Switching to Very Low Nicotine Content Cigarettes vs Reducing Cigarettes Per Day

Primary:

1. Determine the relative feasibility of switching to VLNC cigarettes vs reducing CPD when
all participants are aided by nicotine replacement therapy (NRT).

2. Determine whether switching to VLNC cigarettes or reducing CPD more effectively reduces
nicotine dependence when all participants are aided by NRT.

Secondary:

3. Determine whether switching to VLNC cigarettes vs reducing CPD increases quit attempts
and 7-day point-prevalence abstinence more when all participants are aided by NRT.

4. Determine the relative effectiveness of switching to VLNC cigarettes and reducing CPD
when all participants are aided by NRT with comparisons of a) craving, b) withdrawal, c)
perceived harm from smoking and d) participants' enjoyment from smoking.

5. Determine whether switching to VLNC cigarettes or reducing CPD increases use of
e-cigarettes or other non-combustible nicotine products more.

Rationale for Proposed Study:

A policy to reduce the nicotine content of cigarettes could be useful for the majority of
smokers who are not ready to quit. Specifically, the FDA recently gained the authority to
regulate cigarettes' nicotine content and switching to very low nicotine content (VLNC)
cigarettes has been proposed as a future regulatory policy to give smokers the option to
decrease nicotine intake from cigarettes in order to decrease nicotine dependence and quit
smoking. A review of clinical trials suggest that switching to VLNC cigarettes with and
without nicotine replacement therapy (NRT) reduces dependence, carcinogens, and carbon
monoxide and increases quitting; however, its long-term effects are unclear.

Nicotine dependence is determined by nicotine intake (i.e., yield) as well as non-nicotine
reinforcers conditioned by the repetitive act of smoking (i.e., multiple cigarettes per day).
Presently, reducing cigarettes per day (CPD) is the most common strategy to reduce nicotine
intake and appears to be an effective method of reducing dependence. However, a regulatory
policy that introduces VLNC cigarettes will provide smokers with the opportunity to reduce
nicotine intake without changing the frequency of their smoking behavior (i.e., CPD). Thus,
reducing nicotine by switching to VLNC cigarettes may affect conditioned reinforcers and
dependence differently than reducing nicotine intake via reducing CPD. The investigators know
of no research that has compared the regulatory policy of reducing nicotine intake via VLNC
cigarettes vs the common method of reducing nicotine intake via reducing CPD. This comparison
will provide important information regarding the components involved in changing nicotine
dependence and the potential effects of a policy that regulates the nicotine content of
cigarettes.

NRT appears to increase the feasibility and effectiveness of switching to VLNC cigarettes as
well as reducing full nicotine CPD. In both scenarios, NRT facilitates a net reduction in
nicotine. Further, NRT is currently available to smokers who reduce CPD, will be available to
smokers if cigarettes' nicotine levels are reduced by the FDA, and is likely to be used as an
aid for both.

The present study will compare participants who switch to VLNC cigarettes vs participants who
reduce CPD when all participants receive NRT patch. Specifically this comparison will examine
differences in feasibility and effectiveness of reducing nicotine dependence.

Study Design:

Consenting participants will be randomly assigned to 1) switch to VLNC cigarettes with NRT or
2) reduce full nicotine CPD with NRT during the 5-week study period. All participants will
complete baseline measures and receive full nicotine or VLNC study cigarettes as well as
weekly supplies of 21-mg nicotine patches with instructions to replace their old patch with a
new patch each morning.

During their first study visit, the investigators will provide all participants with a
one-week supply of full nicotine study cigarettes (16.5 ± 0.17 mg/g) that totals 150% of
their normal number of CPD in order to establish a baseline CPD with novel study cigarettes
that are being provided free of charge. The 16.5 mg/g nicotine content NIDA research
cigarette is estimated to have a nicotine yield (0.8 mg) similar to many commercial
cigarettes. Participants will be instructed to smoke only study cigarettes, but to smoke as
usual during the first week of the study. All study cigarettes are for investigational
purposes only and are not available or intended for commercial use.

Switching to VLNC cigarettes Participants who are randomized to switch to VLNC cigarettes
will receive a supply of 100% of their baseline number of CPD during study visits (determined
during week 1) throughout weeks 2 to 5 and instructed to smoke as usual (e.g., not to attempt
to reduce CPD). They will receive study cigarettes with progressively lower nicotine content
(mg/g tobacco) beginning with 11.26 ± 0.11 mg/g during week 2, 5.54 ± 0.27 mg/g during week
3, 2.54 ± 0.05 mg/g during week 4, and 0.44 ± 0.01 mg/g during week 5. Participants will also
receive a supply of NRT patches with instructions to wear one patch per day every day
throughout weeks 2 through 5. This schedule was selected based on available VLNC cigarettes
and findings that indicate that a gradual transition to cigarettes with a nicotine content of
approximately 1 mg/g or less with the NRT patch is safe, effective and feasible. The
investigators will estimate NRT use and compliance with VLNC study cigarettes with daily and
weekly self report.

Reducing CPD The investigators will provide participants who are randomized to reduce CPD
with full nicotine study cigarettes (16.5 ± 0.17 mg/g) during each study visit throughout the
5-week study period and instruct them to only smoke cigarettes provided by the study. After
establishing a baseline CPD during week 1, participants will receive progressively fewer
cigarettes beginning with 70% of their baseline CPD during week 2, 35% during week 3, 15%
during week 4, and 3% during week 5. Participants will receive a minimum of 1 CPD during week
5. Participants will also receive a supply of NRT patches with instructions to wear one patch
per day every day throughout weeks 2 through 5. This schedule was selected to match the
percent reduction in nicotine content of cigarettes for smokers randomized to switch to VLNC
cigarettes. Further, this schedule of NRT aided reductions in CPD appears to be safe,
feasible and effective. The investigators will estimate reductions in CPD, compliance with
study cigarettes, and NRT use with daily and weekly self-report.

Eligibility will be determined based on:

- participants' age,

- their cigarettes smoked per day,

- their intention to quit,

- their willingness to use medications,

- prior use of tobacco and non-tobacco nicotine products,

- prior use of stop-smoking services or medications,

- DSM 5 criteria for Tobacco Use Disorder,

- current use of opioid maintenance medications,

- access to a telephone and the Internet,

- proximity to the University of Vermont,

- their bed time,

- status as a US citizen,

- comfort speaking, reading and writing in English, and

- whether or not the participant is breast feeding, pregnant or has the potential to
become pregnant or begin breastfeeding during the study period.