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.

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.

Exogenous progesterone for smoking cessation in men and women: a pilot double-blind, placebo-controlled randomized clinical trial.

BACKGROUND AND AIMS: In some clinical studies men and women have been found to differ in their ability to quit smoking, perhaps as a result of progesterone. The primary aim of this study was to provide a preliminary test of whether progesterone (PRO), compared with placebo (PBO), was more effective for smoking cessation in men and women. DESIGN: Pilot double-blind, placebo-controlled randomized clinical trial. SETTING: Minneapolis/St Paul metro area, Minnesota, USA. PARTICIPANTS: A total of 216 participants were randomized, including 113 men (18-60 years; PRO = 56, PBO = 57) and 103 women (18-50 years, pre-menopausal with self-reported regular menstrual cycles; PRO = 51, PBO = 52). INTERVENTION: Participants were randomized (1 : 1 within sex group) to either PRO (200 mg twice daily) or PBO. Participants were assigned a quit date approximately 7 days after starting medication (luteal phase for women) and were followed for 12 weeks to assess relapse. MEASUREMENTS: The primary outcome was self-reported 7-day point prevalence abstinence (PPA) at week 4. Secondary outcomes included 7-day PPA at weeks 8 and 12, prolonged abstinence, continuous abstinence, urine cotinine < 50 ng/ml, expired carbon monoxide ≤ 5 parts per million (p.p.m.) and days to relapse. FINDINGS: There was a significant difference in 7-day PPA at week 4 among women [PRO: 18 (35.3%) versus PBO: 9 (17.3%), odds ratio (OR) = 2.61, 95% confidence interval (CI) = 1.04, 6.54, P = 0.041], but not among men [PRO: 13 (23.2%) versus PBO: 12 (21.1%), 1.13 (0.47, 2.76), P = 0.782]. There was some evidence that PRO delayed relapse in women (days to relapse; PRO: 20.5 ± 29.6 versus PBO: 14.3 ± 26.8, P = 0.03) but not in men (PRO: 13.4 ± 25.9 versus PBO: 13.3 ± 23.8, P = 0.69). CONCLUSIONS: Oral micronized progesterone may aid smoking cessation in women.

Longitudinal stability in cigarette smokers of urinary eicosanoid biomarkers of oxidative damage and inflammation.

The urinary metabolites (Z)-7-[1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3S)-3-hydroxyoct-1-enyl]cyclopentyl]hept-5-enoic acid (8-iso-PGF2α), an F2-isoprostane and biomarker of oxidative damage, and "prostaglandin E2 metabolite" (PGE-M), a biomarker of inflammation, are elevated in cigarette smokers. However, there is little information in the literature on the longitudinal stability of these widely used biomarkers. In a large clinical trial involving 10 institutional sites, smokers were given, free of charge over a period of 20 weeks, Spectrum NRC600/601 research cigarettes containing 15.5 mg nicotine/g tobacco. All participants were instructed to smoke these cigarettes for the duration of the study. At weeks 4, 8, 12, 16, and 20, first morning urine voids were collected and analyzed for 8-iso-PGF2α and PGE-M using validated liquid chromatography-electrospray ionization-tandem mass spectrometry methods. The mean level of 8-iso-PGF2α at Week 4 was 1.34 ± 1.08 (S.D.) pmol/mg creatinine (N = 226) while that of PGE-M was 73.7 ± 113 (S.D.) pmol/mg creatinine (N = 232). The corresponding levels at Week 20 were 1.35 ± 0.93 (S.D.) pmol/mg creatinine (N = 209) for 8-iso-PGF2α and 74.2 ± 142 (S.D.) pmol/mg creatinine (N = 210) for PGE-M. There was variation in these values in the intervening weeks. The intra-class correlation coefficients (ICC) were 0.51 (95% CI, 0.45, 0.57) and 0.36 (0.30, 0.43), for 8-iso-PGF2α and PGE-M, respectively, indicating fair longitudinal stability for 8-iso-PGF2α and poorer longitudinal stability for PGE-M in cigarette smokers. Males had higher ICC values than females for both 8-iso-PGF2α and PGE-M. These results indicate that, in addition to cigarette smoking, endogenous processes of oxidative damage and inflammation influence the levels of these biomarkers over time among current smokers.

