Daily and Momentary Associations Between Gender Minority Stress and Resilience With Alcohol Outcomes.

BACKGROUND AND PURPOSE: Minority stressors have been linked with alcohol use among transgender and gender diverse (TGD); however, no ecological momentary assessment studies have examined daily links between minority stress and alcohol use specifically among TGD. This study examined gender minority stressors and resilience as predictors of same-day or momentary alcohol-related outcomes. Feasibility and acceptability of procedures were evaluated. METHODS: Twenty-five TGD adults (mean age = 32.60, SD = 10.82; 88% White) were recruited Canada-wide and participated remotely. They completed 21 days of ecological momentary assessment with daily morning and random surveys (assessing alcohol outcomes, risk processes, gender minority stressors, resilience), and an exit interview eliciting feedback. RESULTS: Gender minority stress had significant and positive within-person relationships with same-day alcohol use (incidence risk ratio (IRR) = 1.12, 95% confidence interval [CI] [1.02, 1.23]), alcohol-related harms (IRR = 1.14, 95% CI [1.02, 1.28]), and coping motives (IRR = 1.06, 95% CI [1.03, 1.08]), as well as momentary (past 30-min) alcohol craving (IRR = 1.32, 95% CI [1.18, 1.47]), coping motives (IRR = 1.35, 95% CI [1.21, 1.51]), and negative affect (IRR = 1.28, 95% CI [1.20, 1.36]). Gender minority stress indirectly predicted same-day drinking via coping motives (ab = 0.04, 95% CI [0.02, 0.08]). Resilience was positively associated with same-day alcohol use (IRR = 1.25, 95% CI [1.03, 1.51]) but not harms. CONCLUSIONS: TGD adults may use alcohol to cope with gender minority stress, which can increase the risk for alcohol-related harms. Interventions are needed to eliminate gender minority stressors and support adaptive coping strategies.

Many transgender and gender diverse (TGD) adults experience discrimination and victimization related to their minoritized gender, referred to as minority stress. Minority stress may put TGD adults at risk of drinking more alcohol and experiencing related harms in order to cope. To examine this possibility, we recruited 25 TGD adults and asked them to complete surveys multiple times per day (i.e., once daily in the morning, and two additional surveys at random times) on their personal cell phones. Using multilevel models, we examined the relations between experiencing minority stressors as well as resilience factors on alcohol-related outcomes. In doing so, we identified that gender minority stress was related to increased alcohol use, alcohol-related harms, negative mood, and drinking to cope motives. Furthermore, it appeared that the increased alcohol use following minority stress could be partly explained by desiring to drink to cope. Resilience did not protect TGD adults from increased alcohol use or harms, and in some cases was related to increased alcohol use. The results support that TGD adults may use alcohol to cope with gender minority stress, which can increase the risk for alcohol-related harms. Interventions are needed to eliminate gender minority stressors and support healthier coping strategies.

The Moderating Role of Sexual Orientation in the Association Between Religiosity and Sexual Behaviors Among College Students.

Past research has shown that religiosity can impact sexual behaviors of college-aged youth in both positive and negative directions. As many world religions promote doctrines that include negative views toward sexual minorities, the current study aimed to examine the potentially differential ways religiosity is related to sexual behaviors across various sexual orientations. College/university students across Oregon (N = 1553) completed an online cross-sectional survey in which they provided information about their sexual orientation, levels of religiosity, religious affiliation, and endorsed recent sexual behavior outcomes. Using logistic models in PROCESS, sexual orientation was examined as a moderator of the relations between religiosity (assessed via the Centrality of Religiosity Scale; Huber & Huber) and religious affiliation and the occurrence (yes vs. no) of three sexual behaviors in the past 6 months: birth control use during sex, sexual activity under the influence of substances, and testing positive for an STI. Covariates were age and natal sex. Religiosity was related to reduced birth control use in heterosexual and gay/lesbian individuals. Religiosity was not associated with sexual behaviors in bi/pansexual college students. Findings show that religiosity was a salient construct for understanding sexual behaviors in heterosexual and gay/lesbian college students, but not in bi/pansexual college students. Given that religiosity has differential effects for various sexual behaviors that can heighten risk of negative sexual health outcomes, recommendations are made for increased and tailored sexual health education to religiously identified college students.

