Bidirectional relationships between pain and patterns of cannabis and tobacco use in a US nationally representative sample.

ABSTRACT: One-fifth of US adults experience chronic pain, which is associated with increased tobacco and cannabis use. Although bidirectional relationships between tobacco and pain have been demonstrated, pathways between pain, cannabis use, and co-use of cannabis and tobacco are understudied. We aimed to estimate the effects of (1) substance use (exclusive and co-use of cannabis and tobacco) on later pain intensity, and (2) pain intensity on later substance use. Data were from 31,983 adults in biennial surveys (2015-2021) of the US nationally representative longitudinal Population Assessment of Tobacco and Health Study (n = 71,055 pairs of consecutive surveys; T1 and T2). Past-week pain intensity was dichotomized (≤4/10 no/low pain; >4/10 moderate/severe pain). Mutually exclusive substance use categories (past 30 days) were no cannabis/tobacco use; exclusive cannabis/tobacco use; and co-use. Logistic regression assessed whether T1 substance use affected moderate/severe pain at T2. Multinomial models assessed whether pain status at T1 affected substance use at T2. Compared with no cannabis/tobacco use at T1, co-use (OR: 2.29 [95% CI: 2.09-2.51]), exclusive tobacco use (2.00 [1.86-2.14]), and exclusive cannabis use (1.35 [1.13-1.61]) were all associated with moderate/severe pain at T2. Moderate/severe pain at T1 increased odds of co-use (2.43 [2.22-2.66]), exclusive tobacco (2.12 [1.98-2.28]), and exclusive cannabis use (1.46 [1.29-1.65]) compared with no cannabis/tobacco use at T2, and increased odds of co-use at T2 compared with exclusive cannabis/tobacco use. Findings demonstrated bidirectional relationships between pain and the exclusive use and co-use of cannabis and tobacco and indicate potential synergy in the co-use of cannabis and tobacco with respect to pain.

Trends in cannabis and tobacco co-use in the United States, 2002-2021.

BACKGROUND: Co-use of cannabis and tobacco poses greater risks than use of either substance individually and may be becoming more prevalent with increasing cannabis medicalization and legalization. We aimed to assess trends in the prevalence of cannabis and tobacco co-use between 2002-2019 and identify the updated prevalence and correlates of co-use in 2021 among US adults. METHODS: This study used data from the 2002-2021 National Survey on Drug Use and Health, a nationally-representative, cross-sectional survey in the US. We assessed prevalence trends in past 30-day cannabis and tobacco co-use, exclusive cannabis use, and exclusive tobacco use overall and by sociodemographic group using joinpoint regression. Additionally, multinomial models identified correlates of co-use in 2021. RESULTS: In 2021, the weighted prevalence of cannabis and tobacco co-use was 6.38 %, the weighted prevalence of exclusive cannabis use was 7.28 %, and the weighted prevalence of exclusive tobacco use was 15.01 %. From 2002 to 2019, the prevalence of past 30-day co-use of cannabis and tobacco increased significantly (annual percentage change [APC]: 1.9 [1.4-2.4], P<0.05) among the overall US population. All subgroups of sex, race/ethnicity, and age also saw significant increases in co-use, other than young adults ages 18-25, for whom co-use was stagnant between 2002-2014 and then decreased significantly between 2014-2019. CONCLUSION: This study identified increasing cannabis and tobacco co-use overall and among most sociodemographic strata in the US. As cannabis policy changes rapidly, co-use requires closer surveillance, clinical screening, and dedicated research.

Rural-urban differences in smoking quit ratios and cessation-related factors: Results from a nationally representative sample.

PURPOSE: There are significant rural/urban disparities that exist in cancer and chronic disease morbidity and mortality, many of which are attributed to increased tobacco use prevalence in rural populations compared to urban. Understanding differences in rural and urban tobacco use patterns is key to developing targeted interventions. METHODS: Using nationally representative data from Wave 5 of the Population Assessment of Tobacco Use and Health (PATH), we examined weighted frequencies and conducted multivariable logistic regression to examine the use of cessation supports in people who currently smoke with a quit attempt in the last 12 months (recent attempters) by rural and urban status and geographic region. Our second objective was to examine lifetime quitting in rural versus urban people who smoke and by geographic region. RESULTS: Rural people who recently attempted to quit were less likely to use any FDA-approved cessation aids, less likely to use Nicoctine Replacement Therapy (NRT), and less likely to be exposed to a home smoking ban in the adjusted analysis. The adjusted odds of quitting were lower in the rural Northeast, Midwest, and South compared to the urban regions. CONCLUSIONS: Findings from this data can serve to inform the development of targeted interventions for rural communities.

