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“The Effect of Smoking on Mental Health: Evidence from a Randomized Trial”, Meckel & Rittenhouse 2022

“The Effect of Smoking on Mental Health: Evidence from a Randomized Trial”⁠, Katherine Meckel, Katherine P. Rittenhouse (2022-03; ):

This paper aims to identify the causal effects of smoking on mental health using data from the Lung Health Study, a randomized trial of smoking cessation treatment with 5 years of follow-up interviews.

In the short-run, distress increases, likely reflecting the effects of nicotine withdrawal. Long-run effects on mental health are small overall, but mask heterogeneity by gender. For women, the cessation program leads to improved mental health, driven by decreases in insomnia and nervousness. Men do not experience these improvements, due in part to a small increase in severe disturbances.

“Does Quitting Smoking Increase Obesity? Evidence From Accounting for Misreporting”, Tchernis et al 2022

“Does Quitting Smoking Increase Obesity? Evidence From Accounting for Misreporting”⁠, Rusty Tchernis, Keith F. Teltser, Arjun Teotia (2022-01; ; similar):

Smoking and obesity are the 2 leading causes of preventable deaths in the United States. Because smoking is subject to heavy government intervention, understanding the effect of smoking on obesity is important in determining the extent of unintended costs or benefits of such intervention. The existing literature on this question is mixed among studies using experimental and observational data, which we attempt to reconcile by accounting for misreporting in observational data.

We use self-reported data from the Behavioral Risk Factor Surveillance System (BRFSS), cigarette taxes to instrument for changes in smoking, and survey completion to instrument for misreporting.

Starting with the baseline 2-stage least squares (2SLS) estimator common in the earlier observational literature, we obtain similar estimates suggesting quitting smoking substantially reduces BMI⁠. However, we find the results are sensitive to specification, functional form, and the presence of misreporting. We show that accounting for misreporting using the 2-step estimator developed by Nguimkeu et al 2019 yields estimates consistent with the experimental literature; quitting smoking has a small positive [increasing] effect on BMI.

Our preferred estimate suggests reduced smoking accounts for 6% of the concurrent rise in obesity.

“Association of E-Cigarette Use With Discontinuation of Cigarette Smoking Among Adult Smokers Who Were Initially Never Planning to Quit”, Kasza et al 2021

“Association of e-Cigarette Use With Discontinuation of Cigarette Smoking Among Adult Smokers Who Were Initially Never Planning to Quit”⁠, Karin A. Kasza, Kathryn C. Edwards, Heather L. Kimmel, Andrew Anesetti-Rothermel, K. Michael Cummings et al (2021-12-28; similar):

Question: Is e-cigarette use associated with discontinuation of cigarette use among smokers initially not planning to ever quit?

Findings: In this US nationally representative cohort study of 1,600 adult daily cigarette smokers who did not initially use e-cigarettes and had no plans to ever quit smoking, subsequent daily e-cigarette use was statistically-significantly associated with an 8× greater odds of cigarette discontinuation compared with no e-cigarette use.

Meaning: These findings call for consideration of smokers who are not planning to quit when evaluating the risk-benefit potential of e-cigarettes for smoking cessation in the population.

Importance: Cigarette smokers not planning to quit are often overlooked in population studies evaluating the risk-benefit potential of electronic nicotine delivery products (e-cigarettes).

Objective: To evaluate whether e-cigarette use is associated with discontinuing cigarette smoking among smokers who were initially never planning to quit.

Design, Setting, & Participants: This cohort study used US nationally representative data from the longitudinal Population Assessment of Tobacco and Health Study (waves 2–5 conducted between October 2014 and November 2019), with participants evaluated in 3 pairs of interviews. Adult daily cigarette smokers initially not using e-cigarettes and with no plans to ever quit smoking for good (2,489 observations from 1,600 individuals) were included.

Exposures: e-Cigarette use (ie. daily use, non-daily use, or no use) at follow-up interview among smokers not using e-cigarettes at baseline interview.

Main Outcomes & Measures: The main outcomes were discontinuation of cigarette smoking (ie. no cigarette smoking) and discontinuation of daily cigarette smoking (ie. no daily cigarette smoking) at follow-up interview. Generalized estimating equations were used to evaluate the association between the exposure and each outcome, controlling for demographic characteristics and cigarettes smoked per day at baseline interview; all estimates were weighted.

