Sharon S. Allen

Reduced nicotine content cigarettes: effects on toxicant exposure, dependence and cessation

AIMS To examine the effects of reduced nicotine cigarettes on smoking behavior, toxicant exposure, dependence and abstinence. DESIGN Randomized, parallel arm, semi-blinded study. Setting University of Minnesota Tobacco Use Research Center. INTERVENTIONS Six weeks of: (i) 0.05 mg nicotine yield cigarettes; (ii) 0.3 mg nicotine yield cigarettes; or (iii) 4 mg nicotine lozenge; 6 weeks of follow-up. Measurements Compensatory smoking behavior, biomarkers of exposure, tobacco dependence, tobacco withdrawal and abstinence rate. FINDINGS Unlike the 0.3 mg cigarettes, 0.05 mg cigarettes were not associated with compensatory smoking behaviors. Furthermore, the 0.05 mg cigarettes and nicotine lozenge were associated with reduced carcinogen exposure, nicotine dependence and product withdrawal scores. The 0.05 mg cigarette was associated with greater relief of withdrawal from usual brand cigarettes than the nicotine lozenge. The 0.05 mg cigarette led to a significantly higher rate of cessation than the 0.3 mg cigarette and a similar rate as nicotine lozenge. CONCLUSION The 0.05 mg nicotine yield cigarettes may be a tobacco product that can facilitate cessation; however, future research is clearly needed to support these preliminary findings.

Characterization of tobacco withdrawal symptoms: transdermal nicotine reduces hunger and weight gain

Abstract The accurate assessment of both tobacco withdrawal and the impact of the nicotine patch on withdrawal may be compromised by attrition of subjects, or by subjects smoking during withdrawal. To reduce these occurrences, 211 participants were provided with intensive cessation counseling while trying to quit smoking with either nicotine (21 mg) or placebo transdermal patches. Subject attrition was low, with 80.5% of participants continuing through the 5-week study period. Abstinence rates were also high over this period (75% and 61% in active and placebo groups, respectively). In this multisite, double-blind trial, withdrawal severity was assessed using a nine-item daily self-report questionnaire, and abstinence was confirmed via CO monitoring. Abrupt smoking cessation increased multiple tobacco withdrawal symptoms/signs including craving for cigarettes, irritability, anxiety, appetite, sleep disruption, difficulty concentrating, restlessness, depression, and impatience. Treatment with transdermal nicotine reduced craving for cigarettes, anxiety, irritability, and appetite, as well as weight gain (1.85 versus 2.88 kg mean gain over 4 weeks in active and placebo groups, respectively).

Combination Varenicline and Bupropion SR for Tobacco Dependence Treatment in Cigarette Smokers: A Randomized Trial

IMPORTANCE Combining pharmacotherapies for tobacco-dependence treatment may increase smoking abstinence. OBJECTIVE To determine efficacy and safety of varenicline and bupropion sustained-release (SR; combination therapy) compared with varenicline (monotherapy) in cigarette smokers. DESIGN, SETTING, AND PARTICIPANTS Randomized, blinded, placebo-controlled multicenter clinical trial with a 12-week treatment period and follow-up through week 52 conducted between October 2009 and April 2013 at 3 midwestern clinical research sites. Five hundred six adult (≥18 years) cigarette smokers were randomly assigned and 315 (62%) completed the study. INTERVENTIONS Twelve weeks of varenicline and bupropion SR or varenicline and placebo. MAIN OUTCOMES AND MEASURES Primary outcome was abstinence rates at week 12, defined as prolonged (no smoking from 2 weeks after the target quit date) abstinence and 7-day point-prevalence (no smoking past 7 days) abstinence. Secondary outcomes were prolonged and point-prevalence smoking abstinence rates at weeks 26 and 52. Outcomes were biochemically confirmed. RESULTS At 12 weeks, 53.0% of the combination therapy group achieved prolonged smoking abstinence and 56.2% achieved 7-day point-prevalence smoking abstinence compared with 43.2% and 48.6% in varenicline monotherapy (odds ratio [OR], 1.49; 95% CI, 1.05-2.12; P = .03 and OR, 1.36; 95% CI, 0.95-1.93; P = .09, respectively). At 26 weeks, 36.6% of the combination therapy group achieved prolonged and 38.2% achieved 7-day point-prevalence smoking abstinence compared with 27.6% and 31.9% in varenicline monotherapy (OR, 1.52; 95% CI, 1.04-2.22; P = .03 and OR, 1.32; 95% CI, 0.91-1.91; P = .14, respectively). At 52 weeks, 30.9% of the combination therapy group achieved prolonged and 36.6% achieved 7-day point-prevalence smoking abstinence compared with 24.5% and 29.2% in varenicline monotherapy (OR, 1.39; 95% CI, 0.93-2.07; P = .11 and OR, 1.40; 95% CI, 0.96-2.05; P = .08, respectively). Participants receiving combination therapy reported more anxiety (7.2% vs 3.1%; P = .04) and depressive symptoms (3.6% vs 0.8%; P = .03). CONCLUSIONS AND RELEVANCE Among cigarette smokers, combined use of varenicline and bupropion, compared with varenicline alone, increased prolonged abstinence but not 7-day point prevalence at 12 and 26 weeks. Neither outcome was significantly different at 52 weeks. Further research is required to determine the role of combination therapy in smoking cessation. TRIAL REGISTRATION clinicaltrials.gov Identifier: http://clinicaltrials.gov/show/NCT00935818.

