Alcohol Effects on Brain Activity During Intoxication

Overseen By Julian Roberts, R.N.

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Ohio State University

Must not be taking: Antipsychotics, Anticoagulants

Disqualifiers: Bipolar, Schizophrenia, Substance use, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 1 day

144 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial seeks to understand how alcohol affects brain activity, particularly in individuals who may exhibit aggressive behavior or have alcohol use issues. Researchers aim to explore how the brain processes social and emotional cues under the influence of alcohol by using brain scans to gather data. The goal is to discover new ways to reduce alcohol-related aggression through potential treatments like cognitive exercises and brain training. Ideal participants are those who consume more than 10 drinks a week or binge drink monthly and have a history of angry outbursts, but are not currently seeking treatment for alcohol use. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people, offering participants a chance to contribute to potentially groundbreaking solutions.

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 a clinically significant medical condition requiring daily prescribed medication or if you are taking antipsychotic medications within two weeks of study entry.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

In a previous study, researchers found that alcohol consumption can significantly alter brain function and structure. Another study showed that alcohol affects brain areas responsible for controlling emotions and behavior. These changes may lead to aggressive actions, particularly in individuals with pre-existing aggressive traits or alcohol problems.

These findings highlight alcohol's impact on the brain and suggest a need for caution due to the potential for increased aggression and other negative effects. The research clarifies what occurs in the brain when alcohol is consumed and serves as a reminder of the serious effects of excessive alcohol consumption. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the cognitive-behavioral based interventions in this trial because they target alcohol-related aggressive behavior in a novel way. Unlike standard treatments that often focus on abstinence or reducing consumption, these interventions aim to rewire the brain's response to alcohol through neuroplasticity-based exercises. By addressing impaired social-emotional information processing and rehabilitating aberrant neuronal circuits, these methods could potentially reduce aggression more effectively during intoxication. Additionally, exploring the neural correlates during alcohol intoxication provides a deeper understanding of how alcohol impacts brain activity, paving the way for targeted interventions. This approach holds promise for more personalized and effective treatments for alcohol-related issues.

What evidence suggests that this trial's treatments could be effective for reducing alcohol-related aggression?

Research shows that alcohol affects the brain, particularly the areas involved in emotions and decision-making. Studies have found that even small amounts of alcohol can alter brain function, impacting attention and increasing aggression. In this trial, participants will receive either an oral alcohol drink or a placebo (non-alcohol drink) to study these effects. Alcohol alters the brain areas that process social and emotional information, potentially causing misinterpretation of social signals and aggressive reactions. The prefrontal cortex, which controls impulses and aggression, may not function properly under the influence of alcohol. Understanding these changes can aid in developing treatments to reduce aggressive behavior linked to alcohol use. ^{2 5 6 7 8}

Who Is on the Research Team?

Emil Coccaro, Dr

Principal Investigator

Ohio State University

Are You a Good Fit for This Trial?

This trial is for right-handed adults aged 21-55 who may or may not have a history of aggressive outbursts and alcohol use disorder (AUD), but no major psychiatric disorders, significant medical conditions, or high psychopathy scores. Smokers must limit to 15 cigarettes per day. Participants should be able to abstain from alcohol for 24 hours and drugs for 48 hours before MRI scans.

Inclusion Criteria

You do not have current or past AUD as classified by DSM-5.

To qualify for this study, you must meet the following requirements:

I am between 21 and 55 years old, right-handed, and have consumed alcohol in the last 3 months.

Exclusion Criteria

Unable to comply with study procedures.

PCL-SV psychopathy score > 18 (see above).

I have not tested positive for drugs like amphetamines or opiates.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either an oral alcohol drink or a placebo drink, followed by fMRI imaging to assess brain activation in response to social-emotional stimuli

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cognitive-behavioral based interventions
• Impaired social-emotional information processing
• Intervention to reduce alcohol-related aggressive behavior
• Neural correlates during alcohol intoxication
• Neuroplasticity-based Remediation Exercises
• Rehabilitation of aberrant neuronal circuits
• Targets for intervention to reduce alcohol-related aggressive behavior

Trial Overview

The study tests how brain activity related to social-emotional information processing changes after drinking alcohol versus a placebo. It involves fMRI imaging in individuals with varying levels of aggression and AUD to identify potential intervention targets that could reduce alcohol-related aggression.

How Is the Trial Designed?

Group I: Oral alcohol drink Experimental Treatment 1 Intervention

Group II: Placebo (non-alcohol drink) Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Ohio State University

Lead Sponsor

Trials

891

Recruited

2,659,000+

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Collaborator

Trials

865

Recruited

1,091,000+

Published Research Related to This Trial

In a study of 180 male Veterans with substance use disorders and a history of severe aggression, those receiving the integrated Motivational Interviewing-Cognitive Behavioral Treatment (MI-CBT) and MI-CBT plus Continuing Care (MI-CBT+CC) showed significant reductions in substance use outcomes compared to the Enhanced Treatment as Usual (E-TAU) group.

