Supplements for ADHD

ADD & ADHD ADD & ADHD Natural Control of ADD & ADHD Billie J. Sahley, Ph.D., CNC In Toxic Psychiatry, Peter Breggin, MD states, Hyperactivity is the most frequent justification for drugging children. Difficult-to-control children are certainly not a new phenomenon, but attempts to give them a medical diagnosis are the product of modern psychology and psychiatry. At first, psychiatrists called hyperactivity a brain disease: minimal brain dysfunction (MBD). When no minimal brain dysfunction could be demonstrated, the label became attention deficit disorder (ADD). Six million children in this country suffer some type of learning disability, ADD, or ADD with hyperactivity (ADHD). Over two million children currently take Ritalin for ADD/ADHD. ADD and ADHD may be caused by psychological problems, including trauma and abuse, nutritional deficiencies, chemical imbalances, allergic responses to food and chemicals, or a poor diet. A failure in the brains inhibitory system (the ability of the brain to inhibit and control itself) may also cause ADD/ADHD. Ritalin, the most commonly used drug for ADD and ADHD, is an amphetamine and a Schedule II class drug (other Schedule II drugs are morphine, opium, and medicinal cocaine). Doctors prescribe Ritalin for many children who do not need it, causing a number of adverse mental and physical side effects. Yet this potent, toxic drug is being used as a quick fix to quiet children. Surprisingly, prescription rates for Ritalin doubled between 1992 and 1996. Children demonstrating symptoms of anxiety, ADHD or ADD often have an imbalance in their brains biochemistry. A biochemical imbalance results from a deficiency of neurotransmitters, the chemical messengers of the brain. If a biochemical imbalance goes untreated, a child can display maladaptive behavior, followed by possible long-term physical and emotional problems. A childs state of health reflects his or her state of nutrition. When minerals, vitamins, amino acids, enzymes, or even hormones are deficient in a childs system, the result can be a disturbed biochemical homeostasis causing impaired functions in the brain. This, in turn, can cause an inability to focus, concentrate, and stay on task. At the Pain and Stress Center in San Antonio, we have successfully treated numerous children with orthomolecular therapy. Orthomolecular therapy corrects the brains biochemical imbalance, without toxic drugs that can produce adverse side effects. ADD/ADHD presents a major problem facing parents today. Most people think of hyperactivity as some type of behavioral problem (a child who is impatient, impulsive, and constantly moving); but not all hyperactive children are aggressive. Some are very passive, withdrawn, and find it hard to communicate their feelings. ADD/ADHD is not a condition that can be measured in precise scientific terms. Nor is it a situation with a quick fix, especially with powerful and addictive drugs such as Ritalin. ADD/ADHD is a complex and intricate condition in which children demonstrate maladaptive or disorganized behaviors, which put them out of sync with the world around them. Numerous clinical studies established that hyperactive children often have low serotonin levels. A proper combination of tryptophan or 5-HTP and B6, elevates the serotonin level and balances the brain; the childs symptoms diminish. The dosage, of course, depends on the childs age, weight, and the degree of hyperactivity. Effectiveness of Amino Acids Neurotransmitters affect behavior and learning. A neurotransmitter deficiency consequently has a dramatic effect on childrens or adults abilities to learn and function in an orderly manner. Most hyperactive and ADD children are born with a shortage of neurotransmitters, establishing a genetic link, most often on the male side. These children also do not manufacture the needed amount of these chemical messengers. Where do we get neurotransmitters? From the amino acids, GABA, glycine, taurine, tyrosine, glutamine and tryptophan. Do children or adults get enough aminos through diet? NO! Balanced amino-acid doses, in the right combination and formulas, produce the needed neurotransmitters naturally. Using a stimulant medication to try to produce neurotransmitters is like a shotgun going off in the childs brain. Our children were not