Associations between biomarkers of nicotine/tobacco exposure and respiratory symptoms among adults who exclusively smoke cigarettes in the U.S.: Findings from the PATH Study Waves 1-4 (2013-2017).

Significance: Determining if tobacco-related biomarkers of exposure (BOE) are associated with respiratory symptoms is an important public health tool that can be used to evaluate the potential harm of different tobacco products. Methods: Adult data from people who exclusively smoked cigarettes (N = 2,438) in Waves 1-4 (2013-2017) of the Population Assessment of Tobacco and Health Study were stacked to examine associations between baseline and follow-up within wave pairs (W1-W2, W2-W3, W3-W4). Weighted generalized estimating equation models were used to evaluate associations between biomarkers of nicotine, tobacco-specific nitrosamines, acrolein, acrylonitrile, cadmium, and lead at baseline/follow-up and respiratory symptom(s) (wheezing/whistling in the chest, wheezing during exercise, and/or dry cough in the past 12 months) at follow-up. Results: Higher acrolein metabolite (CEMA) levels at follow-up were associated with increased odds of respiratory symptoms at follow-up for people who exclusively smoked cigarettes (aOR = 1.34; 95% CI = 1.06, 1.70), including when limited to those without a diagnosed respiratory disease (aOR = 1.46; 95% CI = 1.12, 1.90) and those who smoked daily (aOR = 1.40; 95% CI = 1.06, 1.84). Higher cadmium levels at baseline (while controlling for follow-up levels) were associated with reduced odds of respiratory symptoms at follow-up (aOR = 0.80; 95% CI = 0.65, 0.98) among people who exclusively smoked cigarettes without a respiratory disease. There were no significant associations between baseline/follow-up BOE and follow-up respiratory symptoms for people who smoked cigarettes non-daily. Conclusions: This research supports measuring biomarkers of acrolein, such as CEMA, as a potential intermediate measurement for increased respiratory symptom development. Measuring these biomarkers could help alleviate the clinical burden of respiratory disease.

The first nicotine product tried is associated with current multiple nicotine product use and nicotine dependence among a nationally representative sample of U.S. youths.

This study examines the demographic factors associated with youths' first product tried (i.e., cigarettes, e-cigarettes, cigars, hookah, or smokeless tobacco). This study also evaluates whether the first product tried is associated with future nicotine product use (i.e., no use, single product use, and multiple product use) and nicotine dependence. Participants were 1999 youths (ages 12-17 years) who had ever tried a nicotine product and completed the Population Assessment of Tobacco Health study's Wave 1 (2013-2014) and Wave 4 (2016-2018) assessments. Two separate multinomial logistic regression models examined the association between 1) demographic factors and the first product tried at Wave 1 and 2) the first product tried at Wave 1 and past-30-day product use status at Wave 4. A two-part multivariable model examined the association between the first product tried and nicotine dependence, with part 1 modeling the presence (or absence) of any symptom of dependence and part 2 modeling the degree of dependence among those with any symptom of dependence. The first product tried was associated with sex, race, urbanicity, and parent education. First trying smokeless tobacco (vs. e-cigarettes) was associated with a greater likelihood of multiple product use (vs. no use and vs. single product use). Regarding the degree of nicotine dependence (n = 713), first trying smokeless tobacco (vs. e-cigarettes) was associated with higher nicotine dependence scores among those with any symptom of dependence. Youths who first try smokeless tobacco (vs. e-cigarettes) may be at higher risk for future multiple product use and more symptoms nicotine dependence. Research should explore tailored interventions for smokeless tobacco users.

Association of racial discrimination in health care settings and use of electronic cigarettes to quit smoking among Black adults.

