GABA Benefits & Side Effects: How This Brain Chemical Rules Your Mood & Anxiety Levels

Functional Medicine Practitioner By William Cole, D.C., IFMCP
Functional Medicine Practitioner
Dr. Will Cole, D.C., IFMCP, is a leading functional medicine expert who specializes in clinically investigating underlying factors of chronic disease and customizing a functional medicine approach for thyroid issues, autoimmune conditions, hormonal imbalances, digestive disorders, and brain problems. Cole is also the bestselling author of Ketotarian and The Inflammation Spectrum.
GABA Benefits & Side Effects: How This Brain Chemical Rules Your Mood & Anxiety Levels

Photo by @PeopleImages

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Inside your brain there are various chemicals called neurotransmitters that reign over your every mood. They have the ability to control whether we are happy, sad, anxious, depressed, or relaxed. Talk about power! Every neurotransmitter has its own specific role in how it affects your mood, and a proper balance of each one is necessary for keeping you feeling your best.

When it comes to optimal brain health, one of the things I make sure to optimize for my patients at my functional medicine clinic is something called GABA. GABA, short for gamma-amino butyric acid, is your body’s "calm down" signal. In cases of anxiety and headaches, the cells in your brain get too excited and ramp up their activity, almost like a child on a sugar high after Halloween. But certain neurons—known as GABAnergic neurons—release GABA to help to bring the other overly rambunctious neurons back to down to reality, which is a pretty important job.

Luckily, your body naturally produces and regulates GABA. That being said, sometimes this process malfunctions, and abnormal GABA function can lead to decreased levels of this neurotransmitter, which can contribute to insomnia, anxiety disorders, and depression. Who knew this one single chemical had such a huge impact on your day-to-day life?

The good news is that there is plenty you can do to support your body's GABA levels and regulation of GABA, naturally. Here’s my guide to everything you’ve ever want to know about GABA.

GABA agonists and the brain.

To stimulate a molecule like GABA's activity, it must first bind to a receptor. These receptor-binding molecules are known as agonists. GABA agonists can be produced in or out of the body and can include anything from drugs to other naturally occurring substances. So when GABA is stimulated and you start to feel calm and relaxed, you’ll have this agonist-receptor relationship to thank.

While there are many different GABA receptors, the two major ones are GABAA and GABAB. When GABAA is activated, you can experience relaxation, reduced anxiety, sedation, and even trouble with short-term memory. With GABAB you’ll still feel these same effects, just on a slightly smaller scale, but modulators of this receptor are important in helping to relieve depression.

Your brain’s hypothalamus contains a particularly high amount of GABA receptors. The hypothalamus is responsible for maintaining homeostasis throughout your body by regulating your appetite, sleep patterns, body temperature, and HPA-axis function through the control it has over your nervous system and pituitary gland. This makes poor GABA function a key underlying source of hypothalamus-related health problems like adrenal fatigue.

Glutamate is another neurotransmitter that has the opposite role of GABA. Its main responsibility is to excite and motivate, and it acts as a precursor to GABA. Excess glutamate is automatically converted to GABA in the brain to calm things down and maintain balance in the body. When there are problems with GABA conversion, glutamate levels continue to rise, GABA continues to drop, and anxiety, depression, and other health problems follow.


The side effects and benefits of GABA

GABA Benefits & Side Effects: How This Brain Chemical Rules Your Mood & Anxiety Levels

Photo: @PeopleImages

The amazing thing is that GABA doesn’t just affect how you feel. Remember, your body is inextricably connected and amazingly designed. The benefits of this neurotransmitter go beyond just keeping you cool, calm, and collected.

1. GABA and sleep

Research has shown time and time again that GABA can play an important role in sleep quality and duration. In fact, taking GABA extracts has been linked to improved sleep quality, even when there is caffeine in the body.


2. GABA and gut health

In medical literature your gut is often referred to as your "second brain." As you are forming in your mother’s womb, your gut and brain actually develop from the same fetal tissue and continue their bond throughout your entire life. Therefore, it only makes sense that our brain health, including the function of GABA, influences what's going on in our gut. In fact, close to 95 percent of your "happy" neurotransmitter serotonin is actually produced and stored in your gut! Additionally, your intestinal lining also has its very own GABA receptors (helping to digest food and regulate gastrointestinal activity through the production of gastric acid).

We all know the importance of a healthy and diverse microbiome, but if you needed yet another reason to cultivate your good bacteria, studies have shown that certain bacterial strains can produce GABA themselves. This neurotransmitter is of particular importance for people diagnosed with inflammatory digestive problems since this neurotransmitter can help regulate pain perception in these gut issues. In one study, rats were given oral bifidobacterium strains and showed an increase in GABA production as well as reduced pain.

