Some theories suggest that GABA is the mind’s natural calming signal. It’s said to be the neurotransmitter that might relieve anxiety, help people get good sleep, relax, and wind down. By reducing overactivity in the brain, GABA might affect empathy, emotional intelligence, attention, and cognition. Read on to learn about the science of GABA.
GABA is the main inhibitory neurotransmitter in the brain, which means that it functions as the mind’s brakes. It slows down and stops the firing of brain cells and brings the mind to a state of relaxation and calmness .
GABA counters the main excitatory neurotransmitter, glutamate. The brain has a smart way to balance activation and relaxation, noise and silence, yin and yang. It does so through glutamate and GABA .
We can think of GABA and glutamate in the brain as if on a scale:
As always, balance is key. On the extreme side, studies suggest too much glutamate can cause seizures and mania. But an overly stimulated GABA system, such from high doses of drugs like Valium, can cause extreme sedation and even coma. In fact, some general anesthetics are hypothesized to bring about a state of deep unconsciousness by enhancing GABA [2, 3, 4].
However, many factors can throw this balance off. In our modern, urban world and fast lifestyles, GABA might often take the toll.
Some studies suggest that when the mind is constantly activated, under stress, or anxious, glutamate increases, GABA levels drop, and so does stress resilience. Have in mind that these are complex scientific theories, and GABA is just one part of the equation [5, 6, 7, 8].
Researchers believe that GABA reduces the rate at which neurons fire, which is important for normal, healthy, daily functioning. But it may be especially relevant when neurons in certain parts of the brain become too excited, which has been linked with anxiety, headaches, muscle tension, chronic pain, and Parkinson’s disease symptoms [9, 10].
It’s questionable how GABA acts on cognition since it seems to be relaxing, not stimulating. On the other hand, we know that people cannot focus when stressed and anxious. Poor cognition is one of the main symptoms of mental health disorders like schizophrenia and anxiety [11, 12].
Other scientists believe GABA might be a sort of peace-promoting neurotransmitter, since some studies have linked its activity with better emotional intelligence, easier socialization, and increased empathy. These links are still inconclusive, however [13, 14].
Many parts of the brain are naturally high in GABA. The concentrations of GABA in some brain regions are > 1000 times higher than of other neurotransmitters in any other part of the brain .
According to the prevailing hypothesis, the main relaxing neurotransmitter, GABA, is made directly from the main stimulating neurotransmitter, glutamate. The brain makes GABA in several important steps :
Once GABA is made, it’s released to achieve its effects. Afterward, neurons quickly take GABA back inside to be stored and used again next time. Neurons seem to selfishly store GABA, where its amounts are 200x higher than outside the cells, in the brain’s bloodstream .
Some research suggests that GABA is especially high in the amygdala, the brain’s gateway for generating fear in response to danger. In anxiety, the fear response is increased without any real danger. In line with this theory, GABA may decrease the fear response in the amygdala and reduce anxiety .
GABA needs to bind to receptors in the brain in order to achieve an effect. It can act on two receptors in the brain called :
What’s the difference between them and why does it matter?
Scientists suspect that GABA-A activation does not have the same effects as GABA-B activation in the brain. GABA-enhancing drugs often target one receptor subtype more – such as to induce rapid relaxation and sleepiness (GABA-A) .
Recently, GABA-C receptors were also discovered. Some researchers believe GABA-C may be especially important for restorative, slow-wave sleep .
GABA-B are slow-acting and more complex. When activated, the wakefulness-boosting cAMP stops being produced. Some researchers posit that this may be a reason why GABA may help with sleep in the long-term [1, 25].
Based on the available research, GABA-B activity may be important for :
Some researchers think that GABA-B activation may be less sedative and less hypnotic. They hypothesize it might be beneficial for cognition and memory, since some drugs that activate GABA-B like Phenibut are nootropics, but more high-quality human studies are needed [31, 32].
When we talk about GABA-associated effects and disorders, it’s important to know that these disorders are not necessarily due to GABA levels or production as such. They can stem from issues with GABA reuptake or the availability of certain GABA receptors.
Additionally, the majority of studies covered in this article deal with associations only, which means that a cause-and-effect relationship hasn’t been established.
GABA supplement studies are separately outlined where available. There is insufficient evidence to support the use of GABA supplements for any health condition.
GABA supplements have not been approved by the FDA for medical use. Supplements generally lack solid clinical research. Regulations set manufacturing standards for them but don’t guarantee that they’re safe or effective. Speak with your doctor before supplementing.
