Association of e-Cigarette Use and Postpartum Depression: Pregnancy Risk Assessment Monitoring System 2016-2019.

Background: Postpartum depression (PPD) is a prevalent public health concern. Combustible cigarette use is associated with increased risk of PPD. While electronic cigarette (e-cigarette) use during pregnancy is linked to increased risk of depressive symptoms during pregnancy, the relationship between e-cigarette use and PPD is not well understood. We sought to examine the association of e-cigarette use with PPD. Materials and Methods: Using Pregnancy Risk Assessment Monitoring System 2016-2019 data, unadjusted and adjusted logistic regression analyses for PPD were conducted via three analyses where e-cigarette use (any vs. none) was retrospectively self-reported (1) in past 2-year, (2) prepregnancy (i.e., 3 months before pregnancy), and (3) during pregnancy (i.e., last 3 months of pregnancy). We conducted an additional past 2-year e-cigarette use analysis excluding those who used combustible cigarette and/or hookah. Covariates included age, race, ethnicity, combustible cigarette, and/or hookah use, prenatal care during the last trimester, health insurance coverage during pregnancy, physical abuse during pregnancy, income, and survey type. Results: Only unadjusted odds ratios from past 2-year e-cigarette use (1.63, 95% confidence interval [CI]: 1.42-1.87) and past 2-year e-cigarette use excluding individuals with cigarette and/or hookah use (1.78, 95% CI: 1.30-2.38) were statistically associated with PPD. No adjusted analyses were statistically significant. Conclusion: Any e-cigarette use, as compared to no use, does not appear to be an independent risk factor of PPD, though it may be a useful clinical marker of increased risk of PPD. Future studies are warranted to advance our knowledge of impact of e-cigarette use on PPD.

Enrollment of Spanish-speaking Latinx adults in clinical trials: Five lessons learned from a randomized study in substance use treatment.

Latinx individuals are the largest ethnic minoritized group in the United States (US) at 19% of the population. However, they remain underrepresented in clinical research, accounting for less than 8% of clinical trial participants. Consideration of cultural values could help overcome barriers to inclusion in clinical trials and result in better recruitment and retention of Latinx individuals. In this commentary, we describe general guidance on culturally responsive modifications to facilitate the successful recruitment and retention of Spanish-speaking Latinx participants in Randomized Clinical Trials (RCTs) for substance use. We identify five culturally responsive strategies to help enroll participants in RCTs: 1. Create an ethnically diverse research team, 2. Assess available community partners, 3. Familiarize oneself with the target community, 4. Establish confianza (trust) with participants, and 5. Remain visible to participants and staff from recruitment sites. Representation of Latinx individuals in clinical trials is essential to ensure treatments are responsive to their needs and equitydriven. Some of these strategies can further research in helping to promote the participation of Latinx individuals experiencing substance use concerns, including outreach to those not seeking treatment.

Diagnostic group differences and exploratory sex differences in intrinsic connectivity during fMRI Stroop in individuals with and without cocaine use disorder.

BACKGROUND: Sex-/gender-related differences in cognitive control and how they relate to addictions may inform novel treatment options. Cognitive control, including Stroop performance, has been linked to addictions and treatment outcomes. The extent to which women and men with cocaine use disorder (CUD) show brain and behavioral differences relating to Stroop performance has not been previously studied. We examined sex-related differences in Stroop-related brain connectivity in female and male CUD and healthy-comparison (HC) subjects. METHODS: 40 individuals with CUD (20 female) and 40 HC (20 female) subjects matched on age, race, and ethnicity completed an fMRI Stroop task. Intrinsic connectivity distribution (ICD) and mean-adjusted ICD analyses were conducted to identify differences related to sex and diagnostic group. Stroop task performance was also considered. RESULTS: Behavioral results confirmed a Stroop effect. A main effect of diagnostic group indicated that the CUD versus HC group showed lower connectivity in the prefrontal cortex, frontal gyrus, cingulate gyrus, precuneus, cerebellum, and somatosensory, visual, and auditory areas. An exploratory main effect of sex suggested that males may show relatively lower connectivity than females in the cerebellum and brainstem, although connectivity was largely similar across sexes. CONCLUSIONS: Intrinsic connectivity during cognitive control varied by diagnostic group and possibly by sex. The findings suggest that interventions targeting cognitive control in CUD should consider sex.

