Nicotine Addiction
Conditions
Keywords
Nicotine, Smoking, Cigarettes, Reinforcement Learning, fMRI
Brief summary
The purpose of this study is to use functional magnetic resonance imaging (fMRI) to investigate the acute and chronic effects of nicotine on motivational behavior and prediction error-related neural activation. Nonsmokers (n = 24) and smokers (n = 24) will undergo fMRI scans on two separate occasions while performing a decision-making task that will elicit prediction error signals in the mesocorticolimbic pathway of the brain. Nonsmokers will be scanned once following an acute dose of nicotine and once following placebo administration. Smokers will be scanned once following smoking as usual and once following 24-hours of smoking abstinence, in order to measure the effects of nicotine withdrawal. The study team hypothesizes that acute nicotine will increase the prediction error signal in nonsmokers compared to placebo, and that nicotine withdrawal will decrease the prediction error signal in smokers compared to the normal satiated condition. Furthermore, nonsmokers (during the placebo condition) will have greater prediction error activation than smokers (during the satiated condition). The results of this study will inform whether the initiation and maintenance of smoking behavior could be facilitated by the effects of nicotine on reinforcement learning.
Interventions
nonsmokers will be measured following nicotine administration
DRUGPlacebo
nonsmokers will be measured following placebo administration
OTHERsatiety
smokers will be measured in a smoking satiated condition
OTHERabstinence
smokers will be measured following 24-hours of smoking abstinence
Sponsors
Duke University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
Inclusion criteria for all subjects: 1. generally healthy 2. between the ages of 18-55 3. right-handed Inclusion criteria for nonsmokers: 1. smoked \< 50 cigarettes of a brand delivering ≥ 0.5 mg nicotine (FTC method) 2. have not smoked in ≥ 6 months 3. afternoon expired CO concentration ≤ 5 ppm and/or morning urinary NicAlert \< 100 ng/ml Inclusion criteria for smokers 1. smoke ≥ 10 cigarettes/day of a brand delivering ≥ 0.5 mg nicotine (FTC method) 2. smoked ≥ 2 years 3. afternoon expired CO concentrations ≥ 10 ppm and/or morning urinary NicAlert \> 100 ng/ml
Exclusion criteria
1. inability to attend all required experimental sessions 2. significant health problems (e.g., current and uncontrolled liver, lung, or heart problems, current or past seizure disorder, serious head trauma) 3. lifetime diagnosis of Axis I psychiatric disorders (e.g., depression, anxiety disorder, schizophrenia) 4. meet DSM-V criteria for past or current substance dependence other than nicotine 5. use of psychoactive medications as indicated by self-report 6. use of smokeless tobacco, nicotine replacement therapy, or desire to change smoking behavior while in the study 7. positive urine drug screen for illicit drugs or positive breath alcohol concentration 8. presence of conditions that would make MRI unsafe 9. having vision that cannot be corrected to 20/40 10. among women, nursing or a positive pregnancy test 11. inability to achieve learning criteria in training session
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Blood Oxygen Level Dependent (BOLD) Signal in Dorsomedial Prefrontal Cortex | Nonsmokers: post nicotine and post placebo. Smokers: 24 hours smoking abstinence or smoking satiety | The acute and chronic effects of nicotine on the blood oxygen level dependent signal will be measured using functional magnetic resonance imaging. Reward-cue related BOLD signal on an outcome expectation task. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Nicotine, Placebo Nonsmokers will be measured following a nicotine polacrilex lozenge (2mg) on one occasion and placebo on another occasion.
Nicotine polacrilex: nonsmokers will be measured following nicotine administration
Placebo: nonsmokers will be measured following placebo administration | 30 |
| Nicotine Withdrawal or Satiety Smokers will be measured in a normal satiated condition and following 24-hours of smoking abstinence
satiety: smokers will be measured in a smoking satiated condition
abstinence: smokers will be measured following 24-hours of smoking abstinence | 24 |
| Total | 54 |
Baseline characteristics
| Characteristic | Nicotine Withdrawal or Satiety | Nicotine, Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 24 Participants | 30 Participants | 54 Participants |
| Age, Continuous | 35 years STANDARD_DEVIATION 10 | 33 years STANDARD_DEVIATION 11 | 34 years STANDARD_DEVIATION 11 |
| Region of Enrollment United States | 24 Participants | 30 Participants | 54 Participants |
| Sex: Female, Male Female | 14 Participants | 17 Participants | 31 Participants |
| Sex: Female, Male Male | 10 Participants | 13 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 30 | 0 / 24 |
| serious Total, serious adverse events | 0 / 30 | 0 / 24 |
Outcome results
Primary
Change in Blood Oxygen Level Dependent (BOLD) Signal in Dorsomedial Prefrontal Cortex
The acute and chronic effects of nicotine on the blood oxygen level dependent signal will be measured using functional magnetic resonance imaging. Reward-cue related BOLD signal on an outcome expectation task.
Time frame: Nonsmokers: post nicotine and post placebo. Smokers: 24 hours smoking abstinence or smoking satiety
Population: Subjects who did not follow MRI task instructions, or those with \> 3 mm of movement, were excluded from the analyses.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nonsmokers | Change in Blood Oxygen Level Dependent (BOLD) Signal in Dorsomedial Prefrontal Cortex | Nicotine or satiety | 7.3 percentage of BOLD signal | Standard Deviation 15 |
| Nonsmokers | Change in Blood Oxygen Level Dependent (BOLD) Signal in Dorsomedial Prefrontal Cortex | Placebo or abstinence | 6.2 percentage of BOLD signal | Standard Deviation 12 |
| Smokers | Change in Blood Oxygen Level Dependent (BOLD) Signal in Dorsomedial Prefrontal Cortex | Nicotine or satiety | 6.3 percentage of BOLD signal | Standard Deviation 12 |
| Smokers | Change in Blood Oxygen Level Dependent (BOLD) Signal in Dorsomedial Prefrontal Cortex | Placebo or abstinence | .02 percentage of BOLD signal | Standard Deviation 8 |