Cannabis cravings predict cigarette use in schizophrenia: a secondary analysis from two cannabis abstinence studies.

CLINICAL TRIAL NAME: Effects of Repetitive Transcranial Magnetic Stimulation (rTMS) on Cannabis Use and Cognitive Outcomes in SchizophreniaURL: www.clinicaltrials.gov; Registration Number: NCT03189810.

Associations between Shyness and Victimization with Substance Use Outcomes in the National Comorbidity and Collaborative Psychiatric Epidemiological Surveys.

Background: There is a lack of consensus among researchers on the association between shyness and substance use. This may be due to unexamined modifiers of this association, such as childhood victimization. Objective: The purpose of this study was to examine if experiencing different types of victimization (emotional, physical, sexual, and poly-victimization) modifies the association between shyness and substance use outcomes in adults. In this study, we performed moderation analyses to investigate whether victimization moderates the association between shyness and substance use/abuse. Data came from the National Comorbidity Survey Baseline (NCS-1; 1990-1992) and the Collaborative Psychiatric Epidemiological Surveys (CPES; 2001-2003). Substance use outcomes included were binge drinking, tobacco use, other drug use, and DSM-III-R (NCS-1)/DSM-IV (CPES) classifications of alcohol and drug abuse. Results: Results from NCS-1 supported a moderating role of childhood victimization on the relationship between shyness and tobacco use only, specifically for emotional (p = .031) and physical (p < .001) victimization, and poly-victimization (p < .001). Results from CPES showed a moderating role of lifetime sexual abuse for binge drinking (p = .017), other drug use (p = .028), and alcohol abuse (p = .004). For both datasets, the associations between shyness and substance use outcomes were stronger when there were no victimization histories. Conclusion: These findings give insight on the complexity of the interaction between shyness and victimization. Future research could focus on mechanisms, such as cognitive processes, that may contribute to interactions between shyness and victimization history on substance outcomes.

Immediate Switching to Reduced Nicotine Cigarettes in a U.S.-Based Sample: The Impact on Cannabis Use and Related Variables at 20 Weeks.

INTRODUCTION: The FDA proposed rule-making to reduce nicotine in cigarettes to minimally addictive levels. Research suggests decreasing nicotine levels (i.e. very low nicotine content cigarettes [VLNCs]) produced greater quit attempts, reduced smoking, and reduced exposure to harmful constituents among smokers. The impact of long-term VLNC use among people who co-use cigarettes and cannabis on non-tobacco-specific toxicant and carcinogen exposure has not been investigated. AIMS AND METHODS: This study presents secondary analyses of a controlled clinical trial examining switching to VLNC (versus a normal nicotine cigarettes control group [NNCs]) between people who co-use cigarettes and cannabis (n = 174) versus smoked cigarettes (n = 555). Linear mixed-effects models compared changes in smoking behavior, and tobacco-specific (i.e. total nicotine equivalents [TNE], 4-[methylnitrosamino]-1-[3-pyridyl]-1-butanone [NNK; total NNAL]) and non-tobacco-specific (i.e. carbon monoxide (CO), 2-cyanoethylmercapturic acid [CEMA], phenanthrene tetraol [PheT]) toxicant and carcinogen exposure at week 20 (with random intercept for participants). Cannabis use was measured among co-use groups. RESULTS: CO was significantly lower only among the cigarette-only group assigned VLNCs (interaction: p = .015). Although both VLNC groups demonstrated decreased CEMA, greater decreases emerged among the cigarette-only group (interaction: p = .016). No significant interactions emerged for TNE, cigarettes per day (CPD), NNAL, and PheT (ps > .05); both VLNC groups decreased in TNE, CPD, and NNAL. Only the cigarette-only group assigned VLNCs demonstrated decreased PheT (p < .001). The VLNC co-use group showed increased cannabis use over time (p = .012; 0.5 more days per week by week 20). CONCLUSIONS: Those who co-use cannabis and cigarettes may still be at risk for greater exposure to non-tobacco-specific toxicants and carcinogens compared to those who only smoke cigarettes. IMPLICATIONS: The present study is the longest longitudinal, prospective comparison study of smoking behavior and exposure to harmful constituents among those who co-use cigarettes and cannabis versus cigarette-only after immediately switching to very low nicotine content cigarettes (VLNC). Those who co-use experienced similar reductions in CPD and tobacco-specific exposure, compared to those who only use cigarettes. However, co-use groups experienced smaller reductions in non-tobacco-specific toxicants and carcinogens compared to the cigarette-only group, potentially because of combustible cannabis use. Additionally, those who co-use and switched to VLNC may be susceptible to slight increases in cannabis use (approximately two more days per year).

