***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background : The U.S. FDA has the authority to reduce cigarette nicotine content if found to benefit public health . Reduced nicotine content ( RNC ) cigarette use does not appear to increase harm exposure , but studies have not rigorously assessed smoking behavior or used a comprehensive panel of biomarkers . This study examined the effects of progressively decreasing RNC cigarettes on smoking behaviors , biomarkers of exposure , and subjective ratings . Methods : One hundred and fifty-eight daily , non – treatment-seeking smokers participated in a 35-day r and omized , unblinded , parallel study . After a 5-day baseline period , participants were r and omly assigned to an experimental group ( n = 80 ) that smoked progressively decreasing RNC cigarettes during three 10-day periods , or control group ( n = 78 ) that smoked their own br and throughout the study . Results : Daily cigarette consumption significantly increased for the intermediate RNCs ( P 's < 0.001 ) but approached baseline rate for the lowest RNC ( P = 0.686 ) ; in contrast , puffing behavior significantly decreased at intermediate levels and increased for the lowest RNC ( P 's < 0.001 ) . Cotinine and NNAL significantly decreased by RNC period ( P 's ≤ 0.001–0.02 ) , whereas CO boost initially increased ( P 's = 0.001–0.005 ) . 1-HOP did not change by period ( P = 0.109 ) . Conclusions : Smoking behaviors changed by RNC period via CPD and puffing behavior . Biomarkers of exposure generally decreased with nicotine content . Impact : Findings suggest that RNC use does not ubiquitously reduce smoking behaviors or biomarkers , yet the lowest RNC level tested may reduce harm exposure . This emphasizes the importance of using multiple behavioral and biologic measures to address the impact of RNC cigarette smoking . Cancer Epidemiol Biomarkers Prev ; 25(7 ) ; 1125–33 . © 2016 AACR Background : The U.S. FDA has the authority to limit the nicotine content of cigarettes ; however , there are concerns that reduced nicotine cigarettes will be smoked more intensely and , therefore , will increase exposure to toxic chemicals in smoke . This study examined changes in consumer behavior and exposure in response to cigarettes with substantially reduced nicotine content . Methods : Seventy-two adult smokers completed an unblinded trial of reduced nicotine cigarettes .  Participants completed a 7-day baseline period during which they smoked their usual cigarette br and , followed by consecutive 7-day periods smoking cigarettes with progressively lower nicotine levels ( 0.6 , 0.3 , and 0.05 mg emission Quest cigarettes ) . Nicotine dependence and withdrawal , smoking behavior , and biomarkers of exposure were assessed for each 7-day period . Results : Significant reductions in nicotine intake were observed between usual br and smoking ( ∼1.2 mg nicotine ) and the 0.3 and 0.05 mg nicotine emission cigarettes , but not the 0.6 mg cigarette . The findings provide little evidence of compensatory smoking of Quest cigarettes , with no increases in exhaled breath carbon monoxide levels , smoking intensity , or levels of 1-hydroxypyrene across study periods . No significant differences were observed for smoking urges or measures of nicotine dependence . Conclusions : The study adds to the evidence that cigarettes with markedly reduced nicotine content are not associated with increased smoking intensity or exposure to smoke toxicants . Impact : The findings add to the evidence base on reduced nicotine content cigarettes and have the potential to inform FDA policy on nicotine levels . Cancer Epidemiol Biomarkers Prev ; 23(10 ) ; 2032–40 . © 2014 AACR INTRODUCTION The Family Smoking Prevention and Tobacco Control Act authorized the FDA to reduce the nicotine content in cigarettes . Research is needed to guide proposed regulations , including evaluation of consequences to public health . This study evaluated how a reduced nicotine product st and ard might be moderated by and impact cannabis use . METHODS Secondary analysis of a controlled clinical trial examining the effects of nicotine content in cigarettes in adult daily smokers . Linear regression assessed whether baseline cannabis use moderated behavioral , subjective , or physiological effects of smoking very low nicotine content ( VLNC ) versus normal nicotine content ( NNC ) cigarettes . Repeated measures analysis of associations between nicotine condition and prevalence and frequency of cannabis use was completed using generalized estimating equations ( GEE ) . RESULTS Cannabis use did not moderate most of the following effects of VLNC cigarettes : Among cannabis users and non-users , smokers r and omized to VLNC cigarettes reported lower nicotine dependence , cigarettes per day , biomarkers of nicotine exposure , and craving compared to smokers r and omized to NNC cigarettes . Non-cannabis using smokers r and omized to VLNC cigarettes also reported lower smoking dependence motives and had lower tobacco-specific nitrosamine exposure and total puff volume versus smokers r and omized to NNC cigarettes . For cannabis users , smokers r and omized to VLNC cigarettes reported decreased positive affect . VLNC cigarette use did not impact the prevalence or frequency of cannabis use . DISCUSSION Findings provide evidence that nicotine reduction in cigarettes could have beneficial effects on cigarette smoking regardless of cannabis use . Results suggest that transitioning to VLNC cigarettes is unlikely to alter current rates of cannabis use AIMS To assess the impact of a reduction in the nicotine content