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The cigarette is the deadliest artifact in the history of human civilization. It is also one of the most beguiling, thanks to more than a century of manipulation at the hands of tobacco industry chemists. In Golden Holocaust, Robert N. Proctor draws on reams of formerly-secret industry documents to explore how the cigarette came to be the most widely-used drug on the planet, with six trillion sticks sold per year. He paints a harrowing picture of tobacco manufacturers conspiring to block the recognition of tobacco-cancer hazards, even as they ensnare legions of scientists and politicians in a web of denial. Proctor tells heretofore untold stories of fraud and subterfuge, and he makes the strongest case to date for a simple yet ambitious remedy: a ban on the manufacture and sale of cigarettes.

Quitting smoking may lead to improvement in substance use, psychiatric symptoms, and pain, especially among high-risk populations who are more likely to experience comorbid conditions. However, causal inferences regarding smoking cessation and its subsequent benefits have been limited. We emulated a hypothetical open-label randomized control trial of smoking cessation using longitudinal observational data of HIV-positive and HIV-negative US veterans from 2003-2015 in the Veterans Aging Cohort Study. We followed individuals from the first time they self-reported current cigarette smoking (baseline). We categorized participants as quitters or non-quitters at the first follow-up visit (approximately 1 year after baseline). Using inverse probability weighting to adjust for confounding and selection bias, we estimated odds ratios for improvement of co-occurring conditions (unhealthy alcohol use, cannabis use, illicit opioid use, cocaine use, depressive symptoms, anxiety symptoms, and pain symptoms) at second follow-up (approximately 2 years after baseline) for those who quit smoking compared to those who did not, among individuals who had the condition at baseline. Of 4,165 eligible individuals (i.e., current smokers at baseline), 419 reported no current smoking and 2,330 reported current smoking at the first follow-up. Adjusted odds ratios (95% confidence intervals) for associations between quitting smoking and improvement of each condition at second follow-up were: 2.10 (1.01, 4.35) for unhealthy alcohol use, 1.75 (1.00, 3.06) for cannabis use, 1.10 (0.58, 2.08) for illicit opioid use, and 2.25 (1.20, 4.24) for cocaine use, 0.78 (0.44, 1.38) for depressive symptoms, 0.93 (0.58, 1.49) for anxiety symptoms, and 1.31 (0.84, 2.06) for pain symptoms. While a causal interpretation of our findings may not be warranted, we found evidence for decreased substance use among veterans who quit cigarette smoking but none for the resolution of psychiatric conditions or pain symptoms. Findings suggest the need for additional resources combined with smoking cessation to reduce psychiatric and pain symptoms for high-risk populations.

Background Smoking is a leading cause of preventable death, disproportionately affecting people with low socioeconomic status (SES) and serious psychological distress (SPD). The U.S. Food and Drug Administration (FDA) has proposed reducing nicotine levels in cigarettes and other combusted tobacco products to minimally addictive levels, a policy with significant public health potential. However, misperceptions about very low nicotine cigarettes (VLNCs), such as beliefs that they are less harmful or ineffective for quitting, may reduce policy effectiveness. While previous randomized controlled trials (RCTs) have examined the effects of using VLNCs, none have incorporated messaging to address misperceptions. This study evaluates the impact of a messaging campaign on smoking behaviors, risk perceptions, and quit intentions among people who smoke, focusing on individuals with low SES, SPD, and neither. The primary objective is to assess whether exposure to VLNC-related messages reduces the number of cigarettes smoked per day compared to VLNC use alone. Secondary objectives include examining effects on other tobacco product use, nicotine dependence, forgoing cigarettes, perceived risks, and quit intentions. Methods This multi-site, open-label, parallel-arm RCT will enroll 1230 adults who smoke ( n  = 410 per group: with SPD, low SES, neither category). After a 1-week baseline period, participants will be randomized (1:1) to receive either (1) VLNCs with messaging or (2) VLNCs only (control). Messaging will include pack inserts and digital ads shown during weekly visits to address misperceptions and encourage quitting. Participants will complete daily logs via text messages and attend weekly visits over 4 weeks for data collection, including self-reported smoking behavior, expired carbon monoxide (CO) samples, and questionnaire assessments. The primary outcome is the number of cigarettes smoked per day in the final study week (week 4). Secondary outcomes include the use of other tobacco products, nicotine dependence, forgoing cigarettes, and quit intentions. Discussion This trial will be the first to examine the effects of a messaging campaign accompanying VLNC use among priority populations. Results will inform FDA regulatory strategies and public health messaging to support nicotine reduction policy implementation. Trial registration ClinicalTrials.gov NCT06787937. Registered on 22 January 2025.

