Natural GABA supplement

Stress and Anxiety:

By Kimberly Pryor
With an increasing array of demands placed upon us during the holidays—from office parties to gift buying to sending cards—stress seems to accumulate at this time of year. Regardless of whether an individual suffers from seasonal stress or a generalized anxiety disorder that persists year round, there are ways to cope with all of life’s challenges in a calm, relaxed manner.

A synergistic blend of GABA, L-Theanine, Ashwagandha, Valerian Root, and Passion Flower may help support individuals who suffer from excessive stress or anxiety.

Gamma-Aminobutyric acid (GABA) is the most important inhibitory neurotransmitter in the central nervous system (CNS). It exerts its actions through the same GABA receptors that are targets for the anti-anxiety drugs known as benzodiazepines (such as Valium) and barbiturates.

Evidence indicates that dysfunction of GABA receptors or a lowered amount of GABA in the central nervous system plays an important role in the development of panic disorder and psychosis.1-2 Researchers have found that increasing endogenous GABA concentrations through the use of drugs that inhibit its breakdown can improve symptoms of panic and anxiety.

Low levels of GABA have been associated with negative effects. Researchers in France measured plasma GABA levels in 108 road traffic accident victims on arrival at a traumatology department and assessed them for posttraumatic stress disorder 6 weeks later.

The mean GABA level in the 55 post traumatic stress disorder (PTSD) patients was significantly lower compared with the 17 trauma-exposed subjects who did not develop PTSD.3

According to the researchers, “Provided that GABA levels in the brain are genetically predetermined, our results would suggest that individuals with low plasma GABA levels are premorbidly more vulnerable to stress-related disorders such as acute PTSD.”

In a study on dogs, GABA also exerted some interesting anti-aging effects. GABA (30 mg/kg) was administered to aged dogs with a recent history of veterinary clinic visits (mean age: 15.3 years old) once per day for two weeks by mixing it with food. The animals’ owners subjectively evaluated the effects of GABA on behavioral signs often associated with aging in dogs.

The results indicated that the dogs’ behavioral signs of aging improved notably after GABA administration without any observable adverse effects. Dogs given GABA tended to experience improved emotional states. The animals also exhibited an improvement in autonomic nervous system dysfunction, though effects on cognitive dysfunction syndrome were not always observed.4

“Thus, GABA administration may be one of the effective means of improving the quality of life of aged dogs,” the researchers wrote.
While similar studies investigating GABA’s effects on aging humans have not been conducted, this dog study raises some intriguing possibilities about GABA’s role in the aging process.

GABA receptors may also have a role to play in premenstrual anxiety, indicating that increasing GABA levels at key times in the menstrual cycle may increase well being.5
Passion Flower
Extracts and fluid extracts from the aerial parts from Passiflora incarnata L. are widely used as components of herbal sedatives. Animal studies have indicated that passion flower has sedative and anti-anxiety effects. Passion flower extracts are used in combination with other natural anti-anxiety agents for tenseness, restlessness and irritability with difficulty in falling asleep.6

Mice treated with passion flower exhibited reduced anxiety when exposed to non-familiar environments. The animals treated with passion flower, when forced to climb a staircase, climbed higher than untreated mice. In addition, when placed in a half-dark/half-light box, the animals treated with passion flower experienced a greater amount of movement and spent more time in the light side of the box compared to untreated mice. Passion flower also acted as a sedative in the mice.7


Use of valerian dates back to the ancient Greeks and Chinese.
When the valepotriates were discovered in 1966 they were thought to be Valerian’s sole active constituents, but since then their breakdown products, the baldrinals, and other components are believed to be responsible for valerian’s actions.8

Valerian interacts with neurotransmitters such as GABA9-10 and triggers a dose-dependent release of GABA.11 Valerian also stops the enzyme-caused breakdown of GABA in the brain, which results in its relaxation actions.12-13

Researchers have explored valerian’s anti-anxiety abilities. In a double-blind trial of 48 adults placed in an experimental situation of social stress, valerian reduced subjective sensations of anxiety and did not cause any measurable sedation.14 In another study, researchers compared valerian to an anti-anxiety drug. When subjects consumed 50 mg three times daily of valerian, they experienced a significant reduction in Hamilton Anxiety Scale scores after four weeks.