Examining racial differences in smoking outcomes among smokers enrolled in an intravenous nicotine infusion study.

INTRODUCTION: Large racial disparities exist in the prevention and treatment of smoking-related diseases, and minoritized populations carry a heavier burden of smoking-related morbidity and mortality. To date, most studies investigating smoking-related illnesses have been conducted in samples in which the majority, or totality, self-identified as White or Caucasian. While Black individuals who smoke tend to have a lower rate of nicotine clearance, in part due to the use of mentholated cigarettes, less is known about how slower clearance affects their acute subjective and physiologic responses in response to either overnight abstinence or subsequent nicotine administration. This study aimed to investigate differences between the experiences of Black and White individuals who smoke across these outcomes after a period of short-term abstinence and after IV nicotine infusion. METHODS: The study included 206 smokers (N = 103 Black, N = 103 White, by self-report). The study investigated self-report, physiological, and biochemical smoking-related outcomes following confirmed overnight abstinence followed by IV nicotine infusion. The outcome measures were separately analyzed with repeated-measures mixed-models. RESULTS: Black individuals had lower rates of nicotine clearance and were more likely to smoke mentholated cigarettes than White individuals. Despite these differences, no differences in withdrawal, cravings, or physiological outcomes were observed between the two groups. There were some trends toward differences in subjective experiences, in that an interaction with trend level significance between race and dose was observed for negative subjective drug effects, with White smokers trending towards endorsing higher levels of negative affect after abstinence and nicotine infusion. We also observed that Black individuals trended towards experiencing more negative drug effects in response to initial nicotine delivery than to saline, whereas White individuals had no differences in negative drug effects across saline or nicotine doses. CONCLUSIONS: Despite slower nicotine clearance, Black participants exhibited withdrawal and urges to smoke as severe as White participants, and did not have blunted physiological responses to overnight abstinence or administration of nicotine, which were contrary to our hypotheses. Our findings suggest minimal differences across races in the acute pharmacologic effects of nicotine. We observed trend-level differences in subjective and affective responses to nicotine. Greater insight into these differences may lead to improved prevention and treatment strategies for smoking-related illnesses for Black individuals who smoke.

Threshold for the pleasurable effects of nicotine are lower than its reinforcing effects during self-administration.

A recent study demonstrated that during a single sampling period, 0.1 mg of intravenous (IV) nicotine (vs. placebo) was found to be the threshold for subjective and physiological drug effects. The present study is a secondary analysis evaluating whether the threshold for subjective and physiological effects is similar when the subject has repeated opportunities to choose blinded doses of nicotine versus placebo. We also examined whether cigarette craving, withdrawal, and rate of nicotine metabolism affected nicotine reinforcement, defined by a greater number of nicotine choices than placebo. Young adult (n = 34; 68% male), daily smokers had five laboratory sessions after overnight abstinence. After sampling an IV dose of nicotine (0.0125, 0.025, 0.05, 0.1, or 0.2 mg/70 kg) versus saline (placebo), participants completed a nicotine self-administration (NSA) procedure that included 10 opportunities to self-administer IV dose of nicotine or placebo. The threshold for subjective positive effects of nicotine during the NSA was equal to or lower than the sampling period, 0.05-0.1 mg versus 0.1 mg. The threshold for nicotine-induced heart rate increase was higher during the NSA than during the sampling period (0.2 mg vs. 0.1 mg). Higher baseline craving and nicotine metabolite ratio (NMR) were associated with nicotine reinforcement at 0.2 mg and 0.1 mg doses, respectively (p < .05). The results suggest that subjective effects during NSA are reported at doses lower than the sampling period. Taken together, tobacco products thought to be subthreshold for reinforcement should be carefully evaluated for their subjective effects, including their discriminative stimulus effects. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Modafinil Does Not Reduce Cocaine Use in Methadone-Maintained Individuals.

