Cigarette Smoking
Conditions
Brief summary
The central objective of this project is to obtain proof-of-concept data demonstrating the effects of propranolol (a beta-adrenergic antagonist) on neurobiological responses to personal smoking environments and behavioral responses in a laboratory smoking behavior task. Human cigarette smokers (N = 50) will take photographs of locations where they do and do not smoke cigarettes. They will then be randomly assigned to receive either propranolol (40 mg) or placebo prior to completing: A) An MRI session assessing neural responses to personal smoking/non-smoking environments, standard smoking/non-smoking environments and proximal smoking/non-smoking cues; and B) A laboratory session examining smoking behavior in response to environmental cues.
Interventions
DRUGPropranolol
Participants will take one dose of Propranolol (40mg IR) on two separate occasions.
DRUGPlacebo
Participants will take one dose of Placebo on two separate occasions.
Sponsors
National Institutes of Health (NIH)
National Institute on Drug Abuse (NIDA)
Duke University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Double-blind
Intervention model description
Participants will be randomly assigned to receive propranolol (40 mg) or placebo
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Between the ages of 18 and 55 * Generally healthy * Right-handed * Smoke \>= 5 cigarettes/day of a brand delivering 0.5 mg nicotine (FTC method) * Have been smoking regularly for \>= 1 year, with a stable smoking pattern over the past 6 months * Have an expired CO concentration of \>= 10 ppm or urinary cotinine \> 100 ng/ml * Are able to identify at least 4 smoking and 4 non-smoking enviornments
Exclusion criteria
* Inability to attend all required sessions * Significant health problems that would interfere with completion of study procedures * Presence of conditions that would make MRI unsafe (e.g. pacemaker) * Presence of exclusionary psychopathology based on MINI interview (current alcohol/substance use disorder moderate or severe pmild is allowable\], any history of bipolar disorder or psychosis). Individuals in early remission from substance use disorder (not in a controlled environment) may also be allowed at the PIs discretion * Current use of psychoactive medications per self-report or urine screen. Certain prescribed medications are allowable at the PI's discretion if appropriate documentation (e.g. copy of prescription or physician letter) is provided * Positive breath alcohol concentraiton Pregnant, breastfeeding, or planning to become pregnant during the course of study * Problems with vision that cannot be corrected with contacts or glasses * Current regular use of smokeless tobacco, smoking cessation medications or non-combustible nicotine products (e.g. e-cigarettes) * Plans to alter smoking pattern (e.g. reduction, uptake, cessation) during course of study * Current use of beta-adrenergic medication * Systolic blood pressure \< 90 mmHg or diastolic blood pressure \< 60 mmHg (sitting or standing) * Low resting heart rate (\< 60 beats per minute) * Abnormal EKG * Presence of severe anemia (per complete blood count) * Presence of electrolyte imbalance that could impact blood pressure (per metabolic panel) * Presence of any other contraindications for propranolol (e.g. cardiovascular disease, bronchial asthma, prior allergic reaction) Note that the above criteria reflect general guidelines for decision-making, but ultimate determinations are left to the discretion of the study physician. Presence of minor (e.g. asymptomatic bradycardia in the range of 50-60 in an otherwise healthy adult) or transient (e.g. electrolyte imbalance readily addressed via changes in fluid intake) may still be deemed eligible to participate.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| BOLD Activation to Smoking Cues - Amygdala | MRI Scan: 2-3 hours post-administration | BOLD activation in amygdala (% Signal Change). These are analyzed as separate units for each Trial Type (6 total: Proximal Non-Smoking, Proximal Smoking, Standard Environment Non-Smoking, Standard Environment Smoking, Personal Environment Non-Smoking, personal Environment Smoking), MRI Run (4 total: The task was divided into 4 runs to allow for participant breaks) and Brain Hemisphere (2 total: Left and Right). These are only presented by trial type as MRI Run and Brain Hemisphere are not variables of interest. |
| BOLD Activation to Smoking Cues - Anterior Insula | MRI Scan: 2-3 hours post-administration | BOLD activation in Anterior Insula (% Signal Change). These are analyzed as separate units for each Trial Type (6 total: Proximal Non-Smoking, Proximal Smoking, Standard Environment Non-Smoking, Standard Environment Smoking, Personal Environment Non-Smoking, personal Environment Smoking), MRI Run (4 total: The task was divided into 4 runs to allow for participant breaks) and Brain Hemisphere (2 total: Left and Right). These are only presented by trial type as MRI Run and Brain Hemisphere are not variables of interest. |
