- What is GABA? Function, Receptors & Supplements
- How the Brain Produces GABA
- GABA Receptors
- The Blood-Brain Barrier Issue
- What About Pharma-GABA?
- When to See a Doctor
- Other Factors that May Increase GABA
- Supplements & Diet
- Synthetic GABA Drugs
- Limitations and Caveats
- Further Reading
- Gaba Supplements: Glorious, Gimmicky or Just Garbage?
- Gamma-aminobutyric acid (GABA)
What is GABA? Function, Receptors & Supplements
Scientists believe that GABA might be the mind’s natural calming signal. It’s thought to help people get good sleep, relax, and wind down. Read on for a deep dive into the science of GABA, its function, receptors, and whether GABA supplements are worth the hype.
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 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].
One theory suggests that when GABA and glutamate are in harmony, the brain can function optimally [5, 6, 7, 8].
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 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].
How the Brain Produces GABA
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 :
- It usually starts with glucose, although the brain can alternatively use amino acids pyruvate
- Glucose is transformed into glutamate
- Glutamate is only then transformed to GABA
- Glutamate decarboxylase (GAD) is the main enzyme needed to make GABA from glutamate. It needs vitamin B6 to function 
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 .
Studies show GABA-A receptors act fast in response to GABA. They quickly block excited neurons and may lead to [1, 19, 20, 21, 22]:
- Relaxation and calmness
- Sedation or unconsciousness in excess
- Reduced anxiety
- Euphoria and pleasure, from stimulating the reward system
- Improved and relaxed breathing
- May impair memory (from medications)
Examples of substances that activate GABA-A are alcohol, benzodiazepines Valium, general anesthetics, and kava [23, 24, 1].
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].
the available research, GABA-B activity may be important for :
- Reducing stress
- Reducing general and social anxiety
- Increasing socialness and empathy
- Improving depression
- Boosting cognition
- Relaxing tense muscles
- Reducing chronic pain and inflammation [27, 28, 29]
- Improving chronic and mental fatigue (possibly) 
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 Phenibut are nootropics, but more high-quality human studies are needed [31, 32].
Baclofen and phenibut both activate GABA-B. They are being researched for muscle spasms, anxiety, and addictions. Phenibut is not approved in the US [33, 34].
The Blood-Brain Barrier Issue
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.
What About Pharma-GABA?
Many people are claiming to have used Pharma-GABA and experienced beneficial effects.
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–not as a dietary supplement-and it 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 .
When to See a Doctor
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 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 that focuses just on factors that may increase GABA.
Other Factors that May Increase GABA
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.
Supplements & Diet
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.
Synthetic GABA Drugs
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.
- Phenibut is made by modifying GABA with a phenyl group (beta-phenyl-GABA). In the US it’s classified as a supplement.
- Picamilon is made of GABA and vitamin B3 (niacin). It’s not approved in the US but some companies still sell it.
- GHB (Gamma-hydroxybutyrate), an illegal and dangerous drug of abuse.
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 GABA receptors, their function, and the issues marketed GABA supplements face. Aside from the research outlined in this post, other studies focused on how fluctuations in brain GABA might impact health.
A couple of clinical trials with GABA supplements have also been carried out, but these are rare. There is insufficient evidence to recommend GABA supplements for any health problem.
- GABA Benefits: Sleep, Anxiety & Mood
Gaba Supplements: Glorious, Gimmicky or Just Garbage?
Take-home message: – gamma-Aminobutyric acid (GABA) is a major neurotransmitter that regulates much of our brain function. It was previously thought that ingested GABA could not cross the blood-brain barrier, but new research suggests that it may be able to.
– Drugs that mimic the action of GABA are numerous, work in a variety of ways, and can have effects ranging from treating epilepsy to causing it.
– GABA supplements have shown some promise in early, small-scale studies, but a lot more research is needed to know if they truly help.
Lately, it seems that GABA supplements are being hawked on the corner of every pharmacy aisle and health food shelf. Marketed to promote relaxation, mental focus and sleep, GABA is even being sold by David’s Tea in the form of GABA guava tea. I found it while trying to buy some matcha powder. I don’t even guava, never mind guava with a side of inflated claims.
While promotions by influencers Olivia Culpo and Sarah Couture are pretty standard for any trendy supplement, (regardless of efficacy) the attention GABA has been given by known quacks Dr. Oz, Joseph Mercola orMike Adams has left me wondering about the science behind, and evidence for, these supplements.
