of nonsmokers, nicotine did not enhance test performance.
|2.3%||starting percent of nicotine in tobacco blend for U.S. Patent No. 5,065,775|
|5.2%||final percent of nicotine in tobacco blend for U.S. Patent No. 5,065,775, following processing|
|2.6%||starting percent of nicotine in flue-cured tobacco, U.S. Patent No. 4,898,188|
|4.8%||final percent of nicotine in tobacco blend, U.S. Patent No. 4,898,188, following processing|
Heishman reported in 1996 the results of a second study, in which he examined nicotine's cognitive enhancement effects on 12 tobacco-naïve men who stayed in an inpatient research unit and were given various doses of nicotine gum over nine days. The men's performance was actually impaired by nicotine, particularly at the highest dose level. Although nicotine enhanced response time on some testing, it also impaired accuracy. Again, the data did not support the hypothesis that nicotine enhances cognition in nonsmokers.
Jacques Le Houezec at Hôpital de la Salpêtrière in Paris and collaborators at the University of California at San Francisco also studied the effects of nicotine administration in nonsmokers. The team evaluated the performance of 12 nicotine-naïve research subjects before and twice after injections of nicotine or injections of a saline solution, along with a nontreatment (or control) condition of no injections. As would be necessary in such research, they balanced the order of the substances (nicotine given first to some subjects, saline given first to others) to control for any possible effects that the order of administration might have, as well as to help control for practice effects in repeated testing. The injections were given in a "double-blind" condition, in which neither the subjects nor the person administering the testing or the injection knew which substance was in the injection. The researchers also administered an EEG-like procedure called an event-related potential, in which brainwave measures were taken repeatedly to assess the subjects' responses.
Le Houezec and his colleagues found that testing given 15 minutes after the administration of nicotine showed significant evidence of cognitive enhancement, but that the enhancement was no longer significant 45 minutes after the injection. They also noted that nicotine increased the number of responses but did not increase accuracy.
Why study nonsmoking, nicotine-naïve subjects? As tolerance develops to a substance such as the nicotine in tobacco, the effects may differ at varying dose levels. By definition, tolerance involves the need for increasing doses of the substance to achieve the desired effect. If nicotine is a cognitive enhancer, and if for the sake of consistency all research subjects must be given the same dose (relative to body weight), then a low dose might not produce the same effect in a dependent smoker that it would yield in a nicotine-naïve subject. Even among a group of dependent smokers, it is unlikely that the same dose will have the same effect. Therefore, it becomes important to use nicotine-naïve participants for some experiments.
A drawback to using nicotine-naïve participants is that nicotine's fundamental toxicity, which makes a teenager nauseous with that first cigarette he or she tries, has the same effect on adult participants in research studies. A limitation to such research, as it turns out, is not that naïve research volunteers will take up smoking, but that they will have difficulty using nicotine without feeling too ill to participate. Fortunately for the sake of research paradigms, nicotine doesn't affect every first-time user quite the same way.
An additional methodological problem comes in comparing data from smokers with data from those who have never smoked or who are former smokers. Never-smokers and ex-smokers are not necessarily equivalent to smokers, and thus comparisons must be made cautiously. David G. Gilbert of Southern Illinois University has recommended randomly assigning smokers to intermediate-term abstinence from tobacco, and offering them a financial incentive sizable enough to compensate them for their trouble and to minimize attrition from the research study. This recruitment strategy would enhance researchers' capacity for making inferences about the effects of nicotine on performance independent of withdrawal symptoms. Gilbert also has recommended that researchers study mood in conjunction with cognition and performance, since mood can affect both.
An important question to address is whether nicotine enhances performance and cognition when it is administered after withdrawal. Frederick R. Snyder and colleagues of NIDA/ARC determined that when smokers were deprived of nicotine for 12 hours, their performance on a computerized battery of tasks worsened. Performance improved when they used nicotine gum containing doses of either 2 or 4 mg; in fact, it returned to baseline predeprivation level. The researchers concluded that the performance drop was specific to nicotine deprivation when the subjects abstained from tobacco longer than would be normal for them. The nicotine they received in the experiment treated their abstinence symptoms and served as a replacement for the nicotine in cigarettes, thus accounting for their improved performance when they used nicotine gum.