| BOLD Activation to Smoking Cues - Anterior Hippocampus | MRI Scan: 2-3 hours post-administration | BOLD activation in Anterior Hippocampus (% Signal Change). These are analyzed as separate units for each Trial Type (6 total: Proximal Non-Smoking, Proximal Smoking, Standard Environment Non-Smoking, Standard Environment Smoking, Personal Environment Non-Smoking, personal Environment Smoking), MRI Run (4 total: The task was divided into 4 runs to allow for participant breaks) and Brain Hemisphere (2 total: Left and Right). These are only presented by trial type as MRI Run and Brain Hemisphere are not variables of interest. |
| BOLD Activation to Smoking Cues - Posterior Hippocampus | MRI Scan: 2-3 hours post-administration | BOLD activation in Posterior Hippocampus (% Signal Change). These are analyzed as separate units for each Trial Type (6 total: Proximal Non-Smoking, Proximal Smoking, Standard Environment Non-Smoking, Standard Environment Smoking, Personal Environment Non-Smoking, personal Environment Smoking), MRI Run (4 total: The task was divided into 4 runs to allow for participant breaks) and Brain Hemisphere (2 total: Left and Right). These are only presented by trial type as MRI Run and Brain Hemisphere are not variables of interest. |
| BOLD Activation to Smoking Cues - Medial Prefrontal Cortex | MRI Scan: 2-3 hours post-administration | BOLD activation in Medial Prefrontal Cortex (% Signal Change). These are analyzed as separate units for each Trial Type (6 total: Proximal Non-Smoking, Proximal Smoking, Standard Environment Non-Smoking, Standard Environment Smoking, Personal Environment Non-Smoking, personal Environment Smoking), MRI Run (4 total: The task was divided into 4 runs to allow for participant breaks) and Brain Hemisphere (2 total: Left and Right). These are only presented by trial type as MRI Run and Brain Hemisphere are not variables of interest. |
| fMRI BOLD Connectivity | MRI Scan: 2-3 hours post-administration | Connectivity with right amygdala when viewing proximal smoking images, using a right anterior hippocampus seed region (psychophysiological interaction analysis; PPI). Larger values represent greater connectivity between these regions while viewing proximal smoking images. |
| Cue-Provoked Craving - Proximal Cues | MRI Scan: 2-3 hours post-administration | During MRI Scans, participants rated their craving in response to the question While focusing on the place/object, I craved a cigarette. using a 1 (Do not agree) to 8 (Strongly agree) scale immediately following each image. Ratings were then averaged within each image category (total scale range of 1-8). Higher values represent greater craving. |
| Cue-Provoked Craving - Standard Environment Images | MRI Scan: 2-3 hours post-administration | During MRI Scans, participants rated their craving in response to the question While focusing on the place/object, I craved a cigarette. using a 1 (Do not agree) to 8 (Strongly agree) scale immediately following each image. Ratings were then averaged within each image category (total scale range of 1-8). Higher values represent greater craving. |
| Cue-Provoked Craving - Personal Environment Cues | MRI Scan: 2-3 hours post-administration | During MRI Scans, participants rated their craving in response to the question While focusing on the place/object, I craved a cigarette. using a 1 (Do not agree) to 8 (Strongly agree) scale immediately following each image. Ratings were then averaged within each image category (total scale range of 1-8). Higher values represent greater craving. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Laboratory Visit - Self-Reported Craving | Lab Task: 2-3 hours post-administration | Self-reported craving to smoke following presentation of personal smoking environments (prior to ad-lib smoking period). Assessed using the average rating across four questions drawn from the Questionnaire on Smoking Urges: (1) While focusing on those places...nothing would have been better than smoking a cigarette; (2) While focusing on those places...I had the urge for a cigarette; (3) While focusing on those places...all I wanted right then was a cigarette; (4) While focusing on those places...I craved a cigarette. Participants rated each item on an 11-point scale ranging from 0 (Do not agree) to 100 (Strongly agree) in 10-point intervals. These ratings were averaged across items for analysis. higher values represent greater craving. Tiffany, S. T., & Drobes, D. J. (1991). The development and initial validation of a questionnaire on smoking urges. British Journal of addiction, 86(11), 1467-1476. |
| Laboratory Visit - # Cigarette Puffs | Lab Task: 2-3 hours post-administration | Number of cigarette puffs taken during ad lib smoking period while participants view images of their personal smoking environment. Smoking was video recorded and puffs were coded by two raters. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled in a laboratory setting at Duke University School of Medicine during a period ranging from January 2018 to June 2019.