Longitudinal stability in cigarette smokers of urinary biomarkers of exposure to the toxicants acrylonitrile and acrolein.

The urinary metabolites cyanoethyl mercapturic acid (CEMA) and 3-hydroxypropyl mercapturic acid (3-HPMA) have been widely used as biomarkers of exposure to acrylonitrile and acrolein, respectively, but there are no published data on their consistency over time in the urine of cigarette smokers. We provided, free of charge over a 20 week period, Spectrum NRC600/601 research cigarettes to cigarette smokers in the control arm of a randomized clinical trial of the reduced nicotine cigarette. Urine samples were collected at weeks 4, 8, 12, 16, and 20 and analyzed for CEMA and 3-HPMA, and total nicotine equivalents (TNE) using validated methods. Creatinine-corrected intra-class correlation coefficients for CEMA, 3-HPMA, and TNE were 0.67, 0.46, and 0.68, respectively, indicating good longitudinal consistency for CEMA, while that of 3-HPMA was fair. A strong correlation between CEMA and TNE values was observed. These data support the use of CEMA as a reliable biomarker of tobacco smoke exposure. This is the first report of the longitudinal stability of the biomarkers of acrylonitrile and acrolein exposure in smokers. The data indicate that CEMA, the biomarker of acrylonitrile exposure, is consistent over time in cigarette smokers, supporting its use. While 3-HPMA levels were less stable over time, this biomarker is nevertheless a useful monitor of human acrolein exposure because of its specificity to this toxicant.

Stressful life events are associated with perinatal cigarette smoking.

Perinatal smoking, including smoking during pregnancy and postpartum smoking relapse, is a persistent public health problem. While childhood trauma has been linked to perinatal smoking, less is known about the association with more proximal stressful life events (SLEs). The objective of this study was to examine the association between SLEs that occurred during the year prior to childbirth with perinatal smoking. Using the Pregnancy Risk Assessment Monitoring System 2009-2011, perinatal smoking was assessed at three time points: (1) three months prior to pregnancy, (2) the last three months of pregnancy, and (3) two to six months postpartum. Survey respondents endorsed up to 13 SLEs (i.e., death of someone close). SLEs were analyzed individually, as well as using a cumulative score (range 0-13). Weighted analyses included unadjusted and adjusted logistic regression. Among those who smoked prior to pregnancy (n = 15,316), 48% (n = 7308) reported quitting smoking during pregnancy. Of those, 44% (n = 3126) reported postpartum smoking relapse. A total of 11 SLEs were associated with smoking during pregnancy and 2 SLEs were associated with postpartum smoking relapse. The odds of continued smoking during pregnancy was 12% higher for each SLE endorsed (adjusted odds ratio [aOR] = 1.12, 95% confidence interval [CI]: 1.09, 1.15) and this association was attenuated in relation to the odds of postpartum smoking relapse (aOR = 1.03, 95% CI: 0.99, 1.08). SLEs are associated with perinatal smoking. Additional research is needed to elucidate the mechanisms of action and to develop interventions specific to the needs of women who experience SLEs.

Association of exercise with smoking-related symptomatology, smoking behavior and impulsivity in men and women.

INTRODUCTION: Despite extensive efforts to develop effective smoking cessation interventions, 70-85% of American cigarette smokers who quit relapse within one year. Exercise has shown promise as an intervention; however, many results have been equivocal. This study explored how exercise is associated with smoking-related symptomatology, smoking behavior and impulsivity in male and female smokers. METHODS: Participants were recruited throughout the United States using the on-line crowdsourcing platform, Amazon's Mechanical Turk. They completed a survey with self-report measures assessing exercise, smoking-related symptomatology, smoking behavior and impulsivity. Differences between men and women were tested using t- and chi-square tests. Regression analyses tested for associations between exercise and smoking-related symptomatology, smoking behavior and impulsivity. RESULTS: Participants (N = 604) were, on average, 32 (SD = 6.2) years old, mostly Caucasian, with at least some college education and approximately half were women. Women exercised slightly less than men and had more negative affect, craving, physical symptoms and withdrawal. Women smoked more cigarettes per day, had greater nicotine dependency and more years of smoking. Positive affect was positively associated with exercise for both men and women; however, this association was significantly stronger in women. Negative affect and withdrawal were inversely associated with exercise for women only. Impulsivity was inversely associated with exercise for both men and women. CONCLUSION: Exercise was significantly associated with several smoking-related symptomatology, smoking behavior and impulsivity variables for both men and women, suggesting that exercise may be a useful intervention for smoking cessation. Future prospective research should determine how exercise directly impacts smoking cessation.

