Top 15 Natural Ways to Increase GABA

GABA is the main inhibitory neurotransmitter in the brain, meaning that it prevents our neurons from over-firing and being over-stimulated. According to some researchers, supplementing GABA may help with stress, anxiety, relaxation, muscle tension, convulsions, insomnia, and epilepsy.

Many herbs could increase GABA, and almost all of them are considered relatively safe; however, none of them have been approved by the FDA. Also, you can find GABA supplements that are (or contain) synthetic GABA agonists, which could cause dependence. These supplements are purchased by many uninformed consumers.

What is GABA?

GABA (gamma-aminobutyric acid) is a neurotransmitter released by the neurons in the brain. It plays an irreplaceable role in the brain and the nervous system. Neurons that produce GABA are called GABAergic neurons and are distributed throughout the brain [1].

GABA is the main inhibitory neurotransmitter preventing over-stimulation of neurons. An abnormal GABA decrease can produce mental illness and symptoms such as anxiety, depression, insomnia, convulsions, and epilepsy [2, 3].

Mechanism

When a molecule binds to a receptor, it stimulates its activity. The molecule that binds to the receptor is the agonist.

When a GABA agonist (can be a drug or any other substance produced inside or outside the body) interacts with the receptor, the person will feel the effects of stimulated GABA activity, which usually results in relaxation and reduced anxiety [4].

However, you don’t need to consume GABA agonists to stimulate GABA activities in the brain. Some drugs, herbs, and supplements increase the effect of GABA by increasing the frequency and duration of the activation of the GABA channel, instead of binding GABA receptors directly like a traditional agonist [5].

These substances are known as positive allosteric modulators (PAMs) of GABA [6].

We will have to dive a little into these pharmacological jargons because there is an intrinsic difference between agonists and positive allosteric modulators. The positive allosteric modulators have significantly less potential for abuse [7].

Barbiturates and benzodiazepines are the exceptions. These are two common positive modulators of GABA that can cause dependence after prolonged usage.

These are two classes of potent tranquilizers, and consistent usage results in a decrease in postsynaptic GABA activities (the neuron is not working as properly as before or is down-regulated) [8].

While some positive modulators of GABA (barbiturates and benzodiazepines) cause dependence, herbal supplements that positively modulate GABA, such as kava, one of the most psychoactive herbs, do not meet the criteria for abuse or dependence [9].

GABA has two major receptors, GABAA and GABAB [10]. Although more GABA receptors exist, we will only discuss these two major families.

GABAA activation results in sedation, relaxation, reduced anxiety, and short-term memory impairment [11].

Examples of substances that are agonists or positively modulate GABAA are alcohol, benzodiazepines, and kava [12, 13].

Agonists and positive allosteric modulators of GABAB play an important role in alleviating stress, general and social anxiety, depression, and muscle tension [14].

GABAB activation causes less sedative, hypnotic, and memory impairment effects than GABAA unless large doses are taken [15, 16].

Examples of drugs that act on GABAB include baclofen and phenibut, which promote muscle relaxation and alleviate anxiety. Phenibut has reported nootropic properties [17, 18].

Why Do Some People Supplement GABA?

Remember to talk to your doctor before adding a new supplement to your daily regimen. Many substances have unexpected interactions, and GABA has not been approved by the FDA due to insufficient evidence and an incomplete safety profile.

The level of GABA activity is correlated with feeling relaxed and calm [19].

In modern society, we often don’t recognize numerous sources of stress. The noise of an urban area or long shifts are factors that increase stress and decrease well-being [20, 21].

A study of 36 volunteers published in a prestigious journal showed that prolonged stress and living in an urban area both increased susceptibility to mental illness and increased amygdala activity, a brain region involved in stress, panic, and threat response [22].

Stress causes cognitive, judgment, and decision-making impairment, decreases attention, and produces memory loss [23, 24, 25]. Having a functional GABA system, along with other genetic traits, enhances the ability to cope with stress, anxiety, and related mental illness.