INTRODUCTION: Black people are disproportionately burdened by tobacco-related diseases and are less successful at cigarette cessation with current treatments. We know little about the effectiveness of e-cigarettes as a smoking cessation method compared to currently approved methods in Black adults who smoke. Many Black adults report experiencing racial discrimination in health care, but if discrimination is related to utilization of smoking cessation aids including e-cigarettes and success with smoking cessation in this population is unclear. Therefore, this exploratory study aimed to understand how negative experiences and racial discrimination in health care influence use of e-cigarettes for cigarette cessation and success with cigarette cessation among Black adults. METHODS: The study interviewed 201 Black adults who used cigarettes and tried to quit in their lifetime from the Family and Community Health Study in 2016. The study asked if they had tried and successfully quit cigarettes with e-cigarettes vs. other methods (support groups, medications, nicotine replacement therapies, call-in help lines, cold turkey [quit on their own], counseling) and asked about their negative experiences and racial discrimination in health care. We performed separate logistic regressions that evaluated the association of negative experiences and racial discrimination in health care with 1) use of e-cigarettes for cigarette cessation vs. other quitting methods and 2) success with cigarette cessation using any method among Black adults while controlling for age, sex, socioeconomic status, health insurance status, and age of onset of cigarette use. RESULTS: More reported negative experiences and racial discrimination in health care were associated with ever trying to quit with e-cigarettes compared to other methods (OR:1.75, 95 % CI [1.05-2.91]), but negative experiences and racial discrimination in health care were not associated with cigarette quitting success. Interestingly, trying e-cigarettes was associated with being less successful at quitting compared to using other methods to quit smoking (OR: 0.40, 95 % CI [0.20, 0.81]). CONCLUSIONS: These results suggest that educating health care professionals that anticipated discrimination in health care settings may be driving Black adults who smoke to engage in non-evidence-based smoking cessation practices, such as e-cigarettes instead of those that are evidence-based, and may be more effective in this population.

Association of Non-Cigarette Tobacco Advertisements and Racial Discrimination With Non-Cigarette Tobacco Product Use Among Black Adults.

INTRODUCTION: Black communities are targeted by more cigarette advertisements than White communities and racial discrimination among Black people is related to cigarette use. However, little is known about these factors with non-cigarette tobacco product use among Black adults. Therefore, this study assessed the association of non-cigarette advertisement exposure and racial discrimination with use of non-cigarette tobacco products among Black adults. AIMS AND METHODS: Black adults (n = 533) from The Family and Community Health Study in 2016 were asked if they had seen advertisements for e-cigarettes, snus pouches, filtered cigars, large cigars, cigarillos, dissolvable tobacco, smokeless tobacco, hookah, and tobacco pipe and if they used these in the past month. For products with the highest past month use and significant correlations with advertisement exposure, separate logistic regression models were performed that evaluated the association between advertisement exposure, racial discrimination, and non-cigarette tobacco product use while controlling for cigarette use, sex, socioeconomic status, and age. RESULTS: Use of cigarillos, large cigars, and hookah were higher than other non-cigarette tobacco products assessed. Logistic regressions revealed that more advertisement exposure in the past month was associated with higher odds of using cigarillos, large cigars, and hookah (p < .01). More experiences of racial discrimination were associated with past month cigarillo use, but not hookah or large cigars (p < .01). CONCLUSIONS: Non-cigarette tobacco advertisement exposure was associated with the use of non-cigarette tobacco products. Experiences of racial discrimination were associated with the most used non-cigarette tobacco product among Black adults, cigarillos. IMPLICATIONS: This is the first time that a specific type of cigar (ie cigarillos) has been associated with experiences of racial discrimination among Black adults. Efforts to reduce non-cigarette tobacco marketing and eradicate exposure to racial discrimination among Black adults may aid in eliminating tobacco-related health disparities.

Use and Product Characteristics of "Tobacco Free Nicotine" E-Cigarettes Among Young Adults.