Menstrual phase effects on smoking relapse.

AIMS To examine if menstrual phase affects relapse in women attempting to quit smoking. DESIGN An intent-to-treat randomized smoking cessation trial where women were assigned to quit smoking in either the follicular (F) or luteal (L) menstrual phase and were followed for up to 26 weeks. They were assessed for relapse by days to relapse and relapse phase to determine if those who begin a quit attempt during the F phase were more successful than those who begin during the L phase. SETTING Tobacco Use Research Center, University of Minnesota, Minneapolis, Minnesota. PARTICIPANTS A total of 202 women. MEASUREMENTS Latency to relapse from continuous and prolonged abstinence, point prevalence, phase of relapse, first slip within the first 3 and 5 days post-quit date, subject completion rates and symptomatology (i.e. withdrawal and craving). FINDINGS The mean days to relapse from continuous abstinence and relapse from prolonged abstinence for the F group were 13.9 and 20.6 days, respectively, and 21.5 and 39.2 days, respectively, for the L group. Using point prevalence analysis at 14 days, 84% of the F group had relapsed compared with 65% of the L group [chi(2)=10.024, P=0.002; odds ratio (OR) = 2.871, 95% confidence interval (CI), 1.474-5.590]. At 30 days, 86% of the F group relapsed, compared with 66% of the L group (chi(2)=11.076, P=0.001; OR=3.178, 95% CI, 1.594-6.334). CONCLUSION Women attempting to quit smoking in the F phase had less favorable outcomes than those attempting to quit in the L phase. This could relate to ovarian hormones, which may play a role in smoking cessation for women.

Effects of transdermal nicotine on craving, withdrawal and premenstrual symptomatology in short-term smoking abstinence during different phases of the menstrual cycle

Gender differences in nicotine response with regard to nicotine sensitivity and withdrawal symptomatology have been reported, with the suggestion that ovarian hormones play a role. Few studies, however, have directly assessed hormonal influences on nicotine response. This study focused on the effects of a transdermal nicotine patch in women during acute smoking abstinence when tested in different phases of their menstrual cycle. Thirty women were randomized to order of menstrual cycle phase (late luteal or follicular) and patch condition (active or placebo). Two 7-day outpatient-testing periods were conducted with 2 days of ad lib baseline smoking and 5 days of smoking abstinence. Dependent measures included scores from the Minnesota Nicotine Withdrawal Scale, Questionnaire on Smoking Urges, and Premenstrual Assessment Form, as well as weight. The severity of both premenstrual symptomatology and nicotine withdrawal symptoms was greater in the late luteal phase. Correlation coefficients confirmed overlap between premenstrual and withdrawal symptomatology, especially for the affect subscale. A significant patch effect was observed, showing diminished craving and premenstrual affect on pain subscale scores for women on active patch. Results showed that nicotine craving and premenstrual pain and water retention symptoms were diminished in women on transdermal patch, and that this effect was greatest in the late luteal phase. In addition, the greatest weight gain was demonstrated for participants in the late luteal phase, placebo condition. In summary, during short-term smoking abstinence in women, transdermal nicotine appears to have a more pronounced effect in the late luteal phase than in the follicular phase in reducing craving and certain premenstrual symptoms.

