2020-kenkel.pdf: “E-Cigarettes and Respiratory Disease: A Replication, Extension, and Future Directions”, (2020-07-01; backlinks):
Electronic cigarettes show potential to reduce the harms from smoking combustible tobacco, but there is uncertainty about the long-term health consequences.
We replicate and extend the study by Bhatta & Glantz 2019, which reports longitudinal statistical associations between e-cigarette use and long-term respiratory disease.
We are able to closely replicate their results. When we use a more flexible empirical specification, among respondents who had never smoked combustible tobacco, we find no evidence that current or former e-cigarette use is associated with respiratory disease. The statistical associations between e-cigarette use and respiratory disease are driven by e-cigarette users who are also current or former smokers of combustible tobacco. A striking feature of the data is that almost all e-cigarette users were either current or former smokers of combustible tobacco. We then discuss the potential for future applied econometric research to credibly identify the causal effects of e-cigarette use on health. Challenges include the potential selection biases that stem from the complex set of consumer choices to initiate and quit smoking combustible tobacco, use of e-cigarettes, and dual use of both products. We suggest using a variety of identification strategies to uncover the causal effects that use a variety of econometric methods.
…In this paper we replicate and extend the analysis of a recent study by Bhatta & Glantz 2019, (hereafter B & G) of the association between e-cigarette use and long-term respiratory disease. B & G analyzed observational data from the first 3 waves of the Population Assessment of Tobacco and Health (PATH) Study. Based on statistically-significant longitudinal associations between former and current e-cigarette use and respiratory disease, B & G conclude that: “Use of e-cigarettes is an independent risk factor for respiratory disease in addition to combustible tobacco smoking.” Major news media reported the results, including NBC (2019), Reuters (2019), and National Public Radio (NPR 2019). For example, NPR reported that the study “found that people who used only e-cigarettes had about a 30% increased risk of developing lung disease, compared with people who didn’t use any nicotine products.” (NPR 2019, emphasis in the original). The accompanying press release (Alvarez 2019) and news media reports interpreted the estimated associations as showing that e-cigarettes are “harmful on their own” (Glantz, quoted in Alvarez 2019).
…A striking feature of the PATH data analyzed by B & G is that almost all e-cigarette users were either current or former smokers of combustible tobacco. In the longitudinal analysis sample with 17,601 observations, there were only 12 current e-cigarette users who had never smoked combustible tobacco. None of the 12 respondents had incident (new) respiratory disease. The number of respondents who only used e-cigarettes is simply not large enough to draw meaningful conclusions about the independent association between e-cigarette use and respiratory disease. More recent data sets will face similar limitations, although to a lesser extent. For example, in the 2018 National Health Interview Survey data the prevalence of current e-cigarette use among people who had never smoked cigarettes was 1.1% (Villarroel et al 2020).
2019-hajek.pdf: “A Randomized Trial of E-Cigarettes versus Nicotine-Replacement Therapy”, Peter Hajek, Anna Phillips-Waller, Dunja Przulj, Francesca Pesola, Katie Myers Smith, Natalie Bisal, Jinshuo Li, Steve Parrott, Peter Sasieni, Lynne Dawkins, Louise Ross, Maciej Goniewicz, Qi Wu, Hayden J. McRobbie
“Nicotine Acutely Enhances Reinforcement from Non-Drug Rewards in Humans”, (2017; backlinks):
Preclinical research documents that, aside from the primary and secondary reinforcing effects of nicotine intake itself, nicotine also acutely enhances the reinforcing efficacy of non-drug reinforcers (“rewards”). Study of these effects in humans has largely been overlooked, but very recent findings suggest they may have clinical implications for more fully understanding the persistence of tobacco dependence. This overview first outlines the topic and notes some recent human studies indirectly addressing nicotine effects on related responses (e.g., subjective ratings), explaining why those findings do not directly confirm enhancement of behavioral reinforcement per se due to nicotine. Then, the methodology used in the subsequently presented studies is described, demonstrating how those studies specifically did demonstrate enhancement of reinforced responding for non-drug rewards. The main section focuses on the limited controlled research to date directly assessing nicotine’s acute reinforcement-enhancing effects in humans, particularly as it relates to reinforced behavioral responding for non-drug rewards in non-human animal models. After detailing those few existing human studies, we address potential consequences of these effects for dependence and tobacco cessation efforts and then suggest directions for future research. This research indicates that nicotine per se increases responding in humans that is reinforced by some rewards (auditory stimuli via music, visual stimuli via video), but perhaps not by others (e.g., money). These reinforcement-enhancing effects in smokers are not due to dependence or withdrawal relief and can be restored by a small amount of nicotine (similar to a smoking lapse), including from e-cigarettes, a non-tobacco nicotine product. Future clinical research should examine factors determining which types of rewards are (or are not) enhanced by nicotine, consequences of the loss of these nicotine effects after quitting smoking, potential individual differences in these effects, and the possibility that nicotine via nicotine replacement therapy and non-nicotine quit medications may attenuate loss of these effects upon quitting. Further study with humans of nicotine’s reinforcement-enhancing effects may provide a more complete understanding of smoking persistence and added mechanisms of cessation medication efficacy.