INTRODUCTION: E-cigarettes are increasingly being marketed as containing tobacco-free nicotine (TFN). There is no data examining use of TFN e-cigarettes by young adults and how use may differ from non-TFN e-cigarettes. The current study aims to characterize young adult TFN e-cigarette use and examine differences between those who report using TFN and non-TFN e-cigarettes. METHOD: U.S. young adults (18-25) with lifetime e-cigarette use (n = 927) were recruited via online panels in Fall 2021 and answered questions about TFN and non-TFN e-cigarettes. Participants were categorized by lifetime TFN e-cigarette use status (yes vs. no; 34% yes). Bivariate comparisons examined differences in e-cigarette characteristics (device type, flavors, nicotine concentration) between the TFN and non-TFN groups. Binary logistic regression models examined associations between lifetime frequency of vaping (<100 vs. ≥100 times), and other tobacco product, cannabis, and/or alcohol use and lifetime TFN e-cigarette use (yes vs. no). Adjusted models include age, race/ethnicity, vaping onset age, and sex. RESULTS: In multivariable adjusted models, lifetime TFN e-cigarette use was associated with younger age, greater lifetime vaping, and nicotine pouch use. Young adults who used TFN e-cigarettes were more likely to report fruit, mint, menthol, and beverage flavors and know their e-liquid nicotine concentration compared with those who used non-TFN e-cigarettes. CONCLUSION: Among young adults who have used e-cigarettes, more frequent e-cigarette use and use of nicotine pouches, which can also contain TFN, were associated with TFN e-cigarette use. Understanding behaviors and characteristics of those using TFN e-cigarettes is critical to regulation of TFN containing products. IMPLICATIONS: This study characterizes young adults who report experience with tobacco free nicotine (TFN) e-cigarettes and compares them to those who have not used TFN e-cigarettes. Young adults with more frequent e-cigarette use and use of nicotine pouches are more likely to report TFN e-cigarette use.

Pharmacological characterization of 5-iodo-A-85380, a ß2-selective nicotinic receptor agonist, in mice.

BACKGROUND: Because of their implications in several pathological conditions, α4ß2* nicotinic acetylcholine receptors (nAChRs) are potential targets for the treatment of nicotine dependence, pain, and many psychiatric and neurodegenerative diseases. However, they exist in various subtypes, and finding selective tools to investigate them has proved challenging. The nicotinic receptor agonist, 5-iodo-A-85380 (5IA), has helped in delineating the function of ß2-containing subtypes in vitro; however, much is still unknown about its behavioral effects. Furthermore, its effectiveness on α6-containing subtypes is limited. AIMS: To investigate the effects of 5IA on nociception (formalin, hot-plate, and tail-flick tests), locomotion, hypothermia, and conditioned reward after acute and repeated administration, and to examine the potential role of ß2 and α6 nAChR subunits in these effects. Lastly, its selectivity for expressed low sensitivity (LS) and high sensitivity (HS) α4ß2 receptors is investigated. RESULTS: 5IA dose-dependently induced hypothermia, locomotion suppression, conditioned place preference, and antinociception (only in the formalin test but not in the hot-plate or tail-flick tests). Furthermore, these effects were mediated by ß2 but not α6 nicotinic subunits. Finally, we show that 5-iodo-A-85380 potently activates both stoichiometries of α4ß2 nAChRs with differential efficacies, being a full agonist on HS α4(2)ß2(3) nAChRs, and a partial agonist on LS α4(3)ß2(2) nAChRs and α6-containing subtypes as well.

Association of youth impulsivity and use of e-cigarette devices, flavors, and frequency of use.

INTRODUCTION: Given high youth e-cigarette use, it is important to investigate how traits, like impulsivity, may be associated with youth e-cigarette use behaviors. The study aim is to determine if impulsivity is associated with trying more e-cigarette flavors and device types, and greater frequency of e-cigarette use. METHOD: Cross sectional survey data from CT high schoolers (n = 4875, 6 schools) were collected in 2019. Lifetime (ever) e-cigarette users (n = 2313) completed the Brief Barrett Impulsivity Scale, which contains two subscales; behavioral impulsivity and impaired self-control. Among lifetime users, associations between impulsivity subscales and number of e-cigarette flavors tried, e-cigarette devices tried, and past 30-day frequency of e-cigarette use were examined using regression models. Additionally, associations of impulsivity and use frequency were examined among only current e-cigarette users (≥1 day of use in past 30; n = 1327). School, age, race/ethnicity, vaping initiation age, other tobacco product use, and sex were included as covariates in models. RESULTS: Higher behavioral impulsivity was associated with greater number of e-cigarette flavors tried (AOR: 1.06, 95% CI: 1.02, 1.11, p <.008) and higher frequency of past 30-day use both among ever and current e-cigarette users (AOR: 1.26, 95%CI:1.10,1.44, p <.001; AOR: 1.12, 95%CI:1.02,1.22, p <.02), but not number of e-cigarette devices tried. Impaired self-control was not associated with any outcomes. CONCLUSION: Youth with higher behavioral impulsivity may be more at risk for using more e-cigarette flavors and using e-cigarettes more frequently. Regulations aimed at reducing flavor availability among youth and interventions targeting impulsive behavior may be important for this population.