3. GABA and brain function

Proper levels of GABA are essential for increasing brain-derived neurotrophic factor (BDNF), a protein that facilitates the growth and function of neurons. It’s important to maintain healthy levels of BDNF since low levels are linked to impaired memory and dementia-related conditions like Alzheimer’s.


GABA supplements

Certain herbs and supplements work to increase the activation of GABA receptors to stimulate activity in the brain. These are just some of my favorite herbs, and not surprisingly, most of them are adaptogens!

1. Kava

This plant contains six different psychoactive compounds, including kavain, which works to stimulate GABAA receptors and has been shown to help relieve anxiety. Kava outperformed other herbal supplements and was found in one study to be comparable to benzodiazepines in reducing anxiety.


2. Valerian root

Valerenic acid is the active compound in this root responsible for increasing GABA. Multiple studies have shown valerian root to be successful at improving both the quality and duration of sleep in people suffering from insomnia. It is also considered a powerful anti-anxiety treatment.

3. Skullcap

This herb is loaded with antioxidants, and when taken as a supplement is linked to improved cognitive function and neuron health.


4. Ashwagandha

Regular supplementation of this adaptogen has been shown to reduce stress and anxiety and can even have a mild sedative effect.

5. Lemon balm

One of the many antioxidant properties in lemon balm is rosmarinic acid. This compound increases GABA by inhibiting the enzyme 4-aminobutyrate transaminase responsible for converting GABA to L-glutamine.

6. Green tea

Anyone who knows me knows that green tea is my beverage of choice for taste and also its numerous health benefits. Most of these benefits have to do with its high EGCG (Epigallocatechin gallatate) content, which has the ability to increase GABA activity.

Some other herbs and supplements that support healthy GABA levels include:

Increasing GABA with lifestyle change

You can also increase GABA without having to add another herbal supplement to your daily routine; here's how:

1. Exercise

Unlike endorphins, which surge immediately after exercise, GABA doesn’t just immediately increase after exercise. However, long-term exercise can enhance GABA synthesis and reduce stress.

2. Meditation

Studies show that GABA levels are higher in people who practice meditation. A regular meditation practice also lowers cortisol, which can inhibit proper GABA function. Just one more reason to get your Zen on!

3. Yoga

One study found a 27 percent increase in GABA after completion of a yoga session.

4. The ketogenic diet

A high-fat, moderate protein, low-carb, ketogenic diet has been shown to be beneficial in helping with seizures and epilepsy, which are both associated with high glutamate. A ketogenic diet can increase the GAD enzyme and actually use ketones as a precursor to GABA as well. My upcoming book, Ketotarian, is my plant-based spin on the ketogenic diet.

GABA and your gut health

If you want to increase the ability of these GABA enhancers, you have to give them an environment to thrive in and get their job done. Going back to the gut-brain axis, it doesn’t matter just how many of these supplements you take or how much you exercise if you are suffering from "leaky brain syndrome."

This unfortunately named condition happens when your protective blood-brain barrier (BBB) is destroyed. The two proteins that control your gut-lining permeability—occludin and zonulin—also control your blood-brain barrier permeability, and when they are elevated, it can lead to both leaky gut and leaky brain. When this protective barrier is compromised, it can activate your brain’s immune cells, known as glial cells, which make up more than half the weight of your brain. Once they are activated, it can create a cascade of ongoing brain inflammation.

A whole area of research known as "the cytokine model of cognitive function" is dedicated to examining just how much this never-ending inflammation is linked to depression, anxiety, brain fog, and other autoimmune brain problems. In people with depression, inflammation can even decrease the firing rate of the neurons in the frontal lobe of the brain, making many antidepressants ineffective since they are not addressing the underlying inflammatory response.

This decreased brain output also decreases its communication with your gut. Due to the gut-brain axis, this can impair the function of your gut as well and continue to perpetuate the cycle of inflammation. Research is also looking at a particular molecule known as microRNA-155, which is elevated with this increased inflammation and can create additional gaps in the blood-brain barrier, furthering brain inflammation. Whew, talk about a vicious cycle!

So what's the moral of the story? It all comes back to the gut. Make sure you are supporting your gut through probiotic supplements and foods like sauerkraut and kimchi and eliminating foods that can be irritating to this precious part of your physiology. Working with a functional medicine practitioner can help you come up with a food medicine plan that is best for your specific health case. Your brain and mood with thank you!

Want to learn more about the science of anxiety? Here's everything you need to know about the vagus nerve.

William Cole, D.C., IFMCP
William Cole, D.C., IFMCP
Will Cole, D.C., IFMCP, is a leading functional-medicine expert and a Doctor of Chiropractic. He...
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William Cole, D.C., IFMCP
William Cole, D.C., IFMCP
Will Cole, D.C., IFMCP, is a leading functional-medicine expert and a...
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