Results: The weighted population of adult daily cigarette smokers who were not using e-cigarettes and had no plans to ever quit smoking, based on data from 1,600 participants, was 56.1% male (95% CI⁠, 53.4%–58.7%), 10.1% Hispanic (95% CI, 8.2%–12.3%), 10.1% non-Hispanic Black (95% CI, 8.7%–11.7%), 75.6% non-Hispanic White (95% CI, 72.9%–78.2%), and 4.2% of other non-Hispanic race (95% CI, 3.3%–5.4%); 29.3% were aged 55 to 69 years (95% CI, 26.2%–32.6%), 8.9% were aged 70 years or older (95% CI, 6.8%–11.5%), 36.8% did not graduate from high school (95% CI, 34.1%–39.6%), 55.2% had an annual household income of less than $25,000 (95% CI, 52.3%–58.1%), 37.6% smoked 20 to 29 cigarettes per day (95% CI, 34.7%–40.6%), and 12.7% smoked 30 or more cigarettes per day (95% CI, 10.9%–14.7%).

Overall, 6.2% of the population (95% CI, 5.0%–7.5%) discontinued cigarette smoking.

Discontinuation rates were higher among those who used e-cigarettes daily (28.0%; 95% CI, 15.2%–45.9%) compared with not at all (5.8%; 95% CI, 4.7%–7.2%; adjusted odds ratio [aOR], 8.11; 95% CI, 3.14–20.97). Furthermore, 10.7% (95% CI, 9.1%–12.5%) discontinued daily cigarette smoking, with higher rates of discontinuation observed among those who used e-cigarettes daily (45.5%; 95% CI, 27.4%–64.9%) compared with not at all (9.9%; 95% CI, 8.2%–11.8%; aOR, 9.67; 95% CI, 4.02–23.25).

Non-daily e-cigarette use was not associated with cigarette discontinuation (aOR, 0.53; 95% CI, 0.08–3.35) or daily cigarette discontinuation (aOR, 0.96; 95% CI, 0.44–2.09).

Conclusions & Relevance: In this cohort study, daily e-cigarette use was associated with greater odds of cigarette discontinuation among smokers who initially had no plans to ever quit smoking. These findings support the consideration of smokers who are not planning to quit when evaluating the risk-benefit potential of e-cigarettes for smoking cessation in the population.

“A Biomarker-based Study of Prenatal Smoking Exposure and Autism in a Finnish National Birth Cohort”, Cheslack-Postava et al 2021

2021-cheslackpostava.pdf: “A biomarker-based study of prenatal smoking exposure and autism in a Finnish national birth cohort”⁠, Keely Cheslack-Postava, Andre Sourander, Susanna Hinkka-Yli-Salomäki, Ian W. McKeague, Heljä-Marja Surcel et al (2021-09-10; ; similar):

This study explored whether prenatal exposure to tobacco smoke in mothers is related to the diagnosis of autism in their children, by measuring the levels of cotinine⁠, a biomarker for tobacco exposure, in stored serum samples drawn from mothers during pregnancy.

The levels of cotinine in the mothers of children diagnosed with autism were similar to those in the mothers of control children of similar age and gender distribution.

Maternal exposure to tobacco smoke during pregnancy is a common and persistent exposure linked to adverse neurodevelopmental outcomes in the offspring. However, previous studies provide mixed evidence regarding the relationship between prenatal smoking and offspring autism.

This study used cotinine level, a biomarker for nicotine⁠, to investigate the relationship between prenatal smoking and autism. The authors conducted a population-based case-control study nested in a national cohort of all births in Finland from 1987 to 2005. Cases diagnosed with childhood autism (ICD-10 /  ​9 code F84.0/​299.0) through 2007 were identified using data from linked national registers. Each case was matched with a control on date of birth (±30 days), sex, and place of birth (n = 962 pairs). Maternal serum cotinine levels were prospectively measured in first-trimester to early second-trimester serum samples archived in a national biobank using a quantitative immunoassay. Data were analyzed using conditional logistic regression⁠.