“Dependence on tobacco and nicotine products: a case for product-specific assessment”, (2012; backlinks):
The International Classification of Diseases and the Diagnostic and Statistical Manual for diagnosing tobacco/nicotine dependence emphasize the dependence-producing drug nicotine. These diagnostic tools have been challenged on grounds of poor predictive validity, and they do not differentiate across various forms of nicotine-containing products. In fact, nicotine-containing products (e.g., tobacco cigarettes, smokeless tobacco [ST], waterpipe, electronic cigarettes [ECIGs], and nicotine replacement [NR] products) have very different characteristics both in terms of sensory and behavioral involvement and also in pharmacokinetic and pharmacodynamic effects. For example, a cigarette and a nicotine patch are very different on almost every one of these dimensions. When ability to stop using a nicotine/tobacco product is used as a criterion for dependence, success rates vary considerably across products: Tobacco cigarette cessation is more difficult than ST cessation that in turn is more difficult than NR product cessation. Based on these results, we hypothesize that there is a continuum of dependence as much as there is a continuum of harm, with tobacco cigarettes and NR products on opposite ends of both continua and other products (waterpipe and ECIGs) somewhere in between. In order to capture more precisely the dependence produced by both nicotine and its administration forms, product-specific instruments may be required. The pros and cons of this approach are discussed.
“Holiday reading: Cigarette smoking: an underused tool in high-performance endurance training”, (2010; backlinks):
The review paper is a staple of medical literature and, when well executed by an expert in the field, can provide a summary of literature that generates useful recommendations and new conceptualizations of a topic. However, if research results are selectively chosen, a review has the potential to create a convincing argument for a faulty hypothesis. Improper correlation or extrapolation of data can result in dangerously flawed conclusions. The following paper seeks to illustrate this point, using existing research to argue the hypothesis that cigarette smoking enhances endurance performance and should be incorporated into high-level training programs.
“Stopping smokeless tobacco with varenicline: randomised double blind placebo controlled trial”, (2010; backlinks):
Objective: To assess the efficacy and safety of varenicline (a licensed cigarette smoking cessation aid) in helping users of smokeless tobacco to quit.
Design: Double blind, placebo controlled, parallel group, multicentre, randomised controlled trial.
Setting: Medical clinics (mostly primary care) in Norway and Sweden.
Participants: Men and women aged ≥18 who used smokeless tobacco at least eight times a day, with no abstinence period over three months within one year before screening, who wanted to quit all tobacco use. Participants were excluded if they used any other form of tobacco (except smokeless tobacco) or medication to stop smoking within three months of screening or had any pre-existing medical or psychiatric condition.
Interventions: Varenicline 1 mg twice daily (titrated during the first week) or placebo for 12 weeks, with 14 weeks’ follow-up after treatment.
Main Outcome Measures: The primary end point was the four week continuous abstinence rate at the end of treatment (weeks 9–12) confirmed with cotinine concentration. A secondary end point was continuous abstinence rate for weeks 9–26. Safety and tolerability were also evaluated.