On top of the factors that could induce stress and mental illness, many of us are more vulnerable to stress, anxiety, and mental health problems due to genetic factors [26]. These variations could increase one’s vulnerability to anxiety, depression, insomnia, bipolarity, schizophrenia, and spasticity [27].

Some people believe that supplementing GABA reduces stress and vulnerability to stress-induced mental illness. GABA promotes peacefulness and relaxation [28].

Also, an active GABA system helps develop neurons by increasing the brain-derived neurotrophic factor (BDNF), a protein that promotes the growth and survival of neurons in the brain [29, 30].

Maintaining normal levels of BDNF is vital for overall brain development and function since low levels of BDNF have been correlated with mental illness and low brain plasticity [31, 32].

Meanwhile, higher levels of BDNF are beneficial for learning, memory, cognitive function, and overall brain health. Sustained BDNF levels could even prevent or reduce cognitive decline associated with aging [33, 34].

Substances that May Increase GABA Activity

Many people turn to supplements in an attempt to increase GABA activity in their brains. The current research on many of these supplements may be promising, but it is in its early stages and is thus considered insufficient to prove increases in GABA activity. Talk to your doctor before adding any new supplements to your health routine.

Non-Herbal Methods

Many unregulated supplements sold in the market could increase GABA directly. However, many of them could lead to dependence. Here are some popular non-herbal ways to increase GABA.

1) Exercise

Exercise promotes well-being, alleviates stress, and reduces the risk of mental illness [35].

However, exercise does not directly increase GABA. In fact, prolonged exercise reduces GABA [36]. But don’t worry, this is a temporary physiological response.

Chronic exercise, on the contrary, enhances GABA synthesis in the brain [37]. Exercise might not be the optimum way to increase GABA activity in the short term.

2) Meditation and Yoga

Many studies have shown that meditation has scientifically confirmed benefits [38].

Meditative exercises, such as yoga, may slightly increase GABA. A study conducted on 19 yoga practitioners has shown that GABA increased by 27% after a yoga session [39].

Another human study (300 volunteers) also showed that yoga practice reduces anxiety [40].

People who meditate have increased GABA and reduced cortisol and norepinephrine levels, which are the enemies of GABA [41, 42].

Herbal Compounds

It is important to note that none of the herbs below have been approved by the FDA for any purpose or medical claim, and some may very well be toxic to the liver, heart, or other organs. Much more testing will be required to determine whether any of them is safe and effective for any medical purpose. Talk to your doctor before trying any of them.

1) Kava (Kavain)

Kava is an unapproved substance which has been flagged as potentially dangerous by the FDA. More clinical studies are required to determine whether it is safe or effective for any purpose.

Kava (Piper methysticum) is a plant traditionally used by people from the South Pacific islands as a beverage and medicine [43].

Kava’s effect on GABA is complex because the plant contains 6 psychoactive compounds. One of the major kava psychoactive compounds is kavain, and it acts by stimulating GABAA receptors as a positive allosteric modulator [44, 45].

Kava is usually prepared as a drink with the powder of its root. The recommended method for drinking kava is using premium kava prepared with the traditional water extract method [46].

In human studies (141, 20, and 101 volunteers), kava improved the symptoms of anxiety, insomnia, depression, sleep quality, cognition, tension, and restlessness [47, 48, 49].

Kava’s anti-anxiety effects are potent and have been comparable to benzodiazepines in animal studies [50].

In a review of human studies on common herbal remedies, kava performed better than other herbal supplements in reducing anxiety [51].

However, the FDA has issued warnings on the potential toxic effects of kava, which has been linked to severe liver disease, heart problems, and eye irritation [52].

Kava has a complex interaction with many cytochrome enzymes, which might affect the liver. Kava interacts with CYP450 and with many other cytochrome enzymes (CYPs) [53].