Assessing Sex, Gender Identity, Sexual Orientation, Race, Ethnicity, Socioeconomic Status, and Mental Health Concerns in Tobacco Use Disorder Treatment Research: Measurement Challenges and Recommendations From a Society for Research on Nicotine and Tobacco Pre-conference Workshop.

This paper reports on topics discussed at a Society for Research on Nicotine and Tobacco pre-conference workshop at the 2019 annual Society for Research on Nicotine and Tobacco meeting. The goal of the pre-conference workshop was to help develop a shared understanding of the importance of several tobacco-related priority groups in tobacco use disorder (TUD) treatment research and to highlight challenges in measurement related to these groups. The workshop focused on persons with minoritized sex, gender identity, and sexual orientation identities; persons with minoritized racial and ethnic backgrounds; persons with lower socioeconomic status (SES); and persons with mental health concerns. In addition to experiencing commercial tobacco-related health disparities, these groups are also underrepresented in tobacco research, including TUD treatment studies. Importantly, there is wide variation in how and whether researchers are identifying variation within these priority groups. Best practices for measuring and reporting sex, gender identity, sexual orientation, race, ethnicity, SES, and mental health concerns in TUD treatment research are needed. This paper provides information about measurement challenges when including these groups in TUD treatment research and specific recommendations about how to measure these groups and assess potential disparities in outcomes. The goal of this paper is to encourage TUD treatment researchers to use measurement best practices in these priority groups in an effort to conduct meaningful and equity-promoting research. Increasing the inclusion and visibility of these groups in TUD treatment research will help to move the field forward in decreasing tobacco-related health disparities. Implications: Tobacco-related disparities exist for a number of priority groups including, among others, women, individuals with minoritized sexual and gender identities, individuals with minoritized racial and ethnic backgrounds, individuals with lower SES, and individuals with mental health concerns. Research on TUD treatments for many of these subgroups is lacking. Accurate assessment and consideration of these subgroups will provide needed information about efficacious and effective TUD treatments, about potential mediators and moderators, and for accurately describing study samples, all critical elements for reducing tobacco-related disparities, and improving diversity, equity, and inclusion in TUD treatment research.

An Evaluation of Potential Unintended Consequences of a Nicotine Product Standard: A Focus on Drinking History and Outcomes.

INTRODUCTION: A nicotine product standard reducing the nicotine content in cigarettes could improve public health by reducing smoking. This study evaluated the potential unintended consequences of a reduced nicotine product standard by examining its effects on (1) smoking behaviors based on drinking history; (2) drinking behavior; and (3) daily associations between smoking and drinking. METHODS: Adults who smoke daily (n = 752) in the United States were randomly assigned to smoke very low nicotine content (VLNC) cigarettes versus normal nicotine content (NNC; control) cigarettes for 20 weeks. Linear mixed models determined if baseline drinking moderated the effects of VLNC versus NNC cigarettes on Week 20 smoking outcomes. Time-varying effect models estimated the daily association between smoking VLNC cigarettes and drinking outcomes. RESULTS: Higher baseline alcohol use (vs no use or lower use) was associated with a smaller effect of VLNC on Week 20 urinary total nicotine equivalents (ps < .05). No additional moderation was supported (ps > .05). In the subsample who drank (n = 415), in the VLNC versus NNC condition, daily alcohol use was significantly reduced from Weeks 17 to 20 and odds of binge drinking were significantly reduced from Weeks 9 to 17. By Week 7, in the VLNC cigarette condition (n = 272), smoking no longer predicted alcohol use but remained associated with binge drinking. CONCLUSIONS: We did not support negative unintended consequences of a nicotine product standard. Nicotine reduction in cigarettes generally affected smoking behavior for individuals who do not drink or drink light-to-moderate amounts in similar ways. Extended VLNC cigarette use may improve public health by reducing drinking behavior. IMPLICATIONS: There was no evidence that a VLNC product standard would result in unintended consequences based on drinking history or when considering alcohol outcomes. Specifically, we found that a very low nicotine standard in cigarettes generally reduces smoking outcomes for those who do not drink and those who drink light-to-moderate amounts. Furthermore, an added public health benefit of a very low nicotine standard for cigarettes could be a reduction in alcohol use and binge drinking over time. Finally, smoking VLNC cigarettes may result in a decoupling of the daily associations between smoking and drinking.