A case study of inclusion of rural populations in research: Implications for science and health equity.

Prior research highlights that rural populations have been historically underrepresented/excluded from clinical research. The primary objective of this study was to describe the inclusion of rural populations within our research enterprise using Clinical Research Management System demographic information at a large academic medical center in the Southeast. This was a cross-sectional study using participant demographic information for all protocols entered into our Clinical Research Management System between May 2018 and March 2021. Descriptive statistics were used to analyze the representation of rural and non-rural participants and demographic breakdown by age, sex, race, and ethnicity for our entire enterprise and at the state level. We also compared Material Community Deprivation Index levels between urban and rural participants. Results indicated that 19% of the research population was classified as rural and 81% as non-rural for our entire sample, and 17.5% rural and 82.5% urban for our state-level sample. There were significant differences in race, sex, and age between rural and non-rural participants and Material Community Deprivation Indices between rural and non-rural participants. Lessons learned and recommendations for increasing the inclusion of rural populations in research are discussed.

Associations between compliance with very low nicotine content (VLNC) cigarettes, abstinence self-efficacy, and quit outcomes in a pilot smoking cessation trial.

BACKGROUND: Switching to Very Low Nicotine Content (VLNC) cigarettes reduces toxicant exposure and nicotine dependence, and may improve smoking cessation. However, non-compliance with VLNCs is often high, which may reduce their effectiveness. Here, we conducted secondary analyses of a pilot smoking cessation trial utilizing VLNCs to examine associations between pre-cessation VLNC compliance and changes in smoking rate, dependence, and abstinence self-efficacy, as well as quit outcomes. METHODS: People who smoke daily (n=35) engaged in a 4-week pre-cessation intervention including VLNCs, transdermal nicotine patch, and behavioral counseling. After quit date, participants received 8 weeks of nicotine replacement therapy and 4 additional behavioral sessions, and were followed for 10 weeks to assess abstinence. Compliance with VLNCs was assessed biweekly during pre-cessation using timeline follow-back. Statistical analyses examined associations between VLNC compliance and a) changes in smoking rate, dependence and abstinence self-efficacy over the course of study cigarette use; and b) time to relapse, controlling for other smoking variables. RESULTS: Greater compliance during the second half of study cigarette use was associated with subsequent improvement in self-efficacy (p<.05). Increased self-efficacy and VLNC compliance both predicted lower likelihood of relapse. Nicotine dependence and cigarettes per day both decreased following study cigarette use, but were unrelated to compliance or relapse. CONCLUSIONS: Compliance with VLNCs prior to quitting increased abstinence self-efficacy and predicted better quit outcomes above and beyond baseline smoking characteristics. Although preliminary, these findings suggest that identifying strategies to promote exclusive use of VLNCs during a brief pre-cessation window may be beneficial.

Reduced nicotine in cigarettes in a marketplace with alternative nicotine systems: randomized clinical trial.

