Neurophysin I is an analytically robust surrogate biomarker for oxytocin.

Oxytocin is a pleiotropic neuropeptide that plays roles in biological processes ranging from birth, lactation, and social bonding to immune function, cardiovascular repair, and regulation of appetite. Although measurements of endogenous oxytocin concentrations have been performed for more than 50 years, the ability to measure oxytocin accurately poses notable challenges. One potential solution for overcoming these challenges involves measurement of oxytocin's carrier molecule - neurophysin I (NP-1) - as a surrogate biomarker. NP-1 is secreted in equimolar concentrations with oxytocin but has a longer half-life, circulates in higher concentrations, and can be measured using a sandwich immunoassay. We report experiments that 1) analytically validate a commercially available NP-1 sandwich immunoassay for use with human plasma and urine samples, 2) confirm the specificity of this assay, based on detection of NP-1 in plasma from wild-type but not oxytocin knockout mice, 3) demonstrate that NP-1 concentrations are markedly elevated in late pregnancy, consistent with studies showing substantial increases in plasma oxytocin throughout gestation, and 4) establish strong correlation between NP-1 and plasma oxytocin concentrations when oxytocin is measured in extracted (but not non-extracted) plasma. The NP-1 assay used in this study has strong analytical properties, does not require time-intensive extraction protocols, and the assay itself can be completed in < 2 h (compared to 16-24 h for a competitive oxytocin immunoassay). Our findings suggest that much like copeptin has become a useful surrogate biomarker in studies of vasopressin, measurements of NP-1 have similar potential to advance oxytocin research.

Menstrual Phase Identification Questionnaire (MPIQ): Development and validation of a cross-sectional survey to identify follicular and luteal phases.

Evidence continues to accumulate on the influence of the menstrual phase on several biobehavioral outcomes (e.g., substance misuse). Expansion of this knowledge is limited due to the burdensomeness of accurate menstrual phase assessment. Thus, we sought to create and validate a questionnaire that can be used as a stand-alone item within low-resource settings and numerous study designs (e.g., cross-sectional) to accurately identify both the follicular phase (FP) and the luteal phase (LP). Participants completed the self-administered four-item Menstrual Phase Identification Questionnaire (MPIQ) in two recently completed clinical trials. We assessed the accuracy of two MPIQ scoring criteria (less restrictive and more restrictive), as compared to self-report of onset of menses alone, with progesterone confirmation via dried blood spots. Participants (n = 59) were, on average, 33.7 (standard deviation [SD]: ± 4.3) years old and provided a total of 83 responses. Assessing FP and LP using the self-reported onset of menses alone classified 65.1% of the responses with an overall phase identification accuracy of 60.2%. While the more restrictive MPIQ scoring classified 100% of the responses, it yielded a similar accuracy (68.4%). In contrast, the less restrictive MPIQ scoring classified 100% of the responses and also significantly improved phase identification accuracy to 92.1% (p < .001). The MPIQ, as a stand-alone item, allows all cross-sectional responses to be classified with a high level of accuracy. This low-burden questionnaire can be used alone to identify FP and LP in studies that may be otherwise limited by study design, finances, and/or participant burden. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

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.

Feasibility of remotely assessing hormonal contraceptive use and smoking-related symptomatology: Evidence from a preliminary prospective cohort study.