Religious and Spiritual Development from Adolescence to Early Adulthood in the U.S.: Changes over Time and Sexual Orientation Differences.

Adolescence is a critical time in the U.S. for religious development in that many young people eschew their religious identity as they enter adulthood. In general, religion is associated with a number of positive health outcomes including decreased substance use and depression. The current study compared the developmental patterns of religiosity and spirituality in heterosexual and sexual minority youth. The design was a secondary data analysis of the first five waves of the Longitudinal Study of Adolescent Health and Wellness (N = 337, 71.8% female). Using multilevel linear (for spirituality) and quadratic (for religiosity) growth models, the initial level and change over time in religiosity and spirituality, as well as the correlations between growth processes, were compared between heterosexual and sexual minority individuals. The heterosexual group had significantly higher initial religiosity levels than the sexual minority group. Religiosity decreased over time at a similar rate for the heterosexual and sexual minority groups. Spirituality significantly increased over time for the sexual minority group but not for the heterosexual youth. The change over time in religiosity and spirituality were significantly and positively correlated for heterosexual individuals but were uncorrelated for sexual minority individuals. Results indicate there are differences in religious development based on sexual minority status. Future research should take into account how these differential religious and spiritual developmental patterns seen in heterosexual and sexual minority youth might predict various health outcomes.

OPRM1 Moderates Daily Associations of Naltrexone Adherence With Alcohol Consumption: Preliminary Evidence From a Mobile Health Trial.

BACKGROUND: Initial evidence that OPRM1 genotype moderates the clinical response to naltrexone has not been replicated in prospective clinical trials. However, the use of traditional statistical analyses and clinical endpoints might limit sensitivity for studying pharmacogenetic associations, whereas the use of intensive daily assessments and person-centered analytic methods might increase sensitivity. This study leveraged person-centered analyses and daily measures of alcohol use, craving, and medication adherence to investigate OPRM1 as a moderator of changes in clinical outcomes during naltrexone treatment. METHODS: Treatment-seeking participants with alcohol use disorder (n = 58; Mage  = 38 years; 71% male) provided daily cell phone reports of craving and consumption while taking naltrexone as part of a mobile health trial. Daily medication adherence was measured remotely using electronic pill cap recordings. Multilevel modeling and multilevel structural equation modeling analyses evaluated the hypotheses that OPRM1 genotype would moderate prospective reductions in daily alcohol use and craving, and would also moderate within-person associations of daily adherence with same-day craving and consumption. RESULTS: OPRM1 genotype moderated the association of daily adherence with reduced same-day consumption (p = 0.007) and craving (p = 0.06), with these associations being stronger for participants with the 118G variant. OPRM1 genotype did not moderate changes in craving and consumption over time. CONCLUSIONS: These findings suggest that high-density assessments and person-centered analytic approaches, including modeling within-person variation in medication adherence, could be advantageous for pharmacogenetic studies.

Changes in Nicotine Metabolite Ratio Among Daily Smokers Receiving Treatment for Alcohol Use Disorder.