Introduction: There are no approved medications for the treatment of cocaine use disorder (CUD). Modafinil, a cognitive-enhancer with weak stimulant-like effects, has shown promise in initial studies as a treatment for CUD. Its potential efficacy has not been examined in individuals dually dependent on cocaine and opioids. Methods: This study examined the efficacy of modafinil, in combination with contingency management (CM), for reducing cocaine and opioid use and improving cognitive function in methadone-stabilized individuals with opioid and cocaine dependence. We conducted a 17-week, double-blind, randomized controlled trial in which participants were randomized to one of four conditions: 1) modafinil + CM; 2) modafinil + yoked-control (YC); 3) placebo +CM; or 4) placebo + YC. Additionally, all subjects received platform treatments of cognitive behavioral therapy (CBT) and methadone. While the original planned sample size was N=160, a total of 91 participants were randomized. The two primary cocaine use outcomes were percentage of urine specimens positive for cocaine and percent of days of self-reported abstinence from cocaine during treatment. Cognitive function, opioid use, and secondary cocaine use outcomes were also considered. Results: Modafinil was well-tolerated with minimal reports of adverse effects. Modafinil was no more effective than placebo in reducing cocaine or opioid use or improving cognitive performance. Conclusions: In the context of a trial with robust control conditions and platform treatments, findings did not provide support for the efficacy of modafinil treatment for the treatment of CUD in methadone-stabilized individuals with dual opioid and cocaine dependence.

Development of pulsed intravenous nicotine infusions as a model for inhaled nicotine in humans.

RATIONALE: Although nicotine from cigarettes is delivered in puff-sized amounts, most preclinical and human intravenous (IV) nicotine studies have used bolus or continuous infusions. OBJECTIVES: To determine the feasibility of a pulsed-nicotine infusion model in smokers. METHODS: Following overnight abstinence, 12 adult smokers underwent 5 laboratory sessions. Using a crossover design, in each session, participants were assigned to 1 of 5 conditions: (1) high/fast: 1.0 mg nicotine delivered over 5 pulsed-infusions, then 15 saline infusions; (2) high/slow: 1.0 mg nicotine delivered over 20 pulsed-infusions; (3) low/fast: 0.2 mg nicotine delivered over 5 pulsed-infusions, then 15 saline infusions; (4) low/slow: 0.2 mg nicotine delivered over 20 pulsed-infusions; and (5) placebo: Saline delivered over 20 pulsed-infusions. Subjective drug effects, urges to smoke, nicotine withdrawal, and cognitive performance were measured in each session. RESULTS: Both the high/fast and high/slow conditions were associated with greater "head rush" and "high" (p < 0.05). The high/fast condition also provided greater suppression of urges to smoke and nicotine withdrawal (p < 0.05), indexed by the Questionnaire of Urges to Smoke-Brief, and the Minnesota Nicotine Withdrawal Scale, respectively. The high/fast and high/slow conditions produced greater increases in heart rate (p < 0.01) than saline. Finally, there were no main effects of dosing conditions on cognitive performance, indexed by the continuous performance test. CONCLUSIONS: These findings demonstrate the feasibility of pulsed-nicotine infusions to model nicotine delivery by smoking. This model could inform future studies testing novel smoking cessation therapies and tobacco regulatory studies testing the impact of nicotine reduction approaches.

Plasma Menthol Glucuronide as a Biomarker for the Behavioral Effects of Menthol and Nicotine in Humans.

This secondary analysis sought to determine if plasma menthol glucuronide (MG) concentrations predict changes in three outcomes, subjective drug effects, urges to smoke, and heart rate, following concurrent inhaled menthol and intravenous nicotine. A total of 45 menthol and non-menthol cigarettes smokers (36 male, nine female, 20 Black, and 23 White) were included in this double-blind, placebo-controlled study. Across three test sessions, participants were assigned to a different flavor condition for each session: 0% (no menthol), 0.5%, or 3.2% menthol. In each test session, participants received in a random order one intravenous delivery of saline and two intravenous deliveries of nicotine (0.25 mg/70 kg and 0.5 mg/70 kg), each 1 h apart, concurrent with menthol delivery by e-cigarettes. The main outcomes were subjective drug effects, urges to smoke, and heart rate. The results showed that following e-cigarette inhalation, changes in plasma MG concentrations or "menthol boost" increased proportionally to the menthol concentration in the e-liquids. While changes in plasma MG concentrations were not predictive of increases in heart rate or subjective drug effects that are reflective of acute effects from nicotine (i.e., feel good effects, stimulated, aversive effects), they were predictive of cooling effect, a typical effect of menthol, but only in menthol smokers in the absence of concurrent active nicotine infusion. These findings demonstrate the utility of plasma MG as a biomarker both for acute menthol exposure by e-cigarette inhalation and for the examination of the concentration-dependent behavioral and physiological effects of menthol in humans.

