What is the function of Gamma-Aminobutyric Acid (GABA)?

From the Guidelines

GABA (gamma-aminobutyric acid) is the major inhibitory neurotransmitter in the central nervous system, enhancing its activity leads to a decrease in neuronal excitability. The function of GABA is to reduce neuronal excitability throughout the nervous system by binding to specific receptors in the brain, causing a decrease in neuron activity by allowing negatively charged chloride ions to enter cells 1.

Key Points about GABA

• GABA plays a crucial role in regulating anxiety, sleep, muscle tone, and seizure threshold
• Low GABA levels have been associated with anxiety disorders, insomnia, and epilepsy
• Medications that enhance GABA activity, such as benzodiazepines (like clonazepam), are often prescribed to treat conditions related to GABA dysfunction, as seen in the treatment of nightmare disorder in adults 1
• These medications work by either increasing GABA production, enhancing its effects, or mimicking its action in the brain

Clinical Relevance of GABA

• GABA supplements are available over-the-counter, but their effectiveness is questionable due to their inability to cross the blood-brain barrier efficiently when taken orally
• Enhancing GABA activity through medications like clonazepam has been studied in clinical trials, including a 5-week randomized, single-blind, placebo-controlled crossover trial that compared placebo with 1 mg of clonazepam at bedtime for one week followed by 2 mg at bedtime for another week 1

From the Research

Function of Gamma-Aminobutyric Acid (GABA)

• GABA is the major inhibitory neurotransmitter in the central nervous system, playing a key role in the regulation of neuronal transmission throughout the brain 2, 3.
• It exerts its effects via ionotropic (GABAA) and metabotropic (GABAB) receptors, affecting numerous physiological and psychological processes 3.
• GABA has been shown to ameliorate various neurological disorders, including insomnia, Alzheimer's disease, Parkinson's disease, and epilepsy 2.
• It promotes parasympathetic activity, providing beneficial effects such as relaxation, anti-stress, and relief from insomnia 4.

Mechanisms of GABA

• GABA's mechanisms include GABAA receptor modulation, GABAB receptor modulation, inhibition of neuroinflammatory responses, repair of oxidative damage, and inter-regulation of the circadian rhythm hormone melatonin 2.
• GABA receptors are targeted by many clinically important drugs, including benzodiazepines, barbiturates, neuroactive steroids, and intravenous and inhalational anesthetics 3, 5, 6.
• The development of subtype-selective drugs that target specific GABA receptors is an area of ongoing research, aiming to achieve therapeutic benefits without undesirable side effects 3, 6.

Therapeutic Potential of GABA

• GABA is a potential therapeutic target in the prevention and treatment of insomnia and other neurological disorders 2.
• GABA analogs and subtype-selective drugs may provide new ideas and methods for the clinical treatment of these disorders 2, 3, 6.
• The safety and efficacy of GABA as a functional food ingredient have been supported by toxicity evaluation studies 4.