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Solar radio bursts have been associated with a number of disruptions in avionic systems. The objective of this work is to develop solar radio burst interference thresholds which account for the technical specifications of aviation-related instrumentation, instrument operating frequencies as well as industry stipulated error tolerances. Solar radio bursts are suggested to be potentially hazardous when exceeding these calculated thresholds. Particular attention is paid to the radio altimeter, an important component in aviation safety. The thresholds suggested in this work for VHF communication, GPS navigation receivers and radio altimeter frequencies are; 102, 103, and 104 sfu respectively. Solar radio burst interference (for solar radio bursts above 104 sfu) is shown to result in large errors (64–251 m) in the altitude estimates for the Frequency Modulated Continuous Waves (FMCW) radio altimeter simulated in this work.

Background: Cigarette smoking and alcohol consumption are positively correlated, and the concurrent use of tobacco and alcohol exacerbates the health risks associated with the singular use of either product. Indoor smoke-free policies have been effective in reducing smoking, but little is known about any impact of these policies on drinking behavior. The purpose of this study was to evaluate the potential association between the implementation of smoke-free bar policies and smokers' alcohol consumption.Methods: A prospective, multi-country cohort survey design was utilized. Participants were nationally representative samples of smokers from the United Kingdom, Australia, Canada, and the United States, who were interviewed as part of the International Tobacco Control Four Country Survey (ITC-4) in 2005, 2007, or 2008 (N=11,914). Changes in the frequency and amount of alcohol consumption were assessed as functions of change in the presence of smoke-free bar policies over time.Results: Overall, changes in alcohol consumption were statistically indistinguishable between those whose bars became smoke-free and those whose bars continued to allow smoking. However, implementation of smoke-free policies was associated with small reductions in the amount of alcohol typically consumed by those who were classified as hazardous drinkers, along with small reductions in the frequency of alcohol consumption among heavy smokers.Conclusions: Smoking bans in public places, which protect millions of non-smokers from the harmful effects of second-hand smoke, do not appear to be associated with sizable reductions in smokers' alcohol consumption in general, but may be associated with small consumption reductions among subgroups. [ABSTRACT FROM AUTHOR]

Background: We investigated the impact of enhancing brief cognitive-behavioral therapy with motivational interviewing techniques for cocaine abuse or dependence, using a focused intervention paradigm.Methods: Participants (n=74) who met current criteria for cocaine abuse or dependence were randomized to three-session cognitive-behavioral therapy (CBT) or three-session enhanced CBT (MET+CBT), which included an initial session of motivational enhancement therapy (MET). Outcome measures included treatment retention, process measures (e.g., commitment to abstinence, satisfaction with treatment), and cocaine use.Results: Participants who received the MET+CBT intervention attended more drug treatment sessions following the study interventions, reported significantly greater desire for abstinence and expectation of success, and they expected greater difficulty in maintaining abstinence compared to the CBT condition. There were no differences across treatment conditions on cocaine use.Conclusions: These findings offer mixed support for the addition of MET as an adjunctive approach to CBT for cocaine users. In addition, the study provides evidence for the feasibility of using short-term studies to test the effects of specific treatment components or refinements on measures of therapy process and outcome. [ABSTRACT FROM AUTHOR]

Background: Despite important gender differences in drinking patterns, physiological effects of alcohol, and co-occurring psychiatric conditions, relatively little is known about the efficacy of naltrexone for the treatment of alcohol dependence in women. This study investigated the safety and efficacy of naltrexone in combination with Cognitive Behavioral Coping Skills Therapy (CBCST) in a sample of alcohol-dependent women, some with comorbid eating pathology. Methods: One hundred three women meeting DSM-IV criteria for alcohol dependence (29 with comorbid eating disturbances) were randomized to receive either naltrexone 50 mg or placebo for 12 weeks in addition to weekly group CBCST. Subjects were enrolled between October 1995 and December 2000 at an outpatient research clinic. Results: No significant differences were observed on the primary outcomes of time to first drinking day, time to first day of heavy drinking, or the percentage of participants who continued to meet the criteria for alcohol dependence. Secondary analyses revealed that naltrexone significantly delayed the time to the second (chi(2)=5.37, p=0.02) and third (chi(2)=4.35, p=0.04) drinking days among subjects who did not maintain abstinence from alcohol. Among those with eating disturbances, symptoms of eating pathology improved during treatment, but the effects did not differ according to medication condition. Conclusion: When used in conjunction with CBCST, naltrexone did not significantly improve drinking outcomes in the overall sample of alcohol-dependent women. However, naltrexone may be of benefit to women who are unable to maintain total abstinence from alcohol. For women with concurrent eating pathology, participation in treatment for alcoholism may be associated with improvements in eating pathology. [ABSTRACT FROM AUTHOR]

Few studies have examined the psychometrics of smoking-related behavioral measures in schizophrenia and questions have been raised about the applicability to smokers with schizophrenia. We examined the reliability of the Fagerström Test for Nicotine Dependence (FTND), Minnesota Nicotine Withdrawal Scale (M-NWS), and the Tiffany Questionnaire for Smoking Urges (TQSU) for smokers with schizophrenia (SS; n=151) and nonpsychiatric smokers (CS; n=181) recruited into three studies with similar inclusion criteria. SS and CS did not differ on a number of demographic and smoking variables (e.g., age). SS reported higher carbon monoxide (CO) levels, plasma cotinine levels, FTND, M-NWS, and TQSU Factor 1 scores. The internal consistencies (Cronbach's alpha) of the smoking measures were found to be high and comparable between diagnostic groups for the FTND, M-NWS total scores, and TQSU Factor 2 (all alpha's>0.70) but higher for the CS than SS for the TQSU Factor 1 (0.86 versus 0.79). Test-retest correlations were lower for SS than CS on the FTND (0.65 versus 0.82), TQSU Factor 1 (0.65 versus 0.79), and TQSU Factor 2 (0.69 versus 0.81), but did not differ between diagnostic groups for M-NWS (0.58 versus 0.64). Our findings suggest that these measures may be reliable for use in smokers with schizophrenia. [ABSTRACT FROM AUTHOR]

Background: Alcohol and cannabis are commonly used together by young adults. With frequent pairings, use of one substance may become a conditioned cue for use of a second, commonly co-used substance. Although this has been examined for alcohol and cannabis in laboratory conditions and with remote monitoring, no research has examined whether pharmacologically induced cross-substance craving occurs in naturalistic conditions., Methods: In a sample of 63 frequent cannabis-using young adults (54% female) who completed 2 weeks of ecological momentary assessment, we tested whether alcohol use was associated with stronger in-the-moment cannabis craving. We also examined whether sex moderated this association and whether cannabis craving was stronger at higher levels of alcohol consumption., Results: Although alcohol use and cannabis craving were not significantly associated at the momentary level, there was evidence that this relation significantly differed by sex. Among female participants, there was a negative association between alcohol use since the last prompt and momentary cannabis craving (b = -0.33, SE = 0.14, p = 0.02), while the association among male participants was positive (b = 0.32, SE = 0.13, p = 0.01). Similarly, alcohol quantity was negatively associated with cannabis craving at the momentary level for female participants (b = -0.10, SE = 0.04, p = 0.009) but was not significantly associated for male participants (b = 0.05, SE = 0.04, p = 0.18)., Conclusions: Alcohol may enhance cannabis craving among male individuals but reduce desire for cannabis among female individuals. This may point to differing functions of co-use by sex, highlighting a need for research to elucidate the mechanisms underlying this increasingly common pattern of substance use., (© 2024 The Author(s). Alcohol, Clinical and Experimental Research published by Wiley Periodicals LLC on behalf of Research Society on Alcohol.)