Results: 431 participants (213 varenicline; 218 placebo) were randomised and received at least one dose of study drug. Participants’ demographics and baseline use of smokeless tobacco were similar (89% (189) and 90% (196), respectively, were men; mean age in both groups was 43.9; participants used smokeless tobacco products about 15 times a day, and about 80% first used smokeless tobacco within 30 minutes after awakening). Continuous abstinence rate at week 9–12 was higher in the varenicline group than the placebo group (59% (125) v 39% (85); relative risk 1.60, 95% confidence interval 1.32 to 1.87, p < 0.001; risk difference 20%; number needed to treat 5). The advantage of varenicline over placebo persisted through 14 weeks of follow-up (continuous abstinence rate at week 9–26 was 45% (95) v 34% (73); relative risk 1.42, 1.08 to 1.79, p = 0.012; risk difference 11%; number needed to treat 9). The most common adverse events in the varenicline group compared with the placebo group were nausea (35% (74) v 6% (14)), fatigue (10% (22) v 7% (15)), headache (10% (22) v 9% (20)), and sleep disorder (10% (22) v 7% (15)). Few adverse events led to discontinuation of treatment (9% (19) and 4% (9), respectively), and serious adverse events occurred in two (1%) and three (1%) participants, respectively.
Conclusion: Varenicline can help people to give up smokeless tobacco and has an acceptable safety profile. The response rate in the placebo group in this study was high, suggesting a population less resistant to treatment than smokers.
Trial Registration: NCT00717093.
2009-froeliger.pdf: “Effects of nicotine on novelty detection and memory recognition performance: double-blind, placebo-controlled studies of smokers and nonsmokers”, (2009-06-02; backlinks):
Rationale: Dependent smokers exhibit deficits in attentional and memory processes when smoking abstinent as compared to when satiated. While nicotine replacement therapy improves attention during abstinence, it is unclear whether this is due to the alleviation of withdrawal-related deficits or inherent beneficial effects of nicotine.
Objectives: The primary aim of these studies was to test whether nicotine exerts a beneficial effect on novelty detection and whether such effects occur in nonsmokers as well as habitual smokers.
Materials and methods: In 2 parallel, double-blind, placebo-controlled studies, 24 smokers (study 1) and 24 nonsmokers (study 2) were tested in two counterbalanced sessions: once while wearing a nicotine patch (smokers = 14 mg; nonsmokers = 7 mg) and once while wearing a placebo patch. On each day, participants performed three content-specific oddball tasks (perceptual, semantic, and emotional) that required them to press a button whenever they saw a novel target (20% of stimuli) embedded in a stream of common nontarget stimuli (80% of stimuli). Recognition memory for targets was subsequently tested. Reports of mood, smoking withdrawal, patch side effects, and blind success were collected in each session.
Results: Among smokers, compared to placebo, nicotine decreased target reaction time during all oddball tasks. Among nonsmokers, nicotine increased target detection accuracy and subsequent memory recognition. Nicotine’s enhancement on each respective measure was not task-content specific in either sample.
Conclusions: These data suggest that acute nicotine administration may exert direct beneficial effects on novelty detection and subsequent memory recognition in both smokers and nonsmokers. Moreover, these effects are not content-specific.
“Nicotine induces resistance to chemotherapy by modulating mitochondrial signaling in lung cancer”, (2009; backlinks):
Continued smoking causes tumor progression and resistance to therapy in lung cancer. Carcinogens possess the ability to block apoptosis, and thus may induce development of cancers and resistance to therapy. Tobacco carcinogens have been studied widely; however, little is known about the agents that inhibit apoptosis, such as nicotine. We determine whether mitochondrial signaling mediates antiapoptotic effects of nicotine in lung cancer. A549 cells were exposed to nicotine (1 muM) followed by cisplatin (35 muM) plus etoposide (20 muM) for 24 hours. We found that nicotine prevented chemotherapy-induced apoptosis, improved cell survival, and caused modest increases in DNA synthesis. Inhibition of mitogen-activated protein kinase (MAPK) and Akt prevented the antiapoptotic effects of nicotine and decreased chemotherapy-induced apoptosis. Small interfering RNA MAPK kinase-1 blocked antiapoptotic effects of nicotine, whereas small interfering RNA MAPK kinase-2 blocked chemotherapy-induced apoptosis. Nicotine prevented chemotherapy-induced reduction in mitochondrial membrane potential and caspase-9 activation. Antiapoptotic effects of nicotine were blocked by mitochondrial anion channel inhibitor, 4,4’diisothiocyanatostilbene-2,2’disulfonic acid. Chemotherapy enhanced translocation of proapoptotic Bax to the mitochondria, whereas nicotine blocked these effects. Nicotine up-regulated Akt-mediated antiapoptotic X-linked inhibitor of apoptosis protein and phosphorylated proapoptotic Bcl2-antagonist of cell death. The A549-rho0 cells, which lack mitochondrial DNA, demonstrated partial resistance to chemotherapy-induced apoptosis, but blocked the antiapoptotic effects of nicotine. Accordingly, we provide evidence that nicotine modulates mitochondrial signaling and inhibits chemotherapy-induced apoptosis in lung cancer. The mitochondrial regulation of nicotine imposes an important mechanism that can critically impair the treatment of lung cancer, because many cancer-therapeutic agents induce apoptosis via the mitochondrial death pathway. Strategies aimed at understanding nicotine-mediated signaling may facilitate the development of improved therapies in lung cancer.