Participants by arm
| Arm | Count |
|---|---|
| Propranolol Propranolol Capsule: 40 mg IR, administered 2x at separate laboratory sessions
Propranolol: Participants will take one dose of Propranolol (40mg IR) on two separate occasions. | 22 |
| Placebo Placebo Capsule: No active ingredients, administered 2x at separate laboratory sessions
Placebo: Participants will take one dose of Placebo on two separate occasions. | 20 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Inappropriate behavior towards staff | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Propranolol | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 37.6 years STANDARD_DEVIATION 9.6 | 35.0 years STANDARD_DEVIATION 10.4 | 36.3 years STANDARD_DEVIATION 10 |
| Cigarettes Per Day | 15.0 Cigarettes/day STANDARD_DEVIATION 6.1 | 15.4 Cigarettes/day STANDARD_DEVIATION 7.3 | 15.2 Cigarettes/day STANDARD_DEVIATION 6.6 |
| Contemplation Ladder (Motivation to Quit) | 4.9 units on a scale STANDARD_DEVIATION 2.5 | 3.3 units on a scale STANDARD_DEVIATION 2.9 | 4.1 units on a scale STANDARD_DEVIATION 2.8 |
| Education Education <= High School Diploma | 10 Participants | 8 Participants | 18 Participants |
| Education Education > High School Diploma | 12 Participants | 12 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 22 Participants | 19 Participants | 41 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Fagerstrom Test for Cigarette Dependence | 4.2 units on a scale STANDARD_DEVIATION 1.7 | 5.4 units on a scale STANDARD_DEVIATION 2.2 | 4.8 units on a scale STANDARD_DEVIATION 2 |
| Income Usual Annual income >= $30,000 | 14 Participants | 7 Participants | 21 Participants |
| Income Usual Annual Income < $30,000 | 8 Participants | 13 Participants | 21 Participants |
| Number of Previous Quit Attempts | 2.5 quit-attempts STANDARD_DEVIATION 2.3 | 2.0 quit-attempts STANDARD_DEVIATION 1.6 | 2.2 quit-attempts STANDARD_DEVIATION 2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants | 11 Participants | 20 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 7 Participants | 18 Participants |
| Sex: Female, Male Female | 11 Participants | 11 Participants | 22 Participants |
| Sex: Female, Male Male | 11 Participants | 9 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 0 / 22 |
| other Total, other adverse events | 1 / 22 | 1 / 22 |
| serious Total, serious adverse events | 0 / 22 | 0 / 22 |
Outcome results
Primary
BOLD Activation to Smoking Cues - Amygdala
BOLD activation in amygdala (% Signal Change). These are analyzed as separate units for each Trial Type (6 total: Proximal Non-Smoking, Proximal Smoking, Standard Environment Non-Smoking, Standard Environment Smoking, Personal Environment Non-Smoking, personal Environment Smoking), MRI Run (4 total: The task was divided into 4 runs to allow for participant breaks) and Brain Hemisphere (2 total: Left and Right). These are only presented by trial type as MRI Run and Brain Hemisphere are not variables of interest.
