Neurobiology of Alcohol and Nicotine Co-Addiction (NAUD)

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

Study Overview

• Status: Completed
• Conditions: Alcohol Use Disorder; Nicotine Use Disorder
• Intervention / Treatment: Behavioral: magnetic resonance imaging (MRI)

Detailed Description

This proposal addresses the critical absence of information about the neurobiology of recovery from Alcohol Use Disorder (AUD) in alcohol and nicotine users. AUD and nicotine use disorder (NUD) are the most commonly abused (non-prescription) substances in the U.S. Co-addiction is particularly high in military veterans. Although nationwide estimates peg the rate of AUD/NUD co-addiction at 80%, the Substance Abuse Treatment Program (SATP) at the Veterans Affairs Portland Health Care System (VAPORHCS) finds that 90% of veterans treated for AUD also meet criteria for NUD. The investigators hypothesize that a support vector machine learning algorithm will be able to use the measures to classify subjects as AUD, NUD both or neither and that the algorithm will predict outcome (sobriety or relapse) at three months.

• Study Type: Observational
• Enrollment (Actual): 109

Contacts and Locations

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97207-2964
      • VA Portland Health Care System, Portland, OR

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 51 years (Adult)
• Accepts Healthy Volunteers: Yes

• 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.

Description

Inclusion Criteria:

• None

Exclusion Criteria:

• None

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Control Group; No history of addiction to any substance or gambling. Less than 20 lifetime cigarettes or equivalent.	Behavioral: magnetic resonance imaging (MRI); 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.
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); 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.
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); 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; 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); 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Collaborators: Oregon Health and Science University
• Investigators: Principal Investigator: William F Hoffman, MD PhD, VA Portland Health Care System, Portland, OR

Study record dates

Study Major Dates

• Study Start (Actual): February 8, 2018
• Primary Completion (Actual): January 3, 2023
• Study Completion (Actual): January 3, 2023

Study Registration Dates

• First Submitted: November 6, 2017
• First Submitted That Met QC Criteria: November 7, 2017
• First Posted (Actual): November 9, 2017

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 11, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Alcoholism; Tobacco Use Disorder
• Other Study ID Numbers: NURA-002-17S; 17321 (Other Identifier: Oregon Health and Science University)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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