What are the effects of alcohol on GABA?

Mina Draskovic, B.Psy., reviewed this content for accuracy on November 24, 2023

Meet GABA, your brain’s chill pill. Years of heavy drinking can disrupt GABA networks and reinforce addiction.

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What is GABA?

Gamma-aminobutyric acid (γ-Aminobutyric acid, or GABA), is the primary inhibitory neurotransmitter in the central nervous system. Its job is to regulate brain activity by inhibiting nerve transmission by helping to reduce or inhibit the activity of nerve cells.

When nerve cells become overactive, GABA steps in. GABA is crucial for maintaining a balance between excitatory and inhibitory signals in the nervous system.

Here’s what you should know about how GABA works:

When GABA binds to its receptors on a neuron, it opens ion channels that allow chloride ions to enter the neuron. This influx of negative ions makes the neuron more negatively charged, which makes it less likely to fire an action potential, the electrical signal that travels along a neuron.
GABA is synthesized from another neurotransmitter, glutamate, through decarboxylation. Glutamate is the brain’s main excitatory neurotransmitter. Even though glutamate is excitatory, synthesizing GABA from glutamate helps maintain the overall equilibrium necessary for proper brain function.
GABA acts on two types of receptors: GABA-A receptors and GABA-B receptors.
- GABA-A receptors are ionotropic, allowing ions to flow through channels when activated by GABA. Opening of these channels leads to a quick inhibitory effect on the neuron.
- GABA-B receptors are metabotropic, which means they activate second messenger systems. These have a more modulatory and slow-acting effect on the neuron.
GABAergic signaling is involved in regulating many physiological processes, including motor control, anxiety, sleep, and overall excitability of the nervous system.
GABA is also associated with the regulation of brain wave patterns. It plays a role in the generation of alpha and theta brain waves, which aid with relaxation and certain states of consciousness.

Does alcohol bind to GABA receptors?

As an indirect agonist of GABA, alcohol doesn’t bind to GABA receptors directly. Instead, it binds to specific allosteric sites on GABA-A receptors, which are the primary mediators of inhibition in the central nervous system. By binding to them, alcohol enhances the inhibitory effects of GABA.

Mihic and Harris suggest that “alcohol enhances the GABAA-mediated chloride flow into cells and may thereby enhance neuronal inhibition,” producing feelings of relaxation and sedation. As you increase the dosage, alcohol starts influencing other neurotransmitters to counteract GABA’s calming effects. This can:

Disrupt the balance between neurotransmitter systems.
Disrupt the delicate balance of inhibition and excitation.
Lead to structural and functional changes in the GABA-A receptors, affecting your tolerance, dependence, and withdrawal from alcohol.

When alcohol binds to those sites on GABA receptors, it kicks off a bunch of effects that play out differently, depending on how much you drink.

How does heavy drinking affect GABA?

Alcohol may initially enhance GABA, but chronic alcohol exposure ultimately disrupts and depletes essential inhibitory signaling in the brain. Your brain becomes hard-wired to ethanol and you start needing more booze to achieve the same effect.

Let us explain.

The more you drink, the less your brain is capable of producing GABA. Fewer GABA molecules available to bind receptors mean your brain signals a lack of vital inhibition. Persistent alcohol exposure prompts GABA receptors to decrease and undergo structural changes.
GABA neurotransmitters pull back from the synapse early, which shortens signaling and reduces GABA’s ability to exert inhibitory effects before being recaptured into the presynaptic neuron.
Brain cells compensate for the depression of activity by becoming less sensitive to alcohol and GABA over time. Without enough GABA inhibition, glutamate excitation goes unchecked. This leads to neuronal injury, cell death, and brain damage.

Neural networks activate excessively whenever alcohol is not present to tamp down firing. …the brain compensates for the acute depressant effects under the conditions of habitual heavy use. These neuroadaptive changes are reflected in neural hyperexcitability via downregulated inhibitory signaling, which becomes apparent as withdrawal symptoms. (Marinkovic, et. al.)