Effect of Immediate vs Gradual Reduction in Nicotine Content of Cigarettes on Biomarkers of Smoke Exposure: A Randomized Clinical Trial.

Importance: The optimal temporal approach for reducing nicotine to minimally or nonaddictive levels in all cigarettes sold in the United States has not been determined. Objectives: To determine the effects of immediate vs gradual reduction in nicotine content to very low levels and as compared with usual nicotine level cigarettes on biomarkers of toxicant exposure. Design, Setting, and Participants: A double-blind, randomized, parallel-design study with 2 weeks of baseline smoking and 20 weeks of intervention was conducted at 10 US sites. A volunteer sample of daily smokers with no intention to quit within 30 days was recruited between July 2014 and September 2016, with the last follow-up completed in March 2017. Interventions: (1) Immediate reduction to 0.4 mg of nicotine per gram of tobacco cigarettes; (2) gradual reduction from 15.5 mg to 0.4 mg of nicotine per gram of tobacco cigarettes with 5 monthly dose changes; or (3) maintenance on 15.5 mg of nicotine per gram of tobacco cigarettes. Main Outcomes and Measures: Between-group differences in 3 co-primary biomarkers of smoke toxicant exposure: breath carbon monoxide (CO), urine 3-hydroxypropylmercapturic acid (3-HPMA, metabolite of acrolein), and urine phenanthrene tetraol (PheT, indicator of polycyclic aromatic hydrocarbons) calculated as area under the concentration-time curve over the 20 weeks of intervention. Results: Among 1250 randomized participants (mean age, 45 years; 549 women [44%]; 958 [77%] completed the trial), significantly lower levels of exposure were observed in the immediate vs gradual reduction group for CO (mean difference, -4.06 parts per million [ppm] [95% CI, -4.89 to -3.23]; P < .0055), 3-HPMA (ratio of geometric means, 0.83 [95% CI, 0.77 to 0.88]; P < .0055), and PheT (ratio of geometric means, 0.88 [95% CI, 0.83 to 0.93]; P < .0055). Significantly lower levels of exposure were observed in the immediate reduction vs control group for CO (mean difference, -3.38 [95% CI, -4.40 to -2.36]; P < .0055), 3-HPMA (ratio of geometric means, 0.81 [95% CI, 0.75 to 0.88]; P < .0055), and PheT (ratio of geometric means, 0.86 [95% CI, 0.81 to 0.92]; P < .0055). No significant differences were observed between the gradual reduction vs control groups for CO (mean difference, 0.68 [95% CI, -0.31 to 1.67]; P = .18), 3-HPMA (ratio of geometric means, 0.98 [95% CI, 0.91 to 1.06]; P = .64), and PheT (ratio of geometric means, 0.98 [95% CI, 0.92 to 1.04]; P = .52). Conclusions and Relevance: Among smokers, immediate reduction of nicotine in cigarettes led to significantly greater decreases in biomarkers of smoke exposure across time compared with gradual reduction or a control group, with no significant differences between gradual reduction and control. Trial Registration: clinicaltrials.gov Identifier: NCT02139930.

Hormonal contraceptive use in smokers: Prevalence of use and associations with smoking motives.

INTRODUCTION: While endogenous sex hormones influence smoking-related outcomes, little is known about the role of hormonal contraceptives (HCs). This is despite dated estimates suggesting that HC use is prevalent among female smokers. Therefore, we sought to update estimates of the prevalence of HC use among female smokers and explore the association of HC use with various smoking motives (SMs). METHODS: This online cross-sectional survey recruited female smokers between the ages of 18-35. Survey questions assessed smoking behavior, SMs, use of HCs, and menstrual cycle regularity. RESULTS: Participants (n=734) were, on average (±standard deviation), 20.7±2.7 years old and smoked 7.3±6.7 cigarettes/day. The majority of females reported a history of HC use (85%) and half reported current use (48%). Cyclical HC users (n=227) scored significantly lower on three SMs compared to naturally-cycling women in the follicular phase (n=62) and significantly higher on 15 SMs compared to naturally-cycling women in the luteal phase (n=29). Women on cyclical HCs differed from women on long-acting HCs (n=128) on two SMs. Further, the naturally-cycling women in the follicular phase scoring significantly higher on 15 SMs compared to those in the luteal phase. DISCUSSION: These observations indicate that HC use remains prevalent in female smokers and may influence SMs. Additional research should replicate these observations and explore the implications on smoking cessation outcomes.

