What Is GABA?

A neurotransmitter known as gamma-aminobutyric acid

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Gamma-aminobutyric acid (GABA) is an amino acid that serves as the primary inhibitory neurotransmitter between nerve cells in the brain and spinal cord. Its natural function is binding to receptors GABA-A and GABA-B on the neurons to modulate and block impulses between nerve cells. 

It plays a role in how people experience anxiety, fear, and stress. GABA acts to slow or block certain nerve signals in the brain, sometimes reducing feelings of anxiety. Without the right level of GABA activity in the body, nerve cells can be activated in ways that exacerbate certain conditions, like anxiety disorders.

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

What Is GABA?

Neurotransmitters are chemical messengers in the nervous system. GABA is a non-protein amino acid that functions as an inhibitory neurotransmitter throughout the central nervous system. It limits nerve transmission by preventing the stimulation of neurons.

GABA reduces a neuron's tendency to produce an action potential (neuron stimulation), making neurons less likely to excite nearby neurons. 

Misfiring in GABA signaling is associated with certain neurologic and psychiatric conditions.

The Difference Between Types of Neurotransmitters

Inhibitory neurotransmitters like GABA block certain brain signals and decrease nervous system activity. Another inhibitory neurotransmitter, serotonin, helps stabilize mood.

Excitatory neurotransmitters have the opposite effect: They promote certain brain signals and increase nervous system activity. An example of an excitatory neurotransmitter is norepinephrine.  

Functions

Unlike excitatory neurons, which promote excitatory nerve action potentials, inhibitory neurons make neurons less likely to fire.

When an action potential arrives at the axon terminal of a gabaminergic neuron and causes the release of GABA into the synaptic cleft, the following occurs:

  • GABA binds to the target cell's post-synaptic receptors.
  • In response, GABA receptors open chloride ion channels.
  • The resulting rush of negatively charged chloride ions into the postsynaptic (receiving) neuron makes it more negative on the inside of the cell membrane, and thus less likely to fire an action potential;.

GABA activates receptors within milliseconds, and its concentration declines within milliseconds. But the effect lasts longer than that because GABA unbinds from its receptor relatively slowly.

In the brain, GABA activity has a calming effect. In the spinal cord, this process allows for sensory information integration and helps to create smooth movements. 

Disorders

It is understood that decreased action of GABA can contribute to mental health conditions.

Anxiety Disorders

Appropriate GABA activity promotes a healthy stress response by preventing excess neuronal excitation.

Many things can impact GABA levels and associated receptor functioning, potentially contributing to anxiety. For example, it's been documented that external stressors and early life stressors can directly influence GABA receptor functioning, creating imbalances.

Schizophrenia

GABA deficits are associated with cognitive deficits, and this has clinical significance for people who have schizophrenia. Problems with GABA membrane transporters and receptors, namely a lack of adequately functioning GABA-A receptors, have been associated with certain clinical features of schizophrenia, including hallucinations and cognitive impairment.

This has opened avenues for understanding how GABA modulation might provide therapeutic benefits to people with schizophrenia.

Autism Spectrum Disorder

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

This illustrates that GABA doesn't work alone, and an imbalance of this neurotransmitter can be affected by and/or affect other neurotransmitters and receptors.

Major Depression

Lower levels of GABA in the body have also been associated with major depressive disorder (MDD). GABA likely works in collaboration with other neurotransmitters, such as serotonin, which is also involved in mood disorders.

It has been suggested that improper GABA functioning may also be one of the factors that has a role in 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 with frequent seizures during infancy that are resistant to treatment with anticonvulsants but respond well to vitamin supplementation.
  • Hepatic encephalopathy has clinical features that are associated with elevated ammonia levels, which may bind to GABA receptors and impact their proper functioning.
  • Huntington's disease is characterized by symptoms that are associated with GABA dysfunction in the area of the brain that regulates voluntary movement.
  • Dystonia (movement disorder) and muscle spasticity are believed to be related to a deficiency in GABA signaling.

Other Associated Neurotransmitters

While GABA is considered the most ubiquitous inhibitory neurotransmitter, it does not work alone. Research suggests that dysfunction of GABA and other neurotransmitters, namely serotonin (5-HT) and corticotrophin releasing hormone (CRH), play a role in depressive disorders.

Uses

Medications

Medications that act on GABA receptors are of clinical significance in the treatment of a variety of disorders.

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 of GABA binding to the GABA-A receptor
  • Vigabatrin: This is used to inhibit the breakdown of GABA, which is effective in helping treat certain types of 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 is available in non-prescription supplement form. 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?

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 are thinking about GABA supplementation, consult with your healthcare provider beforehand. 

Risks

Substances that exert effects on the GABA receptors, like alcohol, are common drugs of abuse. Self-medicating to achieve the effects of modulation of GABA production or uptake is dangerous.  

Alcohol, for example, promotes GABA receptor activity, often creating a temporary feeling of calm and relaxation. But the effect is artificial and risky. You will not get the same effect over time, and issues can quickly arise with tolerance, which makes the body require more of the substance to achieve the same feeling.

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 your body's natural production of GABA has many benefits, artificial means of altering GABA activity can be a serious problem. 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 and an increase in potential toxicity.

If you are unsure if your medication or supplement use is becoming problematic, talk with your healthcare provider. 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 (which as of yet have limited research to support their benefits), talk to your healthcare provider. Mood and anxiety disorders are complex and require professionally directed treatment.

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

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