Table 1.
Summaries of Studies Investigating Very Low Nicotine Content (VLNC) Cigarettes in Vulnerable Populations
| Authors, year | Population (sample size) | Demographic Characteristics | Main Outcomes timepoint | Main Outcome Measures | Findings |
|---|---|---|---|---|---|
| Adults with Mental Health Conditions | |||||
| Tidey et al., 2013 | Adults ages 18+ with schizophrenia spectrum disorder (n=30) and controls (n=26) | Mean age=45 % female=41 % non-white=29 |
Acute exposure | Craving, withdrawal, subjective effects, usual brand smoking, psychiatric symptoms | 5-hour VLNC use with placebo or nicotine patches reduced craving, withdrawal symptoms, and usual brand smoke intake compared to abstinence. Cigarette satisfaction and reward were lower for VLNC than for NNC cigarettes. No effects on psychiatric symptoms among participants with schizophrenia. |
| AhnAllen et al., 2015; Secondary analysis of Tidey et al., 2013 | Same as Tidey et al. (2013) | Assessments of attention, visual working memory, inhibitory control, processing speed | Across both the schizophrenia and control groups, inhibitory control, processing speed, and response variability were impaired in the VLNC + placebo patches condition compared to the VLNC + nicotine replacement and usual brand conditions. | ||
| Tidey et al., 2016; Secondary analysis of Tidey et al., 2013 | Same as Tidey et al. (2013) | Puff topography | Across cigarette conditions, participants with schizophrenia smoked more puffs and had shorter inter-puff intervals than controls. VLNC use was associated with longer puff duration and shorter inter-puff interval, but participants smoked fewer puffs, resulting in lower smoke volume. | ||
| Higgins et al., 2017 * | Adults ages 18–70 with affective disorders (n=56) or opioid use disorder (n=60); women ages 18–44 with ≤ 12 years of education (n=53) | Mean age=36 % female=71 % non-white=27 |
Acute exposure | Cigarette demand, cigarette choice, subjective effects, puff topography | Across groups, VLNC cigarettes were less reinforcing than NNC cigarettes. All doses reduced craving and withdrawal. No effects on topography or smoke exposure. |
| Gaalema et al., 2017; Secondary analysis of Higgins et al., 2017 | Same as Higgins et al., 2017 | Cigarette choice, craving, withdrawal, puff topography | Neither diagnosis nor symptom severity moderated the effects of nicotine reduction on cigarette choice, craving, withdrawal, or topography. | ||
| Tidey et al., 2017; Secondary analysis of Donny et al., 2015 | Adults ages 18+ with clinically-significant (n=109) vs. lower (n=608) depressive symptoms | Mean age=42 % female=42 % non-white=47 |
6 weeks | CPD, craving, dependence, depressive symptoms | Participants assigned to cigarettes with ≤ 2.4 mg nicotine/g tobacco had lower CPD, dependence, and craving; effects were not moderated by baseline depressive symptoms. Among those with higher depressive symptoms at baseline, VLNCs reduced depressive symptoms at week 6. |
| Tidey et al., 2019 | Adults 18–70 with schizophrenia, schizoaffective disorder, or bipolar disorder (n=58) | Mean age=43 % female=41 % non-white=41 |
6 weeks | CPD, craving, withdrawal, subjective responses, toxicant exposure, psychiatric symptoms | Those assigned to VLNC cigarettes had lower CPD, CO levels and craving, and reported lower cigarette satisfaction and reward than those assigned to NNC cigarettes. No effects on dependence, nicotine exposure, withdrawal, or psychiatric symptoms. |
| Denlinger-Apte et al., 2020; Secondary analysis of Tidey et al., 2019 | Same as Tidey et al., 2019 | Puff topography, CO boost | At week 6, participants in the VLNC condition smoked fewer puffs per cigarette and had shorter inter-puff intervals than those in the NNC condition. No effects on puff volume, puff duration, peak flow rate, or CO boost. | ||
| Reed et al., 2022; Secondary analysis of Tidey et al., 2019 | Same as Tidey et al. 2019, focused on participants in the VLNC condition only (n = 30) | Biochemically-verified compliance with VLNC cigarettes | Few participants were completely adherent to using only VLNC cigarettes. Lower enjoyment of respiratory tract sensations predicted less adherence. | ||