2007-anstey.pdf: “Smoking as a Risk Factor for Dementia and Cognitive Decline: A Meta-Analysis of Prospective Studies”, (2007-06-14; backlinks):
The authors assessed the association of smoking with dementia and cognitive decline in a meta-analysis of 19 prospective studies with at least 12 months of follow-up. Studies included a total of 26,374 participants followed for dementia for 2–30 years and 17,023 participants followed up for 2–7 years to assess cognitive decline. Mean study age was 74 years. Current smokers at baseline, relative to never smokers, had risks of 1.79 (95% confidence interval (CI): 1.43, 2.23) for incident Alzheimer’s disease, 1.78 (95% CI: 1.28, 2.47) for incident vascular dementia, and 1.27 (95% CI: 1.02, 1.60) for any dementia. Compared with those who never smoked, current smokers at baseline also showed greater yearly declines in Mini-Mental State Examination scores over the follow-up period (effect size (β) = −0.13, 95% CI: −0.18, −0.08). Compared with former smokers, current smokers at baseline showed an increased risk of Alzheimer’s disease (relative risk = 1.70, 95% CI: 1.25, 2.31) and an increased decline in cognitive abilities (effect size (β) = −0.07, 95% CI: −0.11, −0.03), but the groups were not different regarding risk of vascular dementia or any dementia. The authors concluded that elderly smokers have increased risks of dementia and cognitive decline.
[Keywords: Alzheimer disease, cognition, dementia, vascular, meta-analysis, smoking]
“High Reinforcing Efficacy of Nicotine in Non-Human Primates”, (2007-01-24; backlinks):
Although tobacco appears highly addictive in humans, there has been persistent controversy about the ability of its psychoactive ingredient nicotine to induce self-administration behavior in laboratory animals, bringing into question nicotine’s role in reinforcing tobacco smoking. Because of ethical difficulties in inducing nicotine dependence in naïve human subjects, we explored reinforcing effects of nicotine in experimentally-naive non-human primates given access to nicotine for periods of time up to two years. Five squirrel monkeys with no experimental history were allowed to intravenously self-administer nicotine by pressing one of two levers. The number of presses on the active lever needed to obtain each injection was fixed (fixed-ratio schedule) or increased progressively with successive injections during the session (progressive-ratio schedule), allowing evaluation of both reinforcing and motivational effects of nicotine under conditions of increasing response cost. Over time, a progressive shift toward high rates of responding on the active lever, but not the inactive lever, developed. The monkeys’ behavior was clearly directed toward nicotine self-administration, rather than presentation of environmental stimuli associated with nicotine injection. Both schedules of reinforcement revealed a high motivation to self-administer nicotine, with monkeys continuing to press the lever when up to 600 lever-presses were needed for each injection of nicotine. Thus, nicotine, by itself, in the absence of behavioral or drug-exposure history, is a robust and highly effective reinforcer of drug-taking behavior in a non-human primate model predictive of human behavior. This supports the use of nicotinic ligands for the treatment of smokers, and this novel preclinical model offers opportunities to test future medications for the treatment of nicotine dependence.
2005-hyland.pdf: “Drug Counselor Report of Adolescents Abuse of Nicotine Replacement Therapy”, (2005; backlinks):
Background: Nicotine replacement products (NRT) are formulated and marketed to reduce their abuse liability among adolescents. Few studies have examined the extent of adolescent abuse. The objective of this manuscript is to describe the youth abuse rate for NRT and other over-the-counter (OTC) abusable substances.