This was similar to the effects seen with the anti-anxiety drug.15

Another study compared valerian and kava kava to each other and placebo in a standardized mental stress test in 54 healthy subjects. Unlike placebo, both preparations decreased systolic blood pressure responsiveness and self-reported feelings of stress, and inhibited a stress-induced rise in heart rate.16 Studies also have confirmed valerian’s safety and shown that it has no side effects.

Furthermore, scientists have studied valerian for its sleep-enhancing effects. In one double-blind, crossover study, researchers found 400 mg valerian improved sleep latency and quality compared to placebo.17 In a study of 128 participants given 400 mg aqueous valerian extract or placebo, improvement was noted in sleep latency and sleep quality. “Poor sleepers” appeared to achieve a greater benefit from valerian compared to self-described “good sleepers.”18

Other studies exploring valerian’s ability to enhance sleep have noted similar results. In a study of 121 patients who consumed 600 mg valerian extract per day for four weeks or a placebo, researchers measured clinical effectiveness using four validated rating scales. After 14 days valerian was superior to the placebo on the Clinical Global Impression Scale (CGIS).

At the study’s end at 28 days, 66 percent of subjects rated valerian effective, compared to only 26 percent of the placebo-treated subjects.19

Other researchers have found that sleep latency was significantly reduced in 16 insomnia patients treated with valerian, compared to placebo-treated patients. Valerian-treated subjects also experienced an increased percentage of slow wave sleep compared to the placebo group.20

Patients who don’t exercise, who can’t calm down mentally and who exhibit stress along with despondency and mental depression have responded best to valerian.21-23
In cell culture experiments, valerian also has protected neurons against amyloid peptides, which are associated with Alzheimer’s disease.24


Ashwagandha (Withania somnifera) is a botanical used extensively in Indian Ayurvedic medicine. In Ayurveda, Ashwagandha is used to promote physical and mental health, to provide defense against disease and adverse environmental factors and to slow aging.25

In India, Ashwagandha is often used to stabilize mood in patients with behavioral disturbances. Researchers sought to confirm these effects by investigating the anti-anxiety and anti-depressant actions of a bioactive component isolated from ashwagandha in rats. The ashwagandha component was administered orally once per day for 5 days. Researchers then compared the results to those achieved with a benzodiazepine drug and with a tricyclic anti-depressant.

The ashwagandha component caused an anti-anxiety effect comparable to that produced by the anti-anxiety drug in a number of tests including a maze test, and a test that included social interaction and delay of feeding in an unfamiliar environment. In addition, after the researchers triggered anxiety in the rats by administering an anxiety-producing agent, both the ashwagandha component and the drug reduced brain levels of tribulin, a marker of clinical anxiety. The ashwagandha component also exhibited an antidepressant effect comparable with that induced by the antidepressant drug.

The investigators noted that the results support the use of ashwagandha as a mood stabilizer in clinical conditions of anxiety and depression.25

Other studies indicate ashwagandha possesses anti-inflammatory, antitumor, antistress, antioxidant, immunomodulatory, and rejuvenating properties. It also appears to exert a positive influence on the endocrine, cardiopulmonary, and central nervous systems.26 In mice, ashwagandha also has stimulated thyroid function.27

L-theanine is an amino acid found in green tea. It is best known for its ability to induce a state of relaxation.

Research on human volunteers has demonstrated that L-theanine creates a sense of relaxation in approximately 30-40 minutes after ingestion via at least two different mechanisms. This amino acid directly stimulates the production of alpha brain waves, creating a state of deep relaxation and mental alertness similar to what is achieved through meditation. L-theanine also is involved in the formation of the inhibitory neurotransmitter, gamma amino butyric acid (GABA). GABA influences the levels of two other neurotransmitters, dopamine and serotonin, producing the key relaxation effect.28