Prenatal maternal levels of serum cotinine were not associated with the odds of autism, whether cotinine was classified continuously, by deciles, or using previously defined categories corresponding to probable maternal smoking status. After adjusting for maternal age, paternal age, previous births, and any history of parental psychiatric disorder, the odds ratio for categorical high versus low cotinine, using a 3-level exposure variable, was 0.98 (95% CI = 0.76, 1.26; p = 0.88).

In conclusion, this national birth cohort-based study does not provide evidence for an association between maternal cotinine, a biomarker of maternal smoking, and risk of autism.

[Keywords: autism, autistic disorder, cotinine, prenatal exposure delayed effects, smoking]

“Familial Confounding Affected the Associations between Maternal Smoking during Pregnancy and Offspring Speech and Language, Scholastic and Coordination Disorders”, Arrhenius et al 2021

“Familial confounding affected the associations between maternal smoking during pregnancy and offspring speech and language, scholastic and coordination disorders”⁠, Bianca Arrhenius, Amir Sariaslan, Auli Suominen, Andre Sourander, David Gyllenberg (2021-08-07; ⁠, ; similar):

  • Finnish national register data were used to examine any associations between prenatal smoking and children diagnosed with selected developmental disorders by the end of 2012.
  • We found a modest association between prenatal smoking and speech and language, scholastic and coordination disorders when cases were compared with unrelated population controls.
  • However, there was no association between those factors when we compared differentially exposed siblings.

Aim: This study examined the associations between prenatal smoking and speech and language, scholastic, coordination and mixed developmental disorders in offspring, using sibling and population controls.

Methods: National Finnish registers were used to identify all 690 654 singletons born between 1996 and 2007 and any cases diagnosed with speech and language, scholastic, coordination and mixed developmental disorders by the end of 2012. Cases were compared to population controls, biological full-siblings and maternal half-siblings born during the same period. Conditional logistic regression was used to assess any associations between smoking during pregnancy and the selected developmental disorders.

Results: Prenatal smoking was higher in the mothers of the 27 297 cases (21.7%) than the 99 876 population controls (14.5%). The adjusted odds ratio for smoking throughout pregnancy, and any diagnosis of speech and language, scholastic, coordination or mixed developmental disorders, was 1.29 (95% confidence interval 1.24–1.34). However, when we compared a subsample of 15 406 cases and their 20 657 siblings, the association was no longer statistically-significant (odds ratio 1.09, 95% confidence interval 0.98–1.21).

Conclusion: The sibling comparisons suggested that the associations between prenatal smoking and speech and language, scholastic, coordination and mixed developmental disorders were confounded by familial factors shared by differentially exposed siblings.

“Genome-wide Methylation Data Improves Dissection of the Effect of Smoking on Body Mass Index”, Amador et al 2021

“Genome-wide methylation data improves dissection of the effect of smoking on body mass index”⁠, Carmen Amador, Yanni Zeng, Michael Barber, Rosie M. Walker, Archie Campbell, Andrew M. McIntosh, Kathryn L. Evans et al (2021-07-28; ; similar):

Variation in obesity-related traits has a genetic basis with heritabilities between 40 and 70%. While the global obesity pandemic is usually associated with environmental changes related to lifestyle and socioeconomic changes, most genetic studies do not include all relevant environmental covariates, so the genetic contribution to variation in obesity-related traits cannot be accurately assessed. Some studies have described interactions between a few individual genes linked to obesity and environmental variables but there is no agreement on their total contribution to differences between individuals. Here we compared self-reported smoking data and a methylation-based proxy to explore the effect of smoking and genome-by-smoking interactions on obesity related traits from a genome-wide perspective to estimate the amount of variance they explain. Our results indicate that exploiting omic measures can improve models for complex traits such as obesity and can be used as a substitute for, or jointly with, environmental records to better understand causes of disease.

Author summary:

Most diseases and health-related outcomes are influenced by genetic and environmental variation. Hundreds of genetic variants associated with obesity-related traits, like body mass index (BMI), have been previously identified, as well as lifestyles contributing to obesity risk. Furthermore, certain combinations of genetic variants and lifestyles may change the risk of obesity more than expected from their individual effects. One obstacle to further research is the difficulty in measuring relevant environmental impacts on individuals. Here, we studied how genetics (genome-wide markers) and tobacco smoking (self-reported) affect BMI. We also used DNA methylation, a blood-based biomarker, as a proxy for to self-reported information to assess tobacco usage. We incorporated the effect of interactions between genetics and self-reported smoking or methylation. We estimated that genetics accounted for 50% of the variation in BMI. Self-reported smoking status contributed only 2% of BMI variation, increasing to 22% when estimated using DNA methylation. Interactions between genes and smoking contributed an extra 10%. This work highlights the potential of using biomarkers to proxy lifestyle measures and expand our knowledge on disease and suggests that the environment may have long-term effects on our health through its impact on the methylation of disease-associated loci.