born with Ritalin in their brain, so how can they have a Ritalin deficiency? Approximately fifty different neurotransmitters exist in the human brain, but communication between brain cells uses only ten (approximately) major neurotransmitters. How we feed the brain directly affects our production of neurotransmitters. With proper nutrition and supplementation, we can correct or enhance mind, mood, memory, and behavior. All major neurotransmitters are made from amino acids and dietary protein. One of the dangers of a low-protein diet is not ingesting enough amino acids to make adequate brain neurotransmitters. Apathy, lethargy, difficulty concentrating, loss of interest, and insomnia all result when the diet does not include adequate amounts of amino acids. Drugs do not produce or increase production of neurotransmitters. Drugs only address symptoms. Amino acids restore the balance nature intended. Some of the major symptoms of neurotransmitter deficiencies are ADD, ADHD, brain fog, mood swings, increased stress, anxiety, depression, insomnia, irritability, and aggression. Stress plays a major role in the depletion of neurotransmitters. Inhibitory neurotransmitters are the keys to behavior, emotions, and pain. Inhibitory amino acids include tryptophan, taurine, GABA, and glycine. Millions of people have turned to drugs known as SSRIs (Selective Serotonin Reuptake Inhibitors). These drugs, such as Prozac, Paxil, Zoloft, and Effexor work by selective enhancement of serotonin levels. SSRIs prevent the presynaptic nerve from reabsorbing serotonin that it previously secreted. Prozac causes an increase in brain serotonin levels; but Prozac and other prescription drugs do not increase neurotransmitters. (See Figure 1). 5-HTP is synergistic with other supplements that enhance neurotransmitters such as GABA, glutamine, tyrosine, phenylalanine, and glycine. Magnesium prolongs the benefits of 5-HTP. Chronic stress depletes available serotonin, as well as interferes with serotonins ability to control behavior. Research demonstrates that low serotonin levels can change brain function and impair learning. Low serotonin may be responsible for an increase in depression and drug use among teens and children. Most teens with low serotonin levels are more prone to try recreational drugs or even prescription drugs, for relief. A low brain serotonin level impairs the ability to focus and reason. 5-HTP shows a lot of promise as a natural answer to a multitude of problems that plague adults and children. Use caution with 5-HTP if your child is taking prescription antidepressant medications. GABA (Gamma-aminobutyric acid) GABA, an inhibitory neurotransmitter, is found throughout the central nervous system. GABA assumes an ever-enlarging role as a significant influence on ADD, ADHD, stress, anxiety, and depression, as well as stress-induced illnesses. According to Candace Pert, a neuroscientist who discovered the GABA receptor, every cell in the body has a GABA receptor, which is one reason why GABA has such positive effects. GABA inhibits the cells from firing, diminishing anxiety-related messages. Tranquilizers provide only temporary relief. We have seen many patients on Xanax that still experience anxiety. They have been told it is not addictive: it is! THERE IS NO SUCH THING AS A TRANQUILIZER DEFICIENCY! Nutrient deficiencies do occur, however; and they can and do change behavior. GABA, glutamine, and glycine prove vital for energy and the smooth running of brain functions. We have successfully used these three amino acids with patients to ease anxiety, irritability, and ADD. Research demonstrates a large number of children who display ADD/ADHD behavior actually experience anxiety. If they use all available GABA, then the receptors in the brain become empty, allowing the brain to be bombarded with random firings of excitatory messages. However, when adequate amounts of GABA are present, the reception of multiple random firings are blocked, so the brain does not become overwhelmed. At the Pain & Stress Center we regularly combine GABA and other amino acids to achieve positive results. Dose amounts vary, depending on the age and weight of the child. GABA now takes its place as a major influence on those taking drugs, and in many cases, replacing the drugs. We have found that, when