Genotypic Differences in the Effects of Menthol on Nicotine Intake and Preference in Mice.

Menthol has been shown to exacerbate elements of nicotine addiction in humans and rodents; however, the mechanisms mediating its effects are not fully understood. This study examined the impact of genetic factors in menthol's effects on oral nicotine consumption by comparing two inbred mouse strains with differing sensitivities to nicotine. C57BL/6J (B6J) mice are nicotine-preferring, while DBA/2J (D2J) mice are not. While the effects of menthol on oral nicotine consumption have been highlighted in B6J mice, it is unknown if they extend to the D2J strain as well. Consequently, adolescent (PND 21) and adult (PND 63), male and female D2J mice were subjected to the nicotine two-bottle choice (2BC) paradigm with orally and systemically administered menthol. Then, we evaluated its impact on nicotine pharmacological responses in conditioned reward and nociception after systemic administration and, lastly, investigated the potential involvement of the TAAR1 gene and α7 nAChRs in menthol's effects. Menthol failed to enhance oral nicotine consumption in adult and adolescent female and male D2J mice. Moreover, this lack in effect was not due to nicotine concentration, oral aversion to menthol, or basal preference for nicotine. Menthol also failed to augment nicotine reward or enhance nicotine-induced antinociception in D2J mice, demonstrating that genetic background plays a significant role in sensitivity to menthol's effects on nicotine. Furthermore, TAAR1 or α7 nAChRs did not seem to mediate menthol's differential effects in D2J mice. These findings support the existence of genotype-specific mechanisms that may contribute to the variable effects of menthol in different populations.

Examining the potential role of e-cigarettes to reduce health disparities associated with menthol cigarette use: Characterizing e-cigarette use, flavors, and reasons for use among US adults smoking menthol cigarettes.

INTRODUCTION: Menthol cigarette use contributes to disproportionate tobacco-related health disparities amongst minoritized race/ethnic groups. E-cigarettes are available in flavors such as menthol and may be a less harmful substitute among adults who smoke. Yet little is known about e-cigarette flavor preference and reasons for use by race/ethnicity among adults who smoke menthol cigarettes. METHODS: Nationally representative PATH wave 4 adult data (Dec. 2016-Jan. 2018) were used to examine how menthol cigarette status and race/ethnicity were associated with past 30-day e-cigarette use, flavors used, and reasons for use with adjusted logistic regression models. RESULTS: Menthol (vs. non-menthol) cigarette use was associated with higher odds of e-cigarette use (AOR=1.33, 95%CI=1.16-1.52). However, non-Hispanic (NH) Black and Hispanic individuals (vs. NH White) had lower odds of e-cigarette use (p's ≤ 0.004). In terms of flavor used, adults smoking menthol cigarettes and NH Black and Hispanic individuals had greater odds of using menthol/mint-flavored e-cigarettes (p's ≤ 0.02), and older adults (vs. 18-24-year-olds) had lower odds of using sweet-flavored e-cigarettes (p's < 0.0001). Regarding reasons for use, adults smoking menthol cigarettes had higher odds of reporting using e-cigarettes due to liking flavors (AOR=1.63, 95%CI=1.30-2.04), while NH Black adults had lower odds of liking flavors (AOR=0.64, 95%CI=0.43-0.96), and Hispanic adults had lower odds of using e-cigarettes to cut down on cigarette smoking (AOR=0.59, 95%CI=0.42-0.83). CONCLUSIONS: Findings suggest menthol flavored e-cigarettes may be important for adults who smoke menthol cigarettes, although racial disparities in current e-cigarette use and reasons for use may exacerbate tobacco-related health disparities.

Cannabis use among youth who vape nicotine E-cigarettes: A qualitative analysis.