Time frame: MRI Scan: 2-3 hours post-administration
Population: Participants who completed the study. Excludes two additional participants in the placebo condition who had excessive motion artifact during scanning and could not be included in neuroimaging analyses.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Propranolol | BOLD Activation to Smoking Cues - Amygdala | Non-Smoking Personal Environments | 0.002471 Percent Signal Change | Standard Deviation 0.367038 |
| Propranolol | BOLD Activation to Smoking Cues - Amygdala | Smoking Personal Environments | 0.009450 Percent Signal Change | Standard Deviation 0.384823 |
| Propranolol | BOLD Activation to Smoking Cues - Amygdala | Non-Smoking Standard Environments | 0.044903 Percent Signal Change | Standard Deviation 0.352711 |
| Propranolol | BOLD Activation to Smoking Cues - Amygdala | Smoking Standard Environments | 0.111746 Percent Signal Change | Standard Deviation 0.321235 |
| Propranolol | BOLD Activation to Smoking Cues - Amygdala | Non-Smoking Proximal | 0.066409 Percent Signal Change | Standard Deviation 0.386921 |
| Propranolol | BOLD Activation to Smoking Cues - Amygdala | Smoking Proximal | 0.025432 Percent Signal Change | Standard Deviation 0.378728 |
| Placebo | BOLD Activation to Smoking Cues - Amygdala | Non-Smoking Proximal | 0.015171 Percent Signal Change | Standard Deviation 0.353829 |
| Placebo | BOLD Activation to Smoking Cues - Amygdala | Non-Smoking Personal Environments | 0.077325 Percent Signal Change | Standard Deviation 0.337887 |
| Placebo | BOLD Activation to Smoking Cues - Amygdala | Smoking Standard Environments | 0.161114 Percent Signal Change | Standard Deviation 0.355927 |
| Placebo | BOLD Activation to Smoking Cues - Amygdala | Smoking Personal Environments | 0.090345 Percent Signal Change | Standard Deviation 0.293101 |
| Placebo | BOLD Activation to Smoking Cues - Amygdala | Smoking Proximal | 0.133363 Percent Signal Change | Standard Deviation 0.409809 |
| Placebo | BOLD Activation to Smoking Cues - Amygdala | Non-Smoking Standard Environments | 0.042836 Percent Signal Change | Standard Deviation 0.341324 |
p-value: 0.019Mixed Models Analysis
Primary
BOLD Activation to Smoking Cues - Anterior Hippocampus
BOLD activation in Anterior Hippocampus (% Signal Change). These are analyzed as separate units for each Trial Type (6 total: Proximal Non-Smoking, Proximal Smoking, Standard Environment Non-Smoking, Standard Environment Smoking, Personal Environment Non-Smoking, personal Environment Smoking), MRI Run (4 total: The task was divided into 4 runs to allow for participant breaks) and Brain Hemisphere (2 total: Left and Right). These are only presented by trial type as MRI Run and Brain Hemisphere are not variables of interest.
Time frame: MRI Scan: 2-3 hours post-administration
Population: Participants who completed the study. Excludes two additional participants in the placebo condition who had excessive motion artifact during scanning and could not be included in neuroimaging analyses.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Propranolol | BOLD Activation to Smoking Cues - Anterior Hippocampus | Non-Smoking Personal Environments | 0.061001 Percent Signal Change | Standard Deviation 0.324934 |
| Propranolol | BOLD Activation to Smoking Cues - Anterior Hippocampus | Smoking Personal Environments | 0.073925 Percent Signal Change | Standard Deviation 0.3008 |
| Propranolol | BOLD Activation to Smoking Cues - Anterior Hippocampus | Non-Smoking Standard Environments | 0.133369 Percent Signal Change | Standard Deviation 0.315323 |
| Propranolol | BOLD Activation to Smoking Cues - Anterior Hippocampus | Smoking Standard Environments | 0.171673 Percent Signal Change | Standard Deviation 0.289132 |
| Propranolol | BOLD Activation to Smoking Cues - Anterior Hippocampus | Non-Smoking Proximal | 0.088852 Percent Signal Change | Standard Deviation 0.323655 |
| Propranolol | BOLD Activation to Smoking Cues - Anterior Hippocampus | Smoking Proximal | 0.024626 Percent Signal Change | Standard Deviation 0.296327 |
| Placebo | BOLD Activation to Smoking Cues - Anterior Hippocampus | Non-Smoking Proximal | 0.000827 Percent Signal Change | Standard Deviation 0.280219 |