Differences in mood and cortisol by menstrual phase during acute smoking abstinence: A within-subject comparison.

There is evidence that smoking-cessation success differs by menstrual phase and sex hormone levels; however, the biological mechanisms underlying these differences are not clear. One possibility is that variation in cortisol throughout the menstrual cycle and early smoking abstinence may be partly responsible. The goal of this secondary-data analysis was to conduct a within-subject examination of the effects of menstrual phase and smoking abstinence on salivary cortisol and mood. Data are from a controlled crossover trial, in which participants completed 2 testing weeks during their follicular and luteal phases. During each testing week, they smoked ad libitum during the first 2 days and then abstained from smoking during the next 4 days. Salivary cortisol and self-reported mood were collected 5 times on the day before abstinence (D0) and the first (D1) and third (D3) days of abstinence. Participants (n = 125) were, on average (mean ± SE), 29.4 ± 0.6 years old and smoked 12.6 ± 0.5 cigarettes/day. Whereas salivary cortisol varied significantly by time of day (p < .0001) and smoking abstinence (D0 to D1: ß = -0.06 ± 0.02 log[ng/ml], p = .0074 and D3: ß = -0.05 ± 0.02 log[ng/ml], p = .0117). no significant differences by menstrual phase were observed. Craving increased from D0 to D1 during the follicular phase but decreased in the luteal phase (+0.31 vs. -0.15, ß = 0.46 ± 0.19, p = .0162). This work builds on prior observations in demonstrating a decrease in cortisol in acute smoking abstinence and menstrual phase differences in craving. The results provide further evidence that cortisol levels do not vary by menstrual phase in the first few days of abstinence. (PsycINFO Database Record

Reduced nicotine content cigarettes and use of alternative nicotine products: exploratory trial.

AIMS: To compare the use of alternative nicotine products, smoking behavior and tobacco biomarker exposure in smokers unwilling to quit who were assigned randomly to normal nicotine content (NNC) cigarettes or very low nicotine content (VLNC) cigarettes. DESIGN: Randomized, parallel-arm 8-week study with assignment to VLNC (VLNC 1, n = 53) or NNC (NNC, n = 27) with access to non-cigarette combusted and non-combusted tobacco/nicotine products or to VLNC with access to only non-combusted products (VLNC2, n = 56). SETTING: Clinics in Minnesota, USA. PARTICIPANTS: Smokers uninterested in quitting smoking with a mean [± standard deviation (SD)] age of 44 (± 14) years and smoking 16 (± seven) cigarettes/day; 51% female, 72% white. MEASUREMENTS: During the experimental period, the measures taken included: rate of alternative products used, amount of and abstinence from combusted tobacco used and tobacco exposure biomarkers. FINDINGS: There were higher rates of non-combusted alternative tobacco/nicotine product use in both VLNC conditions versus the NNC condition [rate ratio (RR) = 2.18, 95% confidence interval (CI) = 1.94, 2.46 and RR = 1.64, 95% CI = 1.46, 1.85, respectively] and in VLNC1 versus VLNC2 condition (RR = 1.33, 95% CI = 1.23, 1.44), accompanied by reduced biomarkers of exposure primarily in VLNC2 condition compared to NNC condition (Ps < 0.05). Fewer combusted products were smoked at almost all visits (Ps ≤ 0.02) and there were higher rates of abstinence for both VLNC conditions compared with the NNC condition (VLNC1 versus NNC: RR = 9.96, 95% CI = 5.01, 19.81; VLNC2 versus NNC: RR = 11.23, 95% CI = 5.74, 21.97). CONCLUSION: The offer of, and instructions to use, reduced nicotine content cigarettes during an 8-week period led to greater use of alternative tobacco/nicotine products compared with continued use of normal nicotine cigarettes and also reductions in smoking rates.