Background: Half of women who smoke cigarettes also use hormonal contraceptives (HCs). Prior research suggests that variations in ovarian hormones may undermine smoking cessation efforts made by premenopausal women. However, clinical findings of these hormonal effects are inconsistent, potentially due to methodological limitations. The goal of this preliminary prospective cohort study is to determine the feasibility and acceptability of a fully remote protocol to longitudinally examine changes in smoking-related behavior and symptoms in relation to hormone use in women of reproductive age. Methods: Eligible participants (n = 60) were biologically female, current age 18-35 years old, smokes ≥ 5 cigarettes/day, and classified into three groups: naturally-cycling (NC; n = 17), using a monophasic oral contraceptive (OC; n = 21), or using depot medroxyprogesterone acetate (DMPA; n = 22). Participants completed daily surveys and weekly dried blood spot collections. Results: Overall, 92% (55/60) participants completed the study with 90% of daily surveys completed and 87% of participants collecting at least 5 of the 6 dried blood spot samples. Participants were "somewhat" (13%) or "extremely" (87%) likely to participate in the study again. Preliminary observations also suggested differences in self-reported cigarettes/day and premenstrual pain over time by study group. Conclusions: This study outlines a fully remote protocol that may be used to clarify the relationships between hormonal contraceptive use and smoking-related outcomes over time. Preliminary results add to existing evidence that HC use may reduce relapse risk for premenopausal women.

A Scoping Review and Meta-analysis of the Use of Remote Biochemical Verification Methods of Smoking Status in Tobacco Research.

INTRODUCTION: Increasing digital delivery of smoking cessation interventions has resulted in the need to employ novel strategies for remote biochemical verification. AIMS AND METHODS: This scoping review and meta-analysis aimed to investigate best practices for remote biochemical verification of smoking status. The scientific literature was searched for studies that reported remotely obtained (not in-person) biochemical confirmation of smoking status (ie, combustible tobacco). A meta-analysis of proportions was conducted to investigate key outcomes, which included rates of returned biological samples and the ratio of biochemically verified to self-reported abstinence rates. RESULTS: A total of 82 studies were included. The most common samples were expired air (46%) and saliva (40% of studies), the most common biomarkers were carbon monoxide (48%) and cotinine (44%), and the most common verification methods were video confirmation (37%) and mail-in samples for lab analysis (26%). Mean sample return rates determined by random-effects meta-analysis were 70% for smoking cessation intervention studies without contingency management (CM), 77% for CM studies, and 65% for other studies (eg, feasibility and secondary analyses). Among smoking cessation intervention studies without CM, self-reported abstinence rates were 21%, biochemically verified abstinence rates were 10%, and 47% of individuals who self-reported abstinence were also biochemically confirmed as abstinent. CONCLUSIONS: This scoping review suggests that improvements in sample return rates in remote biochemical verification studies of smoking status are needed. Recommendations for reporting standards are provided that may enhance confidence in the validity of reported abstinence rates in remote studies. IMPLICATIONS: This scoping review and meta-analysis included studies using remote biochemical verification to determine smoking status. Challenges exist regarding implementation and ensuring high sample return rates. Higher self-reported compared to biochemically verified abstinence rates suggest the possibility that participants in remote studies may be misreporting abstinence or not returning samples for other reasons (eg, participant burden, inconvenience). Remote biochemical confirmation of self-reported smoking abstinence should be included in smoking cessation studies whenever feasible. However, findings should be considered in the context of challenges to sample return rates. Better reporting guidelines for future studies in this area are needed.

COVID-19 vaccination and changes in the menstrual cycle among vaccinated persons.

