Mitigating the Disinhibiting Effects of Alcohol With Transcranial Magnetic Stimulation

This study aims to understand how brain stimulation affects decision-making and behavioral control after alcohol consumption. Many harmful events related to alcohol use are the result of impaired decision-making while intoxicated. Although there are medications that reduce alcohol cravings, there are few tools available to reduce the negative behavioral effects of alcohol once someone has already consumed it.

This clinical trial uses non-invasive brain stimulation, known as transcranial magnetic stimulation (TMS), to target a brain area called the prefrontal cortex, which helps regulate decision-making and self-control. TMS can increase or decrease activity in targeted brain areas using magnetic pulses. Two specific types of stimulation will be tested:

• iTBS (intermittent theta burst stimulation): typically increases brain activity
• cTBS (continuous theta burst stimulation): typically decreases brain activity

Participants will be healthy adults who report regularly drinking alcohol. Each participant will attend five sessions in a randomized, within-subject design. Across the sessions, participants will experience each of the following conditions:

• Alcohol + iTBS
• Alcohol + cTBS
• Placebo drink + iTBS
• Placebo drink + cTBS
• Alcohol + sham (placebo) stimulation

Each session will be conducted on a separate day and will include:

• A baseline set of tasks (before drinking or stimulation)
• Drinking either an alcoholic or placebo beverage
• TMS delivered during the rise and peak of blood alcohol concentration
• A second round of behavioral tasks administered at peak intoxication and again during the descending limb of the blood alcohol curve

The behavioral Go/No-Go Task will measure:

• How well participants can stop themselves from making automatic responses

The study's goals are to:

• Test whether brain stimulation can reduce impulsive behaviors under the influence of alcohol
• Understand the separate and combined effects of alcohol and TMS on decision-making
• Identify which type of TMS is most effective in modulating intoxicated behavior

The stimulation dose and session timing are designed to align with the typical rise and fall of blood alcohol levels. Each stimulation session will use a "ramping" protocol to gradually increase stimulation intensity, improving tolerability. Safety and tolerability will be carefully monitored.

This study builds on previous work showing that TMS can influence decision-making but is the first to examine whether TMS can be used during alcohol intoxication to improve behavioral control. If successful, the findings may lead to new interventions for preventing risky or harmful behaviors associated with alcohol use.

Inclusion criteria

• Age 21-29
• Must be competent in English
• BMI between 19 and 26
• At least a high school education
• Moderate alcohol users (e.g., at least occasional alcohol use, without meeting criteria for alcohol use disorder)
• Negative urine drug screen for illicit drugs
• Negative urine pregnancy test (if applicable) on testing days

Exclusion criteria

• History of seizures or a first-degree relative with seizure history
• History of head trauma or other CNS injuries
• Current or past psychiatric disorders (including substance use disorder, except nicotine or caffeine)
• Contraindications for non-invasive brain stimulation (e.g., metal implants, pacemaker)
• Currently pregnant or breastfeeding
• Current use of medications that lower seizure threshold
• Positive alcohol withdrawal symptoms
• Smokes more than five cigarettes per day (to avoid acute nicotine effects or withdrawal during visits)