Kava’s interactions with other drugs have not been studied in depth and can potentially result in adverse effects [54]. Do not mix kava with prescription drugs.

Due to these enzymatic interactions, kava has been linked to liver toxicity when mixed with medications or drugs, as well as in kava users with pre-existing liver disease [55].

Despite reports on liver toxicity, at moderate doses, kava is well tolerated by healthy individuals with minimal side effects [56].

Nevertheless, regular kava users should have regular liver function testing [46].

Kava has shown no evidence of potential addiction or withdrawal symptoms [57, 58].

2) Magnolia Bark (Magnolia officinalis, honokiol, magnolol)

Magnolia bark is an unapproved substance without clinical data to back up the claims of traditional practitioners. Clinical studies will be required to determine whether it is safe or effective for any purpose.

Magnolia officinalis, also known as magnolia bark, has been widely used in traditional Chinese medicine and has many benefits. Its active components include honokiol and magnolol, which are found in the bark of the tree [59].

Honokiol and magnolol act as positive allosteric modulators of GABAA receptors and alleviate symptoms of anxiety, depression, and seizures by promoting relaxation [60, 61].

Magnolia bark or honokiol and magnolol pure extracts can be taken as supplements. In animal studies, honokiol and magnolol supplements reduced depression, anxiety, and epileptic seizures [62, 61, 63].

Honokiol and magnolol have immense potential as supplements due to their wide range of medical properties.

In animal and test-tube studies, both honokiol and magnolol showed antioxidant properties. Magnolia extracts also protect the brain, heart, liver, and have anti-cancer and anti-inflammatory properties [64, 65, 66, 67, 68, 69].

Supplementation with honokiol has reported antithrombotic effects (reduced blood’s ability to form clots). Therefore, it should not be taken if you are on antithrombotic medication or you have a blood clotting condition such as hemophilia [70].

No cases of dependence or addiction have been reported.

3) Valerian (Valeriana officinalis, valerenic acid)

Valerian has a long tradition of medicinal use, dating back to ancient Greece. This plant is found in many continents and has been widely used due to its stress relieving and relaxing properties [71].

The active component in valerian, found mostly in its root, is called valerenic acid. Valerenic acid positively modulates GABA through multiple GABAA receptor subunits [72].

Valerenic acid seems to be the most potent active component since valerian plants without valerenic acid don’t increase GABA receptors [73, 74].

In around 20 human studies, 1261 patients with sleep disorders were treated with a dosage of between 300 to 1000 mg of valerian. Valerian reliably improved sleep latency and quality in people with insomnia, obsessive-compulsive disorder (OCD), and restlessness [75, 76, 77, 78].

Valerian also reduced pain notably in menopausal women [79, 80].

Valerian seems to be as effective as benzodiazepines for treating generalized anxiety disorder (GAD) compared to placebo. However, a review states that these results should be interpreted with caution due to the reduced number of participants (12 per treatment group) [81, 82].

Another study performed on 36 patients showed no significant difference between valerian and placebo for treating anxiety [83].

One study (128 participants) noted a significant increase in morning sleepiness and lethargy from valerian purchased over the counter as compared to their own extract [84].

One case of valerian withdrawal resulting in cardiac complications and delirium has been reported. Nevertheless, valerian and its root extract are well tolerated without reported dependence or major side effects in numerous studies [85].

In summary, valerian root extract appears to be well tolerated and may promote relaxation, reduce stress, and improve sleep. Despite many anecdotal reports on valerian’s effects on anxiety, several undersized studies provided inconclusive results.

Note, however, that valerian has not been approved by the FDA for any medical purpose or health claim. Talk to your doctor before adding any new supplement to your daily regimen.

4) Skullcap Herbs (Scutellaria baicalensis, Scutellaria lateriflora, Baikal skullcap, and Chinese skullcap)

Scutellaria baicalensis, also known as Chinese or Baikal skullcap, is an herb used in traditional Chinese medicine. It contains bioactive flavonoids, which act as potent antioxidants with numerous health benefits [86].