Background: Trend estimates from national surveys over the last 20 years have suggested converging rates of alcohol use over time between adult men and women. However, limited research has utilized an intersectional lens to examine how sociodemographic characteristics influence gender differences in these trends., Methods: The current study used data from the National Survey on Drug Use and Health (NSDUH) to examine whether gender intersected with race/ethnicity, age, education level, marital status, employment status, household income, and urbanicity on temporal trends (2009-2019) in alcohol use disorder (AUD). Logistic regression and linear trend analyses were conducted to examine interaction effects of sociodemographic variables and changes in rates of AUD over time in males and females., Results: We observed decreasing rates of AUD over time in males and females, with larger declines in males (p=0.01; OR=0.96 in males vs. OR=0.98 in females). We identified subpopulations of females that demonstrated little or no reductions during this timeframe (2009-2019), which varied by race/ethnicity, age, marital status, employment, and income but not by education or urbanicity. In adults aged 49 years and younger (overall p=0.02; ages 18-25 OR=0.92 in males vs. 0.96 in females, ages 26-29 OR=0.97 in males vs. OR=0.99 in females), and in those employed (overall p=0.05; OR=0.96 in males vs. OR=0.99 in females), women demonstrated smaller declines in comparison to men. Additionally, women who reported that they were Black (p=0.006; OR=0.94 in males vs. OR=1 in females), single (p=0.009; OR=0.94 in males vs. 0.96 in females) or earning between $20,000 and $49,000 (p=0.012; OR=0.96 in males vs. 0.98 in females), had smaller or no declines in AUD in compared to men with the same demographic characteristic., Conclusions: Our findings provide support for converging rates of AUD between genders and newly identify subpopulations of females that may be at heightened risk., Competing Interests: Declaration of Competing Interest The authors have no financial or personal conflicts of interest to share., (Copyright © 2024. Published by Elsevier Inc.)

The purpose of this study was to systematically review the types of stigmatized attributes that have been assessed and the causes and consequences of stigma for individuals involved in the criminal legal system. PubMed, GoogleScholar, and PsycInfo databases were searched to identify studies for inclusion through March 2021. Eligible studies were peer-reviewed, quantitative, and assessed stigma from the perspective of the person involved in the criminal legal system. 59 studies were included (total n=21,738), assessing stigma associated with criminal involvement, HIV, substance use, race/ethnicity, help-seeking, and others. Experiencing criminal involvement stigma was linked to poor well-being, but less so for racial/ethnic minorities. Experiencing racial/ethnic stigma was associated with recidivism risk, and substance use stigma was associated with substance use risk. Several stigmas intersected to impact treatment engagement and well-being. In conclusion, individuals involved in the criminal legal system experience many stigmatized statuses that impact their well-being, treatment adherence, community integration, and criminal behavior. Stigma must be addressed among individuals involved in the criminal legal system and the systems they interact with to reduce health inequity and recidivism risk., Competing Interests: Declarations of Interest: The authors have no conflicts of interest to disclose.

Rates of alcohol use disorder (AUD) are increasing in men and women and there are high rates of concurrent posttraumatic stress disorder (PTSD) and AUD. AUD and PTSD synergistically increase symptomatology and negatively affect treatment outcomes; however, there are very limited pharmacological treatments for PTSD/AUD. Neurosteroids have been implicated in the underlying neurobiological mechanisms of both PTSD and AUD and may be a target for treatment development. This review details the past ten years of research on pregnenolone, progesterone, allopregnanolone, pregnanolone, estradiol, testosterone and dehydroepiandrosterone/dehydroepiandrosterone-sulfate (DHEA/DHEA-S) in the context of PTSD and AUD, including examination of trauma/alcohol-related variables, such as stress-reactivity. Emerging evidence that exogenous pregnenolone, progesterone, and allopregnanolone may be promising, novel interventions is also discussed. Specific emphasis is placed on examining the application of sex as a biological variable in this body of literature, given that women are more susceptible to both PTSD diagnoses and stress-related alcohol consumption., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