BACKGROUND: Nicotine vaping and cannabis use are common among youth. Among youth who use e-cigarettes, little is known about how and why they use cannabis and patterns of cannabis and nicotine co-use. Given the popularity of both products among youth, the study aim is to utilize qualitative data to better understand cannabis use among youth who use e-cigarettes. METHOD: Six focus groups of high schoolers who reported past-month e-cigarette use (N = 50; 52% male) were conducted to inform e-cigarette cessation programming. We conducted secondary data analysis examining report of cannabis use during focus groups. Transcripts were examined for report of cannabis use, reasons for use, and nicotine and cannabis co-use. RESULTS: In focus groups, cannabis was commonly discussed. Youth reported vaping cannabis, however other forms of cannabis delivery were common (e.g. blunts, joints). Themes related to reasons for simultaneous use of nicotine and cannabis were to experience stronger psychoactive effects than using either product alone and needing to use less nicotine product overall. Reasons for liking cannabis were positive psychoactive effects and stress relief. Reasons for disliking were related to health concerns. Notably, when youth reported disliking cannabis due to health concerns, a common discussion was strategies to acquire and continue cannabis use in ways that they perceived mitigated health concerns. CONCLUSION: Qualitative evidence identified associations between e-cigarette use and cannabis use among youth. Research and interventions targeting youth using e-cigarettes should consider how to address dual use of these products.

Psychometric Evaluation of the Short-Form Vaping Consequences Questionnaire for Use With High School Adolescents Who Use and Do Not Use E-cigarettes.

INTRODUCTION: Assessing youth vaping expectancies using a psychometrically sound measure can improve understanding of e-cigarette susceptibility and use. AIMS AND METHODS: We evaluated the psychometric properties of the Short-Form Vaping Consequences Questionnaire (SF-VCQ), an expectancy measure previously validated with adults, within a sample of 1753 high school adolescents who completed an online, school-based survey in Fall 2020 (51.6% female; 15.56 [1.22] years old; 46.6% non-Hispanic white; 26.9% reported lifetime but no past-30-day vaping; 12.6% reported past-30-day vaping). Analyses included confirmatory factor analysis, internal consistency, measurement invariance, between-group differences, and test-criterion relationships. RESULTS: The four-factor structure was confirmed and was scalar invariant by lifetime and past-month vaping status, sex, and race. All subscales were internally reliable (mean α = 0.94). The subscales were sensitive to differences based on sex, race, vaping susceptibility among never users, and lifetime and past-month vaping status. For example, students who vaped in the past-month held weaker expectancies for negative consequences but stronger expectancies for positive reinforcement, negative reinforcement, and appetite/weight control compared to lifetime vapers. Unadjusted relationships within the subsamples of lifetime and past-month vapers provided evidence of convergent validity. Evidence for concurrent validity was observed for all samples after accounting for covariates. For example, expectancies for positive reinforcement, negative reinforcement, and appetite/weight control remained significantly associated with past-month vaping frequency. CONCLUSIONS: The SF-VCQ evidenced excellent internal reliability, scalar measurement invariance, and construct, convergent, and concurrent validity in samples of never, lifetime, and past-month adolescent e-cigarette users. Findings support using the SF-VCQ for assessing youths' vaping-related expectancies. IMPLICATIONS: The current study established the psychometric properties of the SF-VCQ for use among adolescents with and without vaping experience, including measurement invariance that permits direct comparisons of expectancies across these two groups. When considered in concert with previously published research in adults, the SF-VCQ provides researchers with a measure that can be used with both youth and adult samples. Observed relationships between positive expectancies and vaping susceptibility in vaping naïve youth and indices of vaping frequency in youth with vaping experience suggest that challenging positive expectancies may be a valuable addition to prevention and intervention efforts to reduce youth vaping.

School-based E-cigarette cessation programs: What do youth want?