Methodological issues also come into play in various other studies that have attempted to look at nicotine's cognition-enhancing properties. A common criticism among scientists (a criticism they level at their own work as well as at colleagues' work) is that typical cognitive and performance testing bears little relationship to performance demands in the outside world. As George J. Spilich of Washington College argued, "Much of the research which investigates the effects of nicotine upon cognitive performance has been conducted with a very restrictive set of tasks." It is important, Spilich insisted, that addiction researchers choose measures that utilize the same processing demands encountered in the everyday world.
|10 mg||amount of tar in a Marlboro Light cigarette, based on machine tests|
|18 36 mg||amount of tar a smoker actually could get from a Marlboro Light|
|0.7 mg||amount of nicotine listed for a Camel Light, based on machine tests|
|1.3 to 2 mg||amount of nicotine a smoker actually could get from a Camel Light|
|13%||smokers of ultra-light cigarettes who know the tar level of their preferred brand|
|1%||smokers of regular (full-flavor) cigarettes who know the tar level of their preferred brand|
|two-thirds||smokers who think that this information is listed on cigarette packs|
|3% 8%||smokers who know that this information is listed in advertisements instead of on cigarette packs|
|www.cancer.org||World Wide Web site where the state of Massachusetts posts nicotine levels|
|nowhere||where tar and nicotine information is published for nonadvertised, generic brands of cigarettes|
|(See Kozlowski et al., 1998)|
That should be simple, right? Why not just have research subjects attempt to program a VCR, insert wood screws in an assemble-it-yourself table, or navigate into a tight parking spot? Part of the problem is that tasks must be uniform, and performance must be measurable and repeatable. It is true that programming a VCR could be a timed task, but it is a task that some research subjects would already be adept at and that others would have an aversion to. Any prior experience programming a VCR could either enhance task performance or hinder it, or perhaps could add to the feelings of aversion. In any case, prior experience would make the findings difficult to interpret accurately. This is why it is important to use tasks that the subject might not have performed before, but that the subject can readily learn. That said, Spilich's point is well taken: For the research findings to be more meaningful, the tasks need to have some generalizability to tasks in everyday life. Determining that someone using nicotine can perform a tapping gesture faster than someone without nicotine might have little direct applicability to life's typical demands.
Neil Sherwood of the University of Surrey in England addressed such concerns by studying the effects of cigarette smoking on a one-hour computer-based driving simulation that involved tests of continuous tracking and brake reaction time tests. Sherwood investigated the effects of nicotine on smokers' driving-simulation performance while varying the nicotine levels in the cigarettes offered to study participants. He found that brake reaction time improved at all nicotine dosage levels, and that the consumption of two moderate-nicotine-level cigarettes enhanced tracking accuracy. He stated that, in retrospect, it would have been useful for him also to have studied the pre-testing baseline usage of tobacco in the subjects, and to use that information statistically. Nonetheless, he concluded that nicotine did have some performance-enhancing effects. He did not, however, advocate tobacco use as a means of sharpening one's wits. Rather, he concluded that smokers use nicotine as "an aid to concentration and to offset the negative effects of fatigue or boredom in everyday tasks like car driving." Using nicotine for these purposes could have implications for many activities requiring vigilance or attentiveness, conducted at home and at work every dayand could also indicate possible hazards associated with performing these activities during the early, difficult days of abstinence.
Sherwood's research represented an effort to explain demographic data indicating that smokers are overrepresented in motor vehicle accidents. Sherwood suggested that the "most cogent explanation" for the higher accident rate was the propensity of smokers to engage in risk-taking behaviors, coupled with smokers' tendency to use alcohol.
In 1992, Sherwood examined performance in smokers after single and repeated doses of nicotine gum. He found that smokers' performance on several tasks improved with the administration of nicotine. Among the measures showing improvement were reaction time, tracking, and memory reaction time. He interpreted the findings as suggesting that the enhanced motor performance smokers experience after the first cigarette can be maintained by repeated smoking. The goal of the study, however, was not to encourage repeated smoking of cigarettes, but rather to profile nicotine's psychoactive (psychologically active) nature.
Researchers have been particularly interested in examining the effects of nicotine on attention and memory. Although at first glance these two aspects of human thought processes may seem to differ, they are sufficiently connected to require careful examination and separation. A person is unlikely to remember something to which he or she had paid little or no attention. In fact, what appear to be memory deficits among people with reversible and treatable conditions such as depression might instead merely reflect their difficulty in focusing attention.