combined with other amino acids, GABA works exceptionally well with ADD children. L-Glutamine Glutamine, along with GABA and Glycine, is rapidly becoming an important therapeutic amino acid of the 21st century. Glutamine, found in many foods, is the third most abundant amino acid in the blood and brain. It also provides a major alternative fuel source for the brain when blood sugar levels are low. Glutamine functions as an inhibitory neurotransmitter, and is the precursor for GABA, the antianxiety amino acid. The amino acid trio of Glutamine, GABA, and Glycine plus B6 are among the major inhibitory neurotransmitters in the brain. Glutamine is found in the nerves of the hippocampus, the memory center of the brain, in the cranial nerves, and in many other areas of the brain. These three amino acids work together as inhibitory neurotransmitters. Anyone taking amino acids must take B6 to metabolize the amino acids. Intellectually impaired children and adults often show an increase in IQ after taking glutamine in combination with Ginkgo biloba and B6. Dr. Roger Williams demonstrated that children and adults diagnosed with ADHD showed a marked improvement when taking 250 mg to 1,000 mg of glutamine daily. GABA and glutamine are not only found in the brain, but also in the receptor sites throughout the body. Glutamine is the memory and concentration amino acid. Seventy five percent of hyperactive and ADD childrens blood tests showed low levels of glutamine. Dr. C. Fredericks research also demonstrated a definite increase in the IQs of children given glutamine. When glutamine was given daily, children showed impressive improvements in their abilities to learn, to retain, and to recall. Glutamine is a major part of my orthomolecular program for hyperactive and ADHD children. Glutamine is one of the amino acids that create the neurotransmitters in the brain that enhance learning and memory. Hyperactive and ADD children have low neurotransmitter levels, especially glutamine. Adding glutamine increases the level of neurotransmitters. Start with 500 mg of glutamine and gradually increase until you reach the optimal dose for your child, to a maximum of 3,000 mg per day. Taurine Taurine is now classified as a conditionally essential amino acid in the adult. In infants and children, however, taurine is an essential amino acid. As one of the sulfur amino acids, adults synthesize taurine from cysteine and methionine, provided B6 and zinc are present. Taurine is found abundantly throughout the body in the heart, olfactory bulb, central nervous system, and brain (hippocampus and pineal gland). As an inhibitory neurotransmitter, taurine, after GABA, is the second-most important inhibitory transmitter in the brain. Taurines inhibitory action in the brain equals that of GABA and glycine. Its inhibitory effect is one source of taurines anticonvulsant and antianxiety properties. Some children with Downs syndrome have shown an increase in IQ levels when taurine was added to their diet along with glutamine, B6, and vitamin E. The need for taurine increases whenever you experience more stress than usual, or have an illness. Tyrosine Tyrosine is the amino acid and inhibitory neurotransmitter that often helps overcome depression. Clinical studies show that tyrosine controls medication-resistant depression. In a 1980 issue of the American Journal of Psychiatry, a study by Dr. Alan Gelenberg of Harvard Medical School discussed the role of tyrosine in the control of anxiety and depression. Dr. Gelenberg postulated that the lack of available tyrosine results in deficiency of the hormone norepinephrine at a specific location in the brain that relates to mood problems such as depression. Children given tyrosine supplementation demonstrated a marked improvement in mental performance and mood stability. Tyrosine, because of its role in assisting the body to cope physiologically with stress and building the bodys natural store of adrenaline, deserves to be called the stress amino acid. Stress exhaustion requires tyrosine. During periods of stress, in order to continue coping with stress physiologically, the brain requires tyrosine. Tyrosine aids children and young teens, as well as adults, with recurrent depression and mood disorders. In children, dosage ranges from 200 to 500 mg daily. Glycine Glycine is