Background: Stress is a potent activator of the hypothalamic-pituitary-adrenal (HPA) axis, initiating the release of glucocorticoid hormones, such as cortisol. Alcohol consumption can lead to HPA axis dysfunction, including altered cortisol levels. Until recently, research has only been able to examine peripheral cortisol associated with alcohol use disorder (AUD) in humans. We used positron emission tomography (PET) brain imaging with the radiotracer [ 18 F]AS2471907 to measure 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), a cortisol-regenerating enzyme, in people with AUD compared to healthy controls., Methods: We imaged 9 individuals with moderate to severe AUD (5 men, 4 women; mean age = 38 years) and 12 healthy controls (8 men, 4 women; mean age = 29 years). Participants received 93.5 ± 15.6 MBq of the 11β-HSD1 inhibitor radiotracer [ 18 F]AS2471907 as a bolus injection and were imaged for 150-180 min on the High-Resolution Research Tomograph. 11β-HSD1 availability was quantified by [ 18 F]AS2471907 volume of distribution ( V T ; mL/cm 3 ). A priori regions of interest included amygdala, anterior cingulate cortex (ACC), hippocampus, ventromedial PFC (vmPFC) and caudate., Results: Individuals with AUD consumed 52.4 drinks/week with 5.8 drinking days/week. Healthy controls consumed 2.8 drinks/week with 1.3 drinking days/week. Preliminary findings suggest that [ 18 F]AS2471907 V T was higher in amygdala, ACC, hippocampus, vmPFC, and caudate of those with AUD compared to healthy controls ( p  < 0.05). In AUD, vmPFC [ 18 F]AS2471907 V T was associated with drinks per week (r = 0.81, p  = 0.01) and quantity per drinking episode (r = 0.75, p  = 0.02)., Conclusions: This is the first in vivo examination of 11β-HSD1 availability in individuals with AUD. Our data suggest higher brain availability of the cortisol-regenerating enzyme 11β-HSD1 in people with AUD (vs. controls), and that higher vmPFC 11β-HSD1 availability is related to greater alcohol consumption. Thus, in addition to the literature suggesting that people with AUD have elevated peripheral cortisol, our findings suggest there may also be heightened central HPA activity. These findings set the foundation for future hypotheses on mechanisms related to HPA axis function in this population., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Alcohol use and the criminal justice (CJ) system have long been integrally connected in the United States and have both disproportionally impacted Communities of Color. Despite this connection, scholarly literature has largely focused on substance use as a whole, and little literature has examined the influence of race on CJ referral to alcohol treatment and treatment outcomes., Methods: A total of 749,349 cases from the treatment episodes dataset discharge were used in the current study. A series of ANOVA and logistic regression analyses were conducted to examine the impact of race on (i) likelihood of referral to alcohol treatment by the CJ system and (ii) the association between CJ referral and treatment completion., Results: Results revealed significant disparities in both who is referred to alcohol treatment by the CJ system and the association of that referral to treatment completion. Notably, American Indian/Alaska Native people were significantly more likely than people of all other races to be referred by the CJ system. However, American Indian/Alaska Native people showed the smallest association between CJ referral and treatment completion., Conclusions: Contrary to previous literature, findings showed that referral of and positive association between CJ referral and treatment completion are not equal across people of different races. Taken together, these results highlight continued racial inequities in the role of the CJ system in alcohol treatment and the unique potential for non-CJ-related treatment to best serve people combatting alcohol use disorder., (© The Author(s) 2024. Medical Council on Alcohol and Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Digital and remote technologies (DRT) are increasingly being used in scientific investigations to objectively measure human behavior during day-to-day activities. Using these devices, psychologists and other behavioral scientists can investigate health risk behaviors, such as drug and alcohol use, by closely examining the causes and consequences of monitored behaviors as they occur naturalistically. There are, however, complex ethical issues that emerge when using DRT methodologies in research with people who use substances. These issues must be identified and addressed so DRT devices can be incorporated into psychological research with this population in a manner that comports the ethical standards of the American Psychological Association. In this article, we discuss the ethical ramifications of using DRT in behavioral studies with people who use substances. Drawing on allied fields with similar ethical issues, we make recommendations to researchers who wish to incorporate DRT into their own research. Major topics include (a) threats to and methods for protecting participant and nonparticipant privacy, (b) shortcomings of traditional informed consent in DRT research, (c) researcher liabilities introduced by real-time continuous data collection, (d) threats to distributive justice arising from computational tools often used to manage and analyze DRT data, and (e) ethical implications of the "digital divide." We conclude with a more optimistic discussion of how DRT may provide safer alternatives to gold standard paradigms in substance use research, allowing researchers to test hypotheses that were previously prohibited on ethical grounds. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Purpose of Review: We review recent research (2018-2023) on gender differences in suicidal behaviors (i.e., suicidal ideations and attempts, death by suicide). We examine research studies in the following areas: developmental period, substance use, and special populations (Veterans, sexual and gender minorities)., Recent Findings: Novel results were found in these different areas. For example, suicide rates for female youth are increasing at a faster rate relative to male youth. Further, some evidence suggests that heavy alcohol use/binge drinking is a significant and growing risk factor for suicidal behaviors in women. Military service may be a more significant risk factor for suicidal behaviors among male Veterans compared to female Veterans. Additionally, suicide rates are rising for gender minority youth/young adults. Recent research on gender differences in suicide outcomes demonstrates findings that align with previous research, as well as new insights on this important topic., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Binge-eating disorder (BED) is a prevalent psychiatric disorder associated with obesity. Few evidence-based treatments exist for BED, particularly pharmacological options. This study tested the efficacy of naltrexone/bupropion for BED., Methods: A randomized, double-blind, placebo-controlled, 12-week trial tested naltrexone/bupropion for BED with and without obesity. Eighty-nine patients (70.8% women, 69.7% White, mean age 45.7 y, mean BMI 35.1 kg/m 2 , 77.5% with BMI ≥ 30 kg/m 2 ) were randomized to placebo (n = 46) or naltrexone/bupropion (n = 43), with randomization stratified by obesity status and gender; 92.1% completed post-treatment assessments., Results: Mixed models of binge-eating frequency revealed significant reductions that did not differ significantly between naltrexone/bupropion and placebo. Logistic regression of binge-eating remission rates revealed that naltrexone/bupropion and placebo did not differ significantly. Obesity status did not predict, or moderate, binge-eating outcomes considered either continuously or categorically. Mixed models revealed that naltrexone/bupropion was associated with significantly greater percentage weight loss than placebo. Logistic regression revealed that naltrexone/bupropion had significantly higher rates of attaining ≥5% weight loss than placebo (27.9% vs. 6.5%). Obesity status did not predict or moderate weight-loss outcomes., Conclusions: Naltrexone/bupropion did not demonstrate effectiveness for reducing binge eating relative to placebo but showed effectiveness for weight reduction in patients with BED. Obesity status did not predict or moderate medication outcomes., (© 2023 The Obesity Society.)

Women who smoke are particularly vulnerable to tobacco craving, smoking behaviors, and relapse in the context of stress when compared to men who smoke. One factor in this sex difference may be sex hormones, including estradiol and progesterone; however, smoking cessation medication trials often do not explore the impact of sex hormones on drug effects. This secondary analysis of a double-blind, placebo-controlled study explored the impact of levels of actual estradiol and progesterone on guanfacine, a noradrenergic α2a agonist, which attenuates stress-induced smoking behaviors in women. Women who smoke ( n = 43) completed a stress induction laboratory paradigm followed by an ad-libitum smoking period. Assessment of tobacco craving, and stress-reactivity (via cortisol response) occurred pre- and post-stress induction. Results indicated that guanfacine attenuated stress-induced tobacco craving ( F = 10.94, p = 0.02) and cortisol response ( F = 14.23, p < 0.001); however, high levels of estradiol overrode guanfacine's effect on craving ( F = 4.00, p = 0.05), cortisol response ( F = 14.23, p < 0.001), and smoking during the ad-libitum period ( F = 12.23, p = 0.001). Additionally, progesterone proved to be protective against tobacco craving and enhanced guanfacine's medication effect on craving ( F = 5.57, p = 0.02). The present study found that sex hormones had a significant impact on medication effects in a smoking cessation trial and thus underscore the importance of examining the role of sex hormones in future medication trials., Competing Interests: Declaration of Competing Interest All authors declare that they have no conflicts of interest.

There is a critical need for interdisciplinary and translational scientists to apply sex as a biological variable (SABV) research to address knowledge gaps in the health of women. In 2018, the Office of Research on Women's Health (ORWH) partnered with several National Institute of Health (NIH) Institutes and Centers to expand the Specialized Centers of Research (SCOR) Excellence (SCORE) Programs (together referred to as SCOR/E) with an important feature-the Career Enhancement Core (CEC). The SCORE CEC mentors early career investigators to become the next generation of biomedical and behavioral researchers focused on SABV and women's health. In this article, we outline our approach at the Yale University SCORE to support early career trajectories through the provision of salary support, educational curricula, translational mentorship, pilot project funding, and professional development. Using the Yale-SCOR/E CEC Programs as instructional models, we highlight critical measures of academic success, namely grant funding and publications, among early career investigators. At Yale University, 12 pilot projects funded by the SCOR/E Programs resulted in 14 extramural grants, amounting to an $80 return on every $1 invested in "seed" funding. So far, our SCOR/E Programs have resulted in 129 publications, 83% of which were first-authored by trainees, and 100% of trainees continued research careers with an emphasis on SABV. Finally, we provide recommendations on how biomedical scientists can apply SABV in their studies of major medical conditions in an interdisciplinary and integrative way.