Participants in the MI-CBT+CC group experienced a greater decrease in partner physical aggression over time, with no reported injuries to partners during follow-up, suggesting that these integrated treatment approaches may effectively reduce both aggression and substance use in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized controlled trial for aggression and substance use involvement among Veterans: Impact of combining Motivational Interviewing, Cognitive Behavioral Treatment and telephone-based Continuing Care. Chermack, ST., Bonar, EE., Goldstick, JE., et al.[2020]

Early traumatic brain injury (TBI) in correctional inmates was linked to more severe and earlier onset of illicit drug use, which in turn predicted greater aggression.

Emotional dysregulation was identified as a key factor that mediates the relationship between TBI and aggression, suggesting that addressing emotional regulation could be important in developing targeted treatments for affected individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relationships Between Traumatic Brain Injury and Illicit Drug Use and Their Association With Aggression in Inmates. Fishbein, D., Dariotis, JK., Ferguson, PL., et al.[2017]

In a study involving male C57BL/6 J mice, self-administered alcohol significantly increased the likelihood of choosing aggressive behavior over sociosexual interactions, suggesting that alcohol may enhance aggression-related decision-making.

Neural activation in the prelimbic area of the medial prefrontal cortex (mPFC) was linked to aggressive choices, indicating that this brain region plays a crucial role in the decision-making process related to aggression under the influence of alcohol.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

To fight or not to fight: activation of the mPFC during decision to engage in aggressive behavior after ethanol consumption in a novel murine model. Miczek, KA., Akdilek, N., Ferreira, VMM., et al.[2023]

The relationship between alcohol consumption and violence is complex and influenced by various social, cognitive, and biological factors, meaning not everyone who drinks will become aggressive.

Research has identified potential intervention strategies, such as cognitive training and psychopharmacology, that could help manage aggressive behavior related to alcohol use, suggesting avenues for clinical treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Translational clinical neuroscience perspectives on the cognitive and neurobiological mechanisms underlying alcohol-related aggression. Beck, A., Heinz, AJ., Heinz, A.[2021]

In a study involving 35 young healthy adults, moderate alcohol consumption was found to increase proactive (unprovoked) aggression while decreasing brain responses in areas associated with self-control, such as the prefrontal cortex, indicating a potential mechanism for alcohol-induced aggression.

The research revealed that individuals with higher baseline aggression levels were more likely to exhibit proactive aggression when intoxicated, while reactive aggression was linked to increased activity in the amygdala and ventral striatum, suggesting different neural pathways for these types of aggression under the influence of alcohol.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neural and Behavioral Correlates of Alcohol-Induced Aggression Under Provocation. Gan, G., Sterzer, P., Marxen, M., et al.[2022]

Cognitive retraining significantly improved cognitive functions such as attention, memory, and information processing in a study of 8 detoxified male alcoholics over six weeks, with daily one-hour sessions for the treatment group.

The control group, which received less frequent counseling, showed no changes in cognitive function, highlighting the effectiveness of structured cognitive rehabilitation for addressing neuropsychological deficits in abstinent alcoholics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuropsychological rehabilitation of alchoholics : a preliminary report. Mathai, G., Rao, SL., Gopinath, PS.[2021]

In a study involving 26 participants (13 with a history of alcohol dependence and 13 healthy controls), those with alcohol dependence exhibited higher rates of aggressive responses compared to controls during a simulated aggression task, indicating a link between chronic alcohol use and increased aggression.

fMRI results showed that healthy controls had greater activation in brain areas associated with emotional and behavioral control (like the frontal and prefrontal cortex) when provoked, suggesting that these regions may help regulate aggressive behavior more effectively than in individuals with a history of alcohol dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neural correlates of impulsive aggressive behavior in subjects with a history of alcohol dependence. Kose, S., Steinberg, JL., Moeller, FG., et al.[2022]

Alcohol dependence is linked to increased violent behavior, with both animal and human studies showing that early-life stress and genetic factors can heighten this risk by affecting brain neurotransmission.

The interaction of these factors leads to heightened activity in the amygdala and reduced function in the prefrontal cortex, which together contribute to impulsive aggression and increased alcohol consumption.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive and neurobiological mechanisms of alcohol-related aggression. Heinz, AJ., Beck, A., Meyer-Lindenberg, A., et al.[2022]

Cognitive bias modification of attention (CBM-A) training effectively reduced alcohol attentional bias in heavy drinking students, but this effect was only observed in the regular training condition, not in the gamified version.

The introduction of gamification in the training did not improve motivation to train and may have even had negative effects on motivation, highlighting the need for careful evaluation of gamified interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Attentional Bias Modification With Serious Game Elements: Evaluating the Shots Game. Boendermaker, WJ., Sanchez Maceiras, S., Boffo, M., et al.[2020]

In a study involving 50 healthy young men, alcohol intoxication led to decreased activity in key brain areas associated with self-control, such as the prefrontal cortex, during aggressive behavior, suggesting that alcohol impairs decision-making related to aggression.

Interestingly, while intoxicated participants showed heightened activation in the hippocampus, their aggressive actions were positively correlated with activity in certain prefrontal regions, reinforcing the idea that alcohol-related aggression may stem from prefrontal dysfunction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The neural correlates of alcohol-related aggression. Denson, TF., Blundell, KA., Schofield, TP., et al.[2019]

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