Progesterone and Postpartum Smoking Relapse: A Pilot Double-Blind Placebo-Controlled Randomized Trial.

INTRODUCTION: Pregnancy is a strong motivator to quit smoking, yet postpartum relapse rates are high. Growing evidence suggests a role of sex hormones in drug abuse behavior and given the precipitous drop in sex hormones at delivery, they may play a role in postpartum relapse. This pilot study evaluates the feasibility and potential role of exogenous progesterone in postpartum smoking relapse. METHODS: This 12-week double-blind placebo-controlled randomized pilot trial randomized 46 abstinent postpartum women to active progesterone (PRO; 200mg twice a day) versus placebo (PBO) for 4 weeks. Participants were followed for relapse for 12 weeks. Main study outcomes include abstinence (point prevalence), feasibility (compliance per number of clinic visits attended, pill counts and Electronic Data Capture [EDC] completed) and self-reported acceptability. Safety was also measured by depressive symptom scores, adverse events, and breastfeeding. RESULTS: Overall retention rate was 87% at week 12. At week 4, abstinence rates were 75% in the PRO group and 68.2% in the PBO group (p = .75). Medication adherence was 68% and clinic visit attendance was 80%, with no differences by randomization. Depressive symptom scores, adverse events, and breastfeeding did not vary by randomization. CONCLUSIONS: Although the study was not powered to evaluate abstinence rates, we did observe a higher prevalence of abstinence at week 4 in the PRO group. Further, exogenous progesterone was well tolerated and did not adversely affect depressive symptoms or breastfeeding. Thus, the results of this pilot study indicate further investigation into progesterone as a postpartum relapse prevention strategy is warranted. IMPLICATIONS: This innovative pilot trial determined the feasibility of delivering exogenous progesterone as a potential prevention of postpartum smoking relapse. We observed high retention and moderate adherence rates, as well as high acceptability among participants. Further, though not statistically significant, more women in the treatment group remained abstinent from smoking during follow-up. This project adds to the growing body of literature on the role of sex hormones in smoking relapse and also provides support for a fully powered clinical trial.

Ovarian hormones, menstrual cycle phase, and smoking: a review with recommendations for future studies.

Cigarette smoking continues to be the leading cause of preventable morbidity and mortality. Similar to other addictive substances, the prevalence of cigarette smoking is greater among men than women, yet women are less successful at quitting smoking. Preclinical and clinical research suggests that ovarian hormones (i.e., estradiol and progesterone), which fluctuate over the course of the menstrual cycle, may contribute to these sex differences. Specifically, research suggests that progesterone may protect against cigarette smoking and nicotine addiction; whereas estradiol may underlie enhanced vulnerability. In this review, we discuss new research on ovarian hormone and menstrual cycle phase effects on smoking-related responses and behavior in women, including studies examining neural responses to smoking cues, hormonal influences on medication-assisted smoking cessation, and acute smoking abstinence. We highlight innovative studies with strong research methodology and provide suggestions for future research that may allow evidence-based knowledge for immediate translation to the clinic to guide novel, hormonally-informed treatment strategies. Thus, rigorous scientific study holds the potential to reduce relapse rates, thus improving the health and saving the lives of the many thousands of women who unfortunately do not respond to current treatments.

Determining menstrual phase in human biobehavioral research: A review with recommendations.

Given the volume and importance of research focusing on menstrual phase, a review of the strategies being used to identify menstrual phase and recommendations that will promote methodological uniformity in the field is needed. We conducted a literature review via Ovid Medline and PsycINFO. Our goal was to review methods used to identify menstrual phase and subphases in biobehavioral research studies with women who had physiologically natural menstrual cycles. Therefore, we excluded articles that focused on any of the following: use of exogenous hormones, the postpartum period, menstrual-related problems (e.g., polycystic ovarian syndrome, endometriosis), and infertility/anovulation. We also excluded articles on either younger (<18 years old) or older (>45 years old) study samples. We initially identified a total of 1,809 articles. After our exclusionary criteria were applied, 146 articles remained, within which our review identified 6 different methods used to identify menstrual phase and subphases. The most common method used was self-report of onset of menses (145/146 articles) followed by urine luteinizing hormone testing (50/146 articles) and measurement of hormones (estradiol and/or progesterone) in blood samples (49/146 articles). Overall, we found a lack of consistency in the methodology used to determine menstrual phase and subphases. We provide several options to improve accuracy of phase identification, as well as to minimize costs and burden. Adoption of these recommendations will decrease misclassification within individual studies, facilitate cross-study comparisons, and enhance the reproducibility of results.