Methods: 2 cross-sectional telephone surveys of Safe and Drug Free School Coordinators were conducted in 1996–7 (n = 562) and 1998/9 (n = 501). Abuse of NRT and other OTC drugs and circumstances surrounding NRT abuse was ascertained.
Results: NRT abuse rates were low and did not change statistically-significantly between the 2 surveys (2.7% in 1996–7 to 4.6% in 1998–9). NRT abuse rates were well below those of other OTC abusable substances (eg., diet pills and inhalants).
Conclusions: Concerns over promotion of youth dependence to nicotine by offering the sale of NRT OTC to adults have not been realized and policymakers should consider reducing barriers to access these products.
[Keywords: adolescent, tobacco, substance abuse, nicotine replacement therapy]
“Nicotine as Therapy”, (2004-11; ; backlinks):
[Discussion of possible therapeutic applications of nicotine: depression, schizophrenia, adult ADHD, through attention; pain relief; weight loss via motivation control and appetite; and nicotine analogues for targeting specific nicotinic receptors (and making patentable drugs).]
2004-tucha.pdf: “Effects of nicotine chewing gum on a real-life motor task: a kinematic analysis of handwriting movements in smokers and non-smokers”, (2003-12-11; backlinks):
Rationale: In laboratory tasks nicotine has consistently been shown to improve psychomotor performance.
Objectives: The aim of the present experiment was to assess the effects of nicotine on a skilled task of everyday life in smoking and non-smoking healthy adults.
Methods: Assessment of handwriting movements of 38 non-deprived smokers and 38 non-smokers was performed following the chewing of gum containing 0 mg, 2 mg or 4 mg of nicotine. A digitising tablet was used for the assessment of fine motor movements. Subjects were asked to perform a simple writing task. Movement time, velocity and acceleration of the handwriting movements were measured. Furthermore, every writing specimen was independently rated by two examiners regarding the quality of handwriting.
Results: Kinematic analysis of writing movements revealed that nicotine could produce absolute improvements in handwriting. Following nicotine administration, reduced movement times, increased velocities and more fluent handwriting movements were observed. These improvements were more striking in smokers than in non-smokers. No effects of nicotine were found with regard to the quality of handwriting.
Conclusion: The results suggest that nicotine can enhance psychomotor performance to a statistically-significant degree in a real-life motor task.
[Keywords: nicotine, human, handwriting, movement analysis, kinematic analysis]
2003-klesges.pdf: “Use of Nicotine Replacement Therapy in Adolescent Smokers and Nonsmokers”, (2003-06-01; backlinks):
Background: Assessing whether and how adolescents use nicotine replacement therapy (NRT) will be important given recent recommendations to make NRT more accessible by lowering its price, increasing its distribution, and advising health care professionals to suggest its use for smoking cessation.
Objectives: To report the prevalence, ease of access, and reasons for NRT use and describe inappropriate use in adolescent smokers and nonsmokers.
Design: Cross-sectional survey of 4078 high school students during the school term of 1998.
Setting: City schools in Memphis, Tenn.
Main Outcome Measures: Community-based self-reported prevalence of NRT use and characteristics of those using NRT.
Results: Approximately 5% of adolescents reported trying or using nicotine gum or patches. Females were less likely than males and African Americans were less likely than others to use NRT. For African American smokers, NRT use was highest at lower smoking levels, while other smokers showed the opposite pattern. Almost 40% of former smokers reported using NRT to try to quit smoking; however, 75% of current smokers endorsed using NRT for reasons other than trying to quit smoking. Other inappropriate use of NRT was reported; 18% of NRT users reported themselves as never smokers. More than 50% of students reported that it would be easy for them to get NRT.
Conclusions: Nicotine replacement therapy is used by adolescent smokers and nonsmokers, is easily accessible, and is used for reasons other than trying to quit smoking. Efforts are needed to discourage NRT use in nonsmoking youth and to encourage appropriate use of NRT in young smokers to maximize its potential for successful cessation.
