Louise Hertsgaard

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.

After 8 Months have Passed: Long-term Recall of Events by 1- to 2-year-old Children

The time course of development of the ability to remember specific past events is a matter of considerable curiosity and debate. Traditional and contemporary theories alike suggest that infants are unable to consolidate and stabilise event knowledge for recall after a long time period. In two experiments, we used elicited imitation, a nonverbal analogue to cued verbal recall, to test 21-, 24-, and 29-month-old childrens recall of events they had experienced eight months previously. At the time of original exposure some of the events were novel, whereas others depicted activities familiar to 1-year-olds. At the eight-month retention test, performance of the experienced children was compared to that of matched naive controls. In both experiments the experienced children produced a greater number of the novel events; there were no differences between the groups on the familiar events. The results demonstrate long-term recall of specific past events by 1- to 2-year-olds. They thus challenge the suggestion that the absence of memories from infancy and early childhood is attributable to the inability to form memories that are enduring and accessible over time.

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.

Effect of Oral Snus and Medicinal Nicotine in Smokers on Toxicant Exposure and Withdrawal Symptoms: A Feasibility Study

Background: Smokeless, spitless tobacco products are being introduced and marketed as cigarette substitutes. Data are needed regarding how smokers interested in cessation would use these products, the levels of resultant toxicant exposure, and the feasibility of using these products as aids for tobacco cessation. Methods: Smokers were randomized to receive Camel Snus (n = 51), Taboka (n = 52), or medicinal nicotine (n = 27) and required to quit smoking for 4 weeks. Measures of toxicant exposure and symptoms of craving and withdrawal were assessed prior to and during product use. Results: Concentrations of exhaled carbon monoxide, urinary cotinine, urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronides (total NNAL), and urinary N′-nitrosonornicotine and its glucuronide (total NNN) were significantly (P values <0.05) lower at the end of treatment in each group except for total NNN in those receiving Camel Snus (P = 0.066). A significant group × time effect was observed for total NNAL concentrations (P = 0.002) with the decrease greatest in the medicinal nicotine group and smallest decrease in the Camel Snus group. No significant differences between groups were found in craving and withdrawal symptoms. Conclusions: Enrolling smokers into a cessation study utilizing newer smokeless tobacco products is feasible. Camel Snus and Taboka use was not found to be superior to medicinal nicotine in reducing withdrawal symptoms but decreases in NNAL were smaller in users of Camel Snus. Impact: This study demonstrates the feasibility of conducting a smoking cessation study utilizing these newer tobacco products. An appropriately powered study is needed to assess smoking cessation rates using these newer products compared with established, safer products such as medicinal nicotine. Cancer Epidemiol Biomarkers Prev; 20(1); 91–100. ©2011 AACR.

Sex differences in response to reduced nicotine content cigarettes

BACKGROUND When switching from usual brand cigarettes, very low nicotine content (VLNC) cigarettes lead to a reduction in the number of cigarettes smoked, toxicant exposure, withdrawal symptoms and dependence. One area that has been relatively unexplored is what factors might moderate the effects of VLNC cigarettes. This exploratory analysis focuses on sex differences in responses to VLNC cigarettes and nicotine replacement therapy. METHODS An exploratory secondary analysis of a randomized trial of 235 participants (58% female, mean age 47 years) comparing a) 0.05-0.09 mg nicotine yield cigarettes; b) 21 mg nicotine patch and 3) 0.05-0.09 nicotine yield cigarettes with 21 mg nicotine patch was conducted. We focused on sex differences in product use, and impact of products on withdrawal response from usual brand cigarettes and abstinence by randomized group. RESULTS The combination of VLNC cigarettes and nicotine patch was more effective in reducing use of VLNC cigarettes and withdrawal symptoms among males than females, whereas females were equally responsive to VLNC cigarettes with and without the nicotine patch. Females were more likely to quit smoking than males when assigned to either of the conditions that incorporated the VLNC cigarettes; however, males were more likely to quit smoking in the nicotine patch alone condition than females. CONCLUSION Sex of the smoker may be an important determinant for effects of VLNC cigarettes and nicotine patch. Future large randomized trials to confirm these results are needed.

Greater reductions in nicotine exposure while smoking very low nicotine content cigarettes predict smoking cessation

Objective Reducing the nicotine content of cigarettes is a potential regulatory strategy that may enable cessation. The present study investigated the effect of nicotine exposure while smoking very low nicotine content (VLNC) cigarettes on cessation outcomes. The roles of possible sources of nicotine were also explored, including the VLNC cigarette and co-use of cigarettes with normal nicotine content. Methods A secondary data analysis of two analogous randomised trials of treatment seeking, adult daily smokers (n=112) who were instructed to smoke VLNC cigarettes for 6 weeks and then make a quit attempt. Controlling for baseline demographic and smoking features, the association between reductions in nicotine exposure during the 6-week trial, assessed by urinary total cotinine and biomarker-confirmed smoking abstinence 1 month later, was tested. Subsequent analyses controlled for the effects of the frequency of VLNC and normal nicotine content cigarette use and the nicotine yield of the VLNC cigarette (0.05 vs 0.09 mg). Results Greater reductions in nicotine exposure while smoking VLNC cigarettes predicted abstinence independent of individual differences in baseline smoking, cotinine, dependence, gender and study. Nicotine reduction was largest among individuals who were assigned to smoke a VLNC cigarette with lower nicotine yield and who smoked fewer normal nicotine content and VLNC cigarettes. Conclusions In the context of nicotine regulations and corresponding research, factors that undermine nicotine reduction must be addressed, including the availability and use of cigarettes with normal nicotine content and not sufficiently reducing the nicotine yield of cigarettes. Maximising nicotine reduction may facilitate smoking cessation. Trial registration numbers NCT 101050569 and NCT 00777569.

Exposure to a tobacco-specific lung carcinogen in adolescent versus adult smokers

Background: Previous studies with adult smokers have shown an association between number of cigarettes smoked per day (CPD) and levels of biomarkers of exposure to the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). This study compared carcinogen and nicotine exposure in adolescent and adult smokers across categories of CPD. Method: Baseline smoking history and biomarker data were merged from six studies to make two samples: one of adolescent smokers and one of adult smokers. Metabolites of NNK, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), and its glucuronides (NNAL-Gluc) and total cotinine were quantified in urine. Results: CPD was stratified into categories of 5 to 10, 11 to 15, and 16 to 20 CPD. Adolescents tended to have lower mean levels of NNAL plus NNAL-Glucs (total NNAL) compared with adults, although differences were not significant overall. Adolescent mean levels of NNAL/CPD were significantly lower than adult levels only in the 11 to 15 CPD category (P = 0.045). However, a significant positive relationship was observed for total NNAL/CPD by age. No significant differences between adolescents and adults were found in mean levels of total cotinine or cotinine/CPD. A subsample of urines from adolescents and adults were analyzed for NNAL-Glucs and NNAL. Adolescents and adults did not significantly differ in the ratio of NNAL-Glucs to NNAL. Conclusions: Adolescent uptake of NNK and nicotine tends to be lower although not statistically different from adults. The lack of significant differences may be due to the wide variation in exposure in adolescents. Some adolescent smokers are exposed to lung carcinogens at levels similar to those of adults. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3337–43)