| Placebo | BOLD Activation to Smoking Cues - Anterior Hippocampus | Non-Smoking Personal Environments | 0.095120 Percent Signal Change | Standard Deviation 0.271027 |
| Placebo | BOLD Activation to Smoking Cues - Anterior Hippocampus | Smoking Standard Environments | 0.186590 Percent Signal Change | Standard Deviation 0.300916 |
| Placebo | BOLD Activation to Smoking Cues - Anterior Hippocampus | Smoking Personal Environments | 0.088399 Percent Signal Change | Standard Deviation 0.267232 |
| Placebo | BOLD Activation to Smoking Cues - Anterior Hippocampus | Smoking Proximal | 0.095598 Percent Signal Change | Standard Deviation 0.291577 |
| Placebo | BOLD Activation to Smoking Cues - Anterior Hippocampus | Non-Smoking Standard Environments | 0.083638 Percent Signal Change | Standard Deviation 0.27752 |
p-value: 0.006Mixed Models Analysis
Primary
BOLD Activation to Smoking Cues - Anterior Insula
BOLD activation in Anterior Insula (% Signal Change). These are analyzed as separate units for each Trial Type (6 total: Proximal Non-Smoking, Proximal Smoking, Standard Environment Non-Smoking, Standard Environment Smoking, Personal Environment Non-Smoking, personal Environment Smoking), MRI Run (4 total: The task was divided into 4 runs to allow for participant breaks) and Brain Hemisphere (2 total: Left and Right). These are only presented by trial type as MRI Run and Brain Hemisphere are not variables of interest.
Time frame: MRI Scan: 2-3 hours post-administration
Population: Participants who completed the study. Excludes two additional participants in the placebo condition who had excessive motion artifact during scanning and could not be included in neuroimaging analyses.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Propranolol | BOLD Activation to Smoking Cues - Anterior Insula | Non-Smoking Personal Environments | -0.179076 Percent Signal Change | Standard Deviation 0.288539 |
| Propranolol | BOLD Activation to Smoking Cues - Anterior Insula | Smoking Personal Environments | -0.127730 Percent Signal Change | Standard Deviation 0.293581 |
| Propranolol | BOLD Activation to Smoking Cues - Anterior Insula | Non-Smoking Standard Environments | -0.118271 Percent Signal Change | Standard Deviation 0.317144 |
| Propranolol | BOLD Activation to Smoking Cues - Anterior Insula | Smoking Standard Environments | -0.146114 Percent Signal Change | Standard Deviation 0.312662 |
| Propranolol | BOLD Activation to Smoking Cues - Anterior Insula | Non-Smoking Proximal | -0.085715 Percent Signal Change | Standard Deviation 0.331652 |
| Propranolol | BOLD Activation to Smoking Cues - Anterior Insula | Smoking Proximal | -0.086867 Percent Signal Change | Standard Deviation 0.35231 |
| Placebo | BOLD Activation to Smoking Cues - Anterior Insula | Non-Smoking Proximal | -0.085873 Percent Signal Change | Standard Deviation 0.270967 |
| Placebo | BOLD Activation to Smoking Cues - Anterior Insula | Non-Smoking Personal Environments | -0.157851 Percent Signal Change | Standard Deviation 0.281748 |
| Placebo | BOLD Activation to Smoking Cues - Anterior Insula | Smoking Standard Environments | -0.149887 Percent Signal Change | Standard Deviation 0.282468 |
| Placebo | BOLD Activation to Smoking Cues - Anterior Insula | Smoking Personal Environments | -0.142636 Percent Signal Change | Standard Deviation 0.269551 |
| Placebo | BOLD Activation to Smoking Cues - Anterior Insula | Smoking Proximal | -0.098181 Percent Signal Change | Standard Deviation 0.318646 |
| Placebo | BOLD Activation to Smoking Cues - Anterior Insula | Non-Smoking Standard Environments | -0.152299 Percent Signal Change | Standard Deviation 0.326875 |
p-value: 0.83Mixed Models Analysis
Primary
BOLD Activation to Smoking Cues - Medial Prefrontal Cortex
BOLD activation in Medial Prefrontal Cortex (% Signal Change). These are analyzed as separate units for each Trial Type (6 total: Proximal Non-Smoking, Proximal Smoking, Standard Environment Non-Smoking, Standard Environment Smoking, Personal Environment Non-Smoking, personal Environment Smoking), MRI Run (4 total: The task was divided into 4 runs to allow for participant breaks) and Brain Hemisphere (2 total: Left and Right). These are only presented by trial type as MRI Run and Brain Hemisphere are not variables of interest.