“Effect of smokeless tobacco (snus) on smoking and public health in Sweden”, (2003; backlinks):
Objective: To review the evidence on the effects of moist smokeless tobacco (snus) on smoking and ill health in Sweden.
Method: Narrative review of published papers and other data sources (for example, conference abstracts and internet based information) on snus use, use of other tobacco products, and changes in health status in Sweden.
Results: Snus is manufactured and stored in a manner that causes it to deliver lower concentrations of some harmful chemicals than other tobacco products, although it can deliver high doses of nicotine. It is dependence forming, but does not appear to cause cancer or respiratory diseases. It may cause a slight increase in cardiovascular risks and is likely to be harmful to the unborn fetus, although these risks are lower than those caused by smoking. There has been a larger drop in male daily smoking (from 40% in 1976 to 15% in 2002) than female daily smoking (34% in 1976 to 20% in 2002) in Sweden, with a substantial proportion (around 30%) of male ex-smokers using snus when quitting smoking. Over the same time period, rates of lung cancer and myocardial infarction have dropped significantly faster among Swedish men than women and remain at low levels as compared with other developed countries with a long history of tobacco use.
Conclusions: Snus availability in Sweden appears to have contributed to the unusually low rates of smoking among Swedish men by helping them transfer to a notably less harmful form of nicotine dependence.
“Persistent use of nicotine replacement therapy: an analysis of actual purchase patterns in a population based sample”, (2003; backlinks):
Background: In 1996, the US Food and Drug Administration (FDA) approved switching nicotine gum and patch from prescription to over-the-counter (OTC) status. Some expressed concerns that broader availability and lack of physician control might increase persistent use of nicotine replacement therapy (NRT)-that is, use beyond the period specified by the FDA approved label.
Objective: To estimate the incidence of persistent use of OTC nicotine gum and patch for periods of > 3 months, > or = 6 months, > or = 12 months, and > or 24 months.
Design: Analysis of NRT purchase patterns in data from a population based panel of US households that electronically scanned all household purchases between January 1997 and March 2000.
Subjects: In a national panel of 40,000 US households, 2690 recorded NRT purchases.
Results: Among 805 households that purchased nicotine gum, 2.3% of new purchase incidents led to continuous monthly purchase of gum for > or = 6 months. For nicotine patches (2050 households) the percentage was 0.9%. For both gum and patch, the incidence of persistent purchase dropped below 0.4% by 24 months. Allowing one month gaps within a “continuous” purchase run resulted in increased estimates (for gum: 6.7% for > or = 6 months and 1.0% for > or = 24 months; for patch: 1.7% for > or = 6 months and 0.05% for > or = 24 months).
Conclusion: Persistent use of nicotine gum and patch is very rare and has not increased with the transition to OTC use, despite removal of physician oversight.
2001-warburton.pdf: “Improved incidental memory with nicotine after semantic processing, but not after phonological processing”, (2001-01-01; backlinks):
Rationale: A number of lines of evidence suggest that a nicotinic cholinergic system is mediating attentional processing. However, the evidence is less clear for a nicotinic system being involved in mnemonic processing.
Objectives: The present study investigated the effects of nicotine on memory using a depth of processing paradigm.
Methods: A double-blind design was used with participants (n = 40) smoking either a nicotine containing cigarette (n = 20) and a denicotinized cigarette (n = 20). After smoking, each set of these participants was further subdivided into two groups (n = 10 for each). One group were presented with a series of trials each beginning with the presentation of a “decision word” which they had to say whether it represented something which was living or non-living (semantic-orienting). The second group had to say whether the word had one syllable or two syllables (phonological or non-semantic orienting condition). This decision was followed by a word in coloured ink whose colour participants were required to name as quickly as possible. On completion of the whole task the participants were given an unexpected free recall test.
Results: The nicotine-containing cigarette reduced the latencies for decision-making and colour naming in comparison with the denicotinized cigarette. The free recall test showed that nicotine-containing cigarette increased the number of words remembered, but only for the semantic-orienting condition and not the non-semantic condition.
Conclusions: There is a nicotinic cholinergic system that mediates effortful processing. It can be deployed for attentional processing, including the associative processing required for memory encoding.