| Higgins et al., 2020 * | Men and women ages 18–70 with affective disorders (n=258) or opioid dependence (n=260); women ages 18–44 with ≤ 12 years of education (n=257) | Mean age=36 % female=71 % non-white=18 |
12 weeks | CPD, CO, dependence, toxicant exposure, craving, withdrawal, cigarette demand, puff topography | Compared to those assigned to NNC cigarettes, those assigned to VLNC cigarettes smoked fewer CPD and had lower dependence and cigarette demand at Week 12, and reported more abstinent days and quit attempts across the trial. No effects on withdrawal and no compensatory smoking. Depression scores were higher in the VLNC condition but still within the minimal range. |
| Adults with Opioid Use Disorder | |||||
| Higgins et al., 2017 * | Adults ages 18–70 with affective disorders (n=56) or opioid use disorder (n=60); women ages 18–44 with ≤ 12 years of education (n=53) | Mean age=36 % female=71 % non-white=27 |
Acute exposure | Cigarette demand, cigarette choice subjective effects, puff topography | Across groups, VLNC cigarettes were less reinforcing than NNC cigarettes. All doses reduced craving and withdrawal. No effects on topography or smoke exposure. |
| Streck et al., (2020); Secondary analysis of Higgins et al., 2017 | Same as Higgins et al., 2017, comparing effects in participants with OUD (n=65) vs. without OUD (n=135) | Craving, withdrawal | Effects of cigarette nicotine content on craving and withdrawal symptoms did not differ as a function of opioid dependence status. | ||
| Higgins et al., 2020 * | Men and women ages 18–70 with affective disorders (n=258) or opioid dependence (n=260); women ages 18–44 with ≤ 12 years of education (n=257) | Mean age=36 % female=71 % non-white=18 |
12 weeks | CPD, CO, dependence, toxicant exposure, craving, withdrawal, cigarette demand, puff topography | Compared to those assigned to NNC cigarettes, those assigned to VLNC cigarettes smoked fewer CPD and had lower dependence and cigarette demand at Week 12, and reported more abstinent days and quit attempts across the trial. No effects on withdrawal and no compensatory smoking. Participants with OUD were less sensitive to effects of VLNC cigarettes on nicotine and toxicant exposure. |
| Adults who use Alcohol and Cannabis | |||||
| Pacek et al., 2016; Secondary analysis of Donny et al., 2015 | Adults 18+ who used cannabis (n=207) vs. non-users (n=510) | Mean age=42 % female=42 % non-white=47 |
6 weeks | CPD, craving, dependence, depressive symptoms | Cannabis users and non-users assigned to cigarettes with ≤ 2.4 mg nicotine/g tobacco had lower CPD, dependence, and craving than those assigned to NNC cigarettes; cannabis users had larger decrease in craving than non-users. VLNC use did not impact cannabis use behaviors. |
| Parker et al., 2018; Secondary analysis of Higgins et al., 2017 | Same as Higgins et al.., 2017, focusing on participants who did (n=63) vs. did not use cannabis (n=106) | Cigarette demand, cigarette choice subjective effects, puff topography | Cannabis use status did not moderate effects of nicotine dose on cigarette choice, demand, subjective effects, or topography. Cannabis users reported higher positive ratings across doses, and longer effects on withdrawal symptoms. | ||
| Dermody et al., 2016; Secondary analysis of Donny et al.., 2015 | Adults who drink alcohol (n=403) | Mean age=39 % female=42 % non-white=42 |
6 weeks | Alcohol intake, binge drinking, CPD, nicotine exposure, nicotine withdrawal | VLNC use was associated with lower alcohol use through reductions in nicotine exposure and CPD. No evidence of compensatory drinking or nicotine withdrawal. |
| Dermody et al., 2021; Secondary analysis of Hatsukami et al., 2018 | Adults who drink alcohol (n=415) vs. non-drinkers (n=337) | Mean age=45 % female=45 % non-white=37 |
20 weeks | Alcohol intake, binge drinking, CPD, CO, nicotine exposure | Baseline alcohol use did not moderate effects of VLNC vs. NNC condition on Week 20 CPD or CO, but was associated with smaller reduction in nicotine exposure. Among alcohol users, daily alcohol use and odds of binge drinking were reduced for the VLNC group. |
