GABA is the main inhibitory neurotransmitter in the brain, meaning that it prevents our neurons from over-firing and being over-stimulated. 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 relatively safe. 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.
This article provides unbiased information about popular supplements that could increase GABA.
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 .
GABA is our 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].
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 .
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 .
These substances are known as positive allosteric modulators (PAMs) of GABA .
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 .
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) .
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 .
GABA has two major receptors, GABAA and GABAB . 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 .
Agonists and positive allosteric modulators of GABAB play an important role in alleviating stress, general and social anxiety, depression, and muscle tension .
Why Should You Supplement GABA?
The level of GABA activity is correlated with feeling relaxed and calm .
A study of 36 volunteers published in a prestigious journal showed that prolonged stress and living in an urban area both increased the susceptibility to mental illness and increased amygdala activity, a brain region involved in stress, panic, and threat response .
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 . These variations could increase one’s vulnerability to anxiety, depression, insomnia, bipolarity, schizophrenia, and spasticity .
Fortunately, we can reduce stress and vulnerability to stress-induced mental illness by supplementing GABA. GABA promotes peacefulness and relaxation, decreasing the risk of mental illness .
Also, an active GABA system is beneficial for developing neurons by increasing the brain-derived neurotrophic factor (BDNF) .
BDNF is a protein that promotes the growth and survival of neurons in the brain .
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].
Struggling with anxiety or other symptoms of low GABA?
Learn about how your genes predispose you to these problems and the best ways to address them in the mood DNA Wellness Report here.
Supplements That Increase GABA Activity
1) Kava (Kavain)
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 [36, 37].
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 .
Kava’s anti-anxiety effects are potent and comparable to benzodiazepines in animal studies .
In a review of human studies on common herbal remedies, kava performed better than other herbal supplements in reducing anxiety .
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) .
Kava’s interactions with other drugs have not been studied in depth and can potentially result in adverse effects . Therefore, 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 .
These reports on liver toxicity involving kava also noticed that most cases had insufficient data to prove the cause .
Despite reports on liver toxicity, at moderate doses, kava is well tolerated by healthy individuals with minimal side effects .
Nevertheless, regular kava users should have regular liver function testing .
2) Magnolia Bark (Magnolia officinalis, honokiol, magnolol)
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 .
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 [53, 52, 54].
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 [55, 56, 57, 58, 59, 60].
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 .
It seems to be relatively safe in otherwise healthy volunteers .
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 .
The active component in valerian, found mostly in its root, is called valerenic acid. Valerenic acid positively modulates GABA through multiple GABAA receptor subunits .
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 [66, 67, 68, 69].
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) [72, 73].
Another study performed on 36 patients showed no significant difference between valerian and placebo for treating anxiety .
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 .
One case of valerian withdrawal resulting in cardiac complications and delirium has been detected. Nevertheless, valerian and its root extract are well tolerated without reported dependence or major side effects in numerous studies .
In summary, the valerian root extract is well tolerated and seems to promote relaxation, reduce stress, and reliably improve sleep. Despite many anecdotal reports on valerian’s effects on anxiety, several undersized studies provided inconclusive results.
4) Skullcap Herbs (Scutellaria baicalensis, Scutellaria lateriflora, Baikal skullcap, and Chinese skullcap)
Scutellaria baicalensis, also known as Chinese or Baikal skullcap, is a herb used in traditional Chinese medicine. It contains bioactive flavonoids, which act as potent antioxidants with numerous health benefits .
Supplementation not only has anti-anxiety and anticonvulsive effects but also may improve cognition, neuron regeneration, and longevity .
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 [79, 80].
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 [81, 82].
Wogonin extracts had anticonvulsant effects in animal studies .
Baikal skullcap also contains small amounts of apigenin, oroxylin A, and other flavonoids that have similar cognitive effects to wogonin .
Scutellaria lateriflora improved anxiety in 19 healthy volunteers without notable adverse effects .
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 .
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 .
Lemon balm has antioxidant properties, with rosmarinic acid as its most potent psychoactive compound .
Rosmarinic acid increases GABA levels by indirectly inhibiting the enzyme (4-aminobutyrate transaminase) that converts GABA to L-glutamate .
This enzyme is a popular target for treating anxiety and epilepsy-related neurological disorders .
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 [91, 92, 93].
Its calming properties also improved sleep quality in 20 volunteers who suffered from sleep disturbances and anxiety disorders .
Lemon balm also relieved heart palpitations in a 55-participants of a human study (DB-RCT) .
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 .
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 .
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) [98, 97, 99, 100, 101].
7) Jasmine Plants
Methyl jasmonate and cis-jasmone found in Jasmine plants (Jasminum officinale) can enhance the function of GABA receptors in cells studies .
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 .
Withanolides found in ashwagandha are thought to be responsible for its benefits .
In animal studies, ashwagandha’s relaxing and sedative properties were hindered by GABA blockers .
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 [106, 107, 108, 109].
Ashwagandha is usually safe but may increase thyroid hormone levels when supplemented consistently, and a case of thyrotoxicosis in humans has been reported .
I personally feel that I need to take quite a lot of ashwagandha to notice a relaxing effect (Joe).
9) Lavender (Lavandula)
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.
Furthermore, it seems that theanine is also able to moderately improve sleep quality in young adolescents with ADHD .
No significant adverse effects of theanine have been found in humans studies, although some online anecdotal reports claim tolerance after daily use .
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% [124, 125, 126].
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 .
Apigenin is a benzodiazepine receptor activator that has anti-anxiety properties .
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, 131].
Apigenin is well tolerated and often found in dietary sources. No notable side effects have been reported .
However, it’s absorption is not great, so apigenin won’t be that effective in humans.
I personally do not feel any significant effects from apigenin (Joe).
12) Green Tea (Camellia Sinensis)
However, its promising properties do not fully translate into significant results in human studies, probably due to its low oral bioavailability .
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 [144, 145].
I personally do not feel any significant effects from taurine, even at high dosages (Joe).
- 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 .
- 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 .
- 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 [148, 149].
- 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 .
- 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 .
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.
However, exercise does not directly increase GABA. In fact, prolonged exercise reduces GABA . But don’t worry, this is a temporary physiological response.
Chronic exercise, on the contrary, enhances GABA synthesis in the brain . Exercise might not be the optimum way to increase GABA activity in the short term.
2) Meditation and Yoga
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 .
Another human study (300 volunteers) also showed that yoga practice reduces anxiety .
Popular Synthetic Supplements
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 .
Picamilon has low toxicity, but only a few studies looked into this supplement. Long-term use might cause mild dependency .
Phenibut is unregulated in many countries such as the United States and can also be purchased online .
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 .
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.
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 [167, 168, 169].
Natural GABA Blockers
GABA antagonists or ‘negative modulators’ block the effects of GABA.
Here is a list of GABA antagonists:
If you want to increase GABA for mild to moderate levels of stress and anxiety, herbal supplements are a promising choice.
A systematic review of herbal remedies that may improve anxiety stated that kava is the most promising, being more extensively researched and more effective, compared to other herbs [R].
Valerian extracts might be the best choice if you want to increase GABA with the intention to improve relaxation, restfulness, and sleep quality. Valerian contains several flavonoid glycoside compounds (linarin and hesperidin), which synergize with valerenic acid in positively modulating GABA [R].
As for the non-herbal ways to increase GABA, meditation seems like the best option. Supplementing GABA directly is problematic since it is unable to cross the blood-brain barrier [R].
On the other hand, synthetic GABA agonists such as phenibut, although able to produce reliable relaxing effects, seem to be associated with the rapid development of tolerance, which can lead to dependence [R].