The Discovery of GABA (Part One)
2019-12-19 13:08 Thursday
Some theories suggest that GABA is the mind’s natural calming signal. It’s said to be the neurotransmitter that might relieve anxiety, help people get good sleep, relax, and wind down. By reducing overactivity in the brain, GABA might affect empathy, emotional intelligence, attention, and cognition. Read on to learn about the science of GABA.
丨What is GABA?
GABA is the main inhibitory neurotransmitter in the brain, which means that it functions as the mind’s brakes. It slows down and stops the firing of brain cells and brings the mind to a state of relaxation and calmness.
GABA counters the main excitatory neurotransmitter, glutamate. The brain has a smart way to balance activation and relaxation, noise and silence, yin and yang. It does so through glutamate and GABA.
We can think of GABA and glutamate in the brain as if on a scale:
As always, balance is key. On the extreme side, studies suggest too much glutamate can cause seizures and mania. But an overly stimulated GABA system, such from high doses of drugs like Valium, can cause extreme sedation and even coma. In fact, some general anesthetics are hypothesized to bring about a state of deep unconsciousness by enhancing GABA.
One theory suggests that when GABA and glutamate are in harmony, the brain can function optimally.
However, many factors can throy this balance off. In our modern, urban world and fast lifestyles, GABA might often take the toll.
Some studies suggest that when the mind is constantly activated, under stress, or anxious, glutamate increases, GABA levels drop, and so does stress resilience. Have in mind that these are complex scientific theories, and GABA is just one part of the equation.
Researchers believe that GABA reduces the rate at which neurons fire, which is important for normal, healthy, daily functioning. But it may be especially relevant when neurons in certain parts of the brain become too excited, which has been linked with anxiety, headaches, muscle tension, chronic pain, and Parkinson’s disease symptoms.
It’s questionable how GABA acts on cognition since it seems to be relaxing, not stimulating. On the other hand, we know that people cannot focus when stressed and anxious. Poor cognition is one of the main symptoms of mental health disorders like schizophrenia and anxiety.
Other scientists believe GABA might be a sort of peace-promoting neurotransmitter, since some studies have linked its activity with better emotional intelligence, easier socialization, and increased empathy. These links are still inconclusive, however.
How the Brain Produces GABA
Many parts of the brain are naturally high in GABA. The concentrations of GABA in some brain regions are > 1000 times higher than of other neurotransmitters in any other part of the brain.
According to the prevailing hypothesis, the main relaxing neurotransmitter, GABA, is made directly from the main stimulating neurotransmitter, glutamate. The brain makes GABA in several important steps:
• It usually starts with glucose, although the brain can alternatively use amino acids like pyruvate.
• Glucose is transformed into glutamate
• Glutamate is only then transformed to GABA
• Glutamate decarboxylase (GAD) is the main enzyme needed to make GABA from glutamate. It needs vitamin B6 to function.
• Once GABA is made, it’s released to achieve its effects. Afterward, neurons quickly take GABA back inside to be stored and used again next time. Neurons seem to selfishly store GABA, where its amounts are 200x higher than outside the cells, in the brain’s bloodstream.
Some research suggests that GABA is especially high in the amygdala, the brain’s gateway for generating fear in response to danger. In anxiety, the fear response is increased without any real danger. In line with this theory, GABA may decrease the fear response in the amygdala and reduce anxiety.
GABA needs to bind to receptors in the brain in order to achieve an effect. It can act on two receptors in the brain called:
What's the difference between them and why does it matter?
Scientists suspect that GABA-A activation does not have the same effects as GABA-B activation in the brain. GABA-enhancing drugs often target one receptor subtype more – such as to induce rapid relaxation and sleepiness (GABA-A).
Recently, GABA-C receptors were also discovered. Some researchers believe GABA-C may be especially important for restorative, slow-wave sleep.
Studies show GABA-A receptors act fast in response to GABA. They quickly block excited neurons and may lead to:
• Relaxation and calmness
• Sedation or unconsciousness in excess
• Reduced anxiety
• Euphoria and pleasure, from stimulating the reward system
• Improved and relaxed breathing
• May impair memory (from medications)
Examples of substances that activate GABA-A are alcohol, benzodiazepines like Valium, general anesthetics, and kava.
GABA-B are slow-acting and more complex. When activated, the wakefulness-boosting cAMP stops being produced. Some researchers posit that this may be a reason why GABA may help with sleep in the long-term.
Based on the available research, GABA-B activity may be important for:
• Reducing stress
• Reducing general and social anxiety
• Increasing socialness and empathy
• Improving depression
• Boosting cognition
• Relaxing tense muscles
• Reducing chronic pain and inflammation
• Improving chronic and mental fatigue (possibly)
Some researchers think that GABA-B activation may be less sedative and less hypnotic. They hypothesize it might be beneficial for cognition and memory, since some drugs that activate GABA-B like Phenibut are nootropics, but more high-quality human studies are needed.
Baclofen and phenibut both activate GABA-B. They are being researched for muscle spasms, anxiety, and addictions. Phenibut is not approved in the US.