Impact of delivery rate on the acute response to intravenous nicotine: A human laboratory study with implications for regulatory science.

Faster delivery rate enhances the abuse potential of drugs of abuse, yet systematic studies on the impact of delivery rate on the acute effects of nicotine in humans are lacking. Using an intravenous (IV) nicotine infusion procedure that allows precise control of rate of delivery, we examined the impact of nicotine delivery rate on the positive subjective drug effects, smoking urges, withdrawal, heart rate, blood pressure and attention function in smokers. Twenty-four male and female (ages 21-35) dependent smokers attended five experimental sessions, following overnight abstinence from smoking. Using a crossover design, participants attended five sessions, where they were assigned to a random sequence of saline infusion or 1 mg nicotine delivered over 1, 2.5, 5 or 10 min at rates of 1, 0.4, 0.2 or 0.1 mg/min, respectively. The positive subjective effects of nicotine were most robust under the two faster delivery rate conditions, 1- and 0.4-mg nicotine/min. In contrast, all nicotine delivery rates were equally more effective than saline in alleviating urges to smoke. Likewise, nicotine-induced heart rate increases did not vary with the rate of nicotine delivery. Lastly, the cognitive enhancing effects of nicotine were observed only under the two slowest delivery rate conditions-0.1- and 0.2-mg nicotine/min. Collectively, these findings support the critical role of delivery rate in optimizing nicotine's abuse potential versus potential therapeutic effects and have timely implications for developing novel therapeutics for nicotine dependence, as well as for tobacco regulatory science.

Religiosity and Spirituality in Latinx Individuals with Substance Use Disorders: Association with Treatment Outcomes in a Randomized Clinical Trial.

Although many studies have examined religiosity as a protective factor for substance use, few have considered its relationship to treatment outcomes among Latinx adults. Using data from 89 individuals participating in a randomized clinical trial evaluating a culturally adapted Spanish-language version of web-based cognitive behavioral therapy (CBT4CBT-Spanish) for substance use, we evaluated the relationship between religiosity, as measured by the Religious Background and Behavior questionnaire, and treatment outcomes. Overall, there were few significant correlations between religiosity scores and treatment outcomes. Past-year religiosity was positively correlated with one measure of abstinence for those randomized to CBT4CBT-Spanish, but this did not persist during a six-month follow-up period. Findings suggest that religiosity may be associated with short-term abstinence outcomes among Latinx adults receiving a culturally adapted cognitive behavioral therapy treatment. However, additional research is needed with larger and more heterogenous Latinx populations.

Catechol-O-Methyltransferase Effects on Smoking: A Review and Proof of Concept of Sex-Sensitive Effects.

Purpose of Review: This article reviews recent research on how catechol-O-methyltransferase (COMT) may impact cigarette smoking behavior, and how effects may be sex-sensitive. Preliminary data are presented on sex-sensitive effects of COMT on response to short-term abstinence in individuals who smoke. Recent Findings: Although research is mixed, functional variants in the COMT gene have been linked with smoking behavior, cessation outcomes and nicotine abstinence-related symptoms. Our proof-of-concept preliminary data from a human laboratory study of individuals who smoke cigarettes found that those with the high COMT enzyme activity genotype (Val/Val) reported more severe smoking urges and withdrawal symptoms following overnight abstinence than Met carriers. These effects were present in women, but not in men and were abstinent-dependent, in that they dissipated following nicotine administration. Summary: The preliminary data showing sex-sensitive pharmacogenetic effects may shed light on mechanisms contributing to sex differences in barriers to smoking cessation or potential sex-specific treatment options.

