Neurobehavioral Substrates of Propranolol's Effects on Drug Cue Reactivity

Duke University44 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

TRIPLE

Enrollment

Conditions

Cigarette Smoking

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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.