Abstract Introduction The majority of women who smoke cigarettes report that concern about weight gain is a barrier to quitting. We developed an intervention incorporating distress tolerance, appetite awareness, and mindful eating skills to target concerns about post-cessation weight gain and emotional eating (DT-W). In the current study, we conducted a pilot randomized controlled trial of DT-W versus a smoking health education (HE) intervention. Methods Participants (N = 69 adult female, weight-concerned smokers) were recruited in cohorts of 4–11. Cohorts were randomized to DT-W or HE. DT-W and HE were matched on format (single individual session followed by eight group sessions), inclusion of cognitive behavioral therapy for smoking cessation (CBT) content, and pharmacotherapy (nicotine patches). Follow-up assessments occurred at 1-, 3-, and 6-months post-treatment. Results The recruitment goal was met; 61 of the 69 participants attended at least one group session. There were no significant differences between DT-W and HE in the number of group sessions attended (DT-W adjusted M = 5.09, HE adjusted M = 5.03, p = .92), ratings of treatment effectiveness or usefulness of skills, or retention at 6-month follow-up (79% in DT-W vs. 78% in HE) (ps > .05), but comprehension ratings were lower in DT-W than in HE (p = .02). Conclusions Overall, these results suggest that the study procedures and interventions were feasible and acceptable, but changes to the DT-W intervention content to improve comprehension should be considered prior to conducting a fully powered trial. Implications A distress tolerance-based treatment targeting fear of weight gain after smoking cessation and post-cessation emotional eating was feasible and acceptable relative to a smoking HE comparison condition, but changes should be considered before conducting a larger trial. Continued innovation in treatment development for weight-concerned smokers is needed.

Abstract Introduction Most people who smoke cigarettes are not willing (ie, not ready) to make a quit attempt (QA) at any given time. Unfortunately, interventions intended to increase QAs and the success of QAs are only modestly effective. Identifying processes leading to QAs and quitting success could guide intervention development. Aims and Methods This is a secondary analysis of a randomized factorial trial of 6 weeks of motivation-phase interventions among primary care patients (N = 517) who were initially unwilling to quit but were willing to reduce their smoking. Using logistic regression, we controlled for treatment condition and tested whether baseline or change in smoking-related constructs after 6 weeks of treatment predicted (1) making an at least 24 h QA between weeks 6 and 26 and (2) quitting success at week 26 (7-day point-prevalence abstinence among those who made a QA). Predictors included cigarettes/day, time to first cigarette, motivation to quit, quitting self-efficacy, anticipated urges to smoke if quit, positive affect, negative affect, and time spent around others who smoke. Results In multivariable models that included all smoking-related constructs, changes in the following variables predicted initiating a QA above and beyond other variables: greater baseline time to first cigarette (odds ratio [OR] = 1.60), increases in time to first cigarette (OR = 1.27), and increases in quitting self-efficacy (OR = 1.14). Increased motivation to quit predicted conversion of a QA into quitting success at 26 weeks (OR = 1.36). Conclusion Predictors of making a QA differed from predictors of quitting success. Predictors of QAs and success could each serve as important treatment targets of motivation-phase interventions. Implications Motivation-phase interventions for people initially unwilling to quit smoking cigarettes may be improved by striving to increase their (1) time to first cigarette and quitting self-efficacy to promote QAs and (2) motivation to quit to promote quit success. Future experimental tests of such interventions are needed to identify causal determinants of QAs and quitting success.

Abstract Introduction Smoking to reduce negative affect has been identified as a key motivational feature of tobacco use. Our recent work suggests that smoking very low nicotine content (VLNC) cigarettes reduces the relationship between negative affect and smoking behavior over a 6-week period. Here, we sought to extend our findings by evaluating whether a gradual or immediate approach to switching to VLNC cigarettes led to a differential reduction in the relationship between affect and smoking behavior over a longer (20-week) period. Aims and Methods Participants (n = 1250) were adult smokers from 10 US sites randomized to one of three groups: gradual nicotine reduction (15.5, 11.7, 5.2, 2.4, and 0.4 mg of nicotine per gram of tobacco [mg/g]), immediate nicotine reduction (0.4 mg/g), or standard nicotine content cigarettes (15.5 mg/g; control), for 20 weeks. We examined whether the relationship between affect—both negative and positive—and cigarettes per day differed as a function of reduction group. Results We found that both negative and positive affect were associated with cigarette consumption in the control group, but not in the gradual or immediate reduction groups across the 20 weeks of exposure. Conclusions Our results extend previous findings that switching to VLNC cigarettes disrupts the relationship between affect and cigarette consumption by showing that either gradually or immediately reducing cigarette nicotine content achieves this disruption. These findings provide further evidence that switching to VLNC cigarettes reduces nicotine-related reinforcement of cigarette smoking. Implications These findings support the notion that switching to very low nicotine content cigarettes reduces the association between affect and smoking behavior, and that either a gradual or immediate nicotine reduction approach achieves this reduction. This provides further evidence that switching to very low nicotine content cigarettes weakens reinforcement mechanisms associated with nicotine dependence.