| Adults with Socioeconomic Disadvantage | |||||
| Higgins et al., 2017 * | Adults ages 18–70 with affective disorders (n=56) or opioid use disorder (n=60); women ages 18–44 with ≤ 12 years of education (n=53) | Mean age=36 % female=71 % non-white=27 |
Acute exposure | Cigarette demand, cigarette choice subjective effects, puff topography | Across groups, VLNC cigarettes were less reinforcing than NNC cigarettes. All doses reduced craving and withdrawal. No effects on topography or smoke exposure. |
| Higgins et al., 2020 * | Men and women ages 18–70 with affective disorders (n=258) or opioid dependence (n=260); women ages 18–44 with ≤ 12 years of education (n=257) | Mean age=36 % female=71 % non-white=18 |
12 weeks | CPD, CO, dependence, toxicant exposure, craving, withdrawal, cigarette demand, puff topography | Compared to those assigned to NNC cigarettes, those assigned to VLNC cigarettes smoked fewer CPD and had lower dependence and cigarette demand at Week 12, and reported more abstinent days and quit attempts across the trial. No effects on withdrawal and no compensatory smoking. Depression scores were higher in the VLNC condition but still within the minimal range. |
| Krebs et al., 2021 | Adults ages 18–65 with ≤ 16 years of education (n=245) | Mean age=45 % female=52 % non-white=38 |
18 weeks | CPD, nicotine exposure, CO attrition, choice to quit with support, continue research cigarette use, or resume usual brand use | The gradual nicotine reduction group had lower CPD, CO and nicotine exposure, but higher attrition and study cigarette nonadherence. Among trial completers, those in the nicotine reduction condition were more likely to make a quit attempt. |
| Carroll et al., 2021*; Secondary analysis of Hatsukami et al., 2018 | Adults 18+ with ≤ 12 years education (n=505); women (n=549); and Black participants (n=373) compared to participants without these characteristics | Mean age=45 % female=44 % non-white=39 |
20 weeks | CPD, CO, nicotine exposure, toxicant exposure | Regardless of education, gender, and race, measures of nicotine and toxicant exposure were lower in the immediate reduction group than in the gradual nicotine or control groups. However, effects of nicotine reduction on nicotine exposure were smaller for Black participants than for White participants. |
| Youth and Young Adults | |||||
| Faulkner et al., 2017 | Young adults ages 18–25 who smoked ≥ 5 CPD (n=46) | Mean age=22 % female=50 % non-white=59 |
Acute exposure | Subjective effects, craving, withdrawal, affect, sustained attention, puff topography | All nicotine doses reduced withdrawal symptoms, craving, and negative affect; normal metabolizers had greater reductions in craving and withdrawal from VLNC cigarettes than slow metabolizers. Lower nicotine cigarettes did not improve attention and had lower positive ratings. No effects on topography. |
| Cassidy et al., 2018 | Adolescents ages 15–19 who smoked daily (n=50) | Mean age=18 % female=50 % non-white=46 |
Acute exposure | Subjective effects, craving, withdrawal, affect, CO | All nicotine doses reduced withdrawal symptoms, craving, and negative affect. VLNC cigarettes were rated as less satisfying. No compensatory increase in CO at lower nicotine doses. |
| Cassidy et al., 2019; Secondary analysis of Cassidy et al., 2018 | Same as Cassidy et al., 2018 | Cigarette purchase task demand indices | Demand for usual brand cigarettes was higher than for research cigarettes at all nicotine doses, with no difference among doses. | ||
| Denlinger-Apte et al., 2019a; Secondary analysis of Cassidy et al., 2018 | Same as Cassidy et al., 2018 | Perceived health risks, subjective effects, CO | Participants perceived VLNC cigarettes as less harmful to health than NNC study cigarettes but not less addictive. Menthol preference did not moderate outcomes. | ||
| Cassidy et al., 2019; Secondary analysis of Donny et al., 2015 | Younger adults ages 18–24 (n=93) vs. older adults ages 25+ (n=595) who smoked ≥ 5 CPD | % female=42 % non-white=42 |