Supplementation not only has anti-anxiety and anticonvulsive effects but also may improve cognition, neuron regeneration, and longevity [87].

There are various active components in Baikal skullcap. Baicalein and its structural analog baicalin are positive allosteric modulators of both benzodiazepine and non-benzodiazepine sites of GABAA receptors [88, 89].

Wogonin and its analogs are also components of Baikal skullcap that act as positive allosteric modulators of the benzodiazepine sites of GABAA receptors. These contribute to the calming effects of Baikal skullcap [90, 91].

Wogonin extracts had anticonvulsant effects in animal studies [92].

Baikal skullcap also contains small amounts of apigenin, oroxylin A, and other flavonoids that have similar cognitive effects to wogonin [93].

Scutellaria lateriflora improved anxiety in 19 healthy volunteers without notable adverse effects [94].

Overall, it appears that species of Scutellaria, lateriflora, and baicalensis are well tolerated due to their non-toxic flavonoids and possess potent antioxidant and calming properties when taken as a supplement [95].

Note, however, that skullcap has not been approved by the FDA for any medical purpose or health claim. Talk to your doctor before adding any new supplement to your daily regimen.

5) Lemon Balm (Melissa officinalis)

Lemon balm is traditionally consumed as a tea and is known for its calming properties. It has a complex pharmacological profile with many psychoactive organic chemicals, ranging from polyphenols to terpenes [96].

Lemon balm has antioxidant properties, with rosmarinic acid as its most potent psychoactive compound [97].

Rosmarinic acid increases GABA levels by indirectly inhibiting the enzyme (4-aminobutyrate transaminase) that converts GABA to L-glutamate [98].

This enzyme is a popular target for treating anxiety and epilepsy-related neurological disorders [99].

Lemon balm can be taken in its extract form. In 3 studies (18, 20, and 20 participants), between 300 – 1,000 mg of lemon balm extract reduced anxiety, insomnia, stress, and alertness, meanwhile improving memory, mood, and mental processing [100, 101, 102].

Its calming properties also improved sleep quality in 20 volunteers who suffered from sleep disturbances and anxiety disorders [103].

Lemon balm also relieved heart palpitations in a 55-participants of a human study (DB-RCT) [104].

Lemon balm is well tolerated. No studies have yet reported serious side effects, tolerance, or dependence associated with lemon balm supplementation. In rats, chronic intake of lemon balm showed consistent calming properties without reported tolerance or side effects [105].

Note, however, that lemon balm has not been approved by the FDA for any medical purpose or health claim. Talk to your doctor before adding any new supplement to your daily regimen.

6) Black Seed Oil (Nigella Sativa)

Thymoquinone, present in Nigella sativa and Monarda fistulosa (bee balm) essential oil extracts, can increase GABA activity in animals [106].

Nigella sativa (black seed oil extract) improves inflammation, blood pressure, and anxiety without notable side effects, as shown by multiple animal and human studies (117 and 103 volunteers) [107, 106, 108, 109, 110].

Note, however, that black seed oil has not been approved by the FDA for any medical purpose or health claim. Talk to your doctor before adding any new supplement to your daily regimen.

7) Jasmine Plants

Methyl jasmonate and cis-jasmone found in Jasmine plants (Jasminum officinale) can enhance the function of GABA receptors in cell studies. However, no human or even animal studies have been conducted to investigate whether this effect holds in a living system [111].

8) Ashwagandha (Withania somnifera)

In cell-based studies, extracts of ashwagandha have shown synergistic effects in combination with other positive allosteric modulators of GABA (such as diazepam) and seem to increase GABA activity when low amounts of GABA are present [112].

Withanolides found in ashwagandha are thought to be responsible for its benefits [113].