INTRODUCTION: Alcohol may influence the nicotine metabolite ratio (NMR), an index of the rate of nicotine metabolism that is associated smoking level and lapses. We examined if NMR changes during alcohol use disorder (AUD) treatment and how changes in NMR relate to reductions in drinking. METHODS: Using an observational design, 22 daily smokers [63.64% male, Mage = 46.77 (11.37)] receiving AUD treatment completed baseline and follow-up appointments 3 weeks apart. At each appointment, daily alcohol and cigarette use, salivary and urinary NMR, nicotine exposure via urinary total nicotine equivalents, and carbon monoxide were assessed. Multilevel models examined the change over time in NMR and its within-person relations with changes in drinks per week. Sex differences were evaluated. RESULTS: There were significant reductions in both salivary and urinary NMR over time for men (p = .02; p = .01, respectively) but not for women (p = .54; p = .90, respectively). There were no changes over time in total nicotine equivalents (p = .09), carbon monoxide (p = .44), or cigarette use (p = .44) in either sex. Drinks per week were significantly reduced for men (29.12 drink reduction, p < .001) but not for women (2.28 drink reduction, p = .80); however, within-person changes in drinking were not associated with changes in salivary or urinary NMR (p = .99; p = .19). CONCLUSIONS: The reduction in alcohol use and NMR in men provides indirect support for alcohol increasing NMR. In contrast, the low baseline drinking and lack of alcohol reduction likely underlie the lack of change in NMR in females. Reasons for NMR reductions during AUD treatment and its effects on smoking require further study. IMPLICATIONS: Three weeks of alcohol use disorder treatment among daily smokers coincided with a significant reduction in both alcohol use and NMR for men; however, neither drinking level nor NMR changed for women. The findings indirectly support that heavy drinking increases NMR, which is reversed with reduced drinking. Additional research is needed to establish if these changes in NMR correlate with smoking and cessation outcomes.

We are in This Together: Promoting Health Equity, Diversity, and Inclusion in Tobacco Research for Sexual and Gender Minority Populations.

INTRODUCTION: Sexual and gender minority (SGM) individuals have higher tobacco use prevalence and consequently higher burden of tobacco-caused diseases, including cancer and cardiovascular disease compared with their heterosexual or cisgender counterparts. Yet, there is a critical gap in research focused on measuring SGM tobacco-related health disparities and addressing unmet needs of SGM individuals in the context of nicotine and tobacco research. AIMS AND METHODS: In this commentary, we summarize recommendations discussed during a pre-conference workshop focused on challenges and opportunities in conducting SGM tobacco control research at the 2019 Society for Research on Nicotine and Tobacco Annual Meeting. RESULTS: Specifically, we recommend defining and measuring SGM identity in all nicotine and tobacco research routinely, using novel methods to engage a demographically diverse sample of the SGM population, and eliciting SGM community voices in tobacco control research. CONCLUSIONS: Addressing these critical research gaps will enable the scientific community to generate the data to fully understand and support SGM individuals in tobacco use prevention and cessation. IMPLICATIONS: Tobacco use and its consequences have become increasingly concentrated in disadvantaged groups, including sexual and gender minority (SGM) populations. Through concrete recommendations in this commentary, we aimed to promote health equity, diversity, and inclusion in tobacco research for SGM populations by urging the scientific community to consider expanding efforts to monitor and address tobacco-related health disparities of SGM populations within their respective research programs.

The Impact of Gradual and Immediate Nicotine Reduction on Subjective Cigarette Ratings.

BACKGROUND: A recent clinical trial showed that an immediate transition to very low nicotine content (VLNC) cigarettes, compared with a gradual transition, produced greater reductions in smoking behavior, smoke exposure, and dependence. However, there was less compliance with the instruction to smoke only VLNC cigarettes in the immediate versus gradual reduction condition. The goal of this study was to test whether nicotine reduction method alters subjective ratings of VLNC cigarettes, and whether subjective ratings mediate effects of nicotine reduction method on smoking behavior, smoke exposure, dependence, and compliance. METHODS: This is a secondary analysis of a randomized trial conducted across 10 sites in the United States. Smokers (n = 1250) were randomized to either a control condition, or to have the nicotine content of their cigarettes reduced immediately or gradually to 0.04 mg nicotine/g of tobacco during a 20-week study period. Participants completed the modified Cigarette Evaluation Questionnaire (mCEQ). RESULTS: After Week 20, the immediate reduction group scored significantly lower than the gradual reduction group on multiple subscales of the mCEQ (ps < .001). The Satisfaction subscale of the mCEQ mediated the impact of nicotine reduction method on smoke exposure, smoking behavior, dependence, compliance, and abstinence. Other subscales also mediated a subset of these outcomes. CONCLUSIONS: An immediate reduction in nicotine content resulted in lower product satisfaction than a gradual reduction, suggesting that immediate reduction further reduces cigarette reward value. This study will provide the Food and Drug Administration with information about the impact of nicotine reduction method on cigarette reward value. IMPLICATIONS: These data suggest that an immediate reduction in nicotine content will result in greater reductions in cigarette satisfaction than a gradual reduction, and this reduction in satisfaction is related to changes in smoking behavior and dependence.