Significance There are sex effects in abstinence outcomes across all smoking cessation medications, but there is limited information regarding sex effects on cessation-related neuropsychiatric adverse events (NPSAEs) or interactions with psychiatric status., Methods: Secondary analysis of data from EAGLES of 8144 adults who smoke cigarettes randomized to varenicline, bupropion, nicotine patch or placebo. Design characteristics included region (within/outside US), psychiatric cohort (absent/present), and treatment. Baseline variables included demographics, smoking history, prior use of study treatments, lifetime suicide-related history, and prior psychiatric co-morbidities and medication use. Design characteristics were forced into logistic regressions models, and then interactions among sex, design elements, and baseline characteristics were evaluated for NPSAEs and 6-month cessation outcomes., Results: Findings demonstrated a significant interaction of sex and race ( p  < 0.02); Black women were more likely to report NPSAEs than Black men. For cessation outcomes, there were no significant interactions with psychiatric cohort and sex. Women vs men with higher baseline levels of smoking had lower odds of continuous abstinence. Women vs men who used varenicline previously had lower odds of continuous abstinence. For 6-month point prevalence, sex interacted with baseline cigarettes per day ( p  < 0.01) similar to the interaction for continuous abstinence. Sex interacted with medication ( p  < 0.03), such that women vs men had relatively greater success at achieving point prevalence abstinence on varenicline., Conclusions: Overall, results demonstrated important sex and racial differences in the incidence of NPSAEs, but psychiatric status did not interact with sex on cessation outcomes. Findings did support prior work demonstrating relative increased efficacy of varenicline for women., Competing Interests: RMA has received research and editorial support from Pfizer and research support from Embera NeuroTherapeutics, Inc. Phillip Saccone PhD, and David E. Lawrence PhD, are employees of Pfizer and stockholders. Thomas McRae MD is a former employee of Pfizer and stockholder., (© 2023 The Author(s).)

Background: Previous studies have identified common trajectories of single type substance use over the course of adolescence; however, no study to date has examined joint trajectories of cannabis and alcohol concurrent use. Given that expansion of legal cannabis has increased availability, it is important to understand patterns of concurrent use in adolescents and factors that place male and female youth at risk for harmful trajectories of concurrent use. The current study sought to identify joint trajectories of cannabis and alcohol use - and predictors of harmful use trajectories - among male and female adolescents., Method: We used 4 waves of data from 6997 early adolescent participants (age 12-14 years at Wave 1) in the Population Assessment of Tobacco and Health, a nationally representative longitudinal study in the United States. Participants reported their cannabis and alcohol use reassessed yearly for 5 years (2013-2018). We used joint trajectory growth mixture modeling to identify trajectory groups as defined by changes in alcohol and cannabis use over time., Results: Five classes of alcohol and cannabis concurrent use trajectories were identified. Both internalizing and externalizing symptoms at Wave 1 increased the odds of membership in trajectory groups characterized by more harmful use trajectories. Internalizing symptomatology was a stronger predictor of membership in escalating use trajectories among girls, whereas externalizing symptomatology stronger predictor among boys., Conclusions: These findings underscore the utility of jointly considering alcohol and cannabis use when describing common developmental trajectories of use and identifying risk factors for trajectories characterized by harmful use., Competing Interests: Declaration of Competing Interest No conflict declared., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: Sex differences exist in tobacco smoking. Women have greater difficulty quitting smoking than men. Tobacco smoking is driven by the reinforcing effects of nicotine, the primary addictive component in cigarettes. Nicotine binds to nicotinic acetylcholine receptors, facilitating dopamine release in striatal and cortical brain regions. Dysregulated dopamine D 2/3 receptor signaling in the dorsolateral prefrontal cortex (dlPFC) is associated with cognitive deficits such as impairments in attention, learning, and inhibitory control that impede quit attempts. Sex steroid hormones, such as estradiol and progesterone, influence drug-taking behaviors, through dopaminergic actions, suggesting that their influence may explain sex differences in tobacco smoking. The goal of this study was to relate dlPFC dopamine metrics to sex steroid hormone levels in people who smoke and healthy controls., Methods: Twenty-four (12 women) people who smoke cigarettes and 25 sex- and age-matched controls participated in two same-day [ 11 C]FLB457 positron emission tomography scans, one before and one after amphetamine administration. D 2 R availability ( BP ND ) at baseline and after amphetamine administration was calculated. On the same day, plasma samples were collected for the analysis of sex steroid hormone levels: estradiol, progesterone, and free testosterone., Results: Women who smoke had trending lower levels of estradiol than their sex-matched counterparts. Men who smoke had higher levels of estradiol and trending higher levels of free testosterone than their sex-matched counterparts. Among women only, lower estradiol levels were significantly associated with lower pre-amphetamine dlPFC BP ND ., Discussion/conclusion: This study demonstrated that lower estradiol levels are associated with lower dlPFC D 2 R availability in women which may underlie difficulty resisting smoking., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zakiniaeiz, Gueorguieva, Peltier, Verplaetse, Roberts, McKee and Cosgrove.)

Background: People with substance use disorders (SUD) who have been involved in the legal system often experience stigma upon reentry into the community after incarceration. Although substance use treatment can sometimes be a source of stigma, it may also reduce stigma by facilitating connections with providers, reducing distress, or helping people feel more integrated in their community. However, research has rarely examined the potential for treatment to reduce stigma., Methods: This study examined stigma experiences and the degree to which substance use treatment reduced stigma among 24 people with SUDs who were receiving care in an outpatient treatment facility after release from incarceration. Qualitative interviews were conducted and analyzed using a content analysis approach., Results: Participants reported negative self-judgements as well as perceiving negative judgments from the community upon reentry. With regard to stigma reduction, themes emerged around substance use treatment repairing strained family relationships and reducing participants' self-stigma. Aspects of treatment that reportedly reduced stigma included the treatment facility having a nonjudgmental atmosphere, patients trusting the staff, and working with peer navigators who had lived experience of SUD and incarceration., Conclusions: Results from this study suggest that substance use treatment has the potential to decrease the negative impacts of stigma upon release from incarceration, which continues to be a major barrier. Though more research on stigma reduction is needed, we suggest some preliminary considerations for treatment programs and providers., (© 2023. The Author(s).)

Background: Multimorbidity is linked to worse health outcomes than single health conditions. However, recent studies show that obesity may reduce the risk of developing substance use disorders (SUDs), particularly in vulnerable populations. We investigated how comorbid obesity and tobacco use disorder (TUD) relate to the risk of SUDs and psychiatric conditions., Methods: Data was used from 36,309 individuals who completed the National Epidemiological Survey on Alcohol and Related Conditions - Wave III. Individuals who met the DSM-5 criteria for TUD in the last year were defined as the TUD group. Obesity was defined as having a body mass index (BMI) greater than 30 kg/m 2 . Using this information, individuals were grouped into categories, with people being identified as either having obesity, TUD, both obesity and TUD, or not having either obesity or TUD (comparison). Groups were compared against their comorbid diagnoses of either an additional SUD or psychiatric conditions., Results: Controlling for demographic characteristics, we found that individuals with obesity including those individuals with TUD, had lower rates of comorbid SUD diagnosis than individuals with TUD alone. Additionally, individuals with combined TUD and obesity, and those with TUD alone, had the highest rates of comorbid psychiatric disorder diagnosis., Conclusions: The current study aligns with previous research suggesting that obesity may reduce risk of substance use disorders, even in individuals who have other risk factors promoting harmful substance use (e.g., tobacco use). These findings may inform targeted intervention strategies for this clinically relevant subpopulation., Competing Interests: Given her role as Associate Editor, Sherry McKee, PhD had no involvement in the peer-review of this article and has no access to information regarding its peer-review. Full responsibility for the editorial process for this article was provided by Teri Franklin, PhD., (© 2023 The Authors. Published by Elsevier B.V.)