PURPOSE: E-cigarette use is a problem among youth, yet few vaping cessation programs exist. This study aimed to understand what youth want in a school-based vaping cessation program to inform intervention development. METHODS: We conducted 8 focus groups in Fall 2019 with Connecticut high school youth (N = 4-10 adolescents per group, total N = 62, 50% female). 6 groups were with youth who were current (i.e., past-month) e-cigarette users and 2 groups were with past users (i.e., lifetime users with no past-month use). Discussions focused on desired features and concerns about a vaping cessation program and analyses used an iterative inductive and deductive approach to identify qualitative themes. We also collected brief survey data assessing skills youth wanted to learn from a vaping cessation program. RESULTS: Qualitative themes emerged indicating that youth want a vaping cessation program to include education about health effects of vaping, relatable personal anecdotes from others, and rewards for quitting. Potential concerns include confidentiality (e.g., ensuring teachers/coaches would not know about e-cigarette use), perceptions that youth may not want to participate due to lack of interest/apathy or embarrassment, and needing methods to verify abstinence to limit inaccurate reporting. The most frequently endorsed skills from the survey indicated youth want to learn ways to deal with stress (92%), relax (60%), and deal with poor concentration/attention (55%). CONCLUSIONS: Findings identified key features to include and issues to address when developing school-based vaping cessation programs. Developing effective vaping cessation programs that appeal to youth is important for addressing youth e-cigarette use.

Assessing knowledge, attitude, practice and training related to COVID-19: a cross-sectional survey of frontline healthcare workers in Nigeria.

OBJECTIVES: Healthcare workers (HCWs) are at the frontline of efforts to treat those affected by COVID-19 and prevent its continued spread. This study seeks to assess knowledge, attitude and practice (KAP) as well as training needs and preferences related to COVID-19 among frontline HCWs in Nigeria. SETTING: A cross-sectional survey was carried out among 1852 HCWs in primary, secondary and tertiary care settings across Nigeria using a 33-item questionnaire. PARTICIPANTS: Respondents included doctors, nurses, pharmacy and clinical laboratory professionals who have direct clinical contact with patients at the various healthcare settings. ANALYSIS: Exploratory factor analysis (EFA) was used to establish independent factors related to COVID-19 KAP. Analysis of variance was used to identify any differences in the factors among different categories of HCWs. RESULTS: EFA identified four factors: safety and prevention (factor 1), practice and knowledge (factor 2), control and mitigation (factor 3) and national perceptions (factor 4). Significant group differences were found on three factors: Factor 1 (F(1,1655)=5.79, p=0.0006), factor 3 (F(1,1633)=12.9, p<0.0.0001) and factor 4 (F(1,1655)=7.31, p<0.0001) with doctors scoring higher on these three factors when compared with nurses, pharmaceutical workers and medical laboratory scientist. The most endorsed training need was how to reorganise the workplace to prevent spread of COVID-19. This was chosen by 61.8% of medical laboratory professionals, 55.6% of doctors, 51.7% of nurses and 51.6% of pharmaceutical health workers. The most preferred modes of training were webinars and conferences. CONCLUSION: There were substantial differences in KAP regarding the COVID-19 pandemic among various categories of frontline HCWs surveyed. There were also group differences on COVID-19 training needs and preferences. Tailored health education and training aimed at enhancing and updating COVID-19 KAP are needed, particularly among non-physician HCWs.

Cooling e-cigarette flavors and the association with e-cigarette use among a sample of high school students.

INTRODUCTION: E-liquid flavor is typically presented by flavor category (e.g. menthol, mint, fruit, dessert). Cooling sensations produced by flavor additives such as menthol enhance appeal of e-cigarettes among youth, but not all e-liquids that produce cooling sensations are labeled as menthol. Sensory experiences produced by flavors may allow for a new way to capture e-cigarette flavor use. This study aims to examine use of flavors that produce cooling sensations among youth and its association with e-cigarette use behaviors. METHODS: A 2019 survey of high school students (n = 4875) examined use of e-cigarette flavors that produced cooling sensations (cooling flavors) among past 30-day e-cigarette users. E-cigarette use behaviors (flavor use, nicotine use, frequency of use) were examined between those who did and did not use cooling flavors. A binary logistic regression was used to examine associations between vaping frequency, nicotine (vs. non-nicotine) use, and vaping cooling flavors while controlling for demographics, number of flavors vaped in the past month, and vaping age of onset. RESULTS: 51.6% (n = 473/916) of the analytic sample endorsed vaping cooling flavors. There were no demographic differences by vaping cooling flavors. Vaping cooling flavors was associated with vaping more frequently (AOR:1.04,95% CI:1.03,1.05) and vaping nicotine (AOR:2.37,95% CI:1.53,3.67). CONCLUSION: Vaping cooling flavors was associated with greater nicotine vaping and frequency of e-cigarette use. Assessing sensory experience, such as cooling, in addition to flavor category may more fully capture e-cigarette flavor use and its impacts on youth e-cigarette use behaviors.