Glutamate is your brain’s main excitatory neurotransmitter. It stimulates neural activity and is involved in learning, memory, and cognition. GABA and glutamate have an important interrelated relationship in the brain: GABA calms the brain, while glutamate fires it up. Together, they help maintain a delicate balance of neuronal activation and inhibition that supports healthy brain functioning.
When alcohol withdrawal kicks in, GABA and glutamate are in an imbalance. This rebound hyperexcitation and glutamate surge provoke destructive rounds of excitotoxicity that can erode cognition over time.

The effects of chronic ethanol administration are influenced by adaptations in GABAA receptor function, expression, trafficking, and subcellular localization that contribute to ethanol tolerance, dependence, and withdrawal hyperexcitability. (Kumar, et. al.)

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The recovery process begins with alcohol detox. This is an essential first step, where we safely and comfortably help your body cleanse from alcohol toxins and bring harmony to your brain’s chemical wiring. The medical professionals at our detox center closely monitor your progress to ensure a smooth and safe detox experience.

How do reduced levels of GABA lead to alcohol dependence?

When alcohol disrupts GABA, it can slowly push you down the slippery slope to addiction.

After a drink or two, alcohol enhances GABA activity, leading to sedation, muscle relaxation, and intoxication. The more often you become exposed to heavy alcohol, the brain adapts to counteract these effects by downregulating GABA receptors and decreasing GABA sensitivity.

Mary-Anne Enoch, M.D. suggests that “ethanol induces plasticity in GABAA receptors: tolerance is associated with generally decreased GABAA receptor activation and differentially altered subunit expression.”

These adaptations reduce the sensitivity to alcohol, so you need a higher dose to achieve the same effects. Eventually, your tolerance to alcohol rises and you find yourself on the highway to addiction.

When subjected to frequent binge episodes, the brain compensates for the acute depressant effects of alcohol to restore homeostasis… The countervailing effects include down-regulation of GABAA-mediated inhibitory signaling, and a hyperresponsive (i.e. upregulated) excitatory glutamatergic function. The resulting hyperexcitability becomes apparent upon cessation of prolonged misuse in alcohol use disorder (AUD), and is reflected in withdrawal symptoms including insomnia, irritability, anxiety, autonomic hyperactivity, and even seizures. (Marinkovic, et. al.)

Marinkovic, et. al. conclude that these neuroadaptive changes lead to tolerance and physiological dependence on alcohol, and may be involved in the increased risk of chronic relapse.

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GABA and alcohol withdrawal

Alcohol’s effects on GABA signaling are central to the development of alcohol withdrawal. When you suddenly stop drinking after a long period of excessive alcohol consumption, your brain and body react physically and emotionally to the absence of alcohol. This happens because of the neurotransmitter imbalance in the central nervous system.

If you’re addicted to alcohol, your brain has adjusted to its presence. Remember those neuroadaptive changes in your brain that happen when you become dependent? Your brain gets used to booze constantly messing with its signaling. GABA activity gets tamped down while glutamate goes into overdrive.

When you suddenly stop drinking, the brain is in shock: there’s no alcohol left to enhance GABA’s calming effects, leaving glutamate to fire faster than GABA can handle. Your neurons become so overwhelmed with too much activity that they may get damaged or die from all that excess energy zipping around.

This is where alcohol’s excitotoxic effects kick in.

Depending on the amount you have been drinking and how often, the severity of alcohol withdrawal can go from mild to more dangerous. In moderate to severe cases, alcohol withdrawal can progress to a dangerous condition called alcohol withdrawal syndrome. This is the most extreme form of withdrawal featuring hallucinations, fever, seizures, confusion, and agitation that can lead to death if left untreated.

How do decreased GABA levels lead to excitotoxicity?

We now know that chronic excessive drinking leads to a depletion of GABA signaling over time, despite the initial enhancement of GABA activity. The more you drink, the more GABA goes down. At the same time, glutamate levels go up.

With less GABA activity, glutamate excitation goes unchecked. This pushes neurons into overdrive, becoming hyperexcitable and firing rapidly without restraint.