Introduction: Tobacco smoking is a major public health burden. The mesocortical dopamine system-including the dorsolateral prefrontal cortex (dlPFC)-plays an important role in cognitive function. Dysregulated dopamine signaling in dlPFC is associated with cognitive deficits such as impairments in attention, learning, working memory, and inhibitory control. We recently showed that dlPFC dopamine D2/3-type receptor (D2R) availability was significantly lower in people who smoke than in healthy-controls and that dlPFC amphetamine-induced dopamine release was lower in females who smoke relative to males who smoke and female healthy-controls. However, we did not examine whether the smoking-related dopamine deficits were related to cognitive deficits., Aims and Methods: The goal of this study was to relate dopamine metrics to cognitive performance in people who smoke and healthy-controls. In total 24 (12 female) people who smoke cigarettes and 25 sex- and age-matched healthy-controls participated in two same-day [11C]FLB457 positron emission tomography (PET) scans before and after amphetamine administration. Two outcome measures were calculated-D2R availability (non-displaceable binding potential; BPND) and amphetamine-induced dopamine release (%ΔBPND). Cognition (verbal learning and memory) was assessed with a computerized test from the CogState battery (International Shopping List)., Results: People who smoke had significantly worse immediate (p = .04) and delayed (p = .03) recall than healthy-controls. Multiple linear regression revealed that for people who smoke only, lower D2R availability was associated with worse immediate (p = .04) and delayed (p < .001) recall. %ΔBPND was not significantly related to task performance., Conclusion: This study demonstrated that lower dlPFC D2R availability in people who smoke is associated with disruptions in cognitive function that may underlie difficulty with resisting smoking., Implications: This is the first study to directly relate dopamine metrics in the prefrontal cortex to cognitive function in people who smoke cigarettes compared to healthy-controls. The current work included a well-characterized subject sample with regards to demographic and smoking variables, as well as a validated neurocognitive test of verbal learning and memory. The findings of this study extend previous literature by relating dopamine metrics to cognition in people who smoke, providing a better understanding of brain-behavior relationships., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Although the use of nondrug rewards (e.g., money) to facilitate smoking cessation is widespread, recent research has found that such rewards may be least effective when people who smoke cigarettes are tempted to do so. Specifically, among people who smoke, the neural response to nondrug rewards appears blunted when access to cigarettes is anticipated, and this blunting is linked to a decrease in willingness to refrain from smoking to earn a monetary incentive. Accordingly, methods to enhance the value of nondrug rewards may be theoretically and clinically important. The current proof-of-concept study tested if real-time fMRI neurofeedback training augments the ability to upregulate responses in reward-related brain areas relative to a no-feedback control condition in people who smoke. Adults (n = 44, age range = 20-44) who reported smoking >5 cigarettes per day completed the study. Those in the intervention group (n = 22, 5 females) were trained to upregulate brain responses using feedback of ongoing striatal activity (i.e., a dynamic "thermometer" that reflected ongoing changes of fMRI signal intensity in the striatum) in a single neurofeedback session with three training runs. The control group (n = 22, 5 females) underwent a nearly identical procedure but received no neurofeedback. Those who received neurofeedback training demonstrated significantly greater increases in striatal BOLD activation while attempting to think about something rewarding compared to controls, but this effect was present only during the first training run. Future neurofeedback research with those who smoke should explore how to make neurofeedback training more effective for the self-regulation of reward-related brain activities., (© 2023. The Psychonomic Society, Inc.)

Childhood maltreatment is associated with risk for committing future violence, but the relationship between subgroups and biological sex is unknown. The relationship between adverse childhood experiences (ACEs), violence, and sex was examined using a nationally representative sample. Results from a latent class analysis suggested a four-class model (low adversity; moderate maltreatment with high household dysfunction; severe maltreatment with moderate household dysfunction; severe multi-type adversities). When compared to low adversity, all typology groups were at significantly higher risk to engage in violence (odds ratio > 2.10, p s < .013). The data supported a linear trajectory, meaning increased childhood trauma was associated with increased risk for violence. Although men endorsed more violent behavior, the relationship between ACEs and violence was significantly stronger among women. Prior findings identify that women are more negatively impacted by ACEs and the current findings newly identify that this extends to violent crime.

Background: Our group previously identified that females with AUD and females engaging in heavy or extreme binge drinking were more likely to report cancers and other medical conditions compared to their male counterparts. This analysis aimed to extend our previous findings to examine relationships between sex and consumption of alcohol by type on past year medical condition diagnoses., Methods: Data from the U.S. National Epidemiologic Survey on Alcohol and Related Conditions (NESARC-III; n  = 36,309) was used to evaluate associations between sex (female vs. male) and alcohol type (liquor, wine, beer, coolers) on past year self-reported doctor-confirmed medical conditions, controlling for frequency of alcohol consumption., Results: A significant interaction demonstrated that females who consumed liquor were more likely to have other medical conditions (OR=1.95) compared to males who consumed liquor. Females who consumed wine in the past year were less likely to have cardiovascular conditions (OR=0.81) compared to males who consumed wine. Those who consumed liquor had increased odds of pain, respiratory, and other conditions (OR=1.11 - 1.21). Females were 1.5 times more likely to have cancers or pain, respiratory, and other medical conditions compared to males (OR=1.36 - 1.81)., Conclusions: Results identify that consumption of higher alcohol content drinks (i.e., liquor) is associated with past year self-reported doctor- or health-professional confirmed medical conditions in females compared to males consuming the same high alcohol content beverage. Not only should AUD status and risky drinking be considered in the clinical care of individuals with poorer health but also alcohol type, especially higher alcohol content beverages., Competing Interests: Given her role as Associate Editor, Sherry McKee, PhD was not involved in the peer-review of this article and has no access to information regarding its peer-review. Full responsibility for the editorial process for this article was delegated to Editor-in-Chief, Teresa Franklin, PhD. All other authors declare that they have no conflicts of interest., (© 2023 The Author(s).)

Background: Roughly half of patients with alcohol use disorder prefer non-abstinence based approaches to treatment. However, only individuals who can limit their alcohol use after low-risk consumption are most likely to benefit from these approaches. This pilot study developed a laboratory-based intravenous alcohol self-administration paradigm to determine the characteristics of individuals who could successfully resist consuming alcohol after an initial exposure., Methods: Seventeen non-treatment seeking heavy drinkers completed two versions of an intravenous alcohol self-administration paradigm designed to assess impaired control over alcohol use. In the paradigm, participants received a priming dose of alcohol and then entered a 120-min resist phase, in which they received monetary rewards if they resisted self-administering alcohol. We used Cox proportional hazards regression to determine the impact of craving and Impaired Control Scale scores on rate of lapse., Results: 64.7% of participants across both versions of the paradigm were unable to resist alcohol for the duration of the session. Craving at baseline (HR = 1.07, 95% CI 1.01-1.13, p = 0.02) and following priming (HR = 1.08, 95% CI 1.02-1.15, p = 0.01) were associated with rate of lapse. Individuals who lapsed endorsed greater attempts to control their drinking over the prior six months compared to individuals who resisted., Conclusions: This study provides preliminary evidence that craving may be predictive of risk of lapse in individuals who are trying to limit alcohol intake after consuming a small initial amount of alcohol. Future studies should test this paradigm in a larger and more diverse sample., Competing Interests: The authors declare that there is no conflict of interest., (© 2022 The Authors. Published by Elsevier B.V.)

