Neural and Hormonal Influences on Alcohol Use Disorder Risk

Recruiting at 1 trial location

Overseen By Jessica Weafer, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Jessica Weafer

Must not be taking: Hormonal contraception

Disqualifiers: Serious medical problems, Substance use disorder, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

100 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you have medical or psychiatric conditions that require medication where alcohol is not allowed.

What evidence supports the effectiveness of the treatment 'Neural and Hormonal Influences on Sex Differences in Risk for AUD'?

Research suggests that sex hormones like testosterone and estrogen play a role in alcohol use and addiction, with testosterone linked to higher alcohol use in males and estrogen linked to higher use in females. Understanding these hormonal influences could help develop targeted treatments for alcohol use disorder (AUD) based on sex differences. ^{1 2 3 4 5}

Is the treatment generally safe for humans?

The research does not provide specific safety data for humans, but it discusses the influence of hormones on alcohol use and the potential for different effects based on gender. Further studies would be needed to determine the safety of any treatment targeting these hormonal influences. ^{1 2 5 6 7}

How does the treatment 'Neural and Hormonal Influences on Sex Differences in Risk for AUD' differ from other treatments for alcohol use disorder?

This treatment is unique because it focuses on the role of sex hormones and their influence on brain structure and function, which may contribute to differences in alcohol use disorder risk between males and females. It considers both the permanent and temporary effects of sex hormones on the brain, potentially offering a novel approach to understanding and treating alcohol addiction by targeting these hormonal influences. ^{1 2 3 4 5}

What is the purpose of this trial?

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).

Research Team

Jessica Weafer, PhD

Principal Investigator

Ohio State University

Eligibility Criteria

This trial is for English-speaking, right-handed individuals with at least a high school education who regularly consume alcohol. Women must have regular menstrual cycles and not be pregnant, nursing, or on hormonal contraception. Participants should weigh between 110 and 210 lbs and not require medication that interacts badly with alcohol.

Inclusion Criteria

fluent in English

I have regular menstrual cycles.

You drink around 4 to 5 alcoholic drinks every week.

Exclusion Criteria

current or recent history of inpatient/intensive treatment for addictive behaviors

I take medication that shouldn't be mixed with alcohol due to my health condition.

My weight is either below 110 lbs or above 210 lbs.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants undergo baseline assessments including neural inhibitory function, negative emotionality, and alcohol cue reactivity tasks

1-2 weeks

1 visit (in-person)

Experimental Sessions

Participants engage in tasks such as the stop signal task, Emotional Pictures Task, and Alcohol Cue Reactivity Task to measure neural responses

Varies per task

Multiple visits (in-person)

Follow-up

Participants are monitored for prospective alcohol consumption and self-reported current alcohol consumption

18 months

Treatment Details

Interventions

• Neural and Hormonal Influences on Sex Differences in Risk for AUD

Trial Overview The study aims to understand why women are increasingly at risk for Alcohol Use Disorder (AUD) by examining brain function and hormone levels related to self-control, emotional response, and reactions to alcohol cues.

Participant Groups

Group I: Males Experimental Treatment 1 Intervention

Participants in this group will be adult male drinkers.

Group II: Females Experimental Treatment 1 Intervention

Participants in this group will be adult female drinkers. Data will be segregated by menstrual cycle phase.

Who Is Running the Clinical Trial?

Jessica Weafer

Lead Sponsor

Trials

5

Recruited

560+

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Collaborator

Trials

865

Recruited

1,091,000+

Findings from Research

Early exposure to sex hormones can lead to structural changes in the brain that increase the risk of alcohol addiction later in life, suggesting a critical developmental window for these effects.

The review highlights the importance of both organizational and activational effects of sex hormones on alcohol-related behaviors, indicating that understanding these mechanisms could help in creating better prevention and treatment strategies for alcohol dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sex hormone activity in alcohol addiction: integrating organizational and activational effects. Lenz, B., Müller, CP., Stoessel, C., et al.[2015]

Recent trends show that the gap in alcohol use disorder (AUD) prevalence between men and women is narrowing, highlighting the need to understand sex-specific factors in alcohol consumption.

The review emphasizes the role of sex hormones and stress-related steroids in influencing alcohol drinking behaviors, suggesting that treatment strategies for AUD may need to be tailored differently for males and females, particularly regarding the targeting of specific hormonal pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Endocrine System and Alcohol Drinking in Females. Finn, DA.[2021]

Alcohol use disorder (AUD) has seen a dramatic increase in women over the past decade, with rates rising by 84%, highlighting the urgent need to understand the neural mechanisms behind this trend.

Current neuroimaging research on AUD shows mixed results regarding sex/gender differences in brain function and structure, indicating a significant gap in understanding how these differences may influence alcohol consumption and the risk of AUD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sex/gender differences in brain function and structure in alcohol use: A narrative review of neuroimaging findings over the last 10 years. Verplaetse, TL., Cosgrove, KP., Tanabe, J., et al.[2021]

A systematic review of 50 studies found that higher testosterone levels are linked to increased alcohol consumption and risk of alcohol use disorder (AUD) in males, while the effects in females remain unclear.

In females, increased estrogen levels are associated with higher alcohol use, but findings in males are mixed, highlighting the need for more research on how different sex hormones influence alcohol behavior in both sexes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sex hormones in alcohol consumption: a systematic review of evidence. Erol, A., Ho, AM., Winham, SJ., et al.[2022]

Gender differences in alcohol intake and response may be significantly influenced by variations in brain organization and neurosteroid levels between males and females.

The study suggests that these brain differences could explain the varying risks for alcoholism and the different behavioral and neurochemical responses to alcohol in men and women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gender differences in the brain: implications for the study of human alcoholism. Lancaster, FE.[2019]

In a study using an ethanol self-administration model with rats, it was found that female rats maintained a preference for alcohol longer than males, suggesting that brain sexual differentiation influences drinking behavior.

Gonadal hormones like dihydrotestosterone in males and estradiol in females modulate alcohol consumption, with dihydrotestosterone reducing intake in castrated males and estradiol decreasing intake in ovariectomized females, indicating hormonal effects on alcohol preference.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gender differences in ethanol preference and ingestion in rats. The role of the gonadal steroid environment. Almeida, OF., Shoaib, M., Deicke, J., et al.[2018]

Ovariectomy in female rats reduced ethanol drinking levels by 15%, indicating that the removal of ovarian steroids can influence alcohol consumption, similar to the drinking levels observed in male rats.

Despite the hormonal changes, both intact and ovariectomized female rats showed similar responses in GABA(A) and NMDA receptor alterations due to chronic ethanol exposure, suggesting that ovarian steroids do not significantly affect the gender differences in receptor changes associated with ethanol dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ovariectomy has minimal effects on neuroadaptations associated with ethanol dependence in female rats. DevaudLL, ., Morrow, AL., Nguyen, UT.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Sex hormone activity in alcohol addiction: integrating organizational and activational effects. [2015]

2. United States pubmed.ncbi.nlm.nih.gov

The Endocrine System and Alcohol Drinking in Females. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Sex/gender differences in brain function and structure in alcohol use: A narrative review of neuroimaging findings over the last 10 years. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Sex hormones in alcohol consumption: a systematic review of evidence. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Gender differences in the brain: implications for the study of human alcoholism. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Gender differences in ethanol preference and ingestion in rats. The role of the gonadal steroid environment. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Ovariectomy has minimal effects on neuroadaptations associated with ethanol dependence in female rats. [2019]