6 weeks | CPD, subjective effects, puff topography, nicotine exposure | Younger adults assigned to cigarettes with ≤ 2.4 mg nicotine/g tobacco smoked fewer CPD and reported lower smoking satisfaction and reward after two weeks of use than older adults. Age differences were diminished after 6 weeks. |
| Davis et al., 2019; Secondary analysis of Higgins et al., 2017 | Same as Higgins et al., 2017, focusing on younger adults ages 18–24 vs. older adults ages 25+ | Cigarette demand, cigarette choice subjective effects, puff topography |
Demand decreased as a function of dose and decreased more steeply in younger vs. older adults. No differences by age were observed on other measures. | ||
| Cassidy et al. 2020 | Adolescents ages 15–19 who smoked daily (n=66) | Mean age=18.5 % female=50 % non-white=35 |
3 weeks | CPD, subjective effects, nicotine exposure | Participants assigned to VLNC cigarettes smoked fewer CPD at week 3 than those assigned to NNC cigarettes. Nicotine exposure and smoking satisfaction were decreased in both groups. |
| Cassidy et al., 2021; Secondary analysis of Hatsukami et al., 2018 | Young adults ages 18–24 (n= 87) compared to older adults ages 25% (n=1163) | Mean age=34 % female=61 % non-white=34 |
20 weeks | CPD; nicotine exposure; subjective effects | Across age groups, CPD was lower in the immediate nicotine reduction condition and nicotine exposure was lower in the immediate and gradual nicotine conditions. Positive subjective effects were lower among young adults than older adults in the immediate reduction condition. |
| Sweitzer et al., 2021 | Young adults ages 18–25 who smoked at least 5 cigarettes per month (n=87) | Mean age=21 % female=49 % non-white=27 |
30 min | CO, subjective responses, cigarette choice | CO boost was higher after smoking a VLNC cigarette than an NNC cigarette. Positive, negative, and dizziness reactions were highest in the NNC condition. Dose did not significantly affect cigarette choice. |
| Other Priority and Vulnerable Populations | |||||
| Denlinger-Apte et al. (2019b); Secondary analysis of Hatsukami et al., 2018 | Adults 18+ who smoke menthol (n=346) vs. non-menthol cigarettes (n=406) | Mean age=45 % female=44 % non-white=39 |
20 weeks | CPD, CO, nicotine exposure, toxicant exposure, abstinence | Across menthol status, VLNC cigarette use led to reductions in smoking and toxicant exposure, and increases in abstinence. However, effects tended to be smaller in menthol smokers. |
| Heil et al., 2020 | Pregnant women (n=10) | Mean age=31 % female=100 % non-white=10 |
Acute exposure | Cigarette demand, cigarette choice subjective effects, puff topography | Demand, choices, and positive subjective effects were lower for VLNC compared to usual brand cigarettes. VLNC cigarettes reduced craving and withdrawal with no compensatory smoking. |
| Carroll et al., 2021*; Secondary analysis of Hatsukami et al., 2018 | Adults 18+ with ≤ 12 years education (n=505); women (n=549); and Black participants (n=373) compared to participants without these characteristics | Mean age=45 % female=44 % non-white=39 |
20 weeks | CPD, CO, nicotine exposure, toxicant exposure | Regardless of education, gender, and race, measures of nicotine and toxicant exposure were lower in the immediate reduction group than in the gradual nicotine or control groups. However, effects of nicotine reduction on nicotine exposure were smaller for Black participants than for White participants. |
| Higgins et al., 2021; Secondary analysis of Higgins et al., 2020 | Adults ages 18–70 (n=775) with vulnerabilities including rurality, affective disorder, substance use disorder, low educational attainment, poverty, unemployment, physical disability | Mean age=36 % female=71 % non-white=18 |
12 weeks | CPD, toxicant exposure, dependence, craving, withdrawal | Number of cumulative vulnerabilities (0–1, 2–3, ≥ 4) was positively associated with CPD but did not moderate responses to nicotine reduction. |
Notes: VLNC, very low nicotine content; NNC, normal nicotine content; CO, carbon monoxide; CPD, cigarettes per day
*
Study addresses more than one vulnerable group and is included in more than one section of this table.