Background: Human laboratory analogues of drinking behavior provide an efficient, cost-effective mechanistic evaluation of a medication signal on drinking. We developed a novel alcohol self-administration paradigm which models the ability to resist drinking and heavy drinking., Methods: We compared a de-escalating schedule of monetary reinforcement (n=16, 50% female) to no schedule (n=16, 50% female) on the ability to resist drinking (i.e., latency to start drinking) and subsequent ad-libitum alcohol consumption of preferred alcoholic beverage in participants with alcohol use disorder (AUD). Participants completed two laboratory sessions designed to model the ability to resist drinking using stress (versus neutral imagery, within-subject factor) as a prime for drinking., Results: Participants consumed more alcohol with no schedule (74.2%) versus with the de-escalating reinforcement schedule (40.3%,). The de-escalating schedule reduced alcohol consumption by 49%. Eighty-one percent of participants drank heavily with no schedule and this was reduced with the schedule. Use of the de-escalating schedule also increased the latency to pour and sip the first drink. Participants poured and sipped alcohol faster following stress imagery (vs. neutral), had greater craving, and consumed more alcohol in the first 30 minutes., Conclusions: Our novel alcohol self-administration model generated heavy drinking. Over 80% of participants without reinforcement consumed more than 2/3 of their preferred alcoholic beverage designed to increase blood alcohol levels to 0.12 mg% within a 2-hour window. Our model was sensitive to stress, and the de-escalating schedule highlighted stress effects on drinking. Thus, this model is ideal for a cross-over design to test medications for AUD., Competing Interests: Declaration of Competing Interest Nothing to declare.

Purpose: Given the health consequences, perinatal substance use is a significant public health concern, especially as substance use rates increase among women; ongoing data regarding the rates of substance use across trimesters of pregnancy is needed., Methods: The present study utilized cross-sectional population-based data from the National Survey of Drug Use and Health (NSDUH) between 2009 and 2019. We aimed to explore both licit and illicit substance use assessed within each trimester among women endorsing past-year substance use. The NSDUH sample included 8,530 pregnant women., Results: Perinatal substance use was less prevalent among women in later trimesters; however, past-month substance use was observed for all substances across trimesters. The prevalence of past-month licit substance use among pregnant women ranged from 5.77 to 22.50% and past-month illicit substance use ranged from 4.67 to 14.81%. In the second trimester, lower odds of past-month substance use were observed across tobacco, alcohol, and marijuana (odds ratios [ORs] ranging from 0.29 to 0.47), when compared to the first trimester. A similar lower rate of past-month substance use was observed in the third trimester compared to the first trimester, across tobacco, alcohol, and marijuana use, as well as cocaine, prescription pain medication, and tranquilizer use (ORs ranging from 0.02 to 0.42). The likelihood of polysubstance use was lower among women in the second and third trimesters compared to the first trimester (ORs ranging from 0.09 to 0.46)., Conclusion: Findings indicate that a minority of women continue to use substances across all trimesters. This is especially true among women using licit substances and marijuana. These results highlight the need for improved interventions and improved access to treatment for these women., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

The blood-brain barrier (BBB) presents a major hurdle in the development of central nervous system (CNS) active therapeutics, and expression of the P-glycoprotein (P-gp) efflux transporter at the blood-brain interface further impedes BBB penetrance of most small molecules. Designing efflux liabilities out of compounds can be laborious, and there is currently no generalizable approach to directly transform periphery-limited agents to ones active in the CNS. Here, we describe a target-agnostic, prospective assessment of P-gp efflux using diverse compounds. Our results demonstrate that reducing the molecular size or appending a carboxylic acid in many cases enables evasion of P-gp efflux in cell-based experiments and in mice. These strategies were then applied to transform a periphery-limited V600E BRAF inhibitor, dabrafenib, into versions that possess potent and selective anti-cancer activity but now also evade P-gp-mediated efflux. When compared to dabrafenib, the compound developed herein (everafenib) has superior BBB penetrance and superior efficacy in an intracranial mouse model of metastatic melanoma, suggesting it as a lead candidate for the treatment of melanoma metastases to the brain and gliomas with BRAF mutation. More generally, the results described herein suggest the actionability of the trends observed in these target-agnostic efflux studies and provide guidance for the conversion of non-BBB-penetrant drugs into versions that are BBB-penetrant and efficacious.

Clinical studies suggest that women are more likely than men to relapse to alcohol drinking in response to stress; however, the mechanisms underlying this sex difference are not well understood. A number of preclinical behavioral models have been used to study stress-induced alcohol intake. Here, we review paradigms used to study effects of stress on alcohol intake in rodents, focusing on findings relevant to sex differences. To date, studies of sex differences in stress-induced alcohol drinking have been somewhat limited; however, there is evidence that amygdala-centered circuits contribute to effects of stress on alcohol seeking. In addition, we present an overview of inflammatory pathways leading to microglial activation that may contribute to alcohol-dependent behaviors. We propose that sex differences in neuronal function and inflammatory signaling in circuits centered on the amygdala are involved in sex-dependent effects on stress-induced alcohol seeking and suggest that this is an important area for future studies., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Substance use continues to contribute to significant morbidity and mortality in the United States, for both women and men, more so than another other preventable health condition. To reduce the public health burden attributable to substances, the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism have identified that medication development for substance use disorder is a high priority research area. Furthermore, both Institutes have stated that research on sex and gender differences in substance use medication development is a critical area. The purpose of the current narrative review is to highlight how sex and gender have been considered (or not) in medication trials for substance use disorders to clarify and summarize what is known regarding sex and gender differences in efficacy and to provide direction to the field to advance medication development that is consistent with current NIH 'sex as a biological variable' (SABV) policy. To that end, we reviewed major classes of abused substances (nicotine, alcohol, cocaine, cannabis, opioids) demonstrating that, sex and gender have not been well-considered in addiction medication development research. However, when adequate data on sex and gender differences have been evaluated (i.e., in tobacco cessation), clinically significant differences in response have been identified between women and men. Across the other drugs of abuse reviewed, data also suggest sex and gender may be predictive of outcome for some agents, although the relatively low representation of women in clinical research samples limits making definitive conclusions. We recommend the incorporation of sex and gender into clinical care guidelines and improved access to publicly available sex-stratified data from medication development investigations., (© 2022. The Author(s).)

Background: The use of pejorative or stigmatizing language to describe individuals with alcohol and drug use disorders adversely affects treatment seeking, quality of care, and treatment outcomes. In 2015, the International Society of Addiction Journal Editors released terminology guidelines that recommended against the use of words that contribute to stigma against individuals with an addictive disorder. This study examined the use of stigmatizing language in National Institutes of Health (NIH)-funded research and reviews published by the journal, Alcoholism: Clinical and Experimental Research (ACER) from 2010 to 2020, with the goal of sharing the results with the alcohol research community to enhance awareness., Methods: The search for stigmatizing language in ACER was limited to NIH-funded articles made publicly available on PubMed Central (PMC). Though ACER is not an open-access journal, original research and reviews directly funded by NIH are published to PMC for open access to the public as required by the conditions of NIH funding. ACER articles published on PMC were searched from 2010 to 2020 with specific queries for individual terms of interest including those considered pejorative ("alcoholic," "addict," and "abuser") and outdated ("alcohol dependent," "alcohol abuse," and "alcoholism"). The number of articles containing a term of interest for a given year was divided by the total number of articles published in that year to determine the percent use of each term per year., Results: Our search of research and reviews (n = 1903) published in ACER on PMC determined that although the use of pejorative and outdated terminology has decreased over time, there is continued use of the term "alcoholic" over the last decade. Specifically, in 2020, over 40% of articles searched for in PMC still included "alcoholic." The results of a separate manual search (n = 110) on the Wiley Online Database showed that approximately 30% of articles used the term "alcoholic" in a stigmatizing manner., Conclusions: Stigmatizing language can perpetuate negative biases against people with alcohol use disorder. We encourage researchers to shift away from language that maintains discriminatory conceptions of alcohol use disorder. Reducing stigma has the potential to increase rates of treatment seeking and improve treatment outcomes for individuals with alcohol use disorder., (© 2022 by the Research Society on Alcoholism.)