In animal studies, ashwagandha’s relaxing and sedative properties were hindered by GABA blockers [114].

In human studies (100, 40, 39, and 64 volunteers), ashwagandha extracts, between 250 and 1000 mg daily, reduced stress, anxiety, insomnia, and blood pressure and induced mild sedation [115, 116, 117, 118].

Ashwagandha is usually safe but may increase thyroid hormone levels when supplemented consistently, and a case of thyrotoxicosis in humans has been reported [119].

Note, however, that ashwagandha has not been approved by the FDA for any medical purpose or health claim. Talk to your doctor before adding any new supplement to your daily regimen.

9) Lavender (Lavandula)

In animal studies, constituents of lavender essential oil, such as linalool and borneol mildly increased GABA activity [120, 121, 122].

Lavender safely and reliably improved anxiety and sleep quality in multiple human studies (221, 77, 47, and 10 participants) [123, 124, 125, 126].

Note, however, that lavender has not been approved by the FDA for any medical purpose or health claim. Talk to your doctor before adding any new supplement to your daily regimen.

10) Theanine

Although theanine can be found in many plants, it is not included in the herbal supplements section because it would be difficult to consume enough theanine to produce a significant effect through herbal supplementation only.

Theanine reduced psychological and physiological stress responses while improving mood and relaxation in human studies (27 and 12 participants) [127, 128].

Furthermore, it seems that theanine is also able to moderately improve sleep quality in young adolescents with ADHD [129].

No significant adverse effects of theanine have been found in humans studies, although some online anecdotal reports claim tolerance after daily use [130].

Theanine can mildly increase monoamine levels in the brain, such as serotonin, dopamine, glycine, and GABA (by about 20%) [131, 132].

These studies are still limited and insufficient to conclude that theanine reliably increases GABA. Future clinical studies will be needed to determine whether theanine is safe and effective for this purpose. Talk to your doctor before adding any new supplement to your daily regimen.

11) Apigenin (mainly found in chamomile, Matricaria recutita L, and in feverfew, Tanacetum parthenium)

Apigenin is a flavonoid found in many traditionally used herbs, including chamomile, feverfew, celery, coneflower, and passionflower. Chamomile has the highest amounts of apigenin, accounting for 1% of its dry weight, followed by feverfew with 0.5% [133, 134, 135].

It can be obtained from chamomile tea or its extract as a supplement. It has anti-cancer and anti-oxidative properties and can even reduce tau and amyloid beta deposition and accumulation, which may potentially reduce the risk of Alzheimer’s disease and neuroinflammation [136].

In human studies (57 and 61 subjects), chamomile extracts (containing apigenin) reduced mild to moderate levels of anxiety, depression, and stress, without serious side effects [137, 138].

Apigenin is a benzodiazepine receptor activator that has anti-anxiety properties [139].

Apigenin enhances GABA transmission, through its activity on the benzodiazepine receptor. It also dampens NMDA receptors of the glutamate family (the main excitatory system, as opposed to GABA) [6, 140].

Unless a large dose is consumed, apigenin is effective in reducing anxiety without sedation [139, 141].

Apigenin is well tolerated and often found in dietary sources. No notable side effects have been reported [142].

The available studies are not considered sufficient to determine whether apigenin can safely and effectively increase GABA. Future clinical trials will be needed.

12) Green Tea (Camellia Sinensis)

EGCG (Epigallocatechin gallate), a compound of green tea, increases GABA activity by positively modulating benzodiazepine receptors [143].

However, its promising properties do not fully translate into significant results in human studies, probably due to its low oral bioavailability [144].

13) Taurine

Taurine is an amino acid involved in the health of the heart and brain [145, 146]. It is found in many dietary sources and can bind to both GABAA and GABAB receptors [147, 148].

Taurine supplements are safe since several human studies (29, 23, 11, and 36 participants) have shown no side effects when less than 3 grams per day are consumed [149, 150, 151, 152].