An example: A (nonsmoking) woman who was an enthusiastic and avid reader experienced a depression lasting several months during a period of unexpected unemployment. She read many books during this period, passing the hours and days between job interviews and social contacts. Among the books she read was a science fiction work by Ursula LeGuin, an engaging and talented writer. Several years later, long after the woman was reemployed and her mood had dramatically improved, she saw a televised dramatization of a LeGuin novel. She wondered how, in her exhaustive reading of LeGuin's works, she had missed that particular story. She found the book tucked away on a bookshelf in her home and noted with surprise that she had not only read the book several years earlier during the job-hunting months, but she had underlined in it and made marginal comments. Her depression had so thoroughly unhinged her attention and focus that she not only did not remember what was in the book, but she didn't even recall ever reading it.
Gilbert, in his 1995 book Smoking, identified aspects of nicotine's cognitive enhancement that could play a role in a smoker's everyday life and could be affected by quitting tobacco use. Among the effects he categorized were these:
Visual Thresholds: In smokers who are temporarily abstinent, nicotine abstinence lengthens the time at which a rapidly repeated stimulus such as a light flicker or light flash can be distinguished from the next flicker or flash. This distinguishing speed also is diminished in Alzheimer's patients.
Reaction Time, Speed, and Accuracy: Abstinent and nonabstinent smokers who are given a dose of nicotine experience a decrease in reaction time in tasks requiring rapid responding. Performance on memory tasks, calculations, and other tasks generally increases in smokers who are likewise given a dose of nicotine. Recall of information does not appear to be facilitated as consistently by the use of nicotine. Nicotine administration in a laboratory setting has been shown to enhance memory functions in nonsmokers.
Usage of Different Parts of the Brain: Gilbert and others have proposed that nicotine tends to cause arousal in the left part of the brain, which is associated with verbal tasks. This lateralized, or left-vs.-right, effect might also explain nicotine's impact on feelings. (See chapter 5.) The tasks that nicotine appears to enhance in smokers are believed to be mediated by the left side of the brain; conversely, functions mediated by the right side of the brain, particularly negative mood states and visual-spatial processing, might be inhibited by nicotine.
|more than 4,000||number of identified chemical compounds in tobacco smoke|
|more than 50||number of identified cancer-causing chemical compounds in tobacco smoke|
|carbon monoxide||biological marker of recent smoking; measured in exhaled breath|
|carboxyhemoglobin||biological marker of tobacco use, measured in blood|
|cotinine||product of nicotine metabolism, measured in saliva, blood, or urine; half-life of 16-20 hours allows measurement of recent nicotine use|
|thiocyanate||biochemical marker of tobacco use; long half-life of 14 days allows measurement of less recent nicotine use|
|pretty low||percentage of smokers worldwide who have heard of carboxyhemoglobin, cotinine, and thiocyanate|
Nicotine's usefulness as a cognitive enhancer is limited. Researchers have found that nicotine use can result in what is called state-dependent learning. In other words, what is learned under the influence of nicotine can be optimally utilized only under the influence of nicotine. This means that a student who smokes all night while he crams for an exam the next morning might find himself unable to remember the material unless he has a comparable amount of nicotine in his system when he takes the exam. Since smokers generally attempt to maintain somewhat steady blood levels of nicotine throughout the day, this might not be a problem under most circumstances. A three-hour exam with no smoking break, on the other hand, could present a problem.
David M. Warburton and colleagues of the University of Reading specifically examined this issue in 1986 in relation to nicotine use. They designed two studies, one with cigarettes and one with nicotine tablets. In the first study, they tested recognition of a visual stimulus by smokers who had been primed by smoking before engaging in the learning task. As a contrast to prior research utilizing word recall, the investigators used Chinese ideograms that would be difficult for subjects to translate into any form of language (the subjects apparently did not know the Chinese language). Subjects were tested in a variety of conditions in which they were told either to smoke or not to smoke before learning, during learning, and during recall. The researchers found that nicotine facilitated the input of information and that the learning was indeed state dependent.