GABA supplements possibly help reduce high blood pressure, according to some clinical studies.
In one clinical study, a fermented milk drink containing GABA (10-12 mg of GABA per 100 mL, taken daily) reduced systolic and diastolic blood in people with high blood pressure after 12 weeks. In another study, a chlorella supplement containing GABA (20 mg twice daily) reduced systolic blood pressure in people with borderline high blood pressure after 12 weeks, but the study had several limitations [35, 36].
GABA seems to play a role in getting a good night’s rest. Scientists have proposed this since the 60s when the first sleep-inducing drugs that activate GABA (called barbiturates) started to be used .
GABA mostly acts on slow-wave, restorative sleep. Drugs that block GABA (GABA-B) increase wakefulness and REM, dreaming sleep .
According to one theory, GABA deficiency is linked with insomnia. Proper large-scale studies are lacking to back up this theory. Small-scale studies point to associations, but the data are mixed.
In one brain imaging study of 32 people, those with insomnia had 30% lower brain GABA levels compared to healthy people. The authors concluded that insomnia sufferers had lower GABA in this study as they weren’t taking sleep medications that could affect GABA levels .
In another study of 40 people, those with insomnia had lower GABA in specific brain regions implicated in emotional balance and cognition (ACC) .
But in another study of 33 people, GABA levels in some brain regions were higher in people with insomnia. Lower GABA was linked to staying awake longer after waking up in the middle of the night and to poorer sleep quality in those with insomnia [41, 42].
Some scientists suspect that people with insomnia may have had increased GABA as a result of the brain’s first attempt to reduce hyperarousal – an adaptive response. Over time, this response is thought to die down and GABA brain levels are hypothesized to drop in the whole brain [43, 42].
Low brain GABA and high glutamate were also linked to sleep apnea in a study of 36 people. Theoretically, low GABA in sleep apnea could be a sign of the body’s inability to relax, which might activate the fight-or-flight response and increase heart disease risk. Data are lacking to back up this speculation, though .
No proper clinical trials support the use of GABA supplements for sleep.
In one clinical trial of 40 people, GABA from fermented rice germ improved insomnia and sleep after 4 weeks. It reduced the amount of time it takes to fall asleep and increased the quality of sleep. This study was funded by the supplement manufacturer (RFE-GABA by Natural Way Co. Ltd) and no other studies have replicated their findings .
In mice, this combination enhanced sleep quality, duration, and reduced the time it takes to fall asleep. Mice given a high dose of GABA experienced better sleep quality even under the influence of caffeine. These findings can’t be extrapolated to humans [47, 48, 49].
The brain’s electrical activity is measured by brainwaves, such as alpha, beta, theta, delta, and gamma. According to one unproven, experimental theory, GABA may play an important role in this process – it might work to synchronizes different brain cells, affecting both cognition and relaxation .
Benzodiazepine drugs, which increase GABA-like activity, increased sustained attention in animals when they needed to focus and enhanced relaxation during rest. Researchers say GABA activation may synchronize neurons by making gamma waves more powerful but less frequent .
But the effects of benzodiazepine drugs on GABA are not the same as GABA produced in the brain or GABA supplements. For example, benzodiazepines can cause memory problems and other side effects if used longer than indicated.
Some scientists believe that a natural boost in GABA is linked to better cognitive function and more powerful gamma waves. Abnormal gamma brainwaves and low GABA were linked to cognitive problems in studies of people with schizophrenia. These associations haven’t been properly verified .
GABA supplements boosted alpha brainwaves – the main meditative, relaxing brainwaves – in a study of 13 people. They also reduced beta brainwaves, which are more linked to regular waking consciousness. But this study was too small to draw any solid conclusions from it .
One theory says that alpha brainwaves are what “helps the brain stay calm.” One of the ways meditation is hypothesized to work – and calm the mind – is by increasing brain GABA levels and alpha brainwaves. This theory hasn’t been verified in large-scale human studies .
Alpha waves have also been linked to creativity, selective attention, and being able to access stored knowledge voluntarily. Some scientists believe that natural GABA activity in the brain possibly drives all alpha brainwaves, but they lack proper human data to support this viewpoint [55, 56].
Higher cortical GABA levels were linked to higher intelligence, IQ, and cognitive performance in a brain imaging study of healthy people. It was suggested that this could be because people who pay attention to everything without discriminating what’s important are less intelligent. GABA is inhibitory – it is thought to suppress irrelevant information from the surroundings to enhance cognition .