OBJECTIVE: To describe the characteristics of people who experience changes to their menstrual cycle after COVID-19 vaccination. DESIGN: Longitudinal study. PATIENT(S): We recruited a volunteer sample with and without a history of SARS-CoV-2 infection who enrolled in the Arizona COVID-19 Cohort (CoVHORT) study and participated in a reproductive sub-cohort who were pre-menopausal, not pregnant, and had received a COVID-19 vaccine in 2021 (n = 545). EXPOSURE(S): Demographic and reproductive characteristics were collected via self-reports. MAIN OUTCOME MEASURE(S): Information on self-reported changes in the menstrual cycle after COVID-19 vaccination was collected from May 2021 to December 2021. We looked at demographic and reproductive characteristics as predictors of menstrual cycle change. RESULT(S): The majority of our vaccinated sample received the Pfizer-BioNTech vaccine (58%), and were 26-35 years old (51%), non-Hispanic (84%), and White (88%). Approximately 25% of vaccinated participants reported a change in their menstrual cycle after vaccination; the majority reported changes after their second dose (56%) as compared with their first (18%) and third (14%) doses. The most commonly reported changes were irregular menstruation (43%), increased premenstrual symptoms (34%), increased menstrual pain or cramps (30%), and abnormally heavy or prolonged bleeding (31%). High self-reported perceived stress levels compared with low perceived stress (OR, 2.22; 95% CI 1.12-4.37) and greater body mass index (OR, 1.04; 95% CI 1.00-1.07) were associated with greater odds of experiencing the menstrual cycle changes after the vaccination. Participants having a history of SARS-CoV-2 infection were less likely to report changes in their menstrual cycle after vaccination compared with the participants with no history of SARS-CoV-2 infection (OR, 0.58; 95% CI 0.32-1.04). CONCLUSION(S): Among vaccinated participants, approximately 25% of them reported predominantly temporary changes in the menstrual cycle, however, we are unable to determine whether these changes are due to normal cycle variability. The COVID-19 vaccines are safe and effective for everyone, including pregnant people and people trying to conceive; hence, these findings should not discourage vaccination.

Risk Factors Associated with Perinatal Relapse to Opioid Use Disorder.

The recent opioid epidemic in the United States has led to rising prevalence of maternal opioid use disorder (OUD). First-line treatment for maternal OUD involves the use of opioid agonist pharmacotherapy, such as methadone or buprenorphine, in addition to cognitive behavioral therapy and counseling. The management of maternal OUD can become overwhelming for both patients and clinicians, especially during the early postpartum period. Therefore, it is imperative that clinicians understand the impact of additional stressors in caring for these patients. Maternal chronic opioid dependence can lead to neonatal opioid withdrawal syndrome after birth. This multisystem condition affects neonatal neurobehavioral functioning and has significant human and socioeconomic consequences. First-line treatment for this syndrome involves intensive nonpharmacologic comforting measures, with maternal presence and involvement being central to ensuring the success of such measures. In this review, we describe the factors that place pregnant and postpartum women with OUD at risk of returning to illicit opioid use. We evaluate these multifaceted personal, social, societal, and systemic factors to inform the development of future clinical care initiatives.

Border Crosser Deaths in the Arizona-Mexico Desert: Data on Remains 2001-2020.

INTRODUCTION: Increased enforcement at U.S.-Mexico border-crossing sites may lead migrants to cross in remote desert areas. METHODS: We reviewed data on migrants' bodies found along the Arizona-Mexico border from 2001 to 2020. We analyzed causes of death, condition of bodies, age, and sex, and the relationship of deaths to enforcement (arrests) by U.S. Border Patrol. RESULTS: From 2001-2020, 3,378 border-crosser bodies were found in the desert. As enforcement increased, bodies were found in more remote areas and later stages of decomposition. Skeletonized bodies increased from 19% in 2001-2004 to 49.1% in 2017-2020. When the cause of death could be identified, exposure to the elements was the most common cause. Abrupt increases in arrests and deaths over the immediately preceding period of 2013-2016 occurred in 2017-2020. CONCLUSIONS: Undetermined cause of death and increased skeletonization became more common, indicating bodies are discovered later. Enforcement does not decrease individuals crossing the border; rather, individuals cross in more remote areas.

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.

Impact of Acute and Chronic Cannabis Use on Stress Response Regulation: Challenging the Belief That Cannabis Is an Effective Method for Coping.