“E-Cigarettes and Respiratory Disease: A Replication, Extension, and Future Directions”, Kenkel et al 2020

2020-kenkel.pdf: “E-Cigarettes and Respiratory Disease: A Replication, Extension, and Future Directions”⁠, Donald S. Kenkel, Alan D. Mathios, Hua Wang (2020-07-01; backlinks; similar):

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).

“A Randomized Trial of E-Cigarettes versus Nicotine-Replacement Therapy”, Hajek et al 2019

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 et al (2019-01-01)

“Creatine Cognition Meta-analysis”, Branwen 2013

Creatine: “Creatine Cognition Meta-analysis”⁠, Gwern Branwen (2013-09-06; ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ; backlinks; similar):

Does creatine increase cognitive performance? Maybe for vegetarians but probably not.

I attempt to meta-analyze conflicting studies about the cognitive benefits of creatine supplementation. The wide variety of psychological measures by uniformly small studies hampers any aggregation. 3 studies measured IQ and turn in a positive result, but suggestive of vegetarianism causing half the benefit. Discussions indicate that publication bias is at work. Given the variety of measures, small sample sizes, publication bias, possible moderators, and small-study biases, any future creatine studies should use the most standard measures of cognitive function like RAPM in a reasonably large pre-registered experiment.

“TF-UIHT130030 354..361”, Romagna et al 2013

2013-romagna.pdf: “TF-UIHT130030 354..361”⁠, Giorgio Romagna, Elena Allifranchini, Elena Bocchietto, Stefano Todeschi, Mara Esposito, Konstantinos E. Farsalinos et al (2013-01-01; backlinks)

“The Potential of Nicotinic Enhancement of Cognitive Remediation Training in Schizophrenia”, Hahn et al 2013

2013-hahn.pdf: “The potential of nicotinic enhancement of cognitive remediation training in schizophrenia”⁠, Britta Hahn, James M. Gold, Robert W. Buchanan (2013-01-01; backlinks)

“Effects of Cigarette Smoking on Neuropsychological Performance in Mood Disorders: A Comparison Between Smoking and Nonsmoking Inpatients”, al 2013

2013-caldirola.pdf: “Effects of Cigarette Smoking on Neuropsychological Performance in Mood Disorders: A Comparison Between Smoking and Nonsmoking Inpatients”⁠, Caldirola et al (2013-01-01; backlinks)

“Dual N-Back Meta-Analysis”, Branwen 2012

DNB-meta-analysis: “Dual n-Back Meta-Analysis”⁠, Gwern Branwen (2012-05-20; ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ; backlinks; similar):

Does DNB increase IQ? What factors affect the studies? Probably not: gains are driven by studies with weakest methodology like apathetic control groups.

I meta-analyze the >19 studies up to 2016 which measure IQ after an n-back intervention, finding (over all studies) a net gain (medium-sized) on the post-training IQ tests.

The size of this increase on IQ test score correlates highly with the methodological concern of whether a study used active or passive control groups⁠. This indicates that the medium effect size is due to methodological problems and that n-back training does not increase subjects’ underlying fluid intelligence but the gains are due to the motivational effect of passive control groups (who did not train on anything) not trying as hard as the n-back-trained experimental groups on the post-tests. The remaining studies using active control groups find a small positive effect (but this may be due to matrix-test-specific training, undetected publication bias, smaller motivational effects, etc.)

I also investigate several other n-back claims, criticisms, and indicators of bias, finding:

“One Man’s Modus Ponens”, Branwen 2012

Modus: “One Man’s Modus Ponens”⁠, Gwern Branwen (2012-05-01; ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ; backlinks; similar):

One man’s modus ponens is another man’s modus tollens is a saying in Western philosophy encapsulating a common response to a logical proof which generalizes the reductio ad absurdum and consists of rejecting a premise based on an implied conclusion. I explain it in more detail, provide examples, and a Bayesian gloss.