Discrete Roles for Impulsivity and Compulsivity in Gambling Disorder.

Background and Objective: Complex associations between gambling disorder (GD) and impulsivity have been identified. However, little is known regarding how compulsivity associates with different impulsivity domains in GD. In this study, we examined associations between self-reported and behavioral measures of impulsivity-assessed through the Barratt Impulsiveness Scale (BIS-11) and the Experiential Discounting Task (EDT), respectively- and compulsivity-measured using the Padua Inventory and the Wisconsin Card Sorting Test (WCST), respectively-, in an adult sample with GD (N = 132, 94 men and 38 women, ages ranging from 18 to 69 years). GD severity was assessed using the South Oaks Gambling Screen. Methods: Structural Equation Modeling was used to examine relationships between impulsivity and compulsivity measures, age, and GD severity. Results: BIS-11 non-planning and BIS-11 total scores positively correlated with GD severity. The standardized coefficients for the SEM showed direct positive contributions of BIS-11 non-planning, Padua and EDT scores to GD severity. Only participants' ages directly contributed to WCST perseverative errors, and no direct or indirect effects were found with respect to GD severity. Conclusion: The findings suggest that specific aspects of impulsivity and compulsivity contribute to GD severity. Interventions specifically targeting domains that are most relevant to GD severity may improve treatment outcomes.

Longitudinal changes in network engagement during cognitive control in cocaine use disorder.

BACKGROUND: Cocaine use disorder (CUD) is characterized by poor cognitive control and has limited empirically supported treatment options. Furthermore, an understanding of brain mechanisms underlying CUD is at a relatively early stage. Thus, this study aimed to investigate longitudinal alterations in functional neural networks associated with cognitive control in cocaine use disorder (CUD). METHODS: Secondary analysis was performed on data from 44 individuals who participated in three randomized clinical trials for CUD and completed an fMRI Stroop task both at baseline and post-treatment. Independent component analysis (ICA) was performed to assess changes in functional network engagement and investigate associations with cocaine-use behaviors. Mixed linear models were performed to test for longitudinal effects on network engagement and relationships with baseline patterns of cocaine use (i.e., past-month frequency and lifetime years of use) and periods of abstinence/use between scans (i.e., percent negative urine toxicology and maximum days of contiguous abstinence). RESULTS: Six functional networks were identified as being related to cognitive control and/or exhibiting changes in engagement following treatment. Results indicated that engagement of amygdala-striatal, middle frontal and right-frontoparietal networks were reduced over time in CUD. Less change in the amygdala-striatal network was associated with greater lifetime years of cocaine use. Additional analyses revealed that negative toxicology results and achievement of continuous abstinence were associated with greater engagement of the right-frontoparietal network. CONCLUSIONS: Neural systems that underlie cognitive control may change over time in individuals with CUD. A longer history of cocaine-use may hinder changes in network activity, potentially impeding recovery.

Electronic Nicotine Delivery Systems (ENDS) Use and Pregnancy I: ENDS Use Behavior During Pregnancy.

PURPOSE OF REVIEW: This review examines Electronic Nicotine Delivery Systems (ENDS) use behavior during pregnancy, including the prevalence of and transitions in use during pregnancy. RECENT FINDINGS: Twenty-two papers addressed the prevalence of and/or transitions in ENDS use during pregnancy. Findings show a complex landscape of ENDS use. A minority (0.4%-7.0%) of pregnant persons use ENDS; most commonly this occurs in the form of dual use (ENDS and combustible cigarettes (CC); 75%). Many pregnant persons report using ENDS because they perceive them to be a lower-risk alternative and/or potential cessation aide for CC smoking. However, while a subset of those who use ENDS do quit all tobacco product use during pregnancy, only a small proportion switch from exclusive CC smoking to exclusive ENDS use. SUMMARY: ENDS are a somewhat new addition to the tobacco product landscape. The perception of ENDS as a lower-risk alternative may contribute to ENDS use in pregnancy. There is insufficient evidence to support the notion that ENDS facilities the cessation of tobacco product use during pregnancy.

