What Is GABA?

A neurotransmitter known as gamma-aminobutyric acid

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GABA, which stands for gamma-aminobutyric acid, is an amino acid that serves as the primary inhibitory neurotransmitter (chemical messenger) blocking impulses between nerve cells in the brain. It is also a major inhibitory neurotransmitter in the spinal cord. Its natural function is binding to neuron receptors GABA-A and GABA-B to slow down their transmission and calm nervous activity. 

It plays a crucial role in how people experience anxiety, fear, and stress. When nerve signals fire too quickly and carry anxiety-inducing signals, GABA acts to slow the signals down, reducing overwhelming feelings of anxiety. Without the right level of GABA in the body, nerve cells are activated too often and can worsen certain mental conditions like anxiety disorder.

NMDA, AMPA and GABA receptors
JUAN GAERTNER/SCIENCE PHOTO LIBRARY / Getty Images

What Is GABA?

Gamma-aminobutyric acid is a non-protein amino acid in the human cortex that works as an inhibitory neurotransmitter throughout the central nervous system. It limits nerve transmission by decreasing a neuron's action potential (when a neuron sends information down an axon, away from the cell body). When the action potential drops below a certain level, the neuron will not generate action potentials and therefore not excite nearby neurons. 

Any misfiring in GABA signalling is associated with both neurologic and psychiatric conditions. Research suggests that GABA signalling is the basis of pharmacological treatments in neurology, psychiatry, and anesthesia.

The Difference Between Types of Neurotransmitters

Inhibitory neurotransmitters like GABA inhibit, or block, certain brain signals and decrease nervous system activity. Another major inhibitory neurotransmitter is serotonin, which helps stabilize mood. Any misfiring or imbalance of GABA consequently impacts nearby neurons and receptors, and therefore influences how one processes hormones like serotonin and dopamine, which are directly related to mood disorders.

Excitatory neurotransmitters have the opposite effect: They excite certain brain signals and increase nervous system activity. An example of an excitatory neurotransmitter is epinephrine, which helps neurons communicate with each other.  

Functions

Unlike excitatory neurons, which pass along a message to the next neuron by causing an excitatory post-synaptic potential, inhibitory neurons make the next neuron less likely to fire by causing an inhibitory post-synaptic potential. So when an action potential arrive at the axon terminal of a gabaminergic neuron and causes the release of GABA into the synaptic cleft to interact with its post-synaptic receptors, these receptors open channels for chloride ions. The rush of these negatively charged chloride ions into the receiving neuron makes it more negative inside, and thus less likely to fire.

GABA activates receptors within milliseconds and its concentration declines within milliseconds, but the synaptic current does not because GABA unbinds relatively slowly. In the brain, this has a calming effect. In the spinal cord, this process allows for sensory information integration and helps to create smooth movements. 

Disorders

Since GABA functions as a calming agent, low levels of this neurotransmitter have been associated with various mental health conditions, such as generalized anxiety. It is understood that decreased concentration of GABA promotes feelings of anxiousness. Low levels of GABA have also been associated with schizophrenia, autism spectrum disorder, and major depressive disorder.

Anxiety Disorders

The right amount of GABA promotes a healthy stress response by calming the system and preventing the excitation of nearby neurons. However, many things can impact GABA levels and associated receptor functioning. For example, it's been documented that external stressors and early life stressors can directly influence GABA receptor functioning, creating imbalances. These imbalances can cause problems in the way your body processes feelings of anxiety.

This also offers insight into how GABA can be harnessed through supplementation to help people suffering with anxiety disorders.

Schizophrenia

GABA deficits are associated cognitive deficits, and this has a clinical significance for people with schizophrenia. Problems with GABA membrane transporters and receptors, namely a lack of adequately functioning GABA-A receptors, have been found to contribute to the clinical features of schizophrenia including hallucinations and cognitive impairment. This is due to the inability of receptors to bind to GABA and the further impact this can have on nearby neurons like dopamine and serotonin.

Without an adequate amount of working GABA receptors (GABA hypofunction), pathologies related to schizophrenia run amok. This has opened avenues for understanding how GABA modulation can provide therapeutic benefit to people with schizophrenia.

Autism Spectrum Disorder

While the exact pathology of autism spectrum disorder (ASD) is still unclear, both animal and human studies have found associations between abnormalities in excitation (glutamate) and inhibition (GABA) neurotransmitter functioning and underlying ASD symptoms, including deficits in restricted interests and social reciprocity.

This highlights that GABA never works alone and any imbalance has a ripple effect on other neurotransmitters and receptors. While directional causality is not known, researchers suggest that ASD pathology is impacted by low concentrations of glutamate in adults and low GABA functioning in children, indicating a potential age-related alteration to these neurotransmitters that requires further study.

Major Depression

Lower levels of GABA in the body have also been associated with major depressive disorder (MDD), AKA bipolar depression. This can be explained by the inhibitory nature of this neurotransmitter impacting nearby neurons, including those related to the release of dopamine (feel good or bonding hormone). Not enough dopamine production is directly linked to the symptoms of depression.