It has also been proposed that functional GABA receptors enhance learning and neuroplasticity, the ability of the brain to change throughout life .
Scientists believe GABA may reduce distraction in the brain, which makes it possible to react and make quicker decisions .
Limited evidence has linked low GABA in certain brain regions to poor cognition in:
Larger, well-designed studies are needed to determine the exact role of GABA in human cognition.
Another experimental theory says that people with low GABA may be prone to emotional imbalances, while those with high GABA may be more empathic and in-tune with other people’s feelings. This scientific hypothesis has not yet been verified in large human studies.
GABA was increased in a brain region called the ACC, which plays a unique role in cognition and emotions. This region connects the emotional brain (limbic system) to the rational brain (prefrontal cortex). Some scientists consider that GABA may enhance emotional connections, while low GABA might reduce empathy in people with autism and schizophrenia [64, 14].
Only a couple of other studies have explored this link:
Larger studies are needed to determine the impact of GABA on emotional intelligence in humans.
Some researchers think GABA may affect digestion both as a neurotransmitter that connects the gut to the brain and as a gut hormone. It’s found throughout the gut and in surrounding nerves. The gut lining also has many GABA receptors that aid in digestion and may help balance electrolyte levels .
It has been suggested that GABA may help digest food, increase gastric acid production, and reduce stomach pain via the gut-brain axis. GABA-producing gut bacteria reduced abdominal pain in rats by stopping nerves from sending pain signals to the brain. Human data are lacking [68, 69].
GABA may affect appetite by acting on the hypothalamus, a part of the brain implicated in appetite regulation and energy use. Fasting increased GABA levels in the hypothalamus in mice. The effects of GABA on appetite in humans are unknown .
According to one unverified theory, depression is linked with GABA deficiency. In some studies, people with depression had reduced GABA levels in the brain and blood as well as abnormal GABA receptors. GABA was proposed to be low in specific brain regions in depression, especially in people with melancholic and treatment-resistant depression .
Some scientists believe that GABA reduces resilience to stress and may contribute to depression in the first place, but this has never been confirmed .
It has been suggested that GABA activity might help the brain make new brain cells – called neurogenesis, which has been linked to improved mood and better chances of overcoming depression in some small-scale studies. Additionally, certain antidepressants may work by increasing brain GABA and neurogenesis [71, 8].
Researchers are investigating these links in animals. Mice deficient in GABA receptors can’t respond to GABA and develop severe depression. Baby mice without genes that code for specific GABA receptors developed depression after being separated from their mothers. We can’t know how these findings relate to mental health in humans [71, 72].
According to the GABA-deficit hypothesis, the main cause of HPA axis overactivation – the body’s central stress response system – in the brain is low GABA. This hypothesis has not been verified in large human studies .
The GABA-deficit hypothesis suggests that chronic stress can reduce brain GABA, which in turn leads to an overactive emotional response via the HPA. Supposedly, stress hormones then rise in the brain (CRH and ACTH), creating a feedback loop that additionally lowers GABA and contributes to anxiety .
Scientists supporting this theory claim that GABA relieves fear and anxiety and calms the HPA axis, acting as a “natural Valium” .
GABA is also suspected to control serotonin activity in some brain areas. Mice with serotonin brain cells unresponsive to GABA develop depression and anxiety .
By using flumazenil, a drug that blocks GABA-A receptors, researchers suggested that people with panic attacks, anxiety, and PTSD have fewer receptors in the brain that can respond to GABA .
When given to healthy people, this drug had no effects since it could not saturate all the receptors that control GABA action. But it could trigger panic attacks during symptom-free periods in people prone to them. The authors speculated that this might be because people with panic disorders have fewer receptors, so the drug occupies them all and completely blocks natural GABA activity .
Other researchers are investigating whether American ginseng may boost GABA in the brain, but its effects on GABA in humans are unknown. This herb protected sleep-deprived mice from anxiety, HPA overactivation, and brain inflammation by increasing GABA. Clinical trials are needed .
On the one hand, drugs of abuse seem to increase GABA, which contributes to feelings of reward, pleasure, craving, and withdrawal. But on the other hand, increasing GABA activity by other means has been proposed as a means to reduce addiction and withdrawal by affecting the same emotional pathways .
