NCT04929288 · Jessica Weafer
Neural and Hormonal Influences on Sex Differences in Risk for AUD
What this study is about
The sex gap in alcohol consumption is closing rapidly, due to alarming increases among women. From 2002-2013, Alcohol Use Disorder (AUD) increased 84% for women, compared to 35% for men. As such, there is an urgent need to determine the factors underlying sex differences in risk for AUD.
View original scientific description
The sex gap in alcohol consumption is closing rapidly, due to alarming increases among women. From 2002-2013, Alcohol Use Disorder (AUD) increased 84% for women, compared to 35% for men. As such, there is an urgent need to determine the factors underlying sex differences in risk for AUD. Current addiction models propose three domains that drive problematic alcohol use and serve as candidate sex-specific risk factors: executive function, negative emotionality, and incentive salience. Data suggest that poor inhibitory control, a key component of executive function, is a stronger risk factor for women than for men. Moreover, there is have preliminary evidence that female drinkers show less engagement of neural inhibitory circuitry, and that this sex difference is influenced by estradiol. However, the degree to which hormonally-moderated sex differences in executive function extend to the negative emotionality and incentive salience domains, and how these sex differences influence current and future drinking is unknown. The goal of this study is to identify the mechanisms underlying sex-specific risk for AUD, and ultimately to help develop sex-specific prevention and treatment efforts. The overall objective of this trial is to determine the neural and hormonal factors contributing to sex-specific risk for AUD in three addiction domains: inhibitory control (executive function), negative emotionality, and alcohol cue reactivity (incentive salience).
Interventions
DRUG
Alcohol
Participants will complete three experimental sessions. In each session, participants will provide detailed reports of their alcohol consumption over the past five days, and they will provide a blood sample for hormone assays. They will perform tasks during fMRI to assess each of the neurofunctional addiction domains: inhibitory control, negative emotionality, and cue reactivity. Following the fMRI scan, subjects will self-administer intravenous alcohol to provide a controlled assessment of pharmacologically-driven alcohol consumption.
Primary outcome measures
Neural inhibitory function
Time frame: 13 minutes
One measure of neural inhibitory function during performance of the stop signal task will be activity (as measured by BOLD % signal change)
Neural inhibitory function
Time frame: 13 minutes
The other measure of neural inhibitory function during performance of the stop signal task will be functional connectivity for the StopInh\>Go contrast.
Neural negative emotionality
Time frame: 14 minutes
One measure of neural negative emotionality during performance of the Emotional Pictures Task will be activity (as measured by BOLD % signal change)
Neural negative emotionality
Time frame: 14 minutes
The other measure of neural negative emotionality during performance of the Emotional Pictures Task will be functional connectivity for the Negative\>Neutral contrast.
Neural alcohol cue reactivity
Time frame: 12 minutes
One measure of neural alcohol cue reactivity during performance of the Alcohol Cue Reactivity Task will be activity (as measured by BOLD % signal change)
Neural alcohol cue reactivity
Time frame: 12 minutes
The other measure of neural alcohol cue reactivity during performance of the Alcohol Cue Reactivity Task will be functional connectivity for the Alcohol\>Neutral contrast.
Intravenous alcohol self-administration (IV-ASA)
Time frame: 60 minutes
One measure of IV-ASA will be peak BrAC (mg%; highest BrAC obtained during the IV-ASA period)
Intravenous alcohol self-administration (IV-ASA)
Time frame: 60 minutes
Another measure of IV-ASA will be whether or not a participant reached binge level of alcohol exposure (80mg%)
Intravenous alcohol self-administration (IV-ASA)
Time frame: 60 minutes
The final measure of IV-ASA will be time to reach binge level of alcohol exposure (80mg%)
Self-reported current alcohol consumption
Time frame: 20 minutes
One measure of current alcohol consumption will be number of binge days (4/5 or more drinks in a sitting for women/men) as determined by responses on the Timeline Followback.
Self-reported current alcohol consumption
Time frame: 20 minutes
The other measure of current alcohol consumption will be average peak BrAC obtained on drinking days over the past 5 days, as determined by responses on the Timeline Followback.
Prospective alcohol consumption
Time frame: 18 months
One measure of prospective alcohol consumption will be number of binge episodes as determined by responses on the 90-day Timeline Followback.
Prospective alcohol consumption
Time frame: 18 months
The other measure of prospective alcohol consumption will be drinking days per month, as determined by responses on the 90-day Timeline Followback.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- consume 4/5 drinks per week
- fluent in English
- high school education
- right-handed
- regular menstrual cycles (women)
Exclusion criteria
- serious medical problems
- body weight \<110 or \>210 lbs
- current medical or psychiatric conditions requiring medication for which alcohol is contraindicated
- substance use disorder other than alcohol
- current or recent history of inpatient/intensive treatment for addictive behaviors
- pregnant, nursing, on hormonal contraception
- contraindications for fMRI
- smoking \> 5 cigarettes per day
Where
- Columbus, Ohio
Collaborators
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced May 22, 2026 · Source of record for eligibility and locations