Research has found low levels of GABA in patients with depression in several areas of the body, including the brain and spinal cord. It has been suggested that improper GABA functioning may also be a factor for people who have died by suicide.

Physical Conditions

Outside of mental health, GABA is also involved in several disease states:

  • Pyridoxine deficiency is a rare disease in which the vitamin pyridoxine is not available for the synthesis of GABA. Deficiency usually presents as frequent seizures during infancy that are resistant to treatment with anticonvulsants, but responds very well to vitamin supplementation
  • Hepatic encephalopathy's (neuropsychiatric abnormalities) has clinical features that are thought to be due to elevated ammonia levels binding to GABA receptors and impacting their proper functioning
  • Huntington's disease has symptoms that are partially caused by GABA deficiencies in the area of the brain that regulates voluntary movement
  • Dystonia (movement disorder) and spasticity are believed to be related to a deficiency in GABA signaling

Other Associated Neurotransmitters

While GABA is considered the most ubiquitous neurotransmitter, it does not work alone. Research suggests that GABA works in collaboration with other neurotransmitters, namely 5-HT and CRH, in affecting depressive disorders.

Uses

Medications

Medications that act on GABA receptors are of such clinical significance, both therapeutically and with regards to substance abuse, that it is said it is unlikely that any physician, regardless of specialty, will not encounter situations that involve GABA.

Drugs that modulate GABA signaling include:

  • Benzodiazepines: They bind to the GABA-A receptor, increasing the calming effect
  • Barbiturates: There are sedative drugs that increase the duration at which GABA binds to the GABA-A receptor
  • Vigabatrin: This is used to inhibit the breakdown of GABA, which is effective in helping treat epilepsy
  • Propofol: It promotes GABA functioning and is a sedative commonly used in general anesthesia
  • Flumazenil: This binds to the GABA-A receptor, and can reverse benzodiazepine intoxication and improve mental status in hepatic encephalopathy
  • Baclofen: It promotes GABA-B binding, and is a muscle relaxant
  • Valproic acid: It inhibits GABA uptake, and acts as a mood stabilizer and anti-epileptic
  • Zolpidem: It works on the GABA-A receptor for a sedative-hypnotic effect
  • Gabapentin: This increases GABA synthesis, and is commonly prescribed to treat neuropathic pain

Supplements

GABA has become widely available in supplement form due to its relevance in mood and stress management. People looking for a non-prescription, over-the-counter methods of treating anxiety turn to GABA for its promise to help them calm down and ease stress.

Manufacturers sell natural GABA in pills and capsules at a range of prices, claiming their products can help reduce stress, induce feelings of calmness, and promote (temporary) relaxation. It can be found as an isolate or blended with other substances like melatonin, which promotes sleep. 

Are GABA Supplements Safe?

Taking GABA supplements is considered safe. As with many other herbal supplements, pregnant and breastfeeding women should avoid taking GABA supplements due to a lack of available research showing its safety in these populations.

If you think GABA supplementation may be right for you, consult with your physician beforehand to rule out any contraindications or risk factors. 

Risks

The relaxing effect of GABA meeting its receptors has a high potential for abuse. In fact, substances that exert effects on the GABA-A receptor, like alcohol, are common drugs of abuse. Alcoholic beverages are just one such example.

Alcohol promotes activity on the GABA receptor, which means you feel temporarily calm and relaxed, but this is artificial and risky. You will not get the same effect over time, and issues can quickly arise when one’s tolerance increases and requires more of the substance (alcohol) to feel calm. Self-medicating to modulate GABA production or uptake is not advised.  

Overdosing or taking multiple GABA-modulating drugs (for example, taking GABA supplements and drinking alcohol) can result in respiratory depression due to increased GABA signaling in the brain stem.

When to Seek Help

While GABA has many benefits, it can also become a problem for people self-medicating with the substance. It is important to be honest with yourself about your consumption of GABA-modulating drugs like alcohol and benzodiazepines. These two substances of abuse, in particular, can create cross-tolerance (they begin to cancel each other out and efficiency is greatly decreased) because they behave in similar ways.

If you are unsure if your medication or supplement use is becoming problematic, talk with your doctor. Other resources you can visit to learn more about substance abuse include:

A Word From Verywell 

If you are experiencing symptoms of anxiety or depression, before self-treating with over-the-counter GABA supplements, talk to your doctor. Mood disorders are complex, and often require a variety of treatments. Plus, there is no way to measure your GABA levels at home. To be sure of any deficiency, neurotransmitter testing is necessary. It is advised to be under the supervision of a professional during and while decreasing or stopping usage of GABA supplements. 

GABA-modulating drugs can have a powerful pull for people struggling to relax, calm themselves, and sleep. But they also put them at increased risk of abuse, which can create even more problems. If you or a loved one is struggling with substance use issues or abuse, seeking treatment sooner rather than later can help minimize the negative effects.

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