Perceived stress and smoking-related behaviors and symptomatology in male and female smokers.

INTRODUCTION: Stress has been found to be a significant risk factor for cigarette smoking. Stress affects males and females differently, as does the use of smoking for stress reduction. Few studies have examined gender differences with the interrelation of perceived stress and smoking behaviors and nicotine related symptomatology. Our study investigates this association, as well as the influence of sociodemographic variables. METHODS: This is a retrospective analysis of 62 smokers (41 males, 21 females) enrolled in a smoking cessation study. At the screening visit sociodemographic information, smoking behaviors and survey measures were completed. These included the Perceived Stress Scale (PSS), Minnesota Nicotine Withdrawal Scale (MNWS), and others. Analyses were conducted using multiple linear regression models. RESULTS: PSS score was found to have a negative association with number of cigarettes smoked in males (slope -0.29±0.08; p=0.0009) and females (slope -0.20±0.18; p=0.26) with no difference in effect between genders (p=0.64). Linear regression of MNWS on PSS revealed a positive association for both males (slope 0.41±0.068; p<0.0001) and females (slope 0.73±0.14; p<0.0001). There was a significant difference in effect between genders (p=0.04). CONCLUSIONS: A strong positive association was observed between perceived stress and nicotine withdrawal symptomatology in smokers of both sexes, with a larger effect seen in women. These findings emphasize the importance of stress reduction in smokers, which may lead to fewer withdrawal symptoms and more effective smoking cessation.

Associations between adrenocortical activity and nicotine response in female smokers by menstrual phase.

Previous research suggests that menstrual phase may influence smoking-related symptomatology. The present study analyzes the relationship between menstrual phase and salivary cortisol with subjective responses to nicotine among female smokers during ad libitum smoking. We hypothesize higher cortisol levels would be associated with increased positive and decreased negative subjective responses to nicotine. We also expected that these associations would vary by menstrual phase. Females aged 18-40 who smoke at least five cigarettes/day, reported regular menstrual cycles and did not use exogenous hormones or psychotropic medications were enrolled into a controlled cross-over trial. Participants completed identical data collection procedures during follicular (F) and luteal (L) phases; including self-collected salivary cortisol samples and completion of a nicotine response lab session involving administration of nicotine nasal spray and monitoring of subjective response to nicotine via the Subjective State Scale and Visual Analog Scale. Participants (n = 116) were 29.1 ± 6.9 years old and smoked an average of 12.3 ± 5.5 cigarettes daily. During F phase, higher morning cortisol was associated with decreased negative affect (r = -0.21, p = 0.03), withdrawal (r = -0.30, p < 0.01) and increased relaxation (r = 0.24, p = 0.02) after administration of nicotine nasal spray. Conversely, during L phase, higher morning cortisol was associated with a decrease in head rush (r = -0.26, p = 0.01) and urge to smoke (r = -0.21, p = 0.04) after administration of nicotine nasal spray. Similar associations between greater diurnal cortisol variation and response to nicotine were seen. These observations indicate that cortisol may have a phase-specific association with some subjective responses to nicotine in female smokers. Additional research should explore how these relationships may influence smoking cessation efforts.

Systematic and meta-analytic review of research examining the impact of menstrual cycle phase and ovarian hormones on smoking and cessation.