Drug and alcohol treatment utilization and barriers among Black, American Indian/Alaskan Native, Latine, Asian/Pacific Islander/Native Hawaiian, and White adults: Findings from NESARC-III.

BACKGROUND: Existing epidemiological data suggest differences across racial/ethnic groups in drug and alcohol treatment utilization and barriers to treatment and typically include only Black, Latine, and White adults. The objective of this study was to examine whether disparities remain for DSM-5 lifetime alcohol use disorder (AUD) and drug use disorder (DUD) treatment utilization and barriers across Black, American Indian/Alaska Native (AI/AN), Latine, Asian/Pacific Islander/Native Hawaiian (Asian/PI/NH), and White adults. METHODS: The current study conducted secondary analyses on data from the National Epidemiological Survey on Alcohol and Related Conditions (NESARC-III). Regression analyses, followed by pairwise comparisons, investigated differences across racial/ethnic groups. RESULTS: Analyses indicated differences across racial/ethnic groups in AUD treatment utilization. White and AI/AN adults were more likely to utilize a health care professional than were Black adults. Asian/PI/NH and Latine adults were more likely to endorse language as a barrier to AUD treatment than were White adults. Black adults were more likely to use 12-step programs for DUD treatment utilization than were White and Latine adults, and Black and White adults were more likely to use outpatient programs than were Latine adults. Further, Black adults were more likely than Asian/PI/NH and Latine adults to use specialty DUD treatment. AI/AN, Asian/PI/NH, and White adults were more likely to endorse fear of what others would think as a barrier to DUD treatment relative to Black adults. AI/AN adults were more likely to endorse fear of being hospitalized relative to Black, Latine, and White adults. Asian/PI/NH and Latine adults were more likely to indicate that the hours were inconvenient relative to Black and White adults. White adults were more likely to endorse a family member objected relative to Black adults. AI/AN and White adults were more likely to endorse they stopped on their own relative to Black, Asian/PI/NH, and Latine adults. Further, AI/AN and White adults reported the greatest number of barriers to DUD treatment. CONCLUSIONS: Differences remain across racial/ethnic group in drug and alcohol treatment utilization and barriers to treatment. Future research aimed at increasing treatment utilization across racial/ethnic groups should focus on social determinants of health.

Individual differences in the associations between risk factors for alcohol use disorder and alcohol use-related outcomes.

BACKGROUND: Family history of alcohol use disorder; AUD (FH +) and impulsivity-related traits are known risk factors for problem drinking that have been investigated in predominately White samples. This cross-sectional study examined whether these risk factors vary by sex in the overall, majority White sample and in a Black subsample. METHOD: A model building regression procedure was used to investigate the combined effect of FH + and impulsivity-related traits on alcohol quantity, frequency, and problems by sex (overall sample: N = 757, 50% female, 73% White, agemean = 33.74, SD = 11.60; Black subsample: n = 138, 47% female, agemean = 33.60, SD = 9.87). RESULTS: Overall Sample. No sex differences were found in the compounding effects of FH + and impulsivity-related traits on alcohol outcomes. Males reported more physical, social, and overall alcohol-related problems than females. FH + was positively associated with all alcohol-related consequences. Poor self-regulation was the only trait associated with all alcohol outcomes. Black Subsample: A three-way interaction suggested a negative association between inhibition and frequency of alcohol use among FH + males only. A two-way interaction also suggested impulse control was associated with more interpersonal alcohol-related problems among males only. Main effects were also found in the expected direction such that higher impulsivity and FH + were associated with poorer alcohol outcomes. CONCLUSION: These findings suggest no sex differences in the overall sample in the interactive effects of established risk factors for AUD on alcohol outcomes, and that poor self-regulation may be key for personality-targeted alcohol prevention and intervention programs. Preliminary findings of sex differences in the Black subsample should be replicated. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Potentiation of (α4)2(ß2)3, but not (α4)3(ß2)2, nicotinic acetylcholine receptors reduces nicotine self-administration and withdrawal symptoms.