Research suggests that “neuronal degeneration in adult brain arising during chronic alcohol exposure is, or is likely to be, via “‘excitotoxicity.’” Excitotoxicity refers to neuronal damage and death triggered by excessive glutamate activity stimulating neurons to the point that they become overactivated. We’re not surprised—alcohol is toxic to your nerves.

This neuronal overexcitation can cause tremors, seizures, and anxiety during alcohol withdrawal. The excitotoxic programming of neuron death contributes to the long-term destruction of brain cells and neurological damage.

…alcohol-induced oxidative stress, heightened glutamatergic excitotoxicity, exacerbated neuroimmune response, and their collective effects [lead] to neurodegeneration and potential association with certain neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease. (Kamal, et. al.)

Are the effects of alcohol on GABA irreversible?

The effects of alcohol on GABA can be serious, but it seems that the activity of this crucial neurotransmitter can improve with abstinence. Because of alcohol’s far-reaching negative effects on health, once you quit, your entire body and mind may improve.

However, some damage may become permanent if there is long-term, excessive alcohol abuse. There’s good news, though: even for those with years of heavy drinking, sobriety allows the brain to start restoring GABA function and recovering neural equilibrium.

Here’s what you need to know:

GABA levels and flow can regenerate over weeks to months of sobriety as the brain rebounds.
GABA receptors and channels also regenerate to some degree, but alterations in subunit composition may remain, especially in people with an extensive drinking history.
Functionality improves in brain regions such as the cortex, reward system, and cerebellum when alcohol is removed, although full reversal takes time.
If drinking has caused neuron death via excitotoxicity and nutritional deficiency, brain volume loss can continue even after weeks of abstinence.

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What health benefits does GABA have?

By slowing certain brain functions, GABA produces a wide range of benefits for the brain and the rest of the body. Let’s take a look at some.

GABA reduces stress and anxiety. By inhibiting excitatory neurotransmission, GABA helps induce feelings of calm and relief.
GABA activity promotes sleep by quieting wake-promoting nerve signals. Enhancing GABAergic transmission can shorten sleep latency, increase deep sleep time, and improve sleep quality.
GABA elevates mood and alleviates depression. Research links low GABA levels with depression and related mood disorders: “increasing evidence points to an association between major depressive disorders (MDDs) and diverse types of GABAergic deficits.”
Proper GABA signaling prevents neuronal overload so attention and focus can sharpen. GABA boosts concentration, working memory, and information processing. A 2012 study suggests that “GABA concentration is reduced in children with ADHD.”
GABA receptors occur along pain pathways. Increased GABAergic signaling is associated with reduced pain perception in migraines, fibromyalgia, and diabetic neuropathy.
GABA supplementation lowers systemic blood pressure in people with hypertension. Chinese researchers show that “GABA injection can enhance the [arterial baroreceptor reflex] function in spontaneously hypertensive rats and adjust heart rate to reduce the blood pressure fluctuation.”
GABA is vital for keeping seizures in check. Many anti-seizure drugs act by amplifying inhibitory GABA function within the brain to prevent uncontrolled neuronal firing.

Any disruptions in GABAergic signaling can have significant implications for brain function, and mental and physical health. Alcohol dampens GABA transmission and allows neurons to fire excessively without restraint, lowering your inhibitions and causing issues with cognition and emotional stability.

The best thing you can do for your brain is to quit alcohol.

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Alcohol and GABA FAQ

What are the symptoms of a lack of GABA?

Deficits in the vital GABAergic inhibition in the cerebral cortex can manifest in many ways:

Increased anxiety
Panic attacks
Insomnia
Tremors
Tingling sensation
In the most severe cases, seizures

People predisposed to psychiatric disorders such as schizophrenia and bipolar disorder may face exacerbated mood instability and potential excitotoxic frontal cortex damage during alcohol withdrawal when they abruptly quit drinking. This happens because alcohol’s enhancive effects on GABAA receptors are lacking. The resulting glutamatergic surge past compromised GABAergic transmission reduces seizure threshold and risks neural injury.

