Insomnia - GABA-based support

Part I: Insomnia and the Potential of GABA Therapy

Insomnia is the inability to fall or stay sleep; it is not only physically and emotionally stressful, but has also been proven to lead to increased risk of heart attack, stroke, diabetes, and depression. Insomnia is a complex problem, and may be influenced by stress hormones as well as imbalances in neurotransmitters such as excess epinephrine or deficient serotonin and melatonin.⁽¹⁾

To date, the most consistently effective sleep supports involve a neurotransmitter in the brain called gamma-aminobutyric acid, or GABA. When GABA is low, it has been shown to contribute to depression, anxiety, and insomnia.⁽²⁾ Medications called benzodiazepines such as valproic acid and zolpidem bind to GABA receptors, mimicking the effects of GABA in the brain, and resulting in anxiety relief and sedation.⁽¹⁾ Studies have also shown however, that these medications are habit-forming, making them difficult to wean off when no longer needed, and can cause considerable drowsiness during the day. This article will discuss non-pharmaceutical GABA-supporting interventions such as L-theanine, passionflower, as well as supplemental GABA, which can assist with sleep support without the side effects of prescription medications.

L-theanine, an amino acid compound found in black or green tea, has the ability to calm the nervous system without sedating effects. Therefore, it is beneficial not only for sleep disorders, but for anxiety, epilepsy, and tremors by interacting with GABA receptors.⁽³⁾ Rather than drinking 10-12 cups daily to get this effect (as the caffeine content of tea may offset benefits on sleep!), animal and human studies have shown great potential for L-theanine supplementation.Animal studies have demonstrated that L-theanine increases levels of GABA in the brain,⁽⁴⁾ and may even counteract the effects of caffeine on sleep. It is also believed that L-theanine does not only access the GABA pathway, but other parts of the brain. Inhuman studies, L-theanine is showing benefit sleep induction and sleep quality. In a recent study conducted in 93 adolescents with ADHD and sleep difficulties, the boys supplemented with 400 mg of L-theanine daily experienced an 80% improvement in measures of restful sleep as well as overall wakefulness. Considering the low cost of supplemental L-theanine, this may represent a worthwhile therapy for sleep support. Our next segment on GABA therapy will examine the evidence on herbal interventions, specifically the herb Passionflower, which is an herb long-used by herbalists for its ability to enhance relaxation and sedation.

Insomnia - GABA-based support
Part II: GABA Therapy for Insomnia: The Effects of Passionflower

One of the major complaints regarding pharmaceutical medications for insomnia is the feeling of a morning hangover, which contributes to an inability to function during the day, impaired memory, as well as impaired ability to function at regular levels of mental activity. Passionflower, also known as Passiflora incarnata, is an herb that has long been known for its ability to decrease feelings of anxiety and promote sleep, but without the side effects of sedative medications.⁽¹⁾ Anxiety is closely associated with, and often contributes to insomnia; the GABA pathway decreases both anxiety and insomnia. In addition, passionflower has been investigated for its ability to modulate the GABA brain signalling system in animal models exposed to stressful situations, and has been shown to increase GABA signalling, which was associated with a resilience to stress.⁽²⁾ In humans, a trial involving 60 patients with anxiety found that taking 500mg of passionflower significantly reduced anxiety without any reported side effects.⁽³⁾ In other studies, passionflower has been used to wean individuals off opiates, medications that are used for pain and are very addictive.⁽⁴⁾ Side effects of opiate withdrawal are anxiety and insomnia; in this study, passionflower controlled withdrawal symptoms as effectively as the drug clonidine, an anti-anxiety medication used to alleviate withdrawal.⁽⁴⁾ In this and other studies, passionflower had a significant benefit on symptoms of irritability and anxiety that are common during drug detoxification.^(4,5) This demonstrates the ability of passionflower to assist with drug detoxification, but how does passionflower compare with medications used to promote sleep? In humans, one study used passionflower as a tea for mild insomnia for one week. Subjects consuming Passionflower tea had improved sleep quality overall compared to those consuming a regular non-sedative herbal tea.⁽⁶⁾ In addition, within naturopathic use, passionflower is often combined with other stress-reducing and sedating herbs in a formula, rather than using it on its own.⁽⁷⁾ This can lead to synergistic effects between herbs. For instance, a recent study examined the effects of a formula containing passionflower along with valerian and hops. Compared to the sleep medication zolpidem, this passionflower formula resulted in equal improvements in total sleep time, the time required to fall asleep (called sleep latency), the number of nightly awakenings and the rating of insomnia severity.⁽⁸⁾ In light of this information, passionflower is likely to be a beneficial agent for anxiety-prone individuals suffering from a sleep disorder or undergoing a period of stress, and may help reduce the need to initiate sleep medication. Part III will discuss the effects of GABA supplementation.