Background: Reducing cigarette addictiveness has the potential to avert millions of yearly tobacco-related deaths worldwide. Substantially reducing nicotine in cigarettes decreases cigarette consumption, but no large clinical trial has determined the effects of reduced-nicotine cigarettes when other nicotine-containing products are available. The aim of this study was to examine the effects of reduced-nicotine cigarettes in the context of the availability of alternative nicotine delivery systems. Methods: In a U.S. six-site, open-label, parallel-arm study, smokers were randomized for twelve weeks to an experimental marketplace containing cigarettes with either 0.4 mg or 15.8 mg nicotine per gram of tobacco; all had access to non-combusted alternative nicotine delivery systems (e.g., e-cigarettes; medicinal nicotine). Group differences in the primary outcomes (cigarettes per day, number of smoke-free days) were examined using linear and negative binomial regression, respectively (Trial Registration: NCT03272685). Findings: Among 438 randomized participants (mean [standard deviation (SD), range] age, 44.5 [11.9, 20-73] years, 225 [51.4%] women, 282 [64.4%] White and 339 [77.4%] trial completers), those in the 0.4 mg vs. 15.8 mg nicotine cigarette condition experienced significantly lower cigarettes per day at the end of intervention (mean [SD], 7.05 [7.88] vs. 12.95 [9.07], adjusted mean difference, -6.21 [95% CI, -7.66 to -4.75], P < 0.0001) and greater smoke-free days during intervention (mean [SD], 18.59 [27.97] vs. 5.06 [13.77], adjusted rate ratio, 4.25 [95% CI, 2.58-6.98], P < 0.0001). Interpretation: A reduced-nicotine cigarette standard in the context of access to other non-combusted nicotine products has the potential to benefit public health. Funding: U.S. NIH/FDA U54DA03165.

Tobacco exposures are associated with health care utilization (HCU) and health care costs in pregnant persons and their newborn babies.

INTRODUCTION: Identifying health care utilization and costs associated with active and passive smoking during pregnancy could help improve health management strategies. METHODS: Data are from the Newborn Epigenetics STudy (NEST), a birth cohort enrolled from 2005-2011 in Durham and adjacent counties in North Carolina, United States. Participants included those for whom prenatal serum samples were assayed and for whom administrative data were obtainable (N=1,045). Zero-inflated Poisson (ZIP) regression models were used to assess associations between cotinine, adjusted for covariates (e.g., race and ethnicity, age at delivery, cohabitation status, education), and health care utilization outcomes. Generalized linear regression models were used to estimate average total charges. Simulation models were conducted to determine the economic benefits of reducing SHS and smoking during pregnancy. RESULTS: Increasing levels of cotinine were positively associated with parent's number of ED visits (coefficient(b)=0.0012, standard error (SE)=0.0002; P<.001), the number of ICU hours (b=0.0079, SE=0.0025; P=.002)), time spent in the ICU (b=0.0238, SE=0.0020, P<.001), and the number of OP visits (b=0.0003, SE=0.0001; P<.001). For infants, higher cotinine levels were associated with higher number of ED (b=0.0012, SE=0.0004; P=.005), ICU (b=0.0050, SE=0.001; P<.001), and OP (b=0.0006, SE=0.0002; P<.001) visits and longer time spent in the ED (b=0.0025, SE=0.0003; P<.001), ICU (b=0.0005, SE=0.0001; P<.001), and IP (b=0.0020, SE=0.0002; P<.001). Simulation results showed that a 5% reduction in smoking would correspond to a potential median cost savings of $150,533 from ED visits of parents and infants. CONCLUSION: Our findings highlight the importance of smoke exposure cessation during pregnancy to reduce health care utilization and costs for both parents and infants. IMPLICATIONS: This study reinforces the importance of reducing smoking and secondhand smoke exposure during pregnancy. Focusing on expanding cessation services to this group could help reduce morbidities observed within this population. Furthermore, there is the potential for health care costs savings to health care systems, especially to those with high delivery numbers. These cost savings are represented by potential reductions in ED, OP, and ICU hours and visits.

Developing a shared understanding of translational science within CTSA hubs through facilitated retreats: A case study.

Translation of critical and broadly impactful health advancements is stymied by insufficient scientific scrutiny of barriers and roadblocks in the process. The Clinical & Translational Science Award (CTSA) funding opportunity announcement released in July 2021 makes clear the distinction between translational research and translational science (TS) and urges a shift from the former to the latter. This represents a significant shift in the overall scientific direction of the CTSA program and necessitates corresponding shifts in CTSA hub operations. To better support TS, the Team Science Core of the Duke CTSA hub designed and facilitated a virtual retreat for hub personnel that (1) enabled organizational learning about TS and (2) identified anticipated challenges and opportunities. A post-retreat survey was utilized to assess the degree to which the retreat met its stated goals. Our survey received a 62% response rate; 100% of respondents would recommend the session to others. Respondents also reported gains in all areas assessed, with evidence for greater understanding of TS and increased perspective of the value and relevance of TS. In this paper, we provide a roadmap for designing and implementing facilitated TS retreats, which we argue is a key step in TS capacity building through workforce development.