a nonessential amino acid, with the simplest structure of all the amino acids resembling glucose (blood sugar) and glycogen (excess sugar converted in the liver for storage). Glycine is sweet to the taste, can be used as a sweetener, and can mask bitterness and saltiness. Pure glycine dissolves readily in water. As the third major inhibitory neurotransmitter in the brain, glycine readily passes the blood-brain barrier. Studies by the late Carl Pfeiffer, MD, Ph.D., demonstrated glycine as an important factor in psychiatric disorders. Glycine decreases the craving for sugar, and, in many cases, can replace sugar on foods such as cereal. Glycine calms aggression in both children and adults. When combined with GABA and glutamine, glycine influences brain function by slowing down anxiety-related messages from the limbic system. As a very nontoxic amino acid, both children and adults can use glycine. Glycine can be mixed with other amino acids. Doses for a child range between 500 to 2,000 mg daily, divided. Magnesium Hyperactive or ADD children are almost always deficient in magnesium. Magnesium proves necessary for proper brain energy and is the first mineral depleted when anyone (child or adult) is under stress. Magnesium is a stress mineral, and deficiency can lead to hyperactive or ADD behavior. Magnesium plays a significant role in sugar metabolism and in the proper utilization of carbohydrates to create energy. Magnesium is so very important in a childs diet, especially if he displays hyperactive behavior, ADD, or other behavioral problems. Magnesium can be taken in liquid form, tablet, or capsule. When added to the ADD/ADHD diet, calming effects sometimes occur immediately. Most magnesium exists inside the cells where it activates enzymes necessary for the metabolism of carbohydrates and amino acids. In 1988, a study published in Alternative Medicine Review linked the development of ADHD to low blood-serum magnesium levels. A group of children followed for six months were given 200 mg of magnesium a day. Researchers noted remarkably decreased hyperactivity in the children. As a major nutrient needed by ADD/ADHD children and adults, magnesium is the number one stress mineral needed by the body. Magnesium is responsible for over three hundred enzyme functions. It cannot be stored by the body, and it must be taken daily. Symptoms of magnesium deficiency include asthma, migraines, eye twitches, anxiety, confusion, muscle spasms, irritability, depression, nervousness, fatigue, mood swings, PMS, hypertension, and insomnia. Calcium A calcium deficiency can also induce ADD/ADHD behavior. A child deficient in calcium exhibits irritability, sleep disturbances, anger, and inattentiveness. The first signs of a calcium deficiency include nervous stomach, cramps, tingling in the arms and legs, and painful joints. A calcium deficiency can also lead to ADD/ADHD behavior. Children sensitive to dairy products must receive daily calcium supplementation in capsule, chewable, or liquid form. Children up to 10 years of age need 1000 mg of calcium daily; adolescents need 1,200 to 1,500 mg daily. For those involved in sports activities, calcium supplementation is a must. Huperzine Recent research reports that Huperzine A improves mental function and learning in adolescents. Chinese researchers designed a study to determine the efficiency of Huperzine on memory and learning. The clinical study included 34 matched pairs of junior middle school students that had significant complaints of poor memory and difficulty in learning. In the double blind trial, half of the students received a placebo while the other half received Huperzine A for four weeks. Academic performance was measured before and after the clinical trial. The Huperzine group scored significantly better on standard memory tests without side effects. Huperzine A is an extract derived from Chinese club moss. Huperzine can be combined with amino acids and other nutrients. The suggested dosage is one 50 mcg capsule in the morning and in the evening for children aged 12 and over. This information is excerpted from my book Control Hyperactivity/ADD Naturally. Other resources include Is Ritalin Necessary? Both are available through: Pain & Stress Center 5282 Medical Dr. #160 San Antonio, TX 78229-6023

Natural treatments for Anxiety.