A logically-valid argument which takes the form of a modus ponens may be interpreted in several ways; a major one is to interpret it as a kind of reductio ad absurdum, where by ‘proving’ a conclusion believed to be false, one might instead take it as a modus tollens which proves that one of the premises is false. This “Moorean shift” is aphorized as the snowclone⁠, “One man’s modus ponens is another man’s modus tollens”.

The Moorean shift is a powerful counter-argument which has been deployed against many skeptical & metaphysical claims in philosophy, where often the conclusion is extremely unlikely and little evidence can be provided for the premises used in the proofs; and it is relevant to many other debates, particularly methodological ones.

“Iodine and Adult IQ Meta-analysis”, Branwen 2012

Iodine: “Iodine and Adult IQ meta-analysis”⁠, Gwern Branwen (2012-02-29; ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ; backlinks; similar):

Iodine improves IQ in fetuses; adults as well? A meta-analysis of relevant studies says no.

Iodization is one of the great success stories of public health intervention: iodizing salt costs pennies per ton, but as demonstrated in randomized & natural experiments, prevents goiters, cretinism, and can boost population IQs by a fraction of a standard deviation in the most iodine-deficient populations.

These experiments are typically done on pregnant women, and results suggest that the benefits of iodization diminish throughout the trimesters of a pregnancy. So does iodization benefit normal healthy adults, potentially even ones in relatively iodine-sufficient Western countries?

Compiling existing post-natal iodization studies which use cognitive tests, I find that—outliers aside—the benefit appears to be nearly zero, and so likely it does not help normal healthy adults, particularly in Western adults.

“Cns_317_LR”, b 2012

2012-echeverria.pdf: “cns_317_LR”⁠, b (2012-01-01; backlinks)

“Prenatal Exposure to Nicotine and Impaired Reading Performance”, Cho et al 2012

2012-cho.pdf: “Prenatal Exposure to Nicotine and Impaired Reading Performance”⁠, Kelly Cho, Jan C. Frijters, Heping Zhang, Laura L. Miller, Jeffrey R. Gruen (2012-01-01; backlinks)

“Cognitive Enhancers for the Treatment of ADHD”, Bidwell et al 2011

2011-bidwell-adhd.pdf: “Cognitive enhancers for the treatment of ADHD”⁠, L. Cinnamon Bidwell, F. Joseph McClernon, Scott H. Kollins (2011-01-01; backlinks)

“The Replication Crisis: Flaws in Mainstream Science”, Branwen 2010

Replication: “The Replication Crisis: Flaws in Mainstream Science”⁠, Gwern Branwen (2010-10-27; ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ; backlinks; similar):

2013 discussion of how systemic biases in science, particularly medicine and psychology, have resulted in a research literature filled with false positives and exaggerated effects, called ‘the Replication Crisis’.

Long-standing problems in standard scientific methodology have exploded as the “Replication Crisis”: the discovery that many results in fields as diverse as psychology, economics, medicine, biology, and sociology are in fact false or quantitatively highly inaccurately measured. I cover here a handful of the issues and publications on this large, important, and rapidly developing topic up to about 2013, at which point the Replication Crisis became too large a topic to cover more than cursorily. (A compilation of some additional links are provided for post-2013 developments.)

The crisis is caused by methods & publishing procedures which interpret random noise as important results, far too small datasets, selective analysis by an analyst trying to reach expected/​desired results, publication bias, poor implementation of existing best-practices, nontrivial levels of research fraud, software errors, philosophical beliefs among researchers that false positives are acceptable, neglect of known confounding like genetics, and skewed incentives (financial & professional) to publish ‘hot’ results.

Thus, any individual piece of research typically establishes little. Scientific validation comes not from small p-values, but from discovering a regular feature of the world which disinterested third parties can discover with straightforward research done independently on new data with new procedures—replication.