The low sensitivity (α4)3(ß2)2 (LS) and high sensitivity (α4)2(ß2)3 (HS) nAChR isoforms may contribute to a variety of brain functions, pathophysiological processes, and pharmacological effects associated with nicotine use. In this study, we examined the contributions of the LS and HS α4ß2 nAChR isoforms in nicotine self-administration, withdrawal symptoms, antinociceptive and hypothermic effects. We utilized two nAChR positive allosteric modulators (PAMs): desformylflustrabromine (dFBr), a PAM of both the LS and HS α4ß2 nAChRs, and CMPI, a PAM selective for the LS nAChR. We found that dFBr, but not CMPI, decreased intravenous nicotine self-administration in male mice in a dose-dependent manner. Unlike dFBr, which fully reverses somatic and affective symptoms of nicotine withdrawal, CMPI at doses up to 15 mg/kg in male mice only partially reduced nicotine withdrawal-induced somatic signs, anxiety-like behavior and sucrose preference, but had no effects on nicotine withdrawal-induced hyperalgesia. These results indicate that potentiation of HS α4ß2 nAChRs is necessary to modulate nicotine's reinforcing properties that underlie nicotine intake and to reverse nicotine withdrawal symptoms that influence nicotine abstinence. In contrast, both dFBr and CMPI enhanced nicotine's hypothermic effect and reduced nicotine's antinociceptive effects in male mice. Therefore, these results indicate a more prevalent role of HS α4ß2 nAChR isoforms in mediating various behavioral effects associated with nicotine, whereas the LS α4ß2 nAChR isoform has a limited role in mediating body temperature and nociceptive responses. These findings will facilitate the development of more selective, efficacious, and safe nAChR-based therapeutics for nicotine addiction treatment.

N-acylethanolamine-hydrolysing acid amidase: A new potential target to treat paclitaxel-induced neuropathy.

BACKGROUND: Although paclitaxel is an effective chemotherapeutic agent used to treat multiple types of cancer (e.g. breast, ovarian, neck and lung), it also elicits paclitaxel-induced peripheral neuropathy (PIPN), which represents a major dose-limiting side effect of this drug. METHODS: As the endogenously produced N-acylethanolamine, palmitoylethanolamide (PEA), reverses paclitaxel-induced mechanical hypersensitivity in mice, the main goals of this study were to examine if paclitaxel affects levels of endogenous PEA in the spinal cord of mice and whether exogenous administration of PEA provides protection from the occurrence of paclitaxel-induced mechanical hypersensitivity. We further examined whether inhibition of N-acylethanolamine-hydrolysing acid amidase (NAAA), a hydrolytic PEA enzyme, would offer protection in mouse model of PIPN. RESULTS: Paclitaxel reduced PEA levels in the spinal cord, suggesting that dysregulation of this lipid signalling system may contribute to PIPN. Consistent with this idea, repeated administration of PEA partially prevented the paclitaxel-induced mechanical hypersensitivity. We next evaluated whether the selective NAAA inhibitor, AM9053, would prevent paclitaxel-induced mechanical hypersensitivity in mice. Acute administration of AM9053 dose-dependently reversed mechanical hypersensitivity through a PPAR-α mechanism, whereas repeated administration of AM9053 fully prevented the development of PIPN, without any evidence of tolerance. Moreover, AM9053 produced a conditioned place preference in paclitaxel-treated mice, but not in control mice. This pattern of findings suggests a lack of intrinsic rewarding effects, but a reduction in the pain aversiveness induced by paclitaxel. Finally, AM9053 did not alter paclitaxel-induced cytotoxicity in lung tumour cells. CONCLUSIONS: Collectively, these studies suggest that NAAA represents a promising target to treat and prevent PIPN. SIGNIFICANCE: The present study demonstrates that the chemotherapeutic paclitaxel alters PEA levels in the spinal cord, whereas repeated exogenous PEA administration moderately alleviates PIPN in mice. Additionally, targeting NAAA, PEA's hydrolysing enzyme with a selective compound AM9053 reverses and prevents the PIPN via the PPAR-α mechanism. Overall, the data suggest that selective NAAA inhibitors denote promising future therapeutics to mitigate and prevent PIPN.