INTRODUCTION: To determine the effect of ovarian hormones on smoking, we conducted a systematic review of menstrual cycle effects on smoking (i.e., ad lib smoking, smoking topography, and subjective effects) and cessation-related behaviors (i.e., cessation, withdrawal, tonic craving, and cue-induced craving). METHODS: Thirty-six papers were identified on MEDLINE that included a menstrual-related search term (e.g., menstrual cycle, ovarian hormones), a smoking-related search term (e.g., smoking, nicotine), and met all inclusion criteria. Thirty-two studies examined menstrual phase, 1 study measured hormone levels, and 3 studies administered progesterone. RESULTS: Sufficient data were available to conduct meta-analyses for only 2 of the 7 variables: withdrawal and tonic craving. Women reported greater withdrawal during the luteal phase than during the follicular phase, and there was a nonsignificant trend for greater tonic craving in the luteal phase. Progesterone administration was associated with decreased positive and increased negative subjective effects of nicotine. Studies of menstrual phase effects on the other outcome variables were either small in number or yielded mixed outcomes. CONCLUSIONS: The impact of menstrual cycle phase on smoking behavior and cessation is complicated, and insufficient research is available upon which to conduct meta-analyses on most smoking outcomes. Future progress will require collecting ovarian hormone levels to more precisely quantify the impact of dynamic changes in hormone levels through the cycle on smoking behavior. Clarifying the relationship between hormones and smoking-particularly related to quitting, relapse, and medication response-could determine the best type and timing of interventions to improve quit rates for women.

Allopregnanolone association with psychophysiological and cognitive functions during acute smoking abstinence in premenopausal women.

Nicotine response may predict susceptibility to smoking relapse. Allopregnanolone, a neuroactive steroid metabolized from progesterone, has been shown to be associated with several symptoms of nicotine response. We sought to explore the association between allopregnanolone and response to nicotine during acute smoking abstinence in premenopausal women. Participants completed 2 nicotine-response laboratory sessions, 1 in their follicular (low allopregnanolone) and 1 in their luteal (high allopregnanolone) menstrual phase, on the fourth day of biochemically confirmed smoking abstinence. During the laboratory sessions, participants self-administered a nicotine nasal spray and completed a timed series of cardiovascular, cognitive, and subjective assessments of response to nicotine. The relationships of allopregnanolone with baseline values and change scores of outcome measures were assessed using covariance pattern modeling. Study participants (N = 77) had a mean age of 29.9 (SD = 6.8) years and smoked an average of 12.2 (SD = 4.9) cigarettes per day. Allopregnanolone concentration measured before nicotine administration was positively associated with systolic (ß = 0.85, p = .04) and diastolic blood pressure (ß = 1.19, p < .001) and self-report of physical symptoms (ß = 0.58, p < .001), dizziness (ß = 0.88, p < .01), jitteriness (ß = 0.90, p = .04), and pleasantness (ß = 2.05, p = .04). Allopregnanolone also had significant positive associations with change in cognition following nicotine nasal spray administration, specifically discriminability as a measure of attention (ß = 1.15, p = .05) and response bias as a measure of impulsivity (ß = 0.13, p = .02). These data suggest that allopregnanolone may be related to cardiovascular and subjective physical state during acute smoking abstinence, as well as cognitive response to nicotine.

Medical school curriculum characteristics associated with intentions and frequency of tobacco dependence treatment among 3rd year U.S. medical students.

OBJECTIVE: Physicians play a critical role in addressing tobacco dependence, yet report limited training. Tobacco dependence treatment curricula for medical students could improve performance in this area. This study identified student and medical school tobacco treatment curricula characteristics associated with intentions and use of the 5As for tobacco treatment among 3rd year U.S. medical students. METHODS: Third year medical students (N=1065, 49.3% male) from 10 U.S. medical schools completed a survey in 2009-2010 assessing student characteristics, including demographics, tobacco treatment knowledge, and self-efficacy. Tobacco curricula characteristics assessed included amount and type of classroom instruction, frequency of tobacco treatment observation, instruction, and perception of preceptors as role models. RESULTS: Greater tobacco treatment knowledge, self-efficacy, and curriculum-specific variables were associated with 5A intentions, while younger age, tobacco treatment self-efficacy, intentions, and each curriculum-specific variable were associated with greater 5A behaviors. When controlling for important student variables, greater frequency of receiving 5A instruction (OR=1.07; 95%CI 1.01-1.12) and perception of preceptors as excellent role models in tobacco treatment (OR=1.35; 95%CI 1.04-1.75) were significant curriculum predictors of 5A intentions. Greater 5A instruction (B=.06 (.03); p<.05) and observation of tobacco treatment (B=.35 (.02); p<.001) were significant curriculum predictors of greater 5A behaviors. CONCLUSIONS: Greater exposure to tobacco treatment teaching during medical school is associated with both greater intentions to use and practice tobacco 5As. Clerkship preceptors, or those physicians who provide training to medical students, may be particularly influential when they personally model and instruct students in tobacco dependence treatment.