Although research has only recently started to examine the impact of cannabis use on stress response, there is some evidence that indicates acute and chronic impacts of cannabis on these processes. In this paper, we review processes involved in regulating the stress response and we review the influence of acute and chronic exposure to cannabis on patterns and regulation of the stress response. We also highlight the role of stress as a risk factor for initiation and maintenance of cannabis use. In this context, we examine moderating variables, including sex and life adversity. In light of recent observations indicating increasing prevalence of cannabis use during pregnancy, we provide additional focus on cannabis use in this vulnerable population, including how acute and chronic stress may predispose some individuals to use cannabis during pregnancy. While this line of research is in its infancy, we review available articles that focus on the perinatal period and that examined the association between cannabis use and various life stressors, including partner violence, job loss, and lack of housing. We also review psychiatric co-morbidities (e.g., post-traumatic stress disorder, anxiety). A better understanding of the way stress and cannabis use relate within the general population, as well as within certain subgroups that may be at a greater risk of using and/or at greater risk for adverse outcomes of use, may lead to the development of novel prevention and intervention approaches.

Impact of nicotine reduction in cigarettes on smoking behavior and exposure: Are there differences by race/ethnicity, educational attainment, or gender?

BACKGROUND: Lowering nicotine in cigarettes may reduce smoking prevalences; however, it is not known whether an immediate or gradual reduction in nicotine is the optimal approach for all population groups. OBJECTIVES: We examined whether the optimal approach to nicotine reduction depended on the education, gender, or race of people who smoke and whether the optimal approach differentially benefited people who smoke based on their education, gender, or race. METHODS: Secondary analysis was conducted on a randomized clinical trial (N = 1250) comparing (1) immediate reduction from 15.5 to 0.4 mg of nicotine per gram of tobacco(mg/g);(2) gradual reduction to 0.4 mg/g;(3) control group with normal nicotine cigarettes(15.5 mg/g). Outcomes included cigarettes per day(CPD), carbon monoxide(CO), total nicotine equivalents(TNE), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronides(NNAL), phenanthrene tetraol(PheT), N-Acetyl-S-(2-cyanoethyl)-l-cysteine(CEMA). Data were analyzed as area under the curve(AUC). RESULTS: Results were presented by education (High school[HS] or less n = 505, more than HS n = 745), gender (males n = 701, females n = 549), and race (Black participants n = 373,White participants n = 758). Regardless of education, gender, and race, CPD, CO, TNE, NNAL, PheT, and CEMA were lower in immediate versus gradual nicotine reduction. Comparing immediate versus the control, outcomes were lower for all subgroups; however, the magnitude of the effect for TNE varied by race. Specifically, geometric mean of the AUC of TNE in immediate versus gradual was 49 % lower in Black participants and 61 % lower in White participants (p-value = 0.047). CONCLUSIONS: Immediately reducing nicotine in cigarettes has the potential to benefit people who smoke across lower and higher educational attainment, male and female gender, and Black and White race.

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.

Feasibility and acceptability of testing a menstrual-cycle timed smoking cessation intervention for women of reproductive age (Project Phase): Protocol of a pilot randomized controlled trial.

BACKGROUND: Compared to men, women have unique barriers to smoking cessation and are less likely to utilize quitline services. While current clinical recommendations have called for sex/gender-specific smoking cessation protocols, quitlines have not been expanded protocols to address the unique needs of women. Menstrual cycles (and/or ovarian hormones) influence quit outcomes in women. This paper presents the study design and protocol for a randomized control trial (Project Phase) designed to test the feasibility and acceptability of utilizing menstrual cycle timing to improve quit outcomes in women of reproductive age. METHODS/DESIGN: Participants include treatment-seeking women (n = 116), between the ages of 18-40 with regular and naturally-occurring menstrual cycles. Eligible participants are randomized to either the mid-Follicular Phase (FP) or Standard Care (SC-control) group. Counseling includes six weekly telephone sessions with four weeks of nicotine replacement therapy. The timing and frequency of sessions is identical to both conditions, with the exception of the quit day (week 3 of counseling). In addition to providing education on menstrual cycle and quitting, quit day for FP participants is set within 6-8 days post onset of menses; the SC group quit day is set for Week 3 of counseling regardless of their menstrual cycle phase. Dried blood spots will be used to bioverify menstrual cycle phase and smoking status. DISCUSSION: If feasible and acceptable, our behavioral counseling intervention that times the quit day to the mid-follicular phase of the menstrual may increase quit outcomes among women of reproductive age and has potential for dissemination across quitlines nationally.

