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GABA and Glutamate

~ Identify the functions of GABA and Glutamate
~ Explore the interaction between these neurotransmitters and the rest f the big 5
~ Identify symptoms of too much of either
~ Explore ways to reduce them
~ Identify symptoms of deficiencies of either
~ Explore ways to increase them
What is GABA
~ GABA reduces the activity of the CNS.
~ Made from and counterbalances Glutamate
~ GABA plays a role in the healthy functioning of the body’s immune and endocrine systems, as well as in the regulation of appetite and metabolism.
~ GABA supports gut motility and control inflammation
~ GABA is an inhibitory transmitter in the mature brain, its but primarily excitatory in the developing brain
~ GABA regulates the growth of embryonic and neural stem cells

What is GABA
~ GABA is synthesized from Glutamate which is synthesized from Glutamine (amino acid)
~ B-6 is required for the synthesis of these neurotransmitters as well as serotonin and dopamine
J Clin Psychiatry. 2003;64 Suppl 3:21-7. The role of GABA in anxiety disorder

Insufficient GABA
~ Low GABA activity in the body can result in:
~ Anxiety, Stress and Depression*
~ Difficulty concentrating and memory problems
~ Muscle pain and headaches
~ Insomnia and other sleep problems
~ Epilepsy
~ Chronic pain and inflammation
~ Alcoholism
~ Hypertension
~ Artificially increasing GABA may trigger a depressive episode
~ People with MDDs show reduced brain concentration of GABA

Insufficient GABA
~ Gamma-Aminobutyric Acid Involvement in Depressive Illness Interactions with Corticotropin-Releasing Hormone and Serotonin
~ The GABAergic Deficit Hypothesis of Major Depressive Disorder

Increasing GABA
~ Valerian
~ Kava
~ Magnesium
~ L-theanine
~ L-arginine
~ Passionflower
~ Magnesium
~ B6
~ Ginseng
~ Green, black, and oolong tea
~ Fermented foods including kefir, yogurt and tempeh
~ Whole grains, oats
~ Fava, soy, lentils and other beans
~ Nuts including walnuts, almonds and sunflower seeds
~ Tomatoes
~ Berries
~ Spinach
~ Broccoli
~ Potatoes
~ Cocoa
~ Whey protein
~ Gabapentin (a GABA analogue)
~ Benzodiazepines
~ Hypnotics
Essential Oils Increase GABA
~ Jatamansi
~ Lemon Balm
~ Valerian
~ Jasmine
~ Chamomile
~ Lavender
~ Bergamot increases GABA and Glutamate but may also protect against glutamate excitotoxcicity Pharmacol Res. 2007 Apr;55(4):255-62
Excess GABA
~ Low Blood Pressure
~ Gastric distress
~ Nausea
~ Diminished appetite
~ Constipation
~ Drowsiness and fatigue
~ Muscle weakness
~ Shortness of breath, at very high doses
Reducing (or Counteracting) GABA
~ Stimulants including: Caffeine, nicotine temporarily may reduce GABA
~ Ginko

~ GABAA antagonists may be possible targets for reducing morphine reward
GABA Interactions
~ Hypertension medications
~ Antidepressants
~ Serotonin increases GABA availability/SSRIs increase GABA
~ Amphetamines change the glutamate levels in the brain
~ a single dose of ATS led to decreased levels of glutamine, glutamate, and GABA suggesting a circulatory disturbance of the glutamine-glutamate-GABA circuit
~ The reduction of the glutamate level was hypothesized to be due to over-excitation of the glutamate system induced by ATS, and an excessive need for glutamate was produced. The decreased GABA level was caused by an insufficiency of glutamate

GABA Interactions
~ Serotonin modulates both GABA and Glutamate
~ GABA inhibits norepinephrine
~ Activation of GABAA receptors increases the release of norepinephrine in the rat hippocampus and cortex
~ Activation of GABAB receptors causes a decrease in norepinephrine
~ Norepinephrine modulates synthesis of GABA in CNS


~ Moderate activation of the glutamatergic neurons plays an important role in synaptic plasticity, which is closely related to cognitive learning
~ Glutamate enhances inflammation
~ The Goldilocks Principle: Too little glutamate excitation can result in difficulty concentrating or mental exhaustion. But too much can result in excitotoxicity, which can damage nerve cells (neurons)
~ Dopamine receptors located on the glutamatergic terminals induced enhancement of the glutamate release (Licata and Pierce, 2003) in the presence of stimulants. Dopamine further increased the excitatory neurotoxicity of glutamate
Psychostimulants and Movement Disorders
~ High levels of glutamate may
~ Act as an excitotoxin and cause cell death
~ Lead to acute movement disorders: tremor, gait disturbances, parkinsonism, dyskinesias and dystonias, myoclonus, and restless legs
~ Excess glutamate is thought to contribute to cell degeneration in Huntington’s Disease
Psychostimulants and Movement Disorders
Glutamate Antagonist
~ Barbiturates
~ Dextromethorphan
~ Alcohol
~ Ketamine which has rapid and potent antidepressant effects in treatment-resistant major depressive disorder and bipolar depression
~ Nitrous oxide
~ Phencyclidine
Normalizing Glutamate Levels
~ Vitamin B3 (niacinamide) is used as coenzyme in glutamate dehydrogenase enzyme
~ Carnitine (from acetyl-L-carnitine) might support and protect metabotropic glutamate receptors
~ Neuroadaptogens including Ginkgo biloba and Rhodiola rosea may protect neurons from excessive glutamate excitation
~ Neurolipid compounds like DHA (an omega 3)are used in cell membranes and appears to support balanced glutamate receptor signaling and function.
~ Magnesium
~ Vitamin D
~ Taurine
Normalizing Glutamate Levels
~ Ashwaganda (Withania somnifera) protects against glutamate damage
~ Alpha Lipoic Acid
~ Chamomile inhibits glutamate
~ “Bee pollen demonstrates ameliorating effects on glutamate excitotoxicity and the impaired glutamine-glutamate-GABA circuit”
~ CBD- Protects against glutamate. “β-Caryophyllene Protects The C6 Glioma Cells Against Glutamate-Induced Excitotoxicity”


~ Amphetamines, depressants and opiates all can impact the levels of glutamate, GABA, serotonin, dopamine and norepinephrine
~ Each of these neurotransmitters has either a potentiating or inhibiting effect on each other neurotransmitter.
~ Changing the level of one chemical will nearly always alter the availability or functioning of all the others
~ All of the big 5 neurotransmitters are involved in some way with inflammation, immunity, mood, GI functioning, heart rate, attention, memory, coordination and pain.
~ Effective transdiagnostic assessment is essential for helping patients help their brains recover.