Although taurine can bind to GABA receptors, no human studies have shown its capability to reduce psychological stress or anxiety. Taurine improved depression and anxiety in animal studies [153, 154].

The available studies are not considered sufficient to determine whether taurine can safely and effectively increase GABA. Future clinical trials will be needed.

Others

The substances below have not been approved by the FDA for any medical purpose or health claim. They may cause adverse side effects or interact with medication or other substances. Talk to your doctor before adding any of them to your daily regimen.

• Red Sage – Terpenoids and diterpenoids (such as miltirone and galdosol), found in Salvia miltiorrhiza and other species of the Salvia family (also known as Salvia, Red sage, or Chinese sage), act as partial activators of benzodiazepine receptors without withdrawal symptoms in animals [155].
• Cussonia Plants – MS-1, MS-2, and MS-3, extracted from the traditional African medicinal herb Cussonia zimmermannii, can stimulate GABA activities by positive allosteric modulation of GABAA receptors [156].
• Cyperus And Curcuma Plants – Isocurcumenol, usually found in Curcuma zedoaria (White turmeric) and Cyperus rotundus (Nutgrass), positively modulates GABAA receptors and, therefore, increased GABA activity in animals [157, 158].
• GABA Supplements – GABA supplements are widely available and sold off the shelves in large grocery stores. However, GABA supplementation does not affect GABA levels in the brain because GABA is unable to cross the blood-brain barrier [159].
• Alcohol – Ethanol is the main component responsible for the effect of alcoholic drinks. Alcohol’s sedative, hypnotic, anti-anxiety, and anticonvulsant effects come from ethanol’s positive allosteric modulation of GABAA receptors [160].

Popular Synthetic Compounds

The FDA considers these substances to be unapproved drugs with possible adverse side effects and incomplete safety profiles. We do not currently have enough evidence to determine whether they are safe or effective for increasing GABA. Talk to your doctor before trying any of them.

1) Picamilon

Picamilon is a synthetic compound developed in the Soviet Union. Picamilon can cross the blood-brain barrier, where it is broken down into GABA and niacin, to produce a calming and relaxing response [161].

Picamilon has low toxicity, but only a few studies have investigated this supplement. Long-term use might cause mild dependency or undiscovered adverse events [162].

2) Phenibut

Phenibut is also a synthetic compound developed in the Soviet Union. Phenibut has strong anti-anxiety effects and could be used as a nootropic to improve cognitive functions [18, 163].

Phenibut is unregulated in many countries such as the United States and can also be purchased online [164].

Phenibut is an agonist of the GABAB receptor and, therefore, can produce tolerance rapidly. Consistent usage of phenibut can easily lead to addiction, dependence, and withdrawal symptoms [165, 166].

Withdrawal symptoms are similar to that of baclofen, alcohol, and benzodiazepines. A study reported a case of phenibut withdrawal after 2 months of usage that lead to psychosis and hallucination. The patient was finally treated with benzodiazepines [167].

Although phenibut seems to produce significant positive cognitive and tranquilizing effects, users supplementing phenibut should do extensive research regarding the correct dosage and frequency of usage to prevent dependence and withdrawal symptoms.

Precaution

Some GABA supplements can cause dependence or addiction. These effects will be noted along with other reported side effects if mentioned in any referenced study. Also, herbal supplements on the market might be adulterated. Therefore, you should purchase reliable and reviewed supplements [168, 169, 170].

Natural GABA Blockers

GABA antagonists or ‘negative modulators’ block the effects of GABA.

Here is a list of substances which may block GABA:

• Pregnenolone [171]
• DHEA and DHEA-S [172, 173]
• Ginkgo/bilobalide and ginkgolide [174]
• Zinc [171]
• Wormwood/thujone – Thujone is also found in sage
• Muira Puama
• Theobromine and theophylline [174]
• Opioids [175]