Cannabis use and stressful life events during the perinatal period: cross-sectional results from Pregnancy Risk Assessment Monitoring System (PRAMS) data, 2016.

AIMS: We aimed to determine the association between stressful life events (SLEs) in the year prior to childbirth with (1) pre-pregnancy cannabis use, (2) cessation of cannabis use during pregnancy and (3) postpartum relapse to cannabis use. DESIGN: We used data from the Pregnancy Risk Assessment Monitoring System (PRAMS) 2016, a cross-sectional, population-based surveillance system. SETTING: Mailed and telephone surveys conducted in five states-Alaska, Colorado, Maine, Michigan and Washington-in the United States. PARTICIPANTS: Women (n = 6061) who delivered a live infant within the last 6 months and had data on cannabis use. MEASUREMENTS: Self-reported data included SLEs (yes/no response for 14 individual events in the 12 months prior to childbirth) and cannabis use [yes/no prior to pregnancy, during pregnancy, and at the time of the survey (approximately 2-6 months postpartum)]. The associations between SLEs and cannabis use (primary outcomes) were examined in logistic regression models adjusted for maternal demographics (e.g. age, race, education), geography (i.e. state of residence) and cigarette smoking. FINDINGS: Pre-pregnancy, 16.4% (997/6061) of respondents endorsed using cannabis, with 36.4% (363/997) continuing cannabis use during pregnancy. Among the 63.6% (634/997) who did not report use during pregnancy, 23.2% (147/634) relapsed to cannabis use during the postpartum. Nine of the 14 possible SLEs were associated with increased odds of pre-pregnancy cannabis use [e.g. husband/partner or mother went to jail, adjusted odds ratio (aOR) = 2.16, 95% confidence interval (CI) = 1.30-3.62] and four were associated with increased odds of continued cannabis use during pregnancy (e.g. husband/partner lost job, aOR = 2.19, 95% CI = 1.21-3.96). The odds of postpartum relapse to cannabis were significantly associated with two SLEs (husband/partner said they did not want pregnancy, aOR = 2.86, CI = 1.10-7.72; husband/partner or mother went to jail, aOR = 0.37, 95% CI = 0.13-1.00). CONCLUSIONS: Stressful life events during the year prior to childbirth appear to be linked to greater odds of women's cannabis use during the perinatal period, especially during pre-pregnancy.

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.

Mammography Screening Practices in Average-Risk Women Aged 40-49 Years in Primary Care: A Comparison of Physician and Nonphysician Providers in Minnesota.

Background: Breast cancer screening practices and the influence of clinical guidelines or recommendations are well documented for physicians, but little is known about the screening practices of nonphysician providers (physician assistants and advanced practice registered nurses). The seven breast cancer screening guidelines or recommendations on the use of mammography have the most variation for screening average-risk women 40-49 years of age. Therefore, to better understand the practices of nonphysicians, this study will compare the practices of physicians with nonphysician providers for women 40-49 years of age. Materials and Methods: Minnesota physicians and nonphysicians were e-mailed an anonymous cross-sectional survey, which asked primary care providers about their mammography screening practices for average-risk women 40-44 and 45-49 years of age and to rate the influence of seven breast cancer screening recommendations on the use of mammography in their practice. Comparisons across providers' demographic and professional characteristics were conducted using chi-squared and Fisher's exact tests, as appropriate, and multivariate logistic regression analyses. Results: Of the respondents who practiced primary care (193 physicians, 50 physician assistants, and 197 advanced practice registered nurses), 66.7% reported recommending mammography for women at ages 40-44 and 77.2% recommended mammography for women at ages 45-49. Nonphysician providers were more likely to recommend screening in both these age groups (p < 0.05). Having a self-identified interest in women's health was associated with more mammography screening in both age groups. The American Cancer Society guideline was endorsed as influential by the most respondents. Conclusions: Breast cancer screening practices vary between physicians and nonphysician providers for women 40-49 years of age at average risk. Targeted interventions may help reduce practice variation and ensure high-value care.