Randomized Trial of Reduced-Nicotine Standards for Cigarettes.

BACKGROUND: The Food and Drug Administration can set standards that reduce the nicotine content of cigarettes. METHODS: We conducted a double-blind, parallel, randomized clinical trial between June 2013 and July 2014 at 10 sites. Eligibility criteria included an age of 18 years or older, smoking of five or more cigarettes per day, and no current interest in quitting smoking. Participants were randomly assigned to smoke for 6 weeks either their usual brand of cigarettes or one of six types of investigational cigarettes, provided free. The investigational cigarettes had nicotine content ranging from 15.8 mg per gram of tobacco (typical of commercial brands) to 0.4 mg per gram. The primary outcome was the number of cigarettes smoked per day during week 6. RESULTS: A total of 840 participants underwent randomization, and 780 completed the 6-week study. During week 6, the average number of cigarettes smoked per day was lower for participants randomly assigned to cigarettes containing 2.4, 1.3, or 0.4 mg of nicotine per gram of tobacco (16.5, 16.3, and 14.9 cigarettes, respectively) than for participants randomly assigned to their usual brand or to cigarettes containing 15.8 mg per gram (22.2 and 21.3 cigarettes, respectively; P<0.001). Participants assigned to cigarettes with 5.2 mg per gram smoked an average of 20.8 cigarettes per day, which did not differ significantly from the average number among those who smoked control cigarettes. Cigarettes with lower nicotine content, as compared with control cigarettes, reduced exposure to and dependence on nicotine, as well as craving during abstinence from smoking, without significantly increasing the expired carbon monoxide level or total puff volume, suggesting minimal compensation. Adverse events were generally mild and similar among groups. CONCLUSIONS: In this 6-week study, reduced-nicotine cigarettes versus standard-nicotine cigarettes reduced nicotine exposure and dependence and the number of cigarettes smoked. (Funded by the National Institute on Drug Abuse and the Food and Drug Administration Center for Tobacco Products; ClinicalTrials.gov number, NCT01681875.).

Predictors of Daily Adherence to Naltrexone for Alcohol Use Disorder Treatment During a Mobile Health Intervention.

Background: Adherence to medications for treating alcohol use disorder (AUD) is poor. To identify predictors of daily naltrexone adherence over time, a secondary data analysis was conducted of a trial evaluating a mobile health intervention to improve adherence. Methods: Participants seeking treatment for AUD (n = 58; Mage = 38 years; 71% male) were prescribed naltrexone for 8 weeks. Adherence was tracked using the Medication Event Monitoring System (MEMS). In response to daily text messages, participants reported the previous day's alcohol use, craving, and naltrexone side effects. Using multilevel structural equation modeling (MSEM), we examined baseline dispositional factors and within-person, time-varying factors as predictors of daily adherence. Results: Naltrexone adherence decreased over time. Adherence was higher on days when individuals completed daily mobile assessments relative to days when they did not (odds ratio [OR] = 2.53, 95% confidence interval [CI] 1.61 to 3.98), irrespective of intervention condition. Days when individuals drank more than their typical amount were related to lower next-day adherence (OR = 0.93, 95% CI 0.88 to 0.99). A similar pattern was supported for craving (OR = 0.88, 95% CI 0.79 to 0.98). Weekend days were associated with lower adherence than weekdays (OR = 0.71, 95% CI 0.58 to 0.86); this effect was partly mediated by heavier daily drinking (indirect effect = -0.02, 95% CI -0.04 to -0.003) and stronger-than-usual craving (indirect effect = -0.01, 95% CI -0.02 to 0.00) on weekend days. Conclusions: The results further demonstrate the need to improve adherence to AUD pharmacotherapy. The present findings also support developing interventions that target daily-level risk factors for nonadherence. Mobile health interventions may be one means of developing tailored and adaptive adherence interventions.

Perceived nicotine content of reduced nicotine content cigarettes is a correlate of perceived health risks.