In a second study, Warburton and his associates examined the effects of nicotine on registration and recall of verbal material. Smokers who came for testing after overnight nicotine deprivation were instructed to learn and recognize 48 words from 12 categories such as fruits, animals, or musical instruments. Participants were given nicotine in tablet form with tabasco sauce added to mask the flavor, so that the subjects wouldn't know whether they were getting a nicotine tablet or a nonnicotine placebo tablet. Again, the researchers found that nicotine facilitated learning and produced state-dependent learning.
Such features of nicotine use are part of what keeps smokers smoking. These features are also part of what makes quitting so difficult. Regarding quitting, researchers have become reluctant to write and speak directly of nicotine withdrawal per se, preferring instead to use the term abstinence effects. Their caution comes from a concern that not everything a smoker experiences when going without the usual amount of tobacco is necessarily related to withdrawal from nicotine dependence. Rather, the term abstinence effects is a larger umbrella that can include both the symptoms of physical withdrawal and the impact of being deprived of the substance's effects. An analog to this condition could be the situation of a wife who loses her husband. Not only is she in mourning because of the loss of her husband, but suddenly now she does not have anyone to help carry in the groceries and carry out the trash. The loss itself causes a grief response that is separate from having to do those tasks by herself. To compare it with smoking, the withdrawal per se would be the grief response; the sudden lack of help with the groceries and garbage would be analogous to the abrupt absence of the effects of the substance.
Both types of effects are pronounced when a tobacco user is abstinent. From within the experience, it is probably difficult (and pointless) to try to sort out which noxious effect is due to which specific cause. For multiple reasons, a smoker's cognition and performance tend to become impaired during abstinence. The effects can last as long as several weeks, although most smokers' abstinence effects subside within two weeks. Other conditions, such as the smoker's overall health, stresses, and even (for women) menstrual state, can interact with abstinence effects to influence cognitive capacity.
In a nasty twist suitable for a Dostoevsky novel, researchers Todd M. Gross and colleagues at the University of California at Los Angeles and the West Los Angeles Veterans Affairs Medical Center found that abstinence not only makes the heart grow fonder, it results in a sort of fixation on smoking. Some scientists had suspected for years that using an addictive substance over a long period of time increases responsiveness to information about the substance. For example, alcoholics tend to notice drinking-related concepts faster than nonalcoholics do. This behavior becomes virtually automatic, requiring no conscious effort. When a substance-dependent person then becomes abstinent, the automatic behavior is "frustrated," and thoughts about the desired substance begin to intrude.
This phenomenon was demonstrated largely by anecdotal evidence until Gross and colleagues set out to investigate it in smokers. They used a neuropsychological test called the Stroop, in which a participant is asked to state the color of ink in which a certain word is printed. To successfully perform the Stroop task, the person must suppress the meaning of the colored word to state its color. Sometimes words intrude to the point that suppression is difficult, requiring concentration and effort. When a person's focus is fixed on a particular concept, this slows the naming of the colors of words that depict the concept. For instance, someone with an eating disorder is likely to name the colors of food-related words more slowly than he or she would name the colors of neutral words.
In the study conducted by Gross, abstinent smokers required more time to name the ink colors of smoking-related words than of neutral words. The investigators suggested that this meant that nicotine abstinence among smokers resulted in some type of preoccupation with smoking. This preoccupation "captures attention" and results in slower performance and interference with the task. They determined that this attentional shift was not due to any cognitive deficits associated with nicotine abstinence. These effects occurred only twelve hours into abstinence. Oddly, the abstinent smokers did not report having more thoughts of smoking than were reported by a complementary group of nonabstinent smokers who performed the same task. The difference showed up only in the results of the testing.
A 1996 conference at Howard University brought together many of the world's experts in the cognitive and performance effects of nicotine. The group included researchers funded by governments, pharmaceutical companies, and tobacco companies. They debated the question of nicotine's enhancing qualities, not attempting to reach a consensus but rather to enhance one another's understanding. For two days, this group of scientists gave half-hour presentations on their latest lab findings. Some talked about the effects of nicotine on brainwaves, others about the effects of nicotine on mood and, indirectly, on cognition. Some explained the limitations of the various methodologies. Some clearly had a point to make, although none appeared to have too much of a bone to pick.