of cigarettes on estimated consumption of reduced nicotine cigarettes and usual br and cigarettes at a variety of hypothetical prices . DESIGN Double-blind study with participants assigned r and omly to receive cigarettes for 6 weeks that were either usual br and or an investigational cigarette with one of five nicotine contents . SETTING Ten sites across the United States . PARTICIPANTS A total of 839 eligible adult smokers r and omized from 2013 to 2014 . INTERVENTION AND COMPARATOR Participants received their usual br and or an investigational cigarette with one of five nicotine contents : 15.8 ( primary control ) , 5.2 , 2.4 , 1.3 , or 0.4 mg/g . MEASUREMENTS The Cigarette Purchase Task was completed at baseline and at the week 6 post-r and omization visit . FINDINGS Compared with normal nicotine content controls , the lowest nicotine content ( 0.4 mg/g ) reduced the number of study cigarettes participants estimated they would smoke at a range of prices [ mean reduction relative to 15.8 mg/g at a price of $ 4.00/pack : 9.50 , 95 % confidence interval ( CI ) = 6.81,12.19 ] . The lowest nicotine content also reduced the maximum amount of money allocated to study cigarettes and the price at which participants reported they would stop buying study cigarettes [ median reduction relative to 15.8 mg/g , 95 % CI = $ 8.21 ( 4.27,12.15 ) per day and $ 0.44 ( 0.17,0.71 ) per cigarette , respectively ] . A reduction in nicotine content to the lowest level also reduced the maximum amount of money allocated to usual br and cigarettes ( median reduction relative to 15.8 mg/g : $ 4.39 per day , 95 % CI = 1.88,6.90 ) . CONCLUSIONS In current smokers , a reduction in nicotine content may reduce cigarette consumption , reduce the reinforcement value of cigarettes and increase cessation if reduced nicotine content cigarettes were the only cigarette available for purchase AIMS To compare the use of alternative nicotine products , smoking behavior and tobacco biomarker exposure in smokers unwilling to quit who were assigned r and omly to normal nicotine content ( NNC ) cigarettes or very low nicotine content ( VLNC ) cigarettes .  DESIGN R and omized , 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 [ ± st and ard 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 Background The Food and Drug Administration can reduce the nicotine content in cigarettes to very low levels . This potential regulatory action is hypothesised to improve public health by reducing smoking , but may have unintended consequences related to weight gain . Methods Weight gain was evaluated from a double-blind , parallel , r and omised clinical trial of 839 participants assigned to smoke 1 of 6 investigational cigarettes with nicotine content ranging from 0.4 to 15.8 mg/g or their own usual br and for 6 weeks . Additional analyses evaluated weight gain in the lowest nicotine content cigarette groups ( 0.4 and 0.4 mg/g , high tar ) to examine the effect of study product in compliant participants as assessed by urinary biomarkers . Differences in outcomes due to gender were also explored . Findings There were no significant differences in weight gain when comparing the reduced nicotine conditions with the 15.8 mg/g control group across all treatment groups and weeks . However , weight gain at week 6 was negatively correlated with nicotine exposure in the 2 lowest nicotine content cigarette conditions . Within the 2 lowest nicotine content cigarette conditions , male and female smokers biochemically verified to be compliant on study product gained significantly more weight than non-compliant smokers and control groups . Conclusions The effect of r and om assignment to investigational cigarettes with reduced nicotine on weight gain was likely obscured by non-compliance with study product . Men and women who were compliant in the lowest nicotine content cigarette conditions gained 1.2 kg over 6 weeks , indicating weight gain is a likely consequence of reduced exposure to nicotine . Trial registration number NCT01681875 , Post- results AIMS To determine ( 1 ) if nicotine content affects study attrition-a potential behavioral measure of acceptability-in a trial that required compliance with three levels of reduced nicotine content ( RNC ) cigarettes , and ( 2 ) if attrition is associated with subjective and behavioral responses to RNC cigarettes . DESIGN Secondary analysis of a 35-day , parallel- design , open-label , r and omized controlled trial . After a 5-day baseline period , participants were r and omized to smoke for three 10-day periods : their preferred br and ( control group ) or RNC cigarettes with three nicotine levels in a within-subject stepdown ( one group : high-moderate-low ) or non-stepdown ( five groups : high-low-moderate , low-moderate-high , low-high-moderate , moderate-low-high , moderate-high-low ) fashion . SETTING A single site in Philadelphia , PA , USA . PARTICIPANTS A total of 246 non-treatment-seeking daily smokers [ mean age = 39.52 , cigarettes per day ( CPD ) = 20.95 , 68.3 % white ] were recruited from October 2007 to June 2013 . MEASUREMENTS The primary outcome was attrition . Key predictors were nicotine content transition and study period . Exploratory predictors 
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While these studies report promising results and suggest that a nicotine reduction rule would be a powerful tool to reduce cigarette smoking , our gap analysis suggests that there is a need for studies that better reflect the use and availability of a wide range of tobacco/nicotine products and the potential for dual- or multi-product use .