BACKGROUND: Reducing cigarette nicotine content may reduce smoking. Studies suggest that smokers believe that nicotine plays a role in smoking-related morbidity. This may lead smokers to assume that reduced nicotine means reduced risk, and attenuate potential positive effects on smoking behaviour. METHODS: Data came from a multisite randomised trial in which smokers were assigned to use cigarettes varying in nicotine content for 6 weeks. We evaluated associations between perceived and actual nicotine content with perceived health risks using linear regression, and associations between perceived nicotine content and perceived health risks with smoking outcomes using linear and logistic regression. FINDINGS: Perceived-not actual-nicotine content was associated with perceived health risks; compared with those perceiving very low nicotine, individuals who perceived low (ß=0.72, 95% CI 0.26 to 1.17), moderate (ß=1.02, 95% CI 0.51 to 1.53) or high/very high nicotine (ß=1.66, 95% CI 0.87 to 2.44) perceived greater health risks. Nevertheless, individuals perceiving low (OR=0.48, 95% CI 0.32 to 0.71) or moderate nicotine (OR=0.42, 95% CI 0.27 to 0.66) were less likely than those perceiving very low nicotine to report that they would quit within 1 year if only investigational cigarettes were available. Lower perceived risk of developing other cancers and heart disease was also associated with fewer cigarettes/day at week 6. CONCLUSIONS: Although the perception of reduced nicotine is associated with a reduction in perceived harm, it may not attenuate the anticipated beneficial effects on smoking behaviour. These findings have implications for potential product standards targeting nicotine and highlight the need to clarify the persistent harms of reduced nicotine combusted tobacco products.

A Critical Review of the Effects of Nicotine and Alcohol Coadministration in Human Laboratory Studies.

Simultaneous use of cigarettes and alcohol is common and may be driven by nicotine increasing alcohol self-administration or vice versa. To better evaluate the causal nature of this relationship, we systematically reviewed human experimental laboratory studies that coadministered nicotine and alcohol with control conditions. Searches of PubMed/MEDLINE and PsycINFO databases and study bibliographies identified 30 studies that met our inclusion criteria. Research methodologies were critically reviewed. Effects of coadministration on drug self-administration and related factors such as craving, subjective response, motivation, and heart rate are reported. Results most strongly supported that alcohol increases nicotine and cigarette self-administration, whereas, depending on the context, nicotine increased, decreased, or had no effect on alcohol self-administration. Craving and subjective drug effects were also impacted by coadministration. Interaction effects of nicotine and alcohol on self-administration and subjective responses were reported infrequently. The effects may be moderated by a number of factors, including dose of administered drug and sex. Recommendations are made for future research, and clinical and policy implications of findings are discussed.

Effects of 6-Week Use of Reduced-Nicotine Content Cigarettes in Smokers With and Without Elevated Depressive Symptoms.

BACKGROUND: The FDA recently acquired regulatory authority over tobacco products, leading to renewed interest in whether reducing the nicotine content of cigarettes would reduce tobacco dependence in the United States. Given the association between depressive symptoms and cigarette smoking, it is important to consider whether smokers with elevated depressive symptoms experience unique benefits or negative consequences of nicotine reduction. METHODS: In this secondary analysis of a randomized clinical trial that examined the effects of cigarettes varying in nicotine content over a 6-week period in non-treatment-seeking smokers, we used linear regression to examine whether baseline depressive symptom severity (scores on the Center for Epidemiologic Studies Depression Scale [CES-D]) moderated the effects of reduced-nicotine content (RNC) cigarettes, relative to normal-nicotine content (NNC) cigarettes, on smoking rates, depressive symptom severity, and related subjective and physiological measures. RESULTS: Of the 717 participants included in this analysis, 109 (15.2%) had CES-D scores ≥ 16, indicative of possible clinical depression. Relative to NNC cigarettes, RNC cigarettes reduced smoking rates, nicotine dependence, and cigarette craving, and these effects were not significantly moderated by baseline CES-D score. A significant interaction between baseline CES-D score and cigarette condition on week 6 CES-D score was observed (p < .05); among those with CES-D scores ≥ 16 at baseline, those assigned to RNC cigarettes had lower week 6 CES-D scores than those assigned to NNC cigarettes. Among those in the lowest nicotine content conditions, biochemically confirmed compliance with the RNC cigarettes was associated with an increase in CES-D score for those with baseline CES-D scores < 16 and no change in CES-D score for those with baseline CES-D scores ≥ 16. CONCLUSIONS: These findings provide initial evidence that a reduced-nicotine standard for cigarettes may reduce smoking, without worsening depressive symptoms, among smokers with elevated depressive symptoms. IMPLICATIONS: This secondary analysis of a recent clinical trial examined whether depressive symptom severity moderated the effects of reduced-nicotine cigarettes on smoking and depressive symptoms. Results indicate that, regardless of baseline depressive symptoms, participants randomized to reduced-nicotine cigarettes had lower smoking rates, nicotine intake, nicotine dependence, and craving at week 6 post-randomization than those assigned to normal-nicotine cigarettes. In participants with higher baseline depressive symptoms, those assigned to reduced-nicotine cigarettes had lower week 6 depressive symptoms than those assigned to normal-nicotine cigarettes. These results suggest that a nicotine reduction policy could have beneficial effects for smokers, regardless of depressive symptom severity.