Threshold dose for intravenous nicotine self-administration in young adult non-dependent smokers.

RATIONALE: Reducing nicotine content of inhaled tobacco products may prevent nicotine addiction, but the threshold for nicotine reinforcement has not been systematically evaluated in controlled human laboratory studies. OBJECTIVES: The current study uses a novel double-blind placebo-controlled intravenous (IV) nicotine self-administration (NSA) model to determine threshold for subjective effects of nicotine and nicotine reinforcement using a forced choice self-administration procedure. METHODS: Young adults (n = 34) had 5 laboratory sessions after overnight nicotine abstinence. In each session, participants sampled and rated the subjective effects of an IV dose of nicotine (0.0125, 0.025, 0.05, 0.1, or 0.2 mg nicotine/70 kg bodyweight) versus saline (placebo), then were given a total of 10 opportunities to self-administer either the IV dose of nicotine or placebo. RESULTS: Mixed effect models revealed a significant effect of nicotine dose for positive (i.e., "stimulatory" and "pleasurable"; p < .0001) effects, but not "aversive" effects during sampling period. Post hoc comparisons showed that higher doses (i.e., 0.1 and 0.2 mg) were associated with greater stimulatory, pleasurable, and physiological effects than placebo and lower doses. Mixed effect models revealed that only the highest dose (i.e., 0.2 mg) was consistently preferred over placebo. Sex differences were generally weak (p = .03-.05). CONCLUSIONS: Using our IV nicotine NSA model, the threshold for detecting positive effects of nicotine in young adult smokers is about 0.1 mg, but a higher dose of nicotine, 0.2 mg, is required to produce a consistent nicotine reinforcement. Regarding the regulatory impact, our findings further support the value of nicotine reinforcement threshold as a tobacco regulatory target.

The effects of inhaled flavors on intravenous nicotine.

Menthol is the only available flavor in combusted tobacco cigarettes; however, e-cigarettes are available in thousands of flavors. Research on flavors and rewarding properties of nicotine is limited. The present study sought to examine the acute rewarding effects of flavors inhaled from an e-cigarette, in combination with intravenous (IV) nicotine among cigarette smokers. In the present study, 24 menthol-preferring young adult (aged 18 to 30) cigarette smokers were tested under 3 different e-cigarette flavor conditions (menthol, green apple, or menthol + green apple) in a within-subject cross-over design. During each test session, each participant received 3 IV infusions (saline, 0.25 mg/70 kg nicotine, 0.5 mg/70 kg nicotine) administered 1 hr apart. The main outcome measures assessed cardiovascular, subjective, and cognitive domains. Compared with green apple or green apple + menthol, menthol produced higher ratings of "cooling" (ps < 0.01). Craving was rated higher following administration of green apple and the combined menthol + apple flavor compared to menthol alone (ps < 0.05). As expected, IV-nicotine dose-dependently increased the ratings of subjective liking/disliking and peak heart rate, improved cognitive performance, and reduced smoking urges (all ps < 0.05). These subjective, cognitive, and physiological effects of nicotine were not affected by any flavor condition. The present findings did not support an interaction between IV-nicotine dose and inhaled flavor for acute effects of nicotine. Green apple flavor, alone or in combination with menthol, could result in higher craving or insufficiently alleviate craving, relative to menthol flavor alone. Additional research is warranted to examine extended exposure to inhaled flavors on the rewarding and addictive effects of nicotine. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Electronic Nicotine Delivery Systems (ENDS) Use and Pregnancy II: Perinatal Outcomes Following ENDS Use During Pregnancy.

Purpose of Review: This review examines the risk of adverse perinatal outcomes following electronic nicotine delivery system (ENDS) use during pregnancy, and considers whether there are sufficient data to support ENDS as a harm reduction approach during pregnancy. Recent Findings: Seven papers assessed perinatal outcomes following ENDS use during pregnancy. There was evidence that ENDS use was associated with increased risk for some adverse perinatal outcomes (e.g., small for gestational age). However, the repeated use of data sets, insufficient data (e.g., timing of ENDS use, type of ENDS products used), and limited samples size, contributed to mixed findings on the degree to which ENDS use (alone or in combination with combustible cigarettes (CC)) impacts the risk of adverse perinatal outcomes relative to CC smoking alone. Summary: The current data are still insufficient to support ENDS as a harm reduction approach, though findings do warrant concern and more detailed investigation of ENDS use during pregnancy. Future research directions, as well as implications for clinical recommendations and tobacco regulatory science are discussed.