In animal and human studies, L-theanine has increased levels of the feel-good neurotransmitter, dopamine, indicating this amino acid may support mental health.29
An interesting effect of L-theanine is its ability to inhibit the stimulation that occurs after caffeine intake. Japanese researchers investigated this ability in animals by intravenously administering caffeine to rats. They then also administered L-theanine intravenously at an equivalent dose to the caffeine and measured the animals’ brain waves. The researchers determined that, depending on the dose, L-theanine could stop the stimulant effects associated with caffeine intake. When given by itself in a smaller dose (20-40 percent of the original dose), theanine administration resulted in excitatory effects, suggesting a dual activity of theanine.30

L-theanine’s ability to induce a state of relaxation may be the reason it has reduced blood pressure in an animal study. When spontaneously hypertensive rats were given L-theanine intraperitoneally, they experienced a dose dependent reduction in blood pressure.31
Increasingly, researchers are reaching beyond L-theanine’s anti-stress effects to explore its role as an adjuvant anti-cancer agent. In animals with tumors, L-theanine stops the depletion of the important antioxidant glutathione in normal body tissues, but not in tumor cells, indicating it protects against chemotherapy damage.32


Combining a number of anti-stress nutrients such as GABA, passion flower, valerian, ashwagandha, and L-theanine (all found in VRP’s Allay™) can increase levels of calm and well-being without drowsiness. This synergistic blend may help anxious individuals cope during the holiday season and beyond.

1. Zwanzger P, Rupprecht R. Selective GABAergic treatment for panic? Investigations in experimental panic induction and panic disorder. J Psychiatry Neurosci. 2005 May;30(3):167-75.

2. D”Souza DC, Gil RB, Zuzarte E, Macdougall LM, Donahue L, Ebersole JS, Boutros NN, Cooper T, Seibyl J, Krystal JH. Aminobutyric Acid-Serotonin Interactions in Healthy Men: Implications for Network Models of Psychosis and Dissociation. Biol Psychiatry. 2005 Sep 1; [Epub ahead of print]

3. Vaiva G, Thomas P, Ducrocq F, Fontaine M, Boss V, Devos P, Rascle C, Cottencin O, Brunet A, Laffargue P, Goudemand M. Low posttrauma GABA plasma levels as a predictive factor in the development of acute posttraumatic stress disorder. Biol Psychiatry. 2004 Feb 1;55(3):250-4.

4. Inagawa K, Seki S, Bannai M, Takeuchi Y, Mori Y, Takahashi M. Alleviative effects of gamma-aminobutyric acid (GABA) on behavioral abnormalities in aged dogs. J Vet Med Sci. 2005 Oct;67(10):1063-6.

5. Smith SS, Ruderman Y, Hua Gong Q, Gulinello M. Effects of a low dose of ethanol in an animal model of premenstrual anxiety. Alcohol. 2004 May;33(1):41-9.

6. Krenn L. [Passion Flower (Passiflora incarnata L.)–a reliable herbal sedative] [Article in German]. Wien Med Wochenschr. 2002;152(15-16):404-6.

7. Soulimani R, Younos C, Jarmouni S, Bousta D, Misslin R, Mortier F. Behavioural effects of Passiflora incarnata L. and its indole alkaloid and flavonoid derivatives and maltol in the mouse. J Ethnopharmacol. 1997 Jun;57(1):11-20.

8. Weiss RF, Fintelmann V. Herbal Medicine. 2nd ed. Stuttgart, Germany: Thieme; 2000:262-263.

9. Hendriks H, Bos R, Allersma DP, et al. Pharmacological screening of valerenal and some other components of essential oil of Valeriana officinalis. Planta Med. 1981;42:62-68.

10. Cavadas C, Araujo I, Cotrim MD, et al. In vitro study on the interaction of Valeriana officinalis L. extracts and their amino acids on GABAA receptor in rat brain. Arzneimittelforschung 1995;45:753-755.

11. Ortiz JG, Nieves-Natal J, Chavez P. Effects of Valeriana officinalis extracts on [3H]flunitrazepam binding, synaptosomal [3H]GABA uptake, and hippocampal [3H]GABA release. Neurochem Res. 1999;24:1373-1378.