“Nootropics”, Branwen 2010

Nootropics: “Nootropics”⁠, Gwern Branwen (2010-01-02; ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ; backlinks; similar)

“Effects of Nicotine on Novelty Detection and Memory Recognition Performance: Double-blind, Placebo-controlled Studies of Smokers and Nonsmokers”, Froeliger et al 2009

2009-froeliger.pdf: “Effects of nicotine on novelty detection and memory recognition performance: double-blind, placebo-controlled studies of smokers and nonsmokers”⁠, Brett Froeliger, David G. Gilbert, F. Joseph McClernon (2009-06-02; backlinks; similar):

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.

“Modafinil”, Branwen 2009

Modafinil: “Modafinil”⁠, Gwern Branwen (2009-02-20; ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ⁠, ; backlinks; similar):

Effects, health concerns, suppliers, prices & rational ordering.

Modafinil is a prescription stimulant drug. I discuss informally, from a cost-benefit-informed perspective, the research up to 2015 on modafinil’s cognitive effects, the risks of side-effects and addiction/​tolerance and law enforcement, and give a table of current grey-market suppliers and discuss how to order from them.

“Dopamine Enables In Vivo Synaptic Plasticity Associated With the Addictive Drug Nicotine”, Tang & Dani 2009

2009-tang.pdf: “Dopamine Enables In Vivo Synaptic Plasticity Associated with the Addictive Drug Nicotine”⁠, Jianrong Tang, John A. Dani (2009-01-01; backlinks)

“Dependence on the Nicotine Gum in Former Smokers”, Etter 2009

2009-etter.pdf: “Dependence on the nicotine gum in former smokers”⁠, Jean-François Etter (2009-01-01; backlinks)

“Melatonin”, Branwen 2008

Melatonin: “Melatonin”⁠, Gwern Branwen (2008-12-19; ⁠, ⁠, ⁠, ⁠, ⁠, ; backlinks; similar):

Melatonin improves sleep, & sleep is valuable

I discuss melatonin’s effects on sleep & its safety with research up to 2015; I segue into the general benefits of sleep and the severely disrupted sleep of the modern Western world, the cost of melatonin use and the benefit (eg. enforcing regular bedtimes), followed by a basic cost-benefit analysis of melatonin concluding that the net profit is large enough to be worth giving it a try barring unusual conditions or very pessimistic safety estimates.

“Smoking As a Risk Factor for Dementia and Cognitive Decline: A Meta-Analysis of Prospective Studies”, Anstey et al 2007

2007-anstey.pdf: “Smoking as a Risk Factor for Dementia and Cognitive Decline: A Meta-Analysis of Prospective Studies”⁠, Kaarin J. Anstey, Chwee von Sanden, Agus Salim, Richard O’Kearney (2007-06-14; backlinks; similar):

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”, Foll et al 2007

“High Reinforcing Efficacy of Nicotine in Non-Human Primates”⁠, Bernard Le Foll, Carrie Wertheim, Steven R. Goldberg (2007-01-24; ; backlinks; similar):

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.

“Drug Counselor Report of Adolescents Abuse of Nicotine Replacement Therapy”, Hyland et al 2005

2005-hyland.pdf: “Drug Counselor Report of Adolescents Abuse of Nicotine Replacement Therapy”⁠, Andrew Hyland, David Bradford, David Bradford (2005; backlinks; similar):

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”, Powledge 2004

“Nicotine as Therapy”⁠, Tabitha M. Powledge (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).]

“Effects of Nicotine Chewing Gum on a Real-life Motor Task: a Kinematic Analysis of Handwriting Movements in Smokers and Non-smokers”, Tucha & Lange 2003

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”⁠, Oliver Tucha, Klaus W. Lange (2003-12-11; backlinks; similar):

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]

“Use of Nicotine Replacement Therapy in Adolescent Smokers and Nonsmokers”, Klesges et al 2003

2003-klesges.pdf: “Use of Nicotine Replacement Therapy in Adolescent Smokers and Nonsmokers”⁠, Lisa M. Klesges, Karen C. Johnson, Grant Somes, Susan Zbikowski, Leslie Robinson (2003-06-01; backlinks; similar):

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.