Background and Objectives: Sexual minority individuals demonstrate disparate rates of substance use. Research suggests that bisexual women are vulnerable to substance use disorders when compared to other sexual minority groups. This study explored differences in prevalence of past-year alcohol use disorder (AUD) with and without concurrent past-year opioid and/or benzodiazepine misuse., Methods: The present study utilized responses from the National Survey on Drug Use and Health (NSDUH) public dataset between the years 2015-2019 (N = 16,002) to examine the association between sexual orientation and concurrent misuse of opioids and/or benzodiazepines among individuals with past-year AUD, stratified by sex., Results: Bisexual females demonstrated higher rates of concurrent opioid and benzodiazepine use compared to all other groups. Although there was no association between sexual orientation and concurrent substance use patterns among males, female respondents with past-year AUD endorsing past-year misuse of opioids and benzodiazepines, both alone and in combination, were more likely to be bisexual compared to heterosexual. Lesbians were less likely to endorse concurrent misuse of opioids and benzodiazepines compared to bisexual females., Discussion and Conclusions: In a national sample, bisexual females demonstrated higher odds of risky concurrent substance use patterns. Identifying sexual minority individuals who exhibit elevated risk of co-occurring alcohol, opioid, and/or benzodiazepine misuse is an important step to targeted prevention efforts and allocation of resources to combat rising overdose deaths., Scientific Significance: For the first time, this study explored risky concurrent alcohol, opioid, and benzodiazepine misuse patterns among individuals of different sexual orientations., (© 2022 American Academy of Addiction Psychiatry.)

Glioblastoma (GBM) is the most lethal primary brain tumor. Currently, frontline treatment for primary GBM includes the DNA-methylating drug temozolomide (TMZ, of the imidazotetrazine class), while the optimal treatment for recurrent GBM remains under investigation. Despite its widespread use, a majority of GBM patients do not respond to TMZ therapy; expression of the O 6 -methylguanine DNA methyltransferase (MGMT) enzyme and loss of mismatch repair (MMR) function as the principal clinical modes of resistance to TMZ. Here, we describe a novel imidazotetrazine designed to evade resistance by MGMT while retaining suitable hydrolytic stability, allowing for effective prodrug activation and biodistribution. This dual-substituted compound, called CPZ, exhibits activity against cancer cells irrespective of MGMT expression and MMR status. CPZ has greater blood-brain barrier penetrance and comparable hematological toxicity relative to TMZ, while also matching its maximum tolerated dose in mice when dosed once-per-day over five days. The activity of CPZ is independent of the two principal mechanisms suppressing the effectiveness of TMZ, making it a promising new candidate for the treatment of GBM, especially those that are TMZ-resistant.

Objectives: Concurrent substance use disorder (SUD) and posttraumatic stress disorder (PTSD) occur at high rates and are typically associated with poor treatment outcomes in both sexes. However, women have a propensity to cope with increased negative affect via substance use in comparison to men; thus, it is important to elucidate the sex-specific bidirectional relationships between SUD and PTSD to improve our understanding of concurrent SUD/PTSD in men and women. Methods: Using data from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC-Wave 3; n  = 36,309), the present study evaluated the impact of sex on the relationship between past-year SUDs (new, remitted, ongoing), including alcohol and drug use, and retrospective transitions in new vs. absent and ongoing vs. remitted diagnoses of PTSD. Additionally, the impact of sex was explored in models examining past year PTSD (new, remitted, ongoing) and retrospective transitions in new vs. absent and ongoing vs. remitted diagnosis of SUDs. Diagnostic transitions were based on retrospective reporting. Results: Results indicated that new, remitted, and ongoing SUDs increase the likelihood of new PTSD diagnoses ( OR range = 2.53-8.11; p  < 0.05). Among individuals with ongoing drug use disorders (DUD), there were greater odds of ongoing PTSD ( OR  = 2.10, p  < 0.01). When examining the relationship reciprocally, new, remitted, and ongoing PTSD increased the likelihood of new SUDs ( OR range = 2.50-8.22; p  < 0.05), and ongoing PTSD increased the likelihood of ongoing SUD and DUD ( OR  = 1.40, 1.70, respectively; p  < 0.05). Sex-specific analyses revealed that the relationship between PTSD and SUDs varies between sexes, particularly among women. For instance, women with new PTSD had higher odds of SUDs, and women with ongoing PTSD were almost 2.5 times more likely to have an ongoing DUD. Women with a new PTSD diagnosis were more likely to be diagnosed with a new SUD ( OR  = 3.27) and an ongoing DUD ( OR  = 3.08). Conclusions: Results indicate a bidirectional relationship between PTSD and SUD that is in many instances larger in women. Thus, illustrating potential sex-specific differences in underlying mechanisms implicated in SUD/PTSD, warranting additional research.

Background: The correlates of legally significant outcomes that have been identified in people with mental disorders are of limited value in understanding the mechanisms by which these outcomes occur., Aims: To describe the relationships between mental disorder, impaired psychosocial function, and three legally significant outcomes in a representative sample of the US population., Methods: We used a population survey, the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC-III, sample size 36,309), to identify people who self-reported serious trouble with the police or the law over the past 12 months and two lifetime outcomes, being incarcerated and engaging in violence to others. DSM-5 categories were generated using the Alcohol Use Disorder and Associated Disabilities Interview Schedule-5. Psychosocial function was assessed using social and role-emotional function scores of the 12-Item Short-Form Health Survey Version 2., Results: Participants with mental disorder, but not people with no diagnosis, who reported serious trouble with the police or with the law during the previous 12 months reported significantly worse psychosocial function than those who did not report such trouble. The size of the statistical effect varied by diagnosis, moderate for some forms of mental illness and for alcohol abuse and nonsignificant for drug abuse and the personality disorders. Effect sizes were largest for diagnoses where legally significant outcomes were least common., Conclusions: The effect of impaired psychosocial function, for instance in disrupting family and social networks that would otherwise protect against these legally significant outcomes, warrants further investigation in studies with longitudinal designs.

Background: The majority of adolescents and young adults (AYA) who use cannabis also use alcohol. Although cannabis use is increasing in the United States (US), it is not known whether the increase contributes to either increased co-use of alcohol and cannabis (e.g., complementarity) or replacement of alcohol with cannabis (e.g., substitution). The current study estimated the prevalence of alcohol use by cannabis use status among US AYA ages 12 to 25 in 2018 and trends in alcohol use by cannabis use status from 2002 to 2018., Methods: Data were drawn from the 2002 to 2018 National Survey on Drug Use and Health public use data files. The analytic sample included AYA ages 12 to 25 (2018 sample, n = 26,924; total combined sample 2002 to 2018, n = 576,053). Linear and logistic regression models were used to estimate past-month alcohol use, daily alcohol use, and average quantity of alcohol consumed among AYA with and without past-month cannabis use from 2002 to 2018., Results: In 2018, any alcohol use and daily alcohol use were significantly more common among AYA who used cannabis use than those who did not use cannabis. Overall, any alcohol use, daily alcohol use, and average drinks per day declined from 2002 to 2018 among AYA irrespective of recent cannabis use. However, the decline in any alcohol use, daily alcohol use, and average alcohol drinks per day was more rapid among AYA who used cannabis (daily and nondaily) than those who did not use cannabis. The rate of decline in average alcohol drinks per day was also higher among AYA with daily compared to nondaily cannabis use., Conclusions: Even with declines in alcohol use over time, drinking is much more common among AYA who report cannabis than those without recent cannabis use, which is consistent with complementarity. Yet, because the decline in alcohol use has been more rapid among AYA who use cannabis, there is also evidence of substitution. Thus, the current data on alcohol and cannabis use are consistent with both complementarity and substitution. However, these relationships may change as cannabis legalization expands over time., (© 2021 by the Research Society on Alcoholism.)