Let’s start with the basics: what is GABA?
gamma-Aminobutyric acid (also written as γ-aminobutyric acid) is a neurotransmitter, specifically the major inhibitory one in all mammal’s central nervous systems (CNS). That means that it’s a chemical that binds to nerve cell receptors and hinders their ability to receive, create or send messages to other nerve cells (neurons).
Functionally, GABA is incredibly important. A lack of GABA leaves your central nervous system with too many neuronal signals and causes conditions epilepsy, seizures or mood disorders. Meanwhile, too much GABA means not enough brain activity and can lead to hypersomnia or daytime sleepiness.
You can learn more about GABA in this lovely video, and more about neurotransmitters in general in this one, although I’ve said all you’ll need to know for this article.
As the chief inhibitory neurotransmitter in the CNS, GABA and its receptors have been major targets for drug development.
Drugs that activate GABA receptors (called agonists) or increase the receptors' sensitivity to GABA (positive allosteric modulators) work to reduce the neuronal signals in the user’s brain, similar to what happens when you sleep.
Logically, they include many common sedatives barbital or Quaaludes, tranquillizers Valium, Ativan or Xanax and the most commonly used sedative, alcohol.
GABA reuptake inhibitors Deramciclane have similar effects, as they help to keep GABA in the vicinity of the receptors for longer.
On the flip side, substances that inhibit the activity of GABA (called antagonists) increase brain activity. That only sounds a good thing. The results are less Scarlett Johansson in Lucy, more uncontrollable seizures and death.
GABA antagonists, gabazine or bicuculline are only useful when studying seizures or to counteract overdoses of sedatives and tranquillizers. Some GABA antagonists are particularly scary poisons, causing death by disrupting the CNS’s control of basic body functions breathing.
The class of drugs we’re most interested in, however, are GABA analogues. These molecules are structurally similar to GABA, though they have different targets of action. GABA analogues include some big names you’ve probably heard of: Lyrica and gabapentin.
While both Lyrica and gabapentin are prescribed to stop seizures, treat neuropathic pain, and anxiety disorders, gabapentin is additionally used for the prevention of migraines.
Gabapentin has been a constant in my life for a few years now, as my mother was prescribed it for diabetic neuropathic pain just a few years after my partner was prescribed it for near constant migraines. I’ve personally seen GABA to be quite effective in its on-label uses, as the evidence shows it to be, but it was recently at the heart of one of the largest court settlements in US history.
The manufacturers of gabapentin were found to have been marketing it extensively for off-label uses the treatment of bipolar disorder, restless leg syndrome, hot flashes and stopping smoking.
While off-label prescribing is not uncommon, and usually fairly safe, there is no evidence that gabapentin is effective for the bipolar disorder it was being prescribed to treat or some of the other conditions for which it's being prescribed.
Presently gabapentin is again making headlines as its use as a recreational drug skyrockets. Many opioid users are misusing gabapentin to extend opioid highs or bypass drugs that block opioids effects, but its status as a non-controlled substance makes it difficult for law enforcement to control its unsanctioned use.
GABA and the Blood-Brain Barrier
GABA drugs are certainly useful, but why do we need all these GABA-receptor-activating or GABA- molecules in the first place? Why not just give patients GABA?
We have a highly selective membrane that keeps our blood and cerebrospinal fluid (or brain juice, if you will) separate: the blood-brain barrier (BBB). Some molecules, water, pass through it easily, other things, bacteria don’t. This membrane also contains special channels to diffuse important molecules one way or the other, glucose.
It’s a really important border, as drugs that cannot cross into the brain, or do so poorly, have much less of an effect than ones that do. For example, morphine can’t cross the BBB very well, but it’s close relative heroin can! Upon entry to the brain, heroin is converted into morphine, which is why heroin is so much more potent than morphine.
A 1958 study was the first to look at GABA’s relationship with the blood-brain barrier, and it found a lack of one: GABA could not cross the barrier.
Later studies in ‘58, ‘71, and ‘88 confirmed the barrier’s impermeability to GABA. The evidence seems all but clear until you throw a few more studies into the mix.
Studies done in ‘80, ‘81, ‘82 and ‘02 found that GABA did cross the blood-brain barrier, just in minuscule amounts.
Why the disagreement? Well, a few things. Some studies used a molecule just GABA in lieu of GABA, assuming the 1 extra OH group featured on 3-hydroxybutyric acid wouldn’t make a difference, but it may have.
Since many studies don’t report the type of GABA used, it’s hard to compare results. Some studies administered their GABA by injecting it straight into animal’s body cavities, others by injecting it into veins.
Most importantly, the BBB permeability of GABA has never been studied in humans!
