Gamma-aminobutyric acid (GABA) is an amino acid that acts as the main inhibitory neurotransmitter between nerve cells in the brain and spinal cord. Its natural function is to bind to GABA-A and GABA-B receptors on neurons to modulate and block impulses between nerve cells.
It plays a role in how people experience anxiety, fear, and stress. GABA slows down or blocks certain nerve signals in the brain, which sometimes reduces feelings of anxiety. Without the proper level of GABA activity in the body, nerve cells can become activated in ways that exacerbate certain conditions, such as anxiety disorders.
What is GABA?
Neurotransmitters are chemical messengers in the nervous system. GABA is a non-protein amino acid that acts as an inhibitory neurotransmitter throughout the central nervous system. It restricts nerve transmission by preventing neuronal stimulation.
GABA reduces a neuron's propensity to produce an action potential (stimulation of neurons), which reduces the likelihood that neighboring neurons will fire.
Errors in GABA signaling are associated with certain neurological and psychiatric conditions.
Difference between types of neurotransmitters
Inhibitory neurotransmitters like GABA block certain brain signals and reduce the activity of the nervous system. Another inhibitory neurotransmitter, serotonin, helps stabilize mood.
Excitatory neurotransmitters have the opposite effect: they stimulate certain brain signals and increase the activity of the nervous system. An example of an excitatory neurotransmitter is norepinephrine .
Unlike excitatory neurons, which stimulate the action potentials of excitatory nerves, inhibitory neurons reduce the likelihood of neurons firing.
When the action potential reaches the end of the axon of the gabaminergic neuron and triggers the release of GABA in the synaptic cleft, the following occurs:
- GABA binds to postsynaptic receptors on the target cell.
- In response, GABA receptors open chloride channels.
- The resulting release of negatively charged chloride ions in the postsynaptic (receptor) neuron makes it more negative on the inner side of the cell membrane and therefore less likely to trigger an action potential.
GABA activates the receptors in milliseconds and their concentration decreases in milliseconds. But the effect lasts longer because GABA is released relatively slowly from its receptor.
It is understood that a decrease in the action of GABA can contribute to mental disorders.
Proper GABA activity promotes a healthy stress response by preventing neuronal overexcitation.
Many things can affect GABA levels and the functioning of associated receptors, potentially contributing to anxiety. For example, it has been documented that external stressors and stressors at a young age can directly affect the functioning of GABA receptors, creating imbalances.
GABA deficiency is associated with cognitive deficits and this has clinical implications for people with schizophrenia . Problems with membrane transporters and GABA receptors, namely the lack of properly functioning GABA-A receptors, have been associated with several clinical features of schizophrenia, including hallucinations and cognitive impairment.
This opened avenues for understanding how GABA modulation can have therapeutic effects in people with schizophrenia.
Autism spectrum disorder
Although the exact pathology of autism spectrum disorder (ASD) is still unclear, studies in animals and humans have found an association between deficiencies in the function of excitatory (glutamate) and inhibitory (GABA) neurotransmitters and the main symptoms of TEA, including a deficit of limited interests and social reciprocity.
This shows that GABA does not work alone and that imbalances in this neurotransmitter can be influenced and / or influenced by other neurotransmitters and receptors.
Lower levels of GABA in the body are also associated with major depressive disorder (MDD). GABA probably works in collaboration with other neurotransmitters such as serotonin, which is also involved in mood disorders.
It has been suggested that GABA malfunction may also be a contributing factor to suicide.
In addition to mental health, GABA is also implicated in several disease states:
- Pyridoxine deficiency is a rare disease in which the vitamin pyridoxine is not available for GABA synthesis. The deficiency usually manifests as frequent seizures in childhood that do not respond to anticonvulsant treatment but respond well to vitamin supplementation.
- Hepatic encephalopathy has clinical features associated with elevated levels of ammonia, which can bind to GABA receptors and interfere with their proper function.
- Huntington's disease is characterized by symptoms associated with GABA dysfunction in the area of the brain that regulates voluntary movement.
- Dystonia (movement disorder) and muscle spasticity are believed to be associated with inappropriate GABA signaling.
Other associated neurotransmitters
Although GABA is considered the most abundant inhibitory neurotransmitter, it does not work on its own. Research suggests that dysfunction in GABA and other neurotransmitters, serotonin (5-HT) and corticotropin-releasing hormone (CRH), play a role in depressive disorders.
Drugs that act on GABA receptors have clinical value in the treatment of various diseases.
Medications that modulate GABA signaling include:
- Benzodiazepines : they bind to the GABA-A receptor, enhancing the sedative effect.
- Barbiturates: there are sedatives that increase the duration of GABA binding to the GABA-A receptor.
- Vigabatrin: used to inhibit the breakdown of GABA, which is effective in treating some types of epilepsy.
- Propofol: Promotes GABA function and is a sedative commonly used in general anesthesia.
- Flumazenil : Binds to the GABA-A receptor and can reverse benzodiazepine poisoning and improve mental status in hepatic encephalopathy.
- Baclofen: It is promotes the binding of GABA-B and is a muscle relaxant
- Valproic acid: inhibits the absorption of GABA, acts as a mood stabilizer and antiepileptic agent.
- Zolpidem: acts on the GABA-A receptor, providing a sedative-hypnotic effect.
- Gabapentin – Increases GABA synthesis and is commonly prescribed to treat neuropathic pain.
GABA is available in supplement form without a prescription. Manufacturers sell natural GABA tablets and capsules at different prices, claiming that their products can help reduce stress, induce a sense of calm, and promote (temporary) relaxation. It can be found isolated or mixed with other substances, such as melatonin, that promote sleep.
Are GABA supplements safe?
As with many herbal supplements, pregnant and lactating women should avoid taking GABA supplements due to the lack of available research demonstrating its safety in these populations.
If you are considering a GABA supplement, check with your doctor in advance.
Substances that affect GABA receptors, such as alcohol, are common drugs. Self-medication to achieve the effect of modulating GABA production or absorption is dangerous.
For example, alcohol promotes GABA receptor activity, often creating a temporary sense of calm and relaxation. But the effect is artificial and risky. You won't get the same effect over time, and tolerance issues can develop quickly, requiring the body to require more substance to achieve the same sensation.
Overdose or intake of multiple GABA regulating drugs (such as taking GABA supplements and drinking alcohol) can lead to 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 major problem. It is important to be honest with yourself about taking GABA modulating drugs, such as alcohol and benzodiazepines. In particular, the abuse of these two substances can cause cross tolerance and increase potential toxicity.
If you are unsure whether taking medications or supplements is becoming problematic, check with your doctor. Other resources you can visit to learn more about substance abuse include:
Get the word of drug information
If you experience symptoms of anxiety or depression, speak with your doctor before self-medicating with over-the-counter GABA supplements (for which there is still little research to support their benefits). Mood and anxiety disorders are complex and require professional treatment.
Medications that regulate GABA can have profound effects on people trying to relax, calm down, and fall asleep. But they carry a high risk of abuse, which can create even more problems. If you or your loved one is struggling with substance use or substance abuse problems, seeking professional treatment sooner rather than later can help minimize negative consequences.
Frequently asked questions
So far, scientists have identified more than 60 different neurotransmitters. They are divided into three groups according to their function: excitatory neurotransmitters, inhibitory neurotransmitters, and modulating neurotransmitters.