It’s important to restore GABAergic function through receptor subunit expression or allosteric modulation and alleviate associated functioning issues.

Does alcohol increase or decrease GABA?

While acute alcohol exposure enhances GABA-A receptors, chronic excessive alcohol consumption depletes GABAergic function. Alcohol initially increases GABA’s sedating effects through positive allosteric interactions and by increasing inhibitory chloride flux. Over time, heavy drinking dampens and depletes GABA receptors through loss of GABAergic neurons, reduced GABA synthesis, and decreases in high-affinity GABAA receptor subtypes.

This receptor downregulation enables tolerance buildup: your brain adapts to higher alcohol concentrations through these GABA signaling deficits. When you stop drinking, this sudden abstinence from alcohol creates a hyperexcitable state from the excessive concentration of glutamate, inciting withdrawal symptoms. Some of the symptoms can be potentially dangerous as they damage the neural tissue of the cerebral cortex.

How do you restore GABA receptors?

After long periods of heavy drinking, getting those GABA receptors back in working order is key to overcoming alcohol use disorder. The brain changes that decrease GABA and allow glutamate to go nuts have to be undone. You can buy some time by using benzodiazepines to directly activate GABAA receptors and rapidly stabilize withdrawal hyperexcitability. This keeps things stable while the brain rewires itself.

It takes some work to grow new GABA neurons and get receptors to bounce back. Some doctor-prescribed meds and supplements may help the recovery process. It’s all about nurturing the rebuilding of a balanced signaling system in the brain’s cortex after too much drinking distorts its equilibrium.

The dual action of alcohol (increasing and decreasing GABA) underlines the importance of understanding how different concentrations of ethanol impact GABAergic signaling. Strike a balance, as deviations can contribute to the complex effects of ethanol on the nervous system, influencing behaviors associated with alcohol use.

Better yet, quit alcohol altogether and let your brain’s chemical wiring recalibrate naturally.

What does high GABA feel like?

By hyperpolarizing the synaptic transmission to inhibit firing, GABA’s actions on both ionotropic GABA-A and metabotropic GABA-B receptors exert an overall calming effect. You feel relaxed and stress-free. Sedative substances such as benzodiazepines and barbiturates can enhance these GABAergic effects recreationally. Even natural GABA supplements may mildly enhance mood and sleep by crossing the blood-brain barrier to activate central receptors.

In certain psychiatric disorders such as bipolar disorder, excessive GABAergic transmission risks depressive phases, requiring caution with GABAergic substances. But for most, heightened GABAergic tone brings stability, resilience, centeredness, and mellow energy by putting the brake pedal on neural excitation. The delicate balance between excitation and inhibition modulates our brain states.

What is the role of allosteric modulators in the treatment of alcohol dependence?

Allosteric modulators play a crucial role in addressing alcohol dependence by influencing neurotransmitter systems, including GABA receptors. Research indicates that certain allosteric modulators, such as those acting on GABA-A receptors, can enhance the inhibitory effects of GABA, mitigating the excitatory impact of alcohol. This modulation helps alleviate withdrawal symptoms and reduces the reinforcing properties of alcohol, making it a potential target for therapeutic interventions.

How does the nucleus accumbens contribute to alcohol-related disorders?

The nucleus accumbens, a key brain region involved in reward and motivation, is heavily implicated in alcohol-related disorders. Research suggests that alcohol stimulates the release of neurotransmitters, affecting the nucleus accumbens and creating a reinforcing loop.

…alcohol administration causes release of dopamine in a brain region (the nucleus accumbens) that is a key member of a group of linked structures associated with the development of addiction.

This neural reward pathway can contribute to excessive alcohol consumption and the development of alcohol-related disorders. It’s important to understand the intricate interplay between the nucleus accumbens, neurotransmitter release, and alcohol-seeking behavior in order to unravel the complexities of alcohol use disorders.

Is alcohol a GABA agonist?