1998-mumenthaler.pdf: “Influence of nicotine on simulator flight performance in non-smokers”, (1998-11-01; backlinks):
In a placebo-controlled study, we investigated the influence of nicotine on late-day aviation performance in 15 non-smoking subjects. In a within-subjects design, subjects were tested on 2 days, each lasting 8 h and consisting of three 75-min simulator flights (late-afternoon practice, evening test, night test). Prior to each test, subjects received either nicotine polacrilex 2 mg or placebo gum. As expected, overall performance was statistically-significantly better after nicotine, compared to placebo (p < 0.01). Post-hoc analysis of individual flight tasks showed that nicotine improved scores on approach to landing, a task which appears to require sustained attention. We conclude that nicotine may improve late-day flight performance in non-smoking aviators.
[Keywords: Nicotine, Cognition, Psychomotor performance, Task performance and analysis, Aerospace medicine, Attention, Workload, Chewing gum, Non-smoker]
1998-parkin.pdf: “The effects of cigarette smoking on overnight performance”, (1998-03-01; backlinks):
15 healthy smokers and 15 non-smokers were enrolled into this study investigating the effects of smoking on overnight performance. Subjects arrived at the test centre at 1930 hours and were assessed at baseline (2000 hours) and at 2200, 0000, 0200, 0400, 0600, and 0800 hours on a battery of tests (including Critical Flicker Fusion, CFF; Choice Reaction Time, CRT; Compensatory Tracking Task, CTT; Short Term Memory Task, STM; and the Line Analogue Rating Scale, LARS). Results showed that the performance of the smokers was more consistent with baseline measures than that of the non-smokers, which became more impaired throughout the night on a number of tasks [CFF (p < 0.005), Total Reaction Time (TRT, p < 0.05), CTT (p < 0.05) and the Reaction Time (RT) aspect of the CTT task (p < 0.0005)]. The Recognition Reaction Time (RRT) aspect of the CRT task showed that the performance of the non-smokers became more impaired from baseline (p < 0.005), while that of the smokers remained at baseline levels until 0400 hours, when it deteriorated to become comparable to that of the non-smoking controls. Subjective sedation ratings (LARS) resulted in comparable levels of impairment for both study groups (p < 0.00005). Findings from the STM task failed to reach statistical-significance. These data suggest that when performance is being measured overnight, smokers show little or no impairment, whilst the performance of non-smokers showed performance decrements.
1998-herzig.pdf: “Effects of cotinine on information processing in nonsmokers”, (1998-01-01; backlinks):
Cotinine, the major proximate metabolite of nicotine, is present in smokers in higher concentrations and for a longer time than nicotine, yet its effects on information processing have not previously been reported. We studied the cognitive effects of cotinine in non-smokers. Sixteen subjects were tested on three doses of cotinine (0.5, 1.0, and 1.5 mg cotinine base/kg), and placebo, on a choice reaction time (RT) task and on a verbal recall task with short and long lists. Cotinine statistically-significantly impaired recall on the long list and displayed non-significant but generally consistent dose-related slowing of RT and N100 latency. The acute effects of cotinine were small, and probably do not account for the cognitive deficits observed in tobacco withdrawal, although the cognitive effects of chronic cotinine administration need to be investigated.
1994-warburton.pdf: “Improvements in performance without nicotine withdrawal”, (1994-01-01; backlinks):
Two tests were made of the withdrawal-relief explanation of the improvements in performance obtained with smoking. Study 1 examined the extent to which abstinence from smoking produced poorer performance in smokers in comparison with non-smokers. No evidence was obtained of differences in performance in smokers who were deprived of cigarettes for 10h and non-smokers. Study 2 tested smokers with a standard cigarette or sham smoking after one hour and 12h of deprivation. There was no difference in performance for the two deprivation intervals either in the sham smoking condition, or after smoking the lit cigarette. This study gave no evidence for withdrawal-relief being an explanation of the improvements in performance obtained with smoking.