Background: Women experience greater health consequences of alcohol compared to their male counterparts. In recent years, rates of drinking and heavy alcohol use have increased in women while remaining relatively steady in men. Thus, our aim was to newly examine associations between sex, AUD, and the presence of medical conditions in a large nationally representative, cross-sectional dataset., Methods: Using data from the U.S. National Epidemiologic Survey on Alcohol and Related Conditions (NESARC-III; n = 36,309), we evaluated relationships among sex and DSM-5 AUD, and their association with past year clinician-confirmed medical conditions., Results: Women were 1.5 to 2 times more likely to be diagnosed with a past year cancer, pain, respiratory, or other significant medical condition compared to men (odds ratio [OR] = 1.331-2.027). Individuals with an ongoing DSM-5 AUD were nearly 1.5 to 2 times more likely to report a confirmed past year liver, cardiovascular, cancer, or other significant medical condition compared to those without an AUD (OR = 1.437-2.073). Interactive effects demonstrated that women with an ongoing AUD were 2 to 3 times more likely to report a past year doctor- or health professional-confirmed medical condition compared to men; specifically, respiratory conditions and cancers (OR = 1.767-2.713)., Conclusions: Results identify that AUD is a critical factor associated with disease that spans organ systems. Associations between AUD and respiratory conditions or cancers are particularly robust in women. Effective interventions for a broad spectrum of medical conditions should consider the role of problematic alcohol use, especially given that rates of drinking in women are increasing., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Heavy alcohol use is associated with increased risk of alcohol-related health consequences. Alcohol consumption has increased in females in the last fifteen years and females are more likely to experience exacerbated health risks due to drinking. Our group identified that females with AUD were more likely to report respiratory conditions or cancers compared to their male counterparts. This analysis sought to further examine relationships between sex and alcohol use on medical conditions by using the new 2020 U.S. Dietary Guidelines risk drinking levels., Methods: Data from the U.S. National Epidemiologic Survey on Alcohol and Related Conditions (NESARC-III; n  = 36,309) was used to evaluate associations between sex (female vs. male) and alcohol risk drinking levels (abstainer, binge, heavy, extreme binge vs. moderate drinking) on past year self-reported doctor-confirmed medical conditions)., Results: Females were 1.5 to 2 times more likely to have pain, respiratory, or other medical conditions in the past year (odds ratio [ OR ]=1.46-2.11) vs. males. Significant interactions demonstrated that heavy drinking females or extreme binge drinking females were 2 to 3 times more likely to have cancers or other conditions ( OR =1.95-2.69) vs. males at the same risk drinking level. Female abstainers were more likely than male abstainers to have other medical conditions ( OR =1.77)., Conclusions: Consistent with our previous findings, results identify that higher risk drinking levels are associated with the presence of past year self-reported doctor-confirmed medical conditions spanning organ systems, particularly in females. Treatment for high-risk drinking should be considered in the clinical care of individuals with significant medical conditions., Competing Interests: All authors declare that they have no conflicts of interest., (© 2021 The Authors. Published by Elsevier B.V.)

Objective: Pain is associated with increased risk for harmful substance use. Substance use also may increase levels of pain, suggesting that these two factors may reciprocally increase risk. The current study examined the reciprocal association between pain and substance use outcomes (i.e., alcohol, cannabis, and painkillers/sedatives/tranquilizers [PSTs]) longitudinally in a nationally representative cohort of non-incarcerated U.S. citizens., Method: Adult (≥18 years old) survey data from Waves 2-4 of the Population Assessment of Tobacco and Health (PATH) study were used. The PATH is a nationally representative multiwave cohort survey (Wave 2: October 2014-October 2015, Wave 3: October 2015-October 2016, Wave 4: December 2016-January 2018). Cross-lagged panel models were used to estimate the reciprocal effects of pain intensity and substance use on subsequent changes in both variables. Substance use outcomes were substance use problems and greater-than-weekly use for cannabis and PSTs, total past-month drinks, and alcohol use exceeding moderate drinking guidelines. All models controlled for autoregressive effects and demographic covariates., Results: Pain intensity showed a positive prospective association with all substance use outcomes. All cannabis and PST use were positively associated with subsequent pain intensity. Alcohol use problems also predicted higher levels of pain intensity. Neither total past-month drinks nor exceeding moderate drinking guidelines predicted subsequent pain intensity., Conclusions: Pain and substance use show a reciprocal association and may act in a positive feedback loop to worsen both conditions over time in people with a history of use.

Background: Rates of alcohol use disorder (AUD) have increased in women in the last decade. Women may be more likely to engage in alcohol use to regulate stress and negative affect compared to men. Findings from our group found that life event stress was more strongly associated with new AUD in women vs. men. Our aim was to extend these findings to psychological distress, a potentially related construct to stress, using a second nationally representative dataset., Methods: Using data from the National Survey on Drug Use and Health (NSDUH; 2008-2017, total n = 562,072), we examined time-varying associations between gender and past year serious psychological distress (SPD; Kessler-6 distress scale: scores > 13 yes, <13 no) with past year vs. absent DSM-IV AUD., Results: A significant (p < 0.0001) gender by SPD interaction for past year vs. absent AUD demonstrated that past year SPD was associated with increased odds of past year AUD in men (OR = 3.33, 95% CI = 3.15, 3.52) and even greater odds of past year AUD in women (OR = 4.39, 95% CI = 4.14, 4.66). The gender by SPD by time interaction was not significant (p = 0.06)., Conclusions: Results highlight that while men with past year SPD were 3 times more likely to have a past year AUD, women with past year SPD were nearly 4.5 times more likely to have a past year AUD. Psychological distress is clearly an important factor in AUD in both men and women, but results suggest that other factors may be driving the increase in rates of AUD in women., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Stress and trauma exposure disturbs stress regulation systems and thus increases the vulnerability for stress-related disorders which are characterized by negative affect, including major depressive disorder, anxiety disorders and posttraumatic stress disorder. Similarly, stress and trauma exposure results in increased vulnerability to problematic alcohol use and alcohol use disorder, especially among women, who are more likely to drink to cope with negative affect than their male counterparts. Given these associations, the relationship between stress-related disorders and alcohol use is generally stronger among women leading to complex comorbidities across these disorders and alcohol misuse. This review highlights the therapeutic potential for progestogen- and androgen-derived neurosteroids, which affect both stress- and alcohol-related disorders, to target the overlapping symptoms related to negative affect. This article is part of the special issue on 'Vulnerabilities to Substance Abuse.', (Published by Elsevier Ltd.)