Abstract Introduction Reports in relatively healthy smokers suggest men are more sensitive than women to the subjective effects of reduced nicotine content cigarettes (RNCCs). We know of no reports examining sex differences in the relative reinforcing effects of RNCCs, an important outcome in assessing smoking’s addiction potential. The aim of the present study is to address this gap by examining sex/gender differences on reinforcing effects while examining whether sex differences in subjective effects are discernible in vulnerable populations. Methods Secondary analysis of a within-subject, double-blinded experiment examining acute effects of cigarettes varying in nicotine content (0.4, 2.4, 5.2, 15.8 mg/g) among 169 adult smokers with psychiatric conditions or socioeconomic disadvantage. Effects of dose, sex, and their interaction were examined on reinforcing (concurrent-choice and Cigarette Purchase Task [CPT] testing), and subjective effects (Cigarette Evaluation Questionnaire [CEQ] and craving/withdrawal ratings). Results Reducing nicotine content decreased the relative reinforcing effects of smoking in concurrent-choice and CPT testing (p’s < .05) with no significant effects of sex nor dose × sex/gender interactions. Reducing nicotine content decreased CEQ ratings with only a single significant effect of sex (higher Psychological Reward scores among women than men, p = .02) and no significant dose × sex/gender interactions. Results on craving/withdrawal paralleled those on the CEQ. Conclusions Reducing nicotine content decreases the addiction potential of smoking independent of sex in populations highly vulnerable to smoking and addiction, with no indication that women are less sensitive to subjective effects of RNCCs or would benefit less from a policy reducing the nicotine content of cigarettes. Implications A policy reducing the nicotine content of cigarettes has the potential to reduce the addiction potential of smoking across men and women who are especially vulnerable to smoking, addiction, and tobacco-related adverse health impacts.

Population-level communication interventions, such as graphic warning labels (GWLs) on cigarette packs, have the potential to reduce or exacerbate tobacco-related health disparities depending on their effectiveness among disadvantaged sub-populations. This study evaluated the likely impact of nine GWLs proposed by the US Food and Drug Administration on (1) African American and (2) Hispanic smokers, who disproportionately bear the burden of tobacco-related illness, and (3) low education smokers, who have higher smoking rates. Data were collected online from current smokers randomly assigned to see GWLs (treatment) or the current text-only warning labels (control). Participants were stratified by age (18-25; 26+) in each of four groups: general population (n = 1246), African Americans (n = 1200), Hispanics (n = 1200), and low education (n = 1790). We tested the effectiveness of GWLs compared to text-only warning labels using eight outcomes that are predictive of quitting intentions or behaviors including negative emotion, intentions to hold back from smoking, intentions to engage in avoidance behaviors, and intentions to quit. Across all outcomes, GWLs were significantly more effective than text-only warning labels more often than expected by chance. Results suggested that African Americans, Hispanics and smokers with low education did not differ from the general population of smokers in their reactions to any of the nine individual GWLs. The nine GWLs were similarly effective for disadvantaged sub-populations and the general population of smokers. Implementation of GWLs is therefore unlikely to reduce or exacerbate existing tobacco-related health disparities, but will most likely uniformly increase intentions and behaviors predictive of smoking cessation.

Abstract Introduction Under the US Family Smoking Prevention and Tobacco Control Act, the US Food and Drug Administration (FDA) has the authority to implement graphic warning labels (GWLs) on cigarette packages. Neither the original labels proposed by the FDA nor the revised labels include a source to indicate sponsorship of the warnings. This study tests the potential impact of adding a sponsor to the content of GWLs. Methods We recruited adult smokers (N = 245) and middle-school youth (N = 242) from low-income areas in the Northeastern US. We randomly assigned participants to view one of three versions of the original FDA–proposed warning labels in a between-subjects experiment: no sponsor, “US Food and Drug Administration,” or “American Cancer Society” sponsor. We tested the effect of varying sponsorship on source attribution and source credibility. Results Compared to unsponsored labels, FDA sponsorship increased source attributions that the FDA sponsored the labels among both middle-school, largely nonsmoking youth and adult smokers. However, sponsorship had no effect on source credibility among either population. Conclusions We found no evidence that adding FDA as the source is likely to boost source credibility judgments, at least in the short term; though doing so would not appear to have adverse effects on credibility judgments. As such, our data are largely consistent with the Tobacco Control Act’s provisions that allow, but do not require, FDA sponsorship on the labels. Implications This study addresses the FDA’s regulatory efforts by informing the possible design and content of future cigarette warning labels. Our results do not offer compelling evidence that adding the FDA name on GWLs will directly increase source credibility. Future work may test more explicit FDA source labeling and continue to examine the credibility of tobacco message content among high–priority populations.