Time frame: MRI Scan: 2-3 hours post-administration
Population: Participants who completed the study. Excludes two additional participants in the placebo condition who had excessive motion artifact during scanning and could not be included in neuroimaging analyses.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Propranolol | BOLD Activation to Smoking Cues - Medial Prefrontal Cortex | Non-Smoking Personal Environments | 0.033030 Percent Signal Change | Standard Deviation 0.32254 |
| Propranolol | BOLD Activation to Smoking Cues - Medial Prefrontal Cortex | Smoking Personal Environments | 0.058184 Percent Signal Change | Standard Deviation 0.378236 |
| Propranolol | BOLD Activation to Smoking Cues - Medial Prefrontal Cortex | Non-Smoking Standard Environments | -0.078483 Percent Signal Change | Standard Deviation 0.350182 |
| Propranolol | BOLD Activation to Smoking Cues - Medial Prefrontal Cortex | Smoking Standard Environments | -0.068693 Percent Signal Change | Standard Deviation 0.311347 |
| Propranolol | BOLD Activation to Smoking Cues - Medial Prefrontal Cortex | Non-Smoking Proximal | -0.039529 Percent Signal Change | Standard Deviation 0.362686 |
| Propranolol | BOLD Activation to Smoking Cues - Medial Prefrontal Cortex | Smoking Proximal | -0.064034 Percent Signal Change | Standard Deviation 0.345958 |
| Placebo | BOLD Activation to Smoking Cues - Medial Prefrontal Cortex | Non-Smoking Proximal | -0.109172 Percent Signal Change | Standard Deviation 0.422732 |
| Placebo | BOLD Activation to Smoking Cues - Medial Prefrontal Cortex | Non-Smoking Personal Environments | 0.012705 Percent Signal Change | Standard Deviation 0.409304 |
| Placebo | BOLD Activation to Smoking Cues - Medial Prefrontal Cortex | Smoking Standard Environments | -0.093598 Percent Signal Change | Standard Deviation 0.447743 |
| Placebo | BOLD Activation to Smoking Cues - Medial Prefrontal Cortex | Smoking Personal Environments | 0.060320 Percent Signal Change | Standard Deviation 0.313844 |
| Placebo | BOLD Activation to Smoking Cues - Medial Prefrontal Cortex | Smoking Proximal | 0.015524 Percent Signal Change | Standard Deviation 0.413311 |
| Placebo | BOLD Activation to Smoking Cues - Medial Prefrontal Cortex | Non-Smoking Standard Environments | -0.167025 Percent Signal Change | Standard Deviation 0.447513 |
p-value: 0.012Mixed Models Analysis
Primary
BOLD Activation to Smoking Cues - Posterior Hippocampus
BOLD activation in Posterior Hippocampus (% Signal Change). These are analyzed as separate units for each Trial Type (6 total: Proximal Non-Smoking, Proximal Smoking, Standard Environment Non-Smoking, Standard Environment Smoking, Personal Environment Non-Smoking, personal Environment Smoking), MRI Run (4 total: The task was divided into 4 runs to allow for participant breaks) and Brain Hemisphere (2 total: Left and Right). These are only presented by trial type as MRI Run and Brain Hemisphere are not variables of interest.