Effect of exogenous progesterone administration on cigarette smoking-related symptomology in oral contraceptive users who smoke.

Cigarette smoking-related symptomatology (e.g., craving; SRS) is linked to relapse after a quit attempt. SRS varies by menstrual phase, possibly due to variations in sex hormones (e.g., progesterone), though much of the research to-date has relied on observations from the menstrual cycle acting as a proxy for hormone levels. The goal of this study was to examine the effect of exogenous progesterone on SRS during ad libitum smoking and following overnight abstinence. Oral contraceptive users who smoked completed two 9-day crossover testing periods (7 days of ad libitum smoking and 2 days following overnight abstinence) while taking double-blind active/placebo exogenous progesterone. Participants completed questionnaires to measure SRS. The effect of exogenous progesterone and endogenous hormones (progesterone, estradiol, and progesterone-to-estradiol [P/E2] ratio) on SRS was assessed with paired t-tests and linear mixed effect models. Participants (n = 53) were, on average, 24 years old and smoked 11 cigarettes per day. During ad libitum smoking, a doubling of the P/E2 ratio was associated with 0.09 points lower anticipated relief from negative affect (95% confidence interval [CI]: 0.03-0.15 points lower; p = 0.008) and 0.11 points lower psychological reward (95% CI: 0.03-0.18 points lower; p = 0.006). After correction for multiple testing, these associations were not statistically significant: anticipated relief from negative effect (p = 0.10) and psychological reward (p = 0.09). No other significant associations were observed. Although substantial previous literature indicates that progesterone influences SRS, exogenous progesterone administration did not alter SRS here. Additional research is needed to elucidate alternative mechanisms involved in menstrual phase effects on SRS.

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

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

Subjective response to intranasal nicotine administration in oral contraceptive users and naturally-cycling women.

INTRODUCTION: Approximately half of premenopausal women who smoke cigarettes also use hormonal contraceptives, with most using oral contraceptives (OCs). While research on the effects of endogenous hormones on smoking-related outcomes continues to expand, little is known about the influence of OCs on similar outcomes. We sought to explore differences in the subjective response to nicotine by OC use after stratifying by testing condition (e.g., smoking status). METHODS: Participants were regular (≥5 cigarettes/day) smokers, classified into OC and naturally cycling (NC) groups. All participants completed four total lab sessions by smoking status (ad libitum smoking, acute smoking abstinence) and anticipated progesterone level (low progesterone week (LPW), high progesterone week (HPW)). Each lab session included self-administration of intranasal nicotine (Time 0 min), assessment of subjective response via the Subjective State Scale (-30 and + 5 min). RESULTS: Compared to the NC group (n = 28), the OC group (n = 14) was younger (26.2 ±â€¯1.1 versus 24.2 ±â€¯1.1; p < 0.001) and had a lower Fagerström Test for Nicotine Dependence score (3.4 ±â€¯0.5 versus 2.6 ±â€¯0.5; p = 0.011). Progesterone-to-estradiol ratios varied significantly by group at three of the four time points (p < 0.05). During ad libitum smoking, the OC group had significantly lower craving after nicotine administration than the NC group (1.93 ±â€¯0.33 versus 2.89 ±â€¯0.23; p = 0.024). No other significant differences in subjective response were identified. CONCLUSIONS: Despite significantly different hormone levels, group differences in subjective response to nicotine were relatively few. Additional research is needed to elucidate the mechanisms involved in these observations, as well as explore how they may influence cessation in women.