New drugs that slightly activate GABA in the brain are being developed for reducing drug addiction. Baclofen is an older drug that acts on GABA and is used to treat alcohol, opioid, cocaine, nicotine, and amphetamine dependence [77, 78].
Baclofen reduced cocaine addiction in mice, possibly by activating GABA-B and decreasing dopamine release. Dopamine is scientists suspect often drives the addictive behavior and reinforces it. Baclofen also reduced activation of the limbic system – implicated in emotions – to cocaine .
Some scientists have described pain as just too much activity in the brain. They explain that pain can arise when signals from brain cells and nerves are not turned off properly within pain pathways. In this sense, nerve overactivity is said to often underlie chronic nerve pain after injury [81, 82].
After an injury, glutamate can become dominant and shunt GABA. According to this theory, glutamate then increases inflammatory substances and free radicals. It activates other surrounding cells, which also become inflamed. Pain arises and the process is said to continue chronically because there is nothing to stop it .
GABA and GABA-like drugs are being researched for putting a stop to chronic nerve pain by relaxing the nerves and blocking excessive signaling .
In a brain imaging study of 39 people, those with more intense osteoarthritis pain had lower brain GABA .
But researchers point to a problem: the amount of GABA activity needed to reduce severe pain may also cause too much sedation. One drug that mimics GABA (THIP) reduced chronic cancer pain in 60% of the cases in a trial of 14 people. But it also caused sedation, euphoria, dizziness, and nausea .
Limited evidence suggests a link between low GABA activity and diseases like Parkinson’s. Stopping or slowing down the decline in brain GABA levels is being researched as a potential means of preventing or improving Parkinson’s Disease. However, clinical trials are still lacking .
A rise in GABA reduced nerve injury in oxygen-deficient brain tissues .
GABA is likely needed for proper brain and nerve development. Although in adults GABA is the “brake,” in early life GABA seems to be excitatory – it acts more as the gas that speeds up brain development. GABA is needed for making new brain cells (neurogenesis), for their development, and for building brain connections and circuits early on in life .
Controversial studies have suggested an association between GABA deficiency and ADHD in children. Some scientists have proposed that low brain GABA can cause too much uncontrolled activity in the brain, which can reduce attention and affect behavior. This theory has not been proven. In one study of 42 children, those with ADHD had lower brain GABA levels. These findings have not been replicated .
There is insufficient evidence to suggest that GABA affects exercise performance. Proper trials are lacking.
In a clinical trial of 11 resistance-trained men, GABA (3g/day) increased two specific GHs after exercise: immunoreactive and immunofunctional GH. These hormones are hypothesized to improve muscle adaptation to resistance training and boost muscle mass .
Despite a lack of evidence, some athletes use GABA supplements to increase sleep quality since a lack of sleep harms performance. Others use valerian to improve sleep. Animal studies suggest that valerian might increase GABA, but no human studies support this mechanism .
Scientists are investigating whether GABA increases GH in rats by acting directly on the pituitary where GH is produced .
Prolonged exercise caused fatigue and reduced glutamate in the brains of rats. GABA levels dropped in some brain regions as well, since GABA is made from glutamate. These pathways remain unexplored in humans .
GABA is said to calm the brain and reduces its activity, thus, scientists suspect it normally helps prevent seizures. One theory suggests that when GABA levels drop, the brain becomes over-excited and the risk of seizures increases. Human studies have yet to explore this link .
Animals with acquired or inherited epilepsy have abnormal GABA brain activity .
Chronic fatigue can be a controversial diagnosis, and some hypotheses have associated glutamate overactivation and low GABA with it. In 2 studies of 66 people, those with fibromyalgia had lower GABA and higher brain glutamate, which scientists suspect might worsen pain and fatigue. Proper human studies are needed [94, 95].
Phenibut stimulates GABA activity and is used to reduce symptoms of chronic and emotional fatigue in some countries, but it has not been approved in the US due to a lack of proper effectiveness and safety data [30, 96].
A beverage with GABA reduced work-related physical and psychological fatigue in a study of 30 men. It improved energy levels and problem-solving abilities. This study was small and had design flaws, however, making its findings unreliable .
As GABA is hypothesized to reduce over-activation, it is also being researched for relaxing tense muscles .
The effects of GABA on libido in humans are not known. Animal findings are mixed.
However, GABA, reduced sexual behavior in female rats .
Some researchers have suggested that glutamate may be more important when it comes to sexual attraction. In mice, sexual attraction increases glutamate in the brain while GABA blocks it .
Unproven theories posit that low GABA and high glutamine may trigger chronic migraine attacks and headaches. GABA activity is suggested to reduce brain overactivity and potentially prevent or reduce headaches, but human studies on pure GABA supplements are lacking [105, 106].
GABA increases heat resistance in plants and reduces heat damage in cells. Its effects on heat resistance in humans are unknown .
Only the GABA-enhancing drug phenibut has been studied for similar effects. Phenibut reduced exertion from physical labor in extreme heat. In one trial, it increased heat resistance, protecting the body from high temperatures .
In physically exhausted people, a single dose of phenibut (250 mg) prevented overheating, increased tolerance to heat, improved oxygen supply, and helped maintain high working capacity .
A balance of GABA and glutamate is hypothesized to promote healthy aging. Aging generally leads to declines in balance, fine motor skills, and motor coordination. Among many other factors, GABA activity is thought to maintain brain function and motor performance in older adults. GABA levels decline with aging, which has been linked with poor motor and cognitive performance. However, this link still remains unclear since large human studies haven’t been carried out .
According to another unproven theory, since GABA might maintain brain plasticity – enabling the brain to continue learning and adapting – then increasing GABA in older adults is hypothesized to promote lifelong plasticity. This is still highly uncertain .
If your goal is to increase GABA to improve your stress-related issues – including those of insomnia or anxiety – it’s important to talk to your doctor, especially your mental health is significantly impacting your daily life.
Your doctor should diagnose and treat the condition causing your symptoms.
Remember that the existing evidence does not suggest that low brain GABA causes cognitive or mental health problems. Complex disorders like anxiety always involve multiple possible factors – including brain chemistry, environment, health status, and genetics – that may vary from one person to another.
There is no way to precisely measure GABA levels in the body. This is because GABA is concentrated in specific regions in the brain, inside the cells. Only brain imaging studies can estimate GABA levels in the brain, but these methods are not available to the public.
Additionally, changes in brain chemistry are not something that people can change on their own with the approaches listed in this article. Instead, the factors listed here are meant to reduce daily stress and support overall mental health and well-being.
Therefore, you may try the additional strategies listed below if you and your doctor determine that they could be appropriate. Read through the approaches outlined here and discuss them with your doctor before trying them out. None of these strategies should ever be done in place of what your doctor recommends or prescribes.
You may also want to read through this post.
No clinical evidence supports the approaches listed below to increase brain GABA. Below is a summary of the existing animal and cell-based research, which should guide further investigational efforts. However, the studies listed below should not be interpreted as supportive of any health effect.
Make sure to speak with your doctor before taking any supplements. Let them know about any prescription or over-the-counter medication you may be taking, including vitamins and herbal supplements.
Remember that dietary supplements have not been approved by the FDA for medical use. Supplements generally lack solid clinical research. Regulations set manufacturing standards for them but don’t guarantee that they’re safe or effective.
A couple of synthetic drugs have been made by modifying GABA and enabling it to cross the blood-brain barrier. They should only be used with a prescription in countries in which they have been approved.
GABA supplements are widely available and found in large health and grocery stores. However, GABA supplementation probably does not affect GABA levels in the brain because GABA can’t cross the blood-brain barrier .
In theory, these supplements may affect GABA in the gut, circulation, and nerves, but these effects have not been proven and little is known about how fast GABA is metabolized.
Many people are claiming to have used Pharma-GABA and experienced beneficial effects. The Asian manufacturers claim that this form of GABA, produced through a fermentation process using a strain of lactic acid bacteria, is superior to other GABA supplements. They state that pharma-GABA is “pure” and that it can cross the blood-brain barrier. Pharma-GABA has been approved by the FDA as a food ingredient and is quite expensive .
However, no evidence exists to show that Pharma-GABA (or any other GABA) can cross into the brain. Studies using brain imaging would need to determine this, and none have been carried out to this date. Theoretically, PharmaGABA might have indirect effects – via the gut and nerves along the gut-brain axis – but this has not been proven either [R, R].
New brain imaging technology recently made it possible to measure neurotransmitter levels in the brain. However, this technology is still new and more studies need to clarify all the scenarios in which GABA levels are low and the brain regions involved.
This article focused on natural GABA fluctuations in the brain in various diseases and states. Some supplement studies also investigated GABA, though most studies are limited to animals. Clinical trials with GABA supplements are rare. There is insufficient evidence to recommend them for any health problem.
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