Time frame: MRI Scan: 2-3 hours post-administration
Population: Participants who completed the study. Excludes two additional participants in the placebo condition who had excessive motion artifact during scanning and could not be included in neuroimaging analyses.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Propranolol | BOLD Activation to Smoking Cues - Posterior Hippocampus | Non-Smoking Personal Environments | 0.161077 Percent Signal Change | Standard Deviation 0.288481 |
| Propranolol | BOLD Activation to Smoking Cues - Posterior Hippocampus | Smoking Personal Environments | 0.156684 Percent Signal Change | Standard Deviation 0.303924 |
| Propranolol | BOLD Activation to Smoking Cues - Posterior Hippocampus | Non-Smoking Standard Environments | 0.137124 Percent Signal Change | Standard Deviation 0.304769 |
| Propranolol | BOLD Activation to Smoking Cues - Posterior Hippocampus | Smoking Standard Environments | 0.179651 Percent Signal Change | Standard Deviation 0.25691 |
| Propranolol | BOLD Activation to Smoking Cues - Posterior Hippocampus | Non-Smoking Proximal | 0.056247 Percent Signal Change | Standard Deviation 0.281092 |
| Propranolol | BOLD Activation to Smoking Cues - Posterior Hippocampus | Smoking Proximal | 0.050077 Percent Signal Change | Standard Deviation 0.260461 |
| Placebo | BOLD Activation to Smoking Cues - Posterior Hippocampus | Non-Smoking Proximal | 0.053026 Percent Signal Change | Standard Deviation 0.271871 |
| Placebo | BOLD Activation to Smoking Cues - Posterior Hippocampus | Non-Smoking Personal Environments | 0.185521 Percent Signal Change | Standard Deviation 0.262021 |
| Placebo | BOLD Activation to Smoking Cues - Posterior Hippocampus | Smoking Standard Environments | 0.176196 Percent Signal Change | Standard Deviation 0.269538 |
| Placebo | BOLD Activation to Smoking Cues - Posterior Hippocampus | Smoking Personal Environments | 0.166154 Percent Signal Change | Standard Deviation 0.252282 |
| Placebo | BOLD Activation to Smoking Cues - Posterior Hippocampus | Smoking Proximal | 0.121240 Percent Signal Change | Standard Deviation 0.262651 |
| Placebo | BOLD Activation to Smoking Cues - Posterior Hippocampus | Non-Smoking Standard Environments | 0.161655 Percent Signal Change | Standard Deviation 0.241679 |
p-value: 0.653Mixed Models Analysis
Primary
Cue-Provoked Craving - Personal Environment Cues
During MRI Scans, participants rated their craving in response to the question While focusing on the place/object, I craved a cigarette. using a 1 (Do not agree) to 8 (Strongly agree) scale immediately following each image. Ratings were then averaged within each image category (total scale range of 1-8). Higher values represent greater craving.
Time frame: MRI Scan: 2-3 hours post-administration
Population: Participants who completed the study. Excludes two additional participants in the placebo condition who had excessive motion artifact during scanning and could not be included in neuroimaging analyses.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Propranolol | Cue-Provoked Craving - Personal Environment Cues | Non-Smoking | 3.369318 units on a scale | Standard Deviation 1.802147 |
| Propranolol | Cue-Provoked Craving - Personal Environment Cues | Smoking | 6.045996 units on a scale | Standard Deviation 1.457661 |
| Placebo | Cue-Provoked Craving - Personal Environment Cues | Non-Smoking | 2.965278 units on a scale | Standard Deviation 1.668703 |
| Placebo | Cue-Provoked Craving - Personal Environment Cues | Smoking | 6.638889 units on a scale | Standard Deviation 1.569405 |
p-value: 0.14Repeated Measures ANCOVA
Primary
Cue-Provoked Craving - Proximal Cues
During MRI Scans, participants rated their craving in response to the question While focusing on the place/object, I craved a cigarette. using a 1 (Do not agree) to 8 (Strongly agree) scale immediately following each image. Ratings were then averaged within each image category (total scale range of 1-8). Higher values represent greater craving.