What we do know is that human’s BBB contains transporters for GABA, implying that GABA can enter/exit the brain through these channels. In mice it was found that GABA was removed from the brain 17 times faster than it entered.
This could explain the conflicting study results. It may not be that GABA cannot enter the brain, but just that it’s removed from it very rapidly.
GABA as a Supplement
Even if it cannot cross the BBB however, GABA could still be affecting your brain.
The enteric nervous system (ENS) is the network of neurons that control your gastrointestinal system. The ENS contains many GABA receptors, and GABA itself, and is connected to the brain through the vagal nerve. It’s been proposed that ingested GABA is able to affect the body even without crossing the BBB through its interactions with the ENS.
We don’t know at this point how GABA is affecting the brain, but we have good evidence that it is. Several studies have shown reductions in markers of stress in patients given dietary GABA.
On their own the success stories from the consumers who buy GABA supplements are meaningless but taken along with the research findings, they may just show that there is something to these supplements.
We’ll need a lot more research to know for sure if GABA supplements are helpful or not. That being said, they are expensive ( most supplements) and if you’re not anxious, experiencing insomnia or very stressed out they’re probably not worth it. There don’t appear to be many side effects or drug interactions, but until more research is done I’d tread carefully.
I did ask my partner, who took gabapentin (a GABA analogue) for years if he ever experienced any focusing of his mind or relaxation as the GABA supplements claim. He said a definitive no.
Want a cheaper option for relaxation? Tea. You can even try some GABA tea, a strain of green tea specially fermented to accumulate GABA. Maybe I’ll pick some up… just not that guava flavoured stuff.
Gamma-aminobutyric acid (GABA)
Also available: HTML version.
During those stressful weeks in school or at work, your brain becomes very excited and as a response, your body normally produces GABA to bring your nervous system back to a state of calm. Without GABA, you will increasingly become restless and anxious, and might experience seizures.
GABA is an amino acid which acts as a neurotransmitter in the central nervous system. GABA’s natural function is to reduce the activity of the neurons to which it binds. It inhibits nerve transmission in the brain, calming nervous activity. This can make a person feel more tranquil and give him or her sense of wellbeing.
The nervous system is made up of individual nerve cells called neurons. They serve as the body's wiring. Nerve signals are transmitted through the length of a neuron as an electrical impulse. When a nerve impulse reaches the end of the neuron it can jump over to the next cell using chemical messengers called neurotransmitters.
In the central nervous system, which consists of the brain and the spinal cord, neurotransmitters pass from neuron to neuron.
Neurotransmitters are stored at the end of each neuron. When neurotransmitters reach neighbouring neuron, the neurotransmitters click into specialized receptor sites much as a key fits into a lock. When enough neurotransmitters attach to the receptors, the neuron “fires,” sending an electrical impulse down its length.
GABA is made in brain cells from glutamate, and functions as an inhibitory neurotransmitter – meaning that it blocks nerve impulses. Glutamate acts as an excitatory neurotransmitter and when bound to adjacent cells encourages them to “fire” and send a nerve impulse. GABA does the opposite and tells the adjoining cells not to “fire”, not to send an impulse.
Without GABA, nerve cells fire too often and too easily. Anxiety disorders such as panic attacks, seizure disorders, and numerous other conditions including addiction, headaches, Parkinson's syndrome, and cognitive impairment are all related to low GABA activity.
GABA hinders the transmission of nerve impulses from one neuron to another. It has a calming or quieting influence. A good example to help understand this effect is caffeine. Caffeine inhibits GABA release. The less GABA, the more nerve transmissions occur.
Think what too much coffee feels : that is the sensation of glutamate without enough GABA.
The reason caffeine does this is that other molecules can bind to the neuron near the GABA binding site and influence GABA's effect.
1883: Gamma-aminobutyric acid was first synthesized, was first known only as a plant and microbe metabolic product.
1950: GABA was discovered to be an integral part of the mammalian central nervous system.
Many people take GABA as a supplement to improve mood and relieve anxiety. However, there has not been enough research to uncover the side effects and risks of GABA supplements.
There is little evidence that it does anything. Recent medical belief is that GABA will not pass the blood brain barrier.
The blood brain barrier is a biologic firewall between the body's general blood circulation and the blood circulation that supplies the brain. It prevents many of the chemicals and drugs which circulate in the blood from reaching the brain.
This would mean GABA cannot cross from the body into the brain; consequently it leaves people dubious if then GABA would work.
Nevertheless, people may still take GABA because it could act as a placebo. Also, it may have some affect that hasn't been reported yet, therefore more research needs to be done.
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