Alcohol may be considered to be an indirect GABA agonist. It doesn’t bind directly to GABA receptors, but it does increase the activity of GABA receptors indirectly by acting as a positive allosteric modulator.

This means that alcohol binds to a site on the GABA receptor that is different from the site that GABA binds to, but it changes the shape of the receptor in a way that makes it easier for GABA to bind and activate the receptor.

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What neurotransmitters are involved in becoming dependent on alcohol?

There are several key neurotransmitters that play a huge role in increasing the risk for alcohol dependence. Systematic reviews and studies showed that “multiple neurotransmitter systems of the brain reward systems including GABA, glutamate, dopamine, serotonin and opioid peptides are involved in alcohol reinforcement.”

Alcohol excites the GABA neurotransmitter and its receptors into inhibitory overdrive at first. But the brain tries to balance things out over time, altering signaling cascades and the composition of tissues like the amygdala to turn down GABA’s volume knob. When you stop heavy drinking, it can then overamplify neural activity, triggering anxiety and restless distress.
Dopamine, the neurotransmitter of reward and motivation, is also heavily tied up in alcohol dependence. Chronic alcohol consumption affects signaling cascades and dopamine receptor availability in pathways like the mesolimbic pathway. This leads to blunted dopamine activity, contributing to low motivation and mood states that can drive continued drinking in a cycle of short-lived relief.
Glutamate, the major excitatory neurotransmitter, experiences alterations linked to dependence. As an antagonist of NMDA glutamate receptors, alcohol significantly impacts their density and subunit composition within areas like the frontal cortex during periods of heavy drinking. Consequences include potential uncontrolled glutamate release during withdrawal, surging activation of compensatory signaling, and excitotoxic damage promoting relapse.

It’s the complex interplay between the dampening of GABA and dopamine alongside possible excessive glutamate activity that becomes “the ball and chain” pulling brains burdened by dependence back to alcohol.

What role does the central amygdala play in alcohol withdrawal syndrome?

The central amygdala is a key player in alcohol withdrawal syndrome. As a part of the brain’s fear circuit, it becomes hyperactive during withdrawal, contributing to anxiety and heightened stress responses. This neuroadaptation is closely tied to GABAergic neurotransmission, where the absence of alcohol disrupts the inhibitory balance.

The neuroadaptation in the central amygdala is particularly significant in the context of psychiatric disorders and bipolar disorder, where the central amygdala’s influence on emotional states becomes even more pronounced.

Systematic reviews emphasize the relevance of receptor subtypes and their activity in the central amygdala during chronic ethanol consumption. Studies on sex differences, such as those conducted by Cagetti E and Finn DA, underscore the intricate interplay between the central amygdala and gender-specific responses to alcohol withdrawal.

Investigations into individuals with alcohol use and alcohol withdrawal symptoms provide valuable insights into the nuanced factors influencing the central amygdala’s hyperactivity during abstinence from alcohol. The impact of chronic ethanol consumption on receptor activity, exemplified by the work of Sieghart W, highlights the long-lasting alterations in the GABAergic system within the central amygdala.

How long do brain changes from addiction persist?

The effects of alcohol dependence on the brain’s structure and neurochemistry can linger long into abstinence, even after alcohol withdrawal symptoms subside. From receptor and neurotransmitter disruptions to erosion of gray matter, recovering addicts fight an uphill neurological battle—one reason why relapse rates remain so discouragingly high.

One study revealed normalization of some prefrontal cortex abnormalities after 5 weeks sober. So while post-acute withdrawal can continue for months, evidence indicates cognitive behavior therapy can help remodel addiction circuits over time.

Resources

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Edden, R. A., Crocetti, D., Zhu, H., Gilbert, D. L., & Mostofsky, S. H. (2012, July 1). Reduced GABA Concentration in Attention-Deficit/Hyperactivity Disorder. Archives of General Psychiatry. https://doi.org/10.1001/archgenpsychiatry.2011.2280

Mihic, S. J., & Harris, R. A. (1997). GABA and the GABAA Receptor. Alcohol Health and Research World, 21(2), 127-131. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826832/

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