IS ANXIETY A FACT OF LIFE? I don't think so. Readers have requested we address the subject of relieving anxiety by using the amino acids Taurine, & GABA, and Vitamin B3 (Niacin). Though setting out to do this, by the time anxiety & taurine were finished, the news was too long, so GABA & B3 will have to wait. Taurine has many other benefits, so if anxiety is not your interest you may want to skip ahead to the Taurine section. I would not begin helping someone with anxiety by giving these single agents alone, & indeed they may not need to be given. Suffice it to say, when you are physically healthy & biochemically balanced you should have no symptoms of anxiety unless you find yourself in an extremely emergent situation. Those under 18 or over 38 who suddenly develop anxiety which disrupts their normal activity may have one of the medical illnesses which can include anxiety & should have appropriate medical evaluation. Apparently, many in our society are anxious because minor tranquilizers are one of the most widely prescribed group of drugs & among the most problematic when regularly used long term, which, unfortunately, they often are. They are highly addicting & over time risk adding to the very symptoms they were originally intended to alleviate. Though the Physicians Desk Reference warns of their addictive potential & suggests only intermittent or short term usage, these warnings are often ignored. Some of these tranquilizers are Xanax, Klonopin, Ativan, Valium, Librium. Tranxene, as well as some of the sleeping meds. PHYSIOLOGICAL OR PSYCHOLOGICAL ANXIETY, OR BOTH? It helps to distinguish whether the anxiety begins with physical symptoms such as racing heart, sweaty palms, shaking, nervous stomach, restlessness, tension, etc. & then perhaps spreads to associated thoughts & fears. Or does it begin with fearful anxious thoughts & spread to become a physiological reaction? Or is it only manifested by thoughts with no physical component or physical symptoms with little associated fear thoughts. When there is a usual thought onset to the symptoms, besides doing all of the next recommended items, it is important to decondition your thought patterns. There are many techniques for doing this. My current favorite is the use of Hypnoperipheral Processing reprogramming tapes. This is a combination of hypnosis & Neurolinguistic Programming. It is a powerful & effective tool for change! You can find such tapes at http://www.metamodels.com/maps/hpp.html. I would suggest the series "Changing Emotions" & "Feeling Better". We also clarify the timing of the anxiety. Is it all the time, or at certain times of the day or night? Is it only in very specific situations? I had a patient who only had severe anxiety when going out in the car. We found she was sensitive to auto fumes & when we had her wear a carbon filtered mask to keep out the fumes, she was able to go out without any anxiety. What percentage of agoraphobics are having their symptoms as a reaction to a specific chemical environment? All of this detective work helps to clarify how much is physical, how much is psychological, or even how much is a psychological conditioned response to a physical trigger. Is the problem related to blood sugar instabilty, which I see quite often & commonly has a pattern of middle of the night, early a.m. or mid-afternoon symptoms. Or is it related to food sensitivities? Is there is a personal or family history of allergies or is a person repetitively eating the same foods, or many of the high allergen foods, such as milk, cheese, wheat, eggs? We also look for a history of high caffeine, alcohol, or sugar intake , or a general junk food diet. Is there a premenstrual or menopausal component? Is the person on medications which can cause anxiety as a side effect? WHAT DOES NUTRITION HAVE TO DO WITH ANXIETY? It is known that deficiencies of certain nutrients can cause anxiety, so begin by improving your diet. Those nutrients are: Vitamins B1, B3, B6, B12, folic acid, calcium, magnesium, phosphorus, omega-3-fatty acids, such as fish or flax seed oil, & certain amino acids, such as L-tryptophan, taurine, GABA. Too much calcium can also cause anxiety. First, clean up your diet. With your diet improvement you may want to add a good multivitamin mineral, an extra B complex, & an omega-3-fatty acid to basically cover most of the above listed nutrients. You would then only add extra items if all of the above failed to make a difference after 2 weeks. My first choice would be extra magnesium & the next choice would be taurine. WHAT IS TAURINE? Taurine is an amino acid which plays a major role in the brain as an "inhibitory" neurotransmitter & neuromodulator. It is similiar in structure to the amino acids GABA & L-Glycine, which are also neuroinhibitory. This means