Insomnia - GABA-based support
Part III: GABA Supplementation

Gamma-aminobutyric acid (GABA) itself is available in supplemental form and is used to deliver this important signalling chemical to individuals who may be suffering from decreased brain levels, which occurs in patients suffering from anxiety or insomnia. GABA supplementation also assists the body in handling stress and stress recovery more effectively. This section will discuss the benefits of direct GABA supplementation. A small study examined the effects of adding 25mg of GABA into chocolate, and then subjected thirteen individuals to performing stressful math tests. The subjects’ heart rate and levels of chromogratin A (CgA), a salivary marker of the stress response, were measured before and after the task to assess response to stress. Supplementation with GABA allowed the body to recover from the stressful event more quickly, with faster normalization of heart rate and CgA levels.⁽¹⁾ Research has gone further, investigating the effect of GABA supplementation on brain wave patterns in individuals exposed to stressful events. In another study, 100 subjects were divided into two groups, with half given 100mg GABA.⁽²⁾ Subjects’ brain waves and salivary IgA antibodies, a measure of immune function during stress, were measured before and after the group was exposed to stress. The group given supplemental GABA demonstrated both higher IgA indicating improved immune function, as well as increased alpha waves on brain testing, which are associated with calmness without drowsiness. These effects were seen as early as within an hour of taking GABA. Similar outcomes have been replicated by other research groups; in this study, supplemental GABA calmed the brain as measured by brain wave patterns, increased IgA, and allowed for enhanced and rapid stress-recovery.⁽³⁾ With several studies demonstrating supplemental GABA’s affinity to calm the nervous system, the question remains: can it actually improve sleep? One study examined a formula of GABA in combination with other amino acids in 18 patients with insomnia. Compared to a placebo, the GABA formulation resulted in significant improvements, including reduced time in falling asleep, increased length of sleep over the course of the night, improved quality of sleep(deeper and more restful as confirmed with heart rate), and reduced feelings of tiredness and “grogginess” in the morning.⁽⁴⁾ In conclusion, GABA as well as L-theanine and passionflower have been shown to modify symptoms of stress, anxiety, and insomnia through modulation of the GABA signalling system in the brain. Part IV will review dosages and combination of these promising natural agents for insomnia.

Insomnia - GABA-based support
Part IV: Synergy Between Natural Sleep Agents L-theanine, Passionflower, and GABA

In the three preceding sections of this series, we reviewed the evidence supporting the use of several non-pharmaceutical sleep enhancing agents, agents that modulate the GABA signalling system, the same system that sleep medications act on, however without the over-sedation, memory-impairing, and addictive properties of benzodiazepine medications. In our discussion, the three interventions L-theanine, passionflower, and supplemental GABA were reviewed and shown to achieve the following with respect to sleep:

1. L-theanine has the ability to influence sedation and reduce anxiety, but does not induce drowsiness; instead it shows the ability to improve cognitive function and mental focus.^{(1, 2)}
2. Passionflower modulates the GABA pathway, reduces anxiety, improves stress recovery, assists in drug withdrawal, and has mild sedative properties; in addition, it may act best in combination with other herbs or nutrients.^(3-5)
3. Supplemental GABA improves the body’s ability to handle stress, enhances stress recovery including immune function, promotes brain wave patterns associated with calmness, andpromotes sleep.⁽⁷⁾

Preliminary guidelines for dosing the above interventions for sleep and anxiety are as follows:

Sleep supplements typically use a combination of several herbs or nutrients. The three agents discussed are three of the premiere agents, however they are not comprehensive. Other agents affecting the GABA pathway include the herbs valerian, kava-kava, chamomile; and the amino acid tryptophan. In addition, other agents that do not affect the GABA pathway specifically may still benefit sleep parameters, for instance melatonin acts on its own specific brain receptors, and 5-HTP acts on serotonin receptors.⁽⁷⁾ There may be the potential for additional benefit, or synergy, when agents acting through different signalling pathways are combined and have benefit beyond their individual effects. In fact this is often the case, since insomnia is a multifactorial problem. Individuals suffering from anxiety and insomnia should be aware that natural solutions to their problem exist, and that these alternatives may assist them in avoiding dependence on potent and habit-forming sleep medications. As the research evolves in the field of insomnia, gentle herbal and nutrient-based interventions will continue to be studies for their ability to re-balance rather than overpower the brain’s neurochemistry.