Withdrawal and pre-menstrual symptomatology during the menstrual cycle in short-term smoking abstinence: Effects of menstrual cycle on smoking abstinence

This study employs a rigorous inpatient laboratory setting to test the hypothesis that withdrawal symptomatology in short-term smoking cessation in women is increased in the late luteal phase when pre-menstrual symptomatology is the highest. Twenty-one female smokers with clinical, anatomical, and hormonal verification of their menstrual cycle phase were randomized to either a smoking abstinence group (n = 16) or a continued smoking group (n = 5). Participants were admitted to the General Clinical Research Center during alternate phases of their cycle for two 7-day admissions with a 1-month interim period when they resumed smoking. Dependent measures, i.e., Minnesota Nicotine Withdrawal Scale scores, Questionnaire on Smoking Urges scores and Pre-menstrual Assessment Form scores were collected during 2 days of baseline and 5 days of smoking deprivation. Smoking behavior was documented by self-report, breath CO levels and saliva cotinine measurements. Withdrawal symptomatology was not affected by menstrual cycle phase during short-term cessation in spite of increased pre-menstrual changes seen in the late luteal phase. In addition, no phase effect on smoking behavior was detected and cigarette consumption remained stable across the cycle in both groups. These results suggest that for some smoking cessation studies, complex strategies to control for menstrual cycle effects may not be necessary. However, Smoking Urges scores did suggest increased desire to smoke and desire to relieve negative affect in the late luteal phase when women have higher pre-menstrual symptomatology. This suggests women may have greater difficulty quitting smoking in late luteal phase, and it seems prudent to recommend that women quit during the follicular phase of their cycle.

Symptomatology and energy intake during the menstrual cycle in smoking women

This study extends our understanding of smoking behavior, withdrawal, and premenstrual symptomatology in smoking women, as well as energy intake as a function of cycle phase. Thirty-two women age 18 to 40 years, smoking ad lib, were followed for an average of two menstrual cycles with hormonal verification. Withdrawal and premenstrual symptomatology as well as energy intake were reported during the follicular (F), luteal (L), and late luteal (LL) cycle phases. Both premenstrual symptomatology and withdrawal symptomatology were higher during the LL phase. Subject response on measurements of craving, irritability, restlessness, increased appetite, and depressed mood tended to be higher in the LL phase. Energy intake did not vary as a function of cycle phase. Participants perceived that they smoked more and had increased appetite in the LL phase but related measurements did not confirm this. Premenstrual and withdrawal symptoms are highly correlated and one needs to be cautious in interpreting cycle effects on withdrawal. Overall symptomatology seems to be lower during the F phase, indicating that this may be a more opportune time for women to quit smoking.

Treatment of spit tobacco users with transdermal nicotine system and mint snuff.

The purpose of this study was to examine the effects of nicotine patch and mint snuff (a nonnicotine product) on craving, withdrawal symptoms, and treatment outcome. This study involved a 2 x 2 factorial design, with Active Nicotine Versus Placebo Patch as one of the factors and Mint Snuff Versus No Mint Snuff as the other factor. Spit tobacco users (N = 402, n = 100-101 in each condition) were randomly assigned to 1 of the 4 treatment conditions for a period of 10 weeks. Treatment outcome was measured up to 62 weeks. The results showed that the nicotine patch was effective in increasing short-term abstinence over the placebo patch and in reducing craving and withdrawal signs and symptoms from spit tobacco. Although mint snuff was not effective in enhancing treatment outcome, it reduced craving and withdrawal symptoms. No interaction effects were observed. At this time, the use of the nicotine patch and mint snuff should be primarily considered for the reduction of craving and withdrawal symptoms.

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.

Reduced Nicotine Content Cigarettes and Nicotine Patch

Background: Reduced nicotine content (RNC) cigarettes have led to smoking fewer cigarettes, withdrawal relief, and facilitation of cessation. The aim of this study is to examine the effects RNC cigarettes with and without nicotine patch and patch alone on smoking behavior, toxicant exposure, withdrawal discomfort, and as an exploratory analysis, on long-term abstinence. Methods: This study involved a randomized, parallel arm design and six weeks of: (i) 0.05–0.09 mg nicotine yield cigarettes (N = 79); (ii) 21 mg nicotine patch (N = 80), or (iii) 0.05–0.09 nicotine yield cigarettes with 21 mg nicotine patch (N = 76); all groups received six weeks of additional behavioral treatment with follow-ups up to six months. Results: Combination approach led to lower rates of smoking assigned cigarettes and hence lower carbon monoxide levels than RNC cigarettes alone. In addition, the combination approach was associated with less withdrawal severity when switching from usual brand to assigned product, and less smoking of usual brand cigarettes during treatment, but not after treatment compared with the other approaches. Conclusion: Combining very low nicotine content cigarettes with nicotine patch may improve the acute effects resulting from switching to either of these products alone. Impact: These findings may have implications for smoking cessation treatment or a policy measure to reduce nicotine content in cigarettes. Cancer Epidemiol Biomarkers Prev; 22(6); 1015–24. ©2013 AACR.