Reducing nicotine exposure results in weight gain in smokers randomised to very low nicotine content cigarettes.

BACKGROUND: The Food and Drug Administration can reduce the nicotine content in cigarettes to very low levels. This potential regulatory action is hypothesised to improve public health by reducing smoking, but may have unintended consequences related to weight gain. METHODS: Weight gain was evaluated from a double-blind, parallel, randomised clinical trial of 839 participants assigned to smoke 1 of 6 investigational cigarettes with nicotine content ranging from 0.4 to 15.8 mg/g or their own usual brand for 6 weeks. Additional analyses evaluated weight gain in the lowest nicotine content cigarette groups (0.4 and 0.4 mg/g, high tar) to examine the effect of study product in compliant participants as assessed by urinary biomarkers. Differences in outcomes due to gender were also explored. FINDINGS: There were no significant differences in weight gain when comparing the reduced nicotine conditions with the 15.8 mg/g control group across all treatment groups and weeks. However, weight gain at week 6 was negatively correlated with nicotine exposure in the 2 lowest nicotine content cigarette conditions. Within the 2 lowest nicotine content cigarette conditions, male and female smokers biochemically verified to be compliant on study product gained significantly more weight than non-compliant smokers and control groups. CONCLUSIONS: The effect of random assignment to investigational cigarettes with reduced nicotine on weight gain was likely obscured by non-compliance with study product. Men and women who were compliant in the lowest nicotine content cigarette conditions gained 1.2 kg over 6 weeks, indicating weight gain is a likely consequence of reduced exposure to nicotine. TRIAL REGISTRATION NUMBER: NCT01681875, Post-results.

The Impact of Smoking Very Low Nicotine Content Cigarettes on Alcohol Use.

BACKGROUND: Reducing the nicotine content in cigarettes could improve public health by reducing smoking and toxicant exposure, but may also have unintended consequences on alcohol use. The primary objective of this study was to examine the effect of reducing the nicotine content in cigarettes on alcohol outcomes. The secondary aim was to examine whether the effects of these cigarettes on alcohol outcomes were mediated by changes in nicotine exposure, smoking behavior, or withdrawal. METHODS: Between June 2013 and July 2014, we conducted a 7-arm, double-blind, randomized clinical trial at 10 U.S.-based sites. Daily smokers not currently interested in quitting (n = 839) were assigned to equally sized groups to smoke for 6 weeks cigarettes containing either normal nicotine content (NNC; 15.8 mg/g, 9 mg tar), moderate nicotine content (5.2 mg/g nicotine, 9 mg tar), or very low nicotine content (VLNC; 0.4 to 2.4 mg/g, 9 to 13 mg tar). This investigation focused on a subsample of current drinkers (n = 403). Each reduced nicotine content cigarette condition was compared to the NNC control condition with respect to trajectories over the 6-week period of average daily alcohol use and occurrence of binge drinking. Moderating variables were considered. Mediation analyses tested potential explanatory processes including changes in nicotine exposure, cigarettes per day, and withdrawal. RESULTS: Over time, reduced nicotine exposure and smoking rate mediated effects of VLNC cigarette use on reduced alcohol use. There was no evidence of compensatory drinking in response to nicotine reduction or nicotine withdrawal, even among subgroups expected to be at greater risk (e.g., relatively heavier drinkers, highly nicotine-dependent individuals). CONCLUSIONS: The findings suggest that compensatory drinking is unlikely to occur in response to switching to VLNC cigarettes. In contrast, reducing the nicotine content of cigarettes may reduce alcohol use (clinicalTrials.gov number, NCT01681875).