12. Santos MS, Ferreira F, Faro C, et al. The amount of GABA present in aqueous extracts of valerian is sufficient to account for [3H]GABA release in synaptosomes. Planta Med 1994;60:475-476.

13. Santos MS, Ferreira F, Cunha AP, et al. An aqueous extract of valerian influences the transport of GABA in synaptosomes. Planta Med 1994;60:278-279. 25.

14. Kohnen R, Oswald WD. The effects of valerian, propranolol, and their combination on activation, performance, and mood of healthy volunteers under social stress conditions. Pharmacopsychiatry. 1988;21:447-448. 17.

15. Andreatini R, Sartori VA, Seabra ML, Leite JR. Effect of valepotriates (valerian extract) in generalized anxiety disorder: a randomized placebo-controlled pilot study. Phytother Res. 2002;16:650-654.

16. Cropley M, Cave Z, Ellis J, Middleton RW. Effect of kava and valerian on human physiological and psychological responses to mental stress assessed under laboratory conditions. Phytother Res. 2002;16:23-27.

17. Leathwood PD, Chauffard F. Aqueous extract of valerian reduces latency to fall asleep in man. Planta Med. 1985;2:144-148.

18. Leathwood PD, Chauffard F, Heck E, MunozBox R. Aqueous extract of valerian root (Valeriana officinalis L.) improves sleep quality in man. Pharmacol Biochem Behav 1982;17:6571.

19. Trevena L. Sleepless in Sydney – is valerian an effective alternative to benzodiazepines in the treatment of insomnia? ACP J Club 2004;141:A14-A16.

20. Donath F, Quispe S, Diefenbach K, et al. Critical evaluation of the effect of valerian extract on sleep structure and sleep quality. Pharmacopsychiatry 2000;33:47-53.

21. King J. The American Dispensatory. 6 ed. Cincinnati, OH: Moore, Wilstach & Baldwin; 1864.

22. Felter HW. The Eclectic Materia Medica, Pharmacology and Therapeutics. Portland, OR: Eclectic Medical Publications; 1983. [Reprint of this 1922 text].

23. No authors listed. Valeriana officinalis. Monograph. Alternative Medicine Review. 2004; 9(4):438-41.

24. Malva JO, Santos S, Macedo T. Neuroprotective properties of Valeriana officinalis extracts. Neurotox Res. 2004;6(2):131-40.

25. Bhattacharya SK, Bhattacharya A, Sairam K, Ghosal S. Anxiolytic-antidepressant activity of Withania somnifera glycowithanolides: an experimental study. Phytomedicine. 2000 Dec;7(6):463-9.

26. Mishra LC, Singh BB, Dagenais S. Scientific basis for the therapeutic use of Withania somnifera (ashwagandha): a review. Altern Med Rev. 2000 Aug;5(4):334-46.

27. Panda S, Kar A. Changes in thyroid hormone concentrations after administration of ashwagandha root extract to adult male mice. J Pharm Pharmacol. 1998 Sep;50(9):1065-8.

28 Mason R. 200 mg of Zen; L-theanine boosts alpha waves, promotes alert relaxation. Alternative & Complementary Therapies. April 2001;7:91-95.

29 Yokogoshi H, Kobayashi M, Mochizuki M, Terashima T. Effect of theanine, r-glutamylethylamide, on brain monoamines and striatal dopamine release in conscious rats. Neurochem Res. 1998 May;23(5):667-73.

30. Kakuda T, Nozawa A, Unno T, Okamura N, Okai O. Inhibiting effects of theanine on caffeine stimulation evaluated by EEG in the rat. Biosci Biotechnol Biochem. 2000 Feb;64(2):287-93.

31. Yokogoshi H, Kato Y, Sagesaka YM, Takihara-Matsuura T, Kakuda T, Takeuchi N. Reduction effect of theanine on blood pressure and brain 5-hydroxyindoles in spontaneously hypertensive rats. Biosci Biotechnol Biochem. 1995 Apr;59(4):615-8.

32. Sugiyama T, Sadzuka Y. Theanine, a specific glutamate derivative in green tea, reduces the adverse reactions of doxorubicin by changing the glutathione level. Cancer Lett. 2004 Aug 30;212(2):177-84.




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