Neurobiology of Alcohol and Nicotine Co-Addiction

NCT03338933 | Completed Results DMC

• 2 other identifiers: NURA-002-17S17321
• Study Type: observational
• Target: 109
• Locations: 1 country
• Sites: 1

Brief Summary

This proposal addresses the critical absence of information about the neurobiology of recovery from Alcohol Use Disorder (AUD) in alcohol and nicotine users.

Conditions

Alcohol Use Disorder; Nicotine Use Disorder

Outcome Measures

Primary Outcomes (4)

• Brain Activation During Functional Magnetic Resonance Imaging (fMRI) in Response to a Stress Modulated Cue Induced Craving Task (DSNBACK)

  The DSN-back is a cognitive task used to assess working memory and attention. Participants view a sequence of letters presented on a screen, flanked by either drug-related or neutral images, and are instructed to identify matches occurring N steps earlier. Neural activation during high working memory demand condition (2-back) relative to the low working memory condition (0-back) was investigated. Inconsistent activation patterns across regions may indicate impaired neural processing in regions critical for cognitive control, emotion regulation, and reward processing, commonly reported in substance use disorders. Values closer to 0 (no change) in regions responsible for emotion regulation and cognitive control (e.g., Amygdala, ACC) may indicate reduced task-specific engagement where drug-related processes may be dominating neural activity.

  Baseline

• Brain Activation During Resting State MRI.

  This outcome measures resting-state functional connectivity (rsFC) of the striatum using seed-based analysis of resting-state fMRI data. FC values, expressed as Fisher z-transformed correlation coefficients, quantify the strength of synchronization between the striatum seed region and other brain areas. Positive values indicate synchronized activity, while negative values reflect anticorrelation. Altered rsFC of the striatum, a hub for reward processing, habit formation, and executive control, is linked to alcohol and nicotine use disorders and may indicate impaired regulation of cravings and heightened sensitivity to substance-related cues. Investigating rsFC patterns may identify biomarkers of addiction severity, predict treatment outcomes, and inform potential therapeutic targets.

  Baseline

• Brain Cortical Thickness Assessed During MRI

  This outcome measures cortical thickness (millimeters) across brain regions using structural MRI. Cortical thickness reflects the integrity of gray matter and is influenced by factors such as neurodegeneration, plasticity, and development. Reductions in cortical thickness, particularly in prefrontal and limbic regions, are associated with impaired cognitive control, emotion regulation, and decision-making in substance use disorders.

  Baseline

• Brain White Matter Integrity as Assessed by Fractional Anisotropy During MRI

  Fractional Anisotropy (FA) is a scalar metric derived from diffusion-weighted MRI that quantifies the degree of directional dependence (anisotropy) of water diffusion in brain white matter, with values ranging from 0 (isotropic diffusion) to 1 (maximally anisotropic diffusion). Increases in FA may reflect greater white matter organization and integrity, while decreases often indicate microstructural damage, demyelination, or axonal loss. FA measurements were averaged within predefined regions of interest (ROIs) to assess the integrity of white matter in various brain regions associated with cognitive, motor, and emotional processing. Decreased FA in tracts such as the corpus callosum or prefrontal pathways may reflect impaired communication between brain regions involved in reward processing and cognitive control in substance use disorders.

  Baseline

Study Arms (4)

Control Group

No history of addiction to any substance or gambling. Less than 20 lifetime cigarettes or equivalent.

Behavioral: magnetic resonance imaging (MRI)

Nicotine Group

Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-V) criteria for Nicotine Use Disorder. Current smoker, at least 10 cigarettes per day. No history of addiction to any other substance

Behavioral: magnetic resonance imaging (MRI)

Nicotine and Alcohol Group

DSM-V criteria for Nicotine Use Disorder and Alcohol Use Disorder. At least 8 heavy drinking episodes in the past month. Current smoker. Alcohol free from 2 to 4 weeks. No history of addiction to other substances or gambling.

Behavioral: magnetic resonance imaging (MRI)

Alcohol Group

DSM-V criteria for Alcohol use Disorder. At least 8 heavy drinking episodes in the past month. Abstinent for at least 2 weeks and no more than 4 weeks. Less than 20 lifetime cigarettes or equivalent. No history of addiction to any other substances or gambling.

Behavioral: magnetic resonance imaging (MRI)

Interventions

magnetic resonance imaging (MRI) BEHAVIORAL

All subjects will undergo a baseline MRI and subjects in both alcohol groups (alcohol use disorder and combined alcohol and nicotine use disorder) will undergo a followup MRI 3 months after baseline.

Alcohol Group; Control Group; Nicotine Group; Nicotine and Alcohol Group

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Probability Sample

Study Population

Participants will be recruited from the Portland VA, Oregon Health \& Science University, community substance abuse treatment programs and by advertisement.

You may qualify if:

• None

You may not qualify if:

• None

Sponsors & Collaborators

• VA Office of Research and Development: lead
• Oregon Health and Science University: collaborator

Study Sites (1)

VA Portland Health Care System, Portland, OR

Portland, Oregon, 97207-2964, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Cheek swab Plasma

MeSH Terms

Conditions

Alcoholism; Tobacco Use Disorder

Interventions

Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Results Point of Contact

• Title: Dr. William Hoffman
• Organization: VA Portland Health Care System

hoffmaw@ohsu.edu

503-220-8262

Study Officials

• William F Hoffman, MD PhD

  VA Portland Health Care System, Portland, OR

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 6, 2017
• First Posted: November 9, 2017
• Study Start: February 8, 2018
• Primary Completion: January 3, 2023
• Study Completion: January 3, 2023
• Last Updated: February 13, 2025
• Results First Posted: February 13, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)