1994-pickworth.pdf: “Transdermal nicotine: reduction of smoking with minimal abuse liability”, (1994-01-01; backlinks):
Cigarette consumption as well as the physiologic, performance and subjective effects of the nicotine patch were evaluated in ten subjects who smoked ad libitum while residing on a residential research ward for 30 days. Nicotine transdermal systems (“patches”) delivering a total of 0, 22 or 44 mg per 24h were applied daily at a constant dose during each 7-day condition; the order of dosing conditions was varied according to a randomized, double-blind, crossover design. Nicotine patches statistically-significantly but modestly reduced spontaneous smoking and statistically-significantly increased venous plasma nicotine levels. Self ratings of patch liking, satisfaction with cigarettes and the ability to identify the patch condition did not change as a function of the nicotine dose, indicating minimal abuse liability. There were no consistent changes in the puffing pattern measures; however, in all patch conditions, subjects with extensive histories of illicit drug use smoked cigarettes faster than subjects with histories of occasional drug use. Small changes in resting heart rate, pulse and blood pressure occurred when the nicotine patch was worn. Thus large changes in venous plasma nicotine levels engender only modest changes in ad libitum cigarette consumption, measures of abuse liability and cardiovascular effects. These findings are consistent with the notion that the addictive and toxic effects of nicotine are partially determined by the rate of drug administration.
1992-west.pdf: “Nicotine addiction: a re-analysis of the arguments”, (1992-09-01; backlinks):
This paper evaluates the arguments put forward by Robinson and Pritchard (R&P, this volume) that the conclusions of the US Surgeon General (USDHHS 1988) that nicotine is addictive were ill founded. R&P state that nicotine does not cause intoxication, that many smokers do not exhibit compulsive use, that nicotine is not a euphoriant, that nicotine is a weak reinforcer in other species, that non-pharmacological aspects of smoking are important and that negative affect control accounts for more of the variance in questionnaire measures of smoking motives than does habit. This paper points out that intoxication and a euphoriant effect are not normally considered to be central to dependence potential, that no addictive drug results in compulsive use in all users in all situations, that animals do reliably self-administer nicotine, that evidence concerning the apparent importance of non-pharmacological components of smoking do not diminish the importance of pharmacological aspects and that “variance accounted for” of self-report measures of smoking motivation do not bear on the issue of the importance of those motives. The paper concludes with a summary of the essence of the argument that cigarettes are addictive and that nicotine is the primary focus of that addiction.
1992-robinson.pdf: “The role of nicotine in tobacco use”, (1992-09-01; backlinks):
The 1988 US Surgeon General’s Report titled “Nicotine Addiction”, is cited frequently in the literature as having established the “fact” that nicotine derived from cigarette smoke is addictive in the same sense as “classic” addicting drugs such as heroin and cocaine. This manuscripts critically evaluates key research findings used in support of this claim and identifies short-comings in the data that seriously question the logic of labeling nicotine as “addictive”. In addition, the manuscript argues that the role of nicotine in tobacco use is not like the role of cocaine in coca leaf use as argued by the 1988 Surgeon General’s Report, but is, in fact, more like the role of caffeine in coffee drinking as concluded in the 1964 US Surgeon General’s Report.
1991-hughes-2.pdf: “Long-term Use of Nicotine vs Placebo Gum”, (1991-10-01; backlinks):
Medical patients (n = 315) who wished to quit smoking were randomly assigned in a double-blind manner to receive either nicotine or placebo gum. Subjects were advised to stop gum use by 4 months. Among abstinent smokers, 46% of those receiving nicotine gum and 17% of those receiving placebo gum used the gum beyond the recommended 4-month period. By 10 months after cessation 17% of quitters receiving nicotine gum and 6% receiving placebo gum were still using gum. Gradual reduction of nicotine gum did not result in withdrawal and cessation of nicotine gum did not increase the probability of relapse to smoking or weight gain. We conclude that use of nicotine gum is due, in part, to the effects of nicotine; however, long-term use is uncommon.
1989-petrie.pdf: “Smoking and human information processing”, (1989-11-01; backlinks):
There is much evidence which indicates that smoking improves various aspects of human information processing (Wesnes 1987). The aim of the present study was to elucidate the stages of human information processing which are improved after cigarette smoking. Twelve regular smokers were tested on three cognitive tasks using a repeated measures design. Tasks used were: rapid visual information processing (RVIP), digit symbol substitution (DSST), and inspection time (IT). Performance parameters derived from these were intended to index different stages of the information processing sequence. Only those measures which involved a motor component were improved after smoking: response time on the RVIP task (p < 0.025) and DSST performance (p < 0.1). These findings suggest that central cholinergic pathways are involved in the late, response-related stages of the processing sequence.