Neurobehavioral Substrates of Propranolol's Effects on Drug Cue Reactivity

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.


Eligibility Criteria:
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.