Parameter Space and Potential for Biomarker Development in 25 Years of fMRI Drug Cue Reactivity: A Systematic Review.

Importance: In the last 25 years, functional magnetic resonance imaging drug cue reactivity (FDCR) studies have characterized some core aspects in the neurobiology of drug addiction. However, no FDCR-derived biomarkers have been approved for treatment development or clinical adoption. Traversing this translational gap requires a systematic assessment of the FDCR literature evidence, its heterogeneity, and an evaluation of possible clinical uses of FDCR-derived biomarkers. Objective: To summarize the state of the field of FDCR, assess their potential for biomarker development, and outline a clear process for biomarker qualification to guide future research and validation efforts. Evidence Review: The PubMed and Medline databases were searched for every original FDCR investigation published from database inception until December 2022. Collected data covered study design, participant characteristics, FDCR task design, and whether each study provided evidence that might potentially help develop susceptibility, diagnostic, response, prognostic, predictive, or severity biomarkers for 1 or more addictive disorders. Findings: There were 415 FDCR studies published between 1998 and 2022. Most focused on nicotine (122 [29.6%]), alcohol (120 [29.2%]), or cocaine (46 [11.1%]), and most used visual cues (354 [85.3%]). Together, these studies recruited 19 311 participants, including 13 812 individuals with past or current substance use disorders. Most studies could potentially support biomarker development, including diagnostic (143 [32.7%]), treatment response (141 [32.3%]), severity (84 [19.2%]), prognostic (30 [6.9%]), predictive (25 [5.7%]), monitoring (12 [2.7%]), and susceptibility (2 [0.5%]) biomarkers. A total of 155 interventional studies used FDCR, mostly to investigate pharmacological (67 [43.2%]) or cognitive/behavioral (51 [32.9%]) interventions; 141 studies used FDCR as a response measure, of which 125 (88.7%) reported significant interventional FDCR alterations; and 25 studies used FDCR as an intervention outcome predictor, with 24 (96%) finding significant associations between FDCR markers and treatment outcomes. Conclusions and Relevance: Based on this systematic review and the proposed biomarker development framework, there is a pathway for the development and regulatory qualification of FDCR-based biomarkers of addiction and recovery. Further validation could support the use of FDCR-derived measures, potentially accelerating treatment development and improving diagnostic, prognostic, and predictive clinical judgments.

Differences in Normative Beliefs and Tobacco Product Use by Age Among Adults Who Smoke: Cross-Sectional Analysis of a Nationally Representative Sample.

BACKGROUND: The prevalence of combusted cigarette (CC) smoking among older adults is stagnant, with 0 declines attributable to e-cigarette (EC) use. Given that normative beliefs are associated with quitting and switching to ECs, we assessed cross-sectional associations between age, CC, and EC descriptive and injunctive norms and potential interactions with tobacco use behavior. METHODS: Data are from people with current, established (≥100 lifetime CCs) CC use (n = 8072) at Wave 5 (2018-2019) of the adult Population Assessment of Tobacco and Health Study. We used adjusted multivariable logistic regressions to model social norms as a function of age (18-24, 25-34, 35-44, 45-54, 55-64, ≥65 years). We also dichotomized age (≥55 vs 18-54) to investigate interactions between age and social norms on past 12-month CC quit attempts and past-month EC use. RESULTS: Older age was positively associated with pro- and anti-CC norms and anti-EC norms. Significant interactive effects revealed that being advised to quit smoking by a healthcare provider was more strongly associated with CC quit attempts among adults ≥55 years (adjusted odds ratio [aOR] [95% CI]: 2.12 [1.66, 2.71]) than adults <55 years (aOR: 1.63 [1.34, 2.00]). Reporting people close to you use ECs was also more strongly associated with EC use among adults ≥55 years (aOR: 4.37 [3.35, 5.69]) than among adults <55 years (aOR: 3.43 [2.89, 4.08]). CONCLUSIONS: This study identified modifiable risk factors for tobacco use that may be particularly beneficial for older adults. Behavioral and communication interventions that target normative beliefs may maximize smoking cessation, or harm reduction when cessation is not possible.