|27%||U.S. whites (non-Hispanic, non-Native American) who smoke|
|35%||U.S. African-Americans who smoke|
|18 25 years||age range in which smoking is higher among whites than African-Americans|
|25 65 years||age range in which smoking is higher among African-Americans than whites|
|10%||African-American smokers who smoke more than 25 cigarettes/day|
|one-third||proportion of white American smokers who smoke more than 25 cigarettes/day|
|75%||percent of African-Americans who smoke mentholated cigarettes|
|23%||percent of white Americans who smoke mentholated cigarettes|
|1.4 times greater||increased risk of cancer death for African-Americans vs. whites|
|1.5 times greater||increased risk of heart attack death for African-Americans vs. whites|
|1.8 times greater||increased risk for stroke death for African-Americans vs. whites|
To those and other scientists, nicotine is neither good nor bad; it simply is. Human use of it may have good or bad consequences, but the substance itself and its effects are topics of inquiry, not matters of moral crusade. In that framework, many researchers have been encouraged and even excited to learn that nicotine may have properties that help patients afflicted with Alzheimer's disease. Early in the 1990s, reports began to be published to the effect that Alzheimer's symptoms might be treatable, to a limited extent, with nicotine. Research both at Duke University and at London's Institute of Psychiatry showed that some aspects of the cognitive deficits associated with Alzheimer's could be attenuatednot eliminated, not cured, but perhaps helped to some degreeby the administration of nicotine.
British researchers G.M.M. Jones and colleagues reported in 1992 that although Alzheimer's patients' short-term memory was not enhanced by nicotine, the perceptual and visual attention deficits that are part of the disease symptoms were improved by the subcutaneous (under-the-skin) administration of nicotine. They compared a group of young normal adults and a group of older normal control subjects with a group of 22 patients diagnosed with relatively early Alzheimer's disease. The tasks measured how well the subjects processed new information, attended to a task, engaged in fine-motor finger-tapping, and exercised short-term memory. The researchers noted that the Alzheimer's patients already had "large perceptual and attentional impairments" that accounted for substantial inability to perform the testing adequately. The subcutaneous administration of nicotine was useful in the research setting because it provided a safe way to administer nicotine in a study of the "acute," or immediate and short-term, effects of the substance. Nicotine from a transdermal patch would not have provided an adequate acute dosage for the research study, although the researchers indicated that it would be a preferred route of administration for a therapeutic dose. Also, it could be difficult to teach Alzheimer's patients to chew nicotine gum correctly, since the gum must be chewed for a short time and then "parked" in the mouth to allow the nicotine to be absorbed. This technique might be beyond the capacity of a dementia patient.
Additional evidence that nicotine might be therapeutically useful with dementia patients came in 1997 from Paul A. Newhouse and his collaborators at the University of Vermont and New York University. They explored the role of the central nervous system's nicotinic systems, or nerve receptors that are sensitive to nicotine, noting that one of the hallmarks of both Alzheimer's and Parkinson's diseases is a loss of nicotinic receptors in the central nervous system (or CNS, which consists of the brain and spinal cord). The team found age-related and disease-related alterations in several cognitive domains associated with CNS functioning. Their findings supported the belief that intact CNS nicotinic mechanisms are important for normal cognitive functioning, and that some of the cognitive deficits seen in Alzheimer's and perhaps Parkinson's patients could be due to the loss of CNS nicotinic receptors.
The Newhouse group used a substance called mecamylamine, which is a nicotinic antagonist, a substance that blocks the effects of nicotine on the CNS receptors. The results of administering mecamylamine, thus blocking the nicotinic receptors, mimicked the effects of a dementing illness. Their work suggested that such dementia-related problems as impaired capacity to acquire, process, and store information in memory could be related to the effects of a dementing disease on nicotinic receptors. Likewise, problems with attention, visual perception, and response speed could also result from inadequate CNS nicotinic reception.
This growing collection of research indicates that it might be possible to improve information acquisition and decrease cognitive errors in Alzheimer's patients through a process of nicotinic stimulation. The ongoing inquiry involves examining possible clinical benefits of nicotinic augmentation.