“Patterns of Over-the-counter Nicotine Gum Use: Persistent Use and Concurrent Smoking”, P 2003

2003-shiffman.pdf: “Patterns of over-the-counter nicotine gum use: persistent use and concurrent smoking”⁠, P (2003-01-01; backlinks)

“NN36-09-changes.p65”, Frost 2003

2003-salinpascual.pdf: “NN36-09-changes.p65”⁠, Frost (2003-01-01; backlinks)

“A Critique of Nicotine Addiction”, Frenk et al 2002

2002-frenkdar.pdf: “A Critique of Nicotine Addiction”⁠, Frenk, Hanan., Dar, Reuven (2002-01-01; backlinks)

“Improved Incidental Memory With Nicotine After Semantic Processing, but Not After Phonological Processing”, Warburton et al 2001

2001-warburton.pdf: “Improved incidental memory with nicotine after semantic processing, but not after phonological processing”⁠, David M. Warburton, Abigail Skinner, Christopher D. Martin (2001; backlinks; similar):

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.

“Preventive Medicine”, Moffatt & 2000

2000-moffatt.pdf: “Preventive Medicine”⁠, Moffatt, R. J. (2000-01-01; backlinks)

“Postmarketing Surveillance and Adverse Drug Reactions: Current Perspectives and Future Needs”, Brewer & Colditz 1999

1999-brewer.pdf: “Postmarketing Surveillance and Adverse Drug Reactions: Current Perspectives and Future Needs”⁠, Timothy Brewer, Graham A. Colditz (1999-03-03; ; backlinks)

“Influence of Nicotine on Simulator Flight Performance in Non-smokers”, Mumenthaler et al 1998

1998-mumenthaler.pdf: “Influence of nicotine on simulator flight performance in non-smokers”⁠, M. S. Mumenthaler, Joy L. Taylor, Ruth O’Hara, Jerome A. Yesavage (1998-11-01; backlinks; similar):

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]

“The Effects of Cigarette Smoking on Overnight Performance”, Parkin et al 1998

1998-parkin.pdf: “The effects of cigarette smoking on overnight performance”⁠, C. Parkin, D. B. Fairweather, Z. Shamsi, N. Stanley, I. Hindmarch (1998-03-01; backlinks; similar):

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.

“Effects of Cotinine on Information Processing in Nonsmokers”, Herzig et al 1998

1998-herzig.pdf: “Effects of cotinine on information processing in nonsmokers”⁠, Karen E. Herzig, Enoch Callaway, R. Halliday, Hilary Naylor, Neal L. Benowitz (1998; backlinks; similar):

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.

“Drug Safety 18: 297-308, Apr 1998”, Greenl et al 1998

1998-greenland.pdf: “Drug Safety 18: 297-308, Apr 1998”⁠, Greenl, S, Satterfield MH, Lanes SF (1998-01-01; backlinks)

“Improvements in Performance without Nicotine Withdrawal”, Warburton & Arnall 1994

1994-warburton.pdf: “Improvements in performance without nicotine withdrawal”⁠, David M. Warburton, Cliff Arnall (1994; backlinks; similar):

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.

“Transdermal Nicotine: Reduction of Smoking With Minimal Abuse Liability”, Pickworth et al 1994

1994-pickworth.pdf: “Transdermal nicotine: reduction of smoking with minimal abuse liability”⁠, Wallace B. Pickworth, Edward B. Bunker, Jack E. Henningfield (1994; backlinks; similar):

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.

“Nicotine Addiction: a Re-analysis of the Arguments”, West 1992

1992-west.pdf: “Nicotine addiction: a re-analysis of the arguments”⁠, Robert West (1992-09-01; backlinks; similar):

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 an 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 an 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.

“The Role of Nicotine in Tobacco Use”, Robinson & Pritchard 1992

1992-robinson.pdf: “The role of nicotine in tobacco use”⁠, John H. Robinson, Walter S. Pritchard (1992-09-01; backlinks; similar):

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.

“Long-term Use of Nicotine vs Placebo Gum”, Hughes et al 1991b

1991-hughes-2.pdf: “Long-term Use of Nicotine vs Placebo Gum”⁠, John R. Hughes, Steven W. Gust, Robert Keenan, James W. Fenwick, Kelli Skoog, Stephen T. Higgins (1991-10-01; backlinks; similar):

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.

“Smoking and Human Information Processing”, Petrie & Deary 1989

1989-petrie.pdf: “Smoking and human information processing”⁠, Rachel X. A. Petrie, Ian J. Deary (1989-11-01; backlinks; similar):

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.

2019–2020 vaping lung illness outbreak