Impulsivity across substance use categories: Consideration of sex/gender.

PURPOSE OF REVIEW: The goal was to review recent (1/2015-2/2020) evidence of impulsivity as a feature of substance use disorders or use of substances (alcohol, cannabis, nicotine, opioids, stimulants) in males compared to females in terms of: a) impulsivity in substance-using groups (or substance-using compared to control groups), and b) relationship between impulsivity and substance use behavior, clinical severity, or treatment outcomes. RECENT FINDINGS: Of 361 papers identified by the searches, 69 met inclusion criteria, and 39 were highlighted for considering sex/gender in relation to impulsivity in substance-using populations. Taken together, findings supported higher impulsivity in males and females who use substances, relative to controls; and higher impulsivity was linked with more substance use/severity in both sex/genders. There were mixed findings regarding male versus female differences in impulsivity among individuals who use substances, or in the magnitude of the relationship between impulsivity and substance use severity. SUMMARY: The current body of evidence does not point to a consistent sex/gender difference in the role of impulsivity within and across substance use disorders. Impulsivity is a clinically-relevant construct for male and female individuals who use substances, across a range of substances.

Modulation of "Protective" Nicotine Perception and Use Profile by Flavorants: Preliminary Findings in E-cigarettes.

INTRODUCTION: Characterizing flavors are widely available in e-cigarettes and motivate initiation and continued use. Flavors may enhance appeal and facilitate development of addiction to tobacco products through modulation of tobacco products' reinforcing or aversive actions. Palatable flavors (eg, fruit) may increase appeal through primary reinforcing properties. Menthol's cooling and anesthetic effects may increase appeal by counteracting nicotine's aversive effects. Genetics provide a method for modeling individual differences in sensitivity to nicotine's effects. A common polymorphism, rs16969968, encoded in the α5 nicotinic acetylcholine receptor subunit gene (CHRNA5), is a well-recognized marker for smoking risk and reduces sensitivity to nicotine aversiveness. METHODS: This pilot study tested how flavors impacted e-cigarette appeal and self-administration. In a single testing day, cigarette smokers (N = 32; 94% menthol-smokers) self-administered e-cigarettes containing e-liquids differing in nicotine level (0 mg/mL, 24 mg/mL) and flavor (unflavored, menthol, fruit-flavored) within directed and ad libitum e-cigarette paradigms. Subjective drug effects, number of puffs, rs16969968 genotype, plasma nicotine, and menthol glucuronide levels were collected. RESULTS: Menthol partially ameliorated nicotine aversiveness; fruit did not. In nicotine's absence, fruit flavor increased self-reported preference and ad libitum use relative to menthol-containing or unflavored e-liquids. Individuals with high-smoking-risk rs16969968 genotype (N = 7) reported greater craving alleviation following directed administration of nicotine-containing e-liquids, showed a trend rating nicotine-containing e-liquids as less harsh, and self-administered more nicotine during ad libitum compared to individuals with low-smoking-risk genotype (N = 23). CONCLUSIONS: While menthol countered aversiveness of nicotine-containing e-liquids, fruit flavor increased appeal of nicotine-free e-liquids. These preliminary findings suggest menthol and fruit flavor increase e-cigarettes' appeal through distinct mechanisms. IMPLICATIONS: This study provides a detailed characterization of the effects of flavors (unflavored, menthol, fruit), nicotine (0 mg/mL, 24 mg/mL) and their interactions on the subjective drug effects and ad libitum self-administration of e-cigarettes. Genetics were used to assess these effects in higher-smoking-risk (diminished sensitivity to nicotine aversiveness) and lower-risk groups. Findings could inform impact of regulation of flavors or nicotine in e-cigarettes, and their impacts on vulnerable sub-populations.