Beta-Adrenergic Modulation of Drug Cue Reactivity

Beta-Adrenergic Modulation of Drug Cue Reactivity: Neural and Behavioral Mechanisms

This study is designed to investigate the effects of a beta-adrenergic antagonist (Propranolol; 40 mg IR) and nicotine patch (14 mg) administered alone and in combination on neurobiological and behavioral responses to smoking cues in ongoing cigarette smokers. This is a basic experimental study in humans and participants will not take these medications for an extended period or make a cessation attempt as part of their involvement in this research project.

Study Overview

• Status: Recruiting
• Conditions: Tobacco Use Disorder; Nicotine Dependence; Cigarette Smoking
• Intervention / Treatment: Drug: Placebo Propranolol; Drug: Placebo Patch; Drug: Propranolol; Drug: Nicotine Patch

Detailed Description

Cigarette use remains a serious public health problem in the United States and worldwide. Effective pharmacological interventions for smoking cessation exist, but these medications primarily target nicotine withdrawal and smoking reinforcement. The cues and contexts associated with smoking also play an important role in driving smoking behavior, but evidence is extremely mixed whether existing interventions can effectively attenuate smoking urges and behavior in response to these cues and contexts.

In a previous pilot trial, the investigators demonstrated that propranolol suppressed smoking cue reactivity and brain activation across a constellation of brain regions implicated in nicotine dependence. Here, the investigators seek to extend this work by examining effects when the drug is administered in combination with an established treatment targeting withdrawal and reinforcement (i.e., nicotine patch).

Following consent and screening/baseline activities, participants will attend four neuroimaging appointments each lasting approximately 5 hours. Participants will be fitted with a nicotine or placebo patch, fed a standard meal and then administered propranolol or placebo. Participants will complete questionnaires and have their heart rate/blood pressure monitored throughout the visit. During the MRI scan, participants will be asked to complete both resting scans and task-based scans during which participants will view images of smoking and non-smoking objects and scenes.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jason A Oliver, PhD; Phone Number: 14005 405-271-8001; Email: Jason-Oliver@ouhsc.edu
• Study Contact Backup: Name: Isabel Brush, B.A.; Email: Isabel-Brush@ouhsc.edu

Study Locations

• United States
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74136
      • Recruiting
      • Hardesty Center for Clinical Research and Neuroscience
      • Contact: Isabel Brush, B.A.; Email: Isabel-Brush@ouhsc.edu
      • Contact: Rebecca Gonzalez, B.A.; Email: Rebecca-Gonzalez@ouhsc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Generally healthy
2. Age 21-60
3. Right-handed using a three-item scale
4. Daily smoker of ≥ 5 cigarettes/day delivering 0.5 mg nicotine (FTC)
5. Smoking regularly for ≥ 1 year, with stable smoking for the past 6 months
6. Afternoon expired Carbon Monoxide (CO) concentration ≥ 6 ppm and/or morning urinary cotinine >100 ng/ml
7. Must identity at least 4 different smoking locations used in a typical week
8. Able to read and understand English

Exclusion Criteria:

1. Inability to attend all required sessions
2. Significant health problems that would preclude active participation
3. Presence of conditions that would make MRI unsafe (e.g. pacemaker) or (e.g. weight and body shape)
4. Current use of psychoactive medications/drugs as indicated by self-report or urine screen
5. Positive breath alcohol concentration
6. Pregnant, breastfeeding, or planning to become pregnant during the course of the study (females)
7. Problems with vision that cannot be corrected with contacts or glasses
8. Current regular use of smokeless tobacco, smoking cessation medications, or other nicotine containing products (e.g. electronic cigarettes)
9. Current use of beta-adrenergic medications (e.g. beta-blockers) or other blood pressure medications
10. Systolic blood pressure < 90 mmHg or diastolic blood pressure < 60 mmHg (sitting or standing)
11. Abnormal EKG
12. Presence of severe anemia
13. Presence of electrolyte imbalance that could impact blood pressure
14. Presence of any other contraindications for propranolol or nicotine patch (e.g. cardiovascular disease, bronchial asthma, prior allergic reactions, diabetes)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo Patch/Placebo Propranolol; Placebo Nicotine Patch Placebo Propranolol	Drug: Placebo Propranolol; Placebo Capsule, no active ingredients; Drug: Placebo Patch; Placebo Patch, no active ingredients
Experimental: Placebo Patch/Active Propranolol; Placebo Nicotine Patch Active Propranolol (40 mg, immediate release)	Drug: Placebo Patch; Placebo Patch, no active ingredients; Drug: Propranolol; Propranolol Capsule; 40 mg IR
Experimental: Active Patch/Placebo Propranolol; Active Nicotine Patch (14 mg) Placebo Propranolol	Drug: Placebo Propranolol; Placebo Capsule, no active ingredients; Drug: Nicotine Patch; Nicotine Patch; 14 mg
Experimental: Active Patch/Active Propranolol; Active Nicotine Patch (14 mg) Active Propranolol (40 mg, immediate release)	Drug: Propranolol; Propranolol Capsule; 40 mg IR; Drug: Nicotine Patch; Nicotine Patch; 14 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cue-Provoked Craving Ratings	Self-reported smoking urges in response to smoking and non-smoking cues during magnetic resonance imaging (MRI) scan. Scores range from 0 to 10 with higher values indicating increased craving for cigarettes.	Approximately 4-5 hours
Blood-Oxygen Level Dependent (BOLD) Activation to Smoking Cues	Blood-Oxygen Level Dependent (BOLD) Contrast (Smoking-Neutral) in Anterior Hippocampus, Amygdala, Dorsal Anterior Insula, Medial Prefrontal Cortex, Posterior Cingulate Cortex and Ventral Striatum	Approximately 4-5 hours
Association between Smoking Urge and Brain Activation	Indices of covariation between cue-provoked craving BOLD activation to smoking cues	Approximately 4-5 hours
Hippocampus-Amygdala connectivity to smoking cues	Index of connectivity between these brain regions	Approximately 4-5 hours
Medial Prefrontal Cortex and Posterior Cingulate Cortex connectivity	Index of connectivity between these brain regions	Approximately 4-5 hours
Association between Smoking Urge and Brain Connectivity	Indices of covariation between cue-provoked craving BOLD activation to smoking cues	Approximately 4-5 hours

Collaborators and Investigators

• Sponsor: University of Oklahoma
• Collaborators: National Institute on Drug Abuse (NIDA); Duke University; National Institutes of Health (NIH); Oklahoma State University Center for Health Sciences
• Investigators: Principal Investigator: Jason A Oliver, PhD, University of Oklahoma

Study record dates

Study Major Dates

• Study Start (Actual): November 26, 2024
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): March 31, 2027

Study Registration Dates

• First Submitted: October 3, 2022
• First Submitted That Met QC Criteria: October 18, 2022
• First Posted (Actual): October 20, 2022

Study Record Updates

• Last Update Posted (Actual): April 28, 2026
• Last Update Submitted That Met QC Criteria: April 27, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Behavior; Smoking; Tobacco Smoking; Tobacco Use; Tobacco Use Disorder; Cigarette Smoking; Organic Chemicals; Therapeutics; Hydrocarbons; Hydrocarbons, Cyclic; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Amines; Alcohols; Phenoxypropanolamines; Propanolamines; Amino Alcohols; Propanols; Propranolol; Tobacco Use Cessation Devices
• Other Study ID Numbers: 2022005-OSU-CHS; 1R01DA053342-01A1 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes