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GABA Benefits: Sleep, Anxiety & Mood

Written by Ana Aleksic, MSc (Pharmacy) | Last updated:
Puya Yazdi
Medically reviewed by
Puya Yazdi, MD | Written by Ana Aleksic, MSc (Pharmacy) | Last updated:

GABA is the mind’s natural calming signal, according to some scientists. 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.

What is GABA?

Overview

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 [1].

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 [1].

One theory suggests that when GABA and glutamate are in harmony, the brain can function optimally [2, 3, 4, 5].

However, many factors can throw this balance off. In our modern, urban world and fast lifestyles, GABA might often take the toll.

Understanding the Research

When we talk about GABA-associated benefits or 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 brain activity is complex. Plus, many GABA studies deal with associations. Remember: association does not equal causation!

Benefits Associated with GABA: Sleep, Anxiety & Brain Health 

1) Sleep

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 [6].

GABA mostly acts on slow-wave, restorative sleep. Drugs that block GABA (GABA-B) increase wakefulness and REM, dreaming sleep [6].

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 [7].

In another study of 40 people, those with insomnia had lower GABA in specific brain regions implicated in emotional balance and cognition (ACC) [8].

US Veterans with PTSD and poor sleep had lower brain GABA levels, according to a brain imaging study of 45 people [9].

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 [8, 9].

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 [10, 9].

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 [11].

Limited human studies show that people with insomnia might have lower whole-brain GABA.

GABA Supplement Studies

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 [12].

Scientists are also investigating a combination of GABA and 5-HTP for sleep and fruit flies. They posit that this combination might raise both GABA and serotonin [13].

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 [14, 15, 16].

No valid human studies support the use of GABA supplements for sleep problems.

2) Brainwaves

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 [17].

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 [17].

Benzodiazepines also increased the power of beta brainwaves and reduced the power of alpha brainwaves in several human brain imaging studies [18, 19, 20].

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 [21].

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 [22].

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 [23].

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 [24, 25].

GABA activity is thought to sync brain cells. It’s been linked with creativity and alpha brainwaves.

3) Cognition and Intelligence

Higher cortical GABA levels were linked to higher intelligence, IQ, and cognitive performance in a brain imaging study of healthy people [26].

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 [26].

It has also been proposed that functional GABA receptors enhance learning and neuroplasticity, the ability of the brain to change throughout life [27].

Scientists believe GABA may reduce distraction in the brain, which makes it possible to react and make quicker decisions [28].

Limited evidence has linked low GABA in certain brain regions to poor cognition in:

  • Schizophrenia [21, 29]
  • Anxiety [30]
  • Depression [30]
  • Children and adolescents with a genetic disorder that causes brain tumors [31].

Larger, well-designed studies are needed to determine the exact role of GABA in human cognition.

A couple of small studies associated higher GABA in specific brain areas with higher IQ and better cognition, but more research is needed.

4) Emotional Intelligence

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.

In a small brain imaging study of 32 people, higher GABA brain levels were linked to higher emotional aspects of empathy [30, 32].

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 [33, 34].

Only a couple of other studies have explored this link:

  • People with schizophrenia had low GABA in some brain regions [21, 29]
  • Phenibut, which activates GABA receptors, increased emotional intelligence in 62 people with anxiety [35]
  • Brain GABA increased when 22 healthy participants saw sad faces, which suggests that GABA plays a role in recognizing and reacting to emotions [36]
  • Rats with autism have low brain GABA. Benzodiazepines, which act on GABA, improved their social interaction and cognition [37].

Larger studies are needed to determine the impact of GABA on emotional intelligence in humans.

One experimental theory says that GABA may increase empathy and emotional intelligence, but this hasn’t been confirmed.

5) Depression

According to one unverified theory, depression is linked with GABA deficiency [38].

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 [38].

Some scientists believe that GABA reduces resilience to stress and may contribute to depression in the first place, but this has never been confirmed [38].

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 [38, 5].

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 [38, 39].

Scientists have suggested that people with depression may have lower brain GABA, but this is still uncertain.

6) Anxiety

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 [38].

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 [38].

Scientists supporting this theory claim that GABA relieves fear and anxiety and calms the HPA axis, acting as a “natural Valium” [40].

Mice with dysfunctional GABA receptors develop anxiety, phobias, depression, and HPA hyperactivity. GABA activity reduces fearful memories and helps adapt to a changing environment [38, 41].

GABA activation reduced anxiety in rats with poor brain blood flow by boosting BDNF [42].

GABA is also suspected to control serotonin activity in some brain areas. Mice with serotonin brain cells unresponsive to GABA develop depression and anxiety [38].

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 [38].

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 [38].

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 [43].

Anxiety might be a state of GABA deficiency, according to one experimental theory that has yet to be verified.

7) Addiction

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 [44].

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 [44, 45].

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 [46].

Drugs or approaches that increase GABA activity are also being investigated for reducing withdrawal, as potential aids in the recovery process [45, 47].

GABA appears to have opposing effects on addiction. Drugs that slightly activate GABA are being researched for reducing drug addiction.

8) Pain

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 [48, 49].

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 [49].

GABA and GABA-like drugs are being researched for putting a stop to chronic nerve pain by relaxing the nerves and blocking excessive signaling [49].

In a brain imaging study of 39 people, those with more intense osteoarthritis pain had lower brain GABA [50].

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 [51].

One theory claims that pain is just too much activity–and too little GABA–in nerve cells. This hasn’t been confirmed in humans. 

9) Brain Cell Stability

Some researchers think GABA stabilizes and protects brain cells. They hypothesize it prevents an excessive rise in calcium that can trigger brain cell death [52].

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 [52].

A rise in GABA reduced nerve injury in oxygen-deficient brain tissues [53].

10) Brain Development

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 [54].

Scientists hypothesize that GABA may stabilize brain cells and aid brain development. Its exact roles in these processes are still unknown.

11) ADHD

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 [55].

12) Seizure Risk

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 [56].

However, we know that GABA-blocking drugs cause seizures, while anti-seizure drugs likely enhance GABA-signalling in the brain [56, 57].

Animals with acquired or inherited epilepsy have abnormal GABA brain activity [56].

Science has yet to clarify the effects of GABA on ADHD and seizures.

GABA Effects Beyond the Brain: Fitness, Heart & Gut Health 

13) Heart Health

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 [58].

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 [59].

In mice fed a high-fat diet, GABA prevented a rise in blood sugar, weight gain, and muscle damage. It was hypothesized to protect the heart from disease by normalizing metabolism [60].

In animals, the GABA-like drug phenibut protected the heart from stress and improved its pumping capacity. It indirectly increased nitric oxide, which relaxes blood vessels [61, 62].

14) Gut Health

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 [63].

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 [64, 65].

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 [66].

Naturally produced GABA seems to support gut and heart health, but more research is needed.

15) Exercise Performance

GABA Supplements

There is insufficient evidence to suggest that GABA affects exercise performance. Proper trials are lacking.

In a study of 9 volunteers, oral GABA increased growth hormone (GH) levels [67].

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 [68].

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 [69].

Scientists are investigating whether GABA increases GH in rats by acting directly on the pituitary where GH is produced [70].

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 [71].

No valid evidence supports the use of GABA supplements for enhancing exercise performance.

16) Energy Levels

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 [72, 73].

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 [74, 75].

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 [76].

17) Muscle Relaxation

As GABA is hypothesized to reduce over-activation, it is also being researched for relaxing tense muscles [77].

Certain drugs that enhance GABA activity reduce muscle spasms [78, 79].

In rats fed a high-fat diet, GABA prevented muscle damage and neutralized oxidative stress. Human data on GABA supplements and muscle damage are lacking [60].

GABA is hypothesized to help relax tense muscles and relieve chronic fatigue, but this hasn’t been proven.

18) Libido

The effects of GABA on libido in humans are not known. Animal findings are mixed.

Scientists suspect that GABA has complex effects on hormones and libido. In women, estrogen seems to suppress GABA while progesterone and its metabolites may increase it [80].

GABA activity might also enhance endorphins, which increase the sensations of pleasure [81].

However, GABA, reduced sexual behavior in female rats [82].

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 [83].

19) Headaches

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 [84, 85].

Two GABA-like drugs, gabapentin and phenibut, both reduce headaches [86, 87].

20) The Immune System

Scientists are investigating the effects of GABA on an overactive immune response and inflammatory cytokines and pathways in cells [88].

Despite some animal experiments, the impact of GABA on libido, headaches, and immune health is unknown.

21) Heat Resistance

GABA increases heat resistance in plants and reduces heat damage in cells. Its effects on heat resistance in humans are unknown [89].

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 [90].

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 [91].

22) Aging

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 [92].

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 [92].

Some research groups believe that GABA might increase heat resistance and act as an anti-aging compound, but future studies have yet to investigate these effects.

Limitations and Caveats

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.

Further Reading

Takeaway

GABA is the brain’s main inhibitory neurotransmitter. Scientists think it might act as the brain’s “breaks,” reducing overactivity and making it possible for people to relax and wind down.

Studies mostly focused on associations between GABA levels in certain brain areas and health problems. A link between low brain GABA and insomnia, anxiety, depression, cognitive impairment, and depression has been suggested.

Yet, there’s more we don’t know about GABA than we know. Future research has yet to verify many of these associations.

Lastly, only a handful of studies with GABA supplements were carried out. There’s no evidence to support their use.

About the Author

Ana Aleksic

Ana Aleksic

MSc (Pharmacy)
Ana received her MS in Pharmacy from the University of Belgrade.
Ana has many years of experience in clinical research and health advising. She loves communicating science and empowering people to achieve their optimal health. Ana spent years working with patients who suffer from various mental health issues and chronic health problems. She is a strong advocate of integrating scientific knowledge and holistic medicine.

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