it helps to calm or stabilize an excited brain. Taurine stabilizes nerve cell membranes thus depressing the firing of brain cells & dampening the nerve cell action of the excitatory amino acids, glutamate, aspartate, & quinolinate. Taurine acts by regulating the sodium & potassium concentration in the cells & the magnesium level between the cells. This has everything to do with the electrical activity of the cells & subsequent communication between cells. By this mechanism, it has anti-anxiety & anti-convulsant activity. It has also been found useful in some cases of migraine, insomnia, agitation, restlessness, irritability, alcoholism, obsessions, depression, hypomania/mania. Dosage is from 500 mg twice daily to a total of 5000 mg daily in 3-4 divided doses, though I rarely recommend that high a dose. The total ideal body pool of taurine for adults is 12,000- 18,000 mg. Since taurine also affects the hypothalamus to help regulate body temperature, a higher dose can decrease your temperature & give chilliness, so be aware of that. Taurine also plays a role in memory & increases the level of a memory neurotransmitter, acetylcholine, in the brain (in animal studies). HOW DO YOU GET TAURINE? Taurine is highly concentrated in animal & fish protein or organ meats. Strict vegetarians can be at risk for taurine deficiency. Your body can make taurine in the liver & brain from the amino acids, L-Cysteine, & L-Methionine. Three enzymes are involved in the conversion, all requiring the pyridoxal-5-phosphate form of Vitamin B6 for this conversion. A B6 deficiency can thus cause a taurine deficiency. Some studies suggest humans are dependent upon dietary taurine to maintain "adequate" taurine reserves. Females tend toward lower taurine levels than males as their production pathways don't work as efficiently. Taurine is closely bound to zinc & manganese so deficiencies of either of these can interfere with its' utilization. Likewise, zinc & manganese enhance the effects of taurine. Taurine is the amino acid present in highest concentration of all amino acids in the fetal & newborn brain, which is the most dependent upon taurine & the least able to synthesize it.. The developing infant must derive taurine from the placenta, the newborn, from breast milk or taurine fortified formula. It is low in cow's milk. Taurine is essential for proper development of the central nervous system & the eyes. Nursing mothers especially need taurine as it stimulates prolactin to promote lactation, which is an interesting twist of nature, since infants need it so much. ( We could speculate that a mother unable to lactate may be taurine deficient, among other possibilites, & the infant is thus protected from receiving taurine deficient breast milk) Premature infants are especially prone to taurine deficiency. WHAT ELSE INFLUENCES TAURINE LEVELS? MSG can decrease taurine. Trauma, surgery, radiation therapy, burns, muscle diseases, steroid use, intestinal dysfunction with bacterial overgrowth of the small bowel can all lead to excess loss of taurine in the urine & subsequent deficiency. The medications Thorazine (a major tranquilizer) & Chloroquine (an antimalarial) can reduce taurine levels. Some depressed patients have decreased taurine. WHAT ELSE DOES TAURINE DO? EYES: It is in high concentration in the eyes where it has multiple functions to maintain normal retinal structure & function. Depletion leads to degeneration of the photoreceptor cells. Degenerative changes in the retinas of taurine deficient cats & dogs resemble retinitis pigmentosa. Taurine may be helpful in preventing cataracts. Age related macular degeneration has responded favorably to "injected" taurine as reported by American Biologics Mexico Hospital. CARDIOVASCULAR: Taurine is the most abundant amino acid in the heart, a particularly electrically excitable tissue, as are the brain & eye. Since taurine participates in electrical stabilization of the cell membranes & the normal regulation of nerve-muscle interaction, it is useful in heart irregularities & mitral valve prolapse, acting similarly to a calcium channel blocker (a class of drugs used in CV Disease) Taurine also helps control high blood pressure & is useful in congestive heart failure. DIABETES: Taurine affects carbohydrate metabolism. It potentiates the effect of insulin, enhances glucose utilization & glycogen (stored glucose) synthesis. FAT METABOLISM: Taurine reduces cholesterol by forming bile acids which are the end products of cholesterol breakdown & are the only route for eliminating cholesterol from the body. This action requires a functioning gall bladder. Taurine has an inhibitory effect on the formation of cholesterol gall stones. It is required for efficient fat absorption & solubilization. It is helpful in states of fat