Scientists also have considered the possibility of using nicotine to treat non-Alzheimer's age-related memory impairment. Gary W. Arendash and associates at the University of South Florida examined the effects of nicotine injections on aged rats. (An aged rat, by the way, is 22 to 24 months old.) Older rats demonstrated severe learning and memory impairments, which were measured by the rats' ability to learn and perform tasks. The elderly rats were compared with younger rats in their ability to utilize a pole-jumping apparatus equipped with a grid floor capable of delivering a mild but aversive electrical shock. The rat had to learn to jump onto a pole within a five-second interval to avoid the shock. The rats also had to learn to run a maze that involved alternating left and right turns at each of six doors. (Do not leak this information to laboratory rats; they are supposed to learn it for themselves.) A third rat task involved determining which eight arms of a maze contained rat food, from among seventeen possible arms of the maze.
As the investigators pointed out in their published report, the aging process impairs learning and memory in rats and other animals. The researchers found that administering nicotine to rats in a regular pattern attenuated but did not eliminate the normal aging impairments of the rat brain. They were encouraged that nicotine demonstrated a broad ability to enhance cognition across diverse tasks that involved avoidance, cognitive "mapping," and spatial discrimination. They also noted that although nicotine had been administered to the rats for as long as a month, none of the rats evinced what is termed behavioral desensitization, or diminished effects of nicotine over time. In contrast, the aged rats were still performing well at the end of the study.
A 1995 study from Minnesota researchers A. Lynn Wilson and colleagues found that learning was enhanced in Alzheimer's patients using nicotine patch treatment. They exposed six patients with Alzheimer's disease to nicotine via a nicotine patch, also comparing their performance when they were using a placebo nonnicotine patch and when they were in a "washout" period in which the nicotine was clearing from their bodies. The researchers used a 22-mg nicotine patch, the highest dosage commercially available, which delivered about 0.9 mg nicotine per hour continuously over a 24-hour period. This dose level was considered intermediate.
The patients, who were mildly to moderately affected by the progression of Alzheimer's disease, were all nonsmokers. Their performance task involved learning the placement of items within a multi-compartment box and following a sequence in locating the items. Investigators also monitored the patients' global cognitive functioning and their behavior in categories reflecting mobility, communication, inappropriate behavior, compliance, and aggression. The use of nicotine improved the patients' learning, as demonstrated on the experimental task, but did not alter their overall cognitive performance and behavior. The research team noted that the patients tolerated the nicotine administration well and experienced minimal side effects. Possible drawbacks to nicotine administration had been suggested in earlier research in which nicotine appeared to bring on increased anxiety and depression in some participants. Two of the Wilson study patients became belligerent and refused to participate in some testing sessions. Whether this was related to their use of nicotine was unknown. The patients also experienced some nighttime sleep disturbance. The investigators noted that any therapeutic use of nicotine should involve careful attention to achieving an optimal dose, which would vary from patient to patient.
No ethical researcher would suggest that patients take up smoking. But since nicotine is now widely available over-the-counter in safer forms than smoking, its therapeutic use has been considered seriously. In sum, now we know that nicotine can enhance some aspects of performance and cognition, at least in long-term use and in abstinent smokers. Nicotine might even offer some relief to dementia patients. This chapter should have a happy ending, right?
As encouraging as nicotine's potential therapeutic uses may be, its continued use by parents who smoke around their children has a deleterious effect on the children's thinking abilities. Even if the parents' cognitive skills might be maintained or in some ways temporarily enhanced through the administration of nicotine, their children do not fare so well. Exposure to environmental tobacco decreases children's performance on some cognitive performance testing, according to work by Karl E. Bauman and colleagues at the University of North Carolina. However, their research indicated that other factors in addition to environmental tobacco exposure also may have caused smokers' offspring to perform poorly on cognitive tests. Parents' mental capacity could be diminished by deleterious health effects from years of smoking and could thus make parents "less effective agents in the cognitive development of their children."
The power of nicotine to foster physical and emotional dependence may seem mystical or even magical. Perhaps nicotine's cognitive and performance enhancement potential is not very different than that of the morning cup of coffee or the mid-afternoon splash of cola. The enhancement itself, though measurable, is not monumental or even marked. The smoker may notice the difference, but others may not. Nicotine isn't a smart-pill that turns a mediocre thinker into a genius. It offers merely a temporary edge, and that edge might come only with repeated use. In any case, for the smoker it is an edge that also comes with a substantial risk.
The magic, it would appear, can be both black and white.
Copyright 1998 National Academy Press