Time frame: MRI Scan: 2-3 hours post-administration
Population: Participants who completed the study. Excludes two additional participants in the placebo condition who had excessive motion artifact during scanning and could not be included in neuroimaging analyses.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Propranolol | Cue-Provoked Craving - Proximal Cues | Non-Smoking | 2.866883 units on a scale | Standard Deviation 1.566946 |
| Propranolol | Cue-Provoked Craving - Proximal Cues | Smoking | 6.103084 units on a scale | Standard Deviation 1.61845 |
| Placebo | Cue-Provoked Craving - Proximal Cues | Non-Smoking | 1.898148 units on a scale | Standard Deviation 0.824614 |
| Placebo | Cue-Provoked Craving - Proximal Cues | Smoking | 6.547619 units on a scale | Standard Deviation 1.685597 |
p-value: 0.024Repeated Measures ANCOVA
Primary
Cue-Provoked Craving - Standard Environment Images
During MRI Scans, participants rated their craving in response to the question While focusing on the place/object, I craved a cigarette. using a 1 (Do not agree) to 8 (Strongly agree) scale immediately following each image. Ratings were then averaged within each image category (total scale range of 1-8). Higher values represent greater craving.
Time frame: MRI Scan: 2-3 hours post-administration
Population: Participants who completed the study. Excludes two additional participants in the placebo condition who had excessive motion artifact during scanning and could not be included in neuroimaging analyses.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Propranolol | Cue-Provoked Craving - Standard Environment Images | Non-Smoking | 2.673052 units on a scale | Standard Deviation 1.681618 |
| Propranolol | Cue-Provoked Craving - Standard Environment Images | Smoking | 4.666937 units on a scale | Standard Deviation 1.588874 |
| Placebo | Cue-Provoked Craving - Standard Environment Images | Non-Smoking | 1.763889 units on a scale | Standard Deviation 0.644389 |
| Placebo | Cue-Provoked Craving - Standard Environment Images | Smoking | 4.868056 units on a scale | Standard Deviation 1.716846 |
p-value: 0.086Repeated Measures ANCOVA
Primary
fMRI BOLD Connectivity
Connectivity with right amygdala when viewing proximal smoking images, using a right anterior hippocampus seed region (psychophysiological interaction analysis; PPI). Larger values represent greater connectivity between these regions while viewing proximal smoking images.
Time frame: MRI Scan: 2-3 hours post-administration
Population: Participants who completed the study. Excludes two additional participants in the placebo condition who had excessive motion artifact during scanning and could not be included in neuroimaging analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Propranolol | fMRI BOLD Connectivity | -0.0740 PPI Index | Standard Deviation 0.0769 |
| Placebo | fMRI BOLD Connectivity | 0.0228 PPI Index | Standard Deviation 0.0997 |
p-value: 0.013Mixed Models Analysis
Secondary
Laboratory Visit - # Cigarette Puffs
Number of cigarette puffs taken during ad lib smoking period while participants view images of their personal smoking environment. Smoking was video recorded and puffs were coded by two raters.
Time frame: Lab Task: 2-3 hours post-administration
Population: Participants who completed the study. Data from one participant in the placebo condition was lost due to technical problems with the recording.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Propranolol | Laboratory Visit - # Cigarette Puffs | 15.2 Puffs | Standard Deviation 7.1 |
| Placebo | Laboratory Visit - # Cigarette Puffs | 17.7 Puffs | Standard Deviation 9.8 |
p-value: 0.463ANCOVA
Secondary
Laboratory Visit - Self-Reported Craving
Self-reported craving to smoke following presentation of personal smoking environments (prior to ad-lib smoking period). Assessed using the average rating across four questions drawn from the Questionnaire on Smoking Urges: (1) While focusing on those places...nothing would have been better than smoking a cigarette; (2) While focusing on those places...I had the urge for a cigarette; (3) While focusing on those places...all I wanted right then was a cigarette; (4) While focusing on those places...I craved a cigarette. Participants rated each item on an 11-point scale ranging from 0 (Do not agree) to 100 (Strongly agree) in 10-point intervals. These ratings were averaged across items for analysis. higher values represent greater craving. Tiffany, S. T., & Drobes, D. J. (1991). The development and initial validation of a questionnaire on smoking urges. British Journal of addiction, 86(11), 1467-1476.
Time frame: Lab Task: 2-3 hours post-administration
Population: Participants who completed the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Propranolol | Laboratory Visit - Self-Reported Craving | 7.3 units on a scale | Standard Deviation 2.7 |
| Placebo | Laboratory Visit - Self-Reported Craving | 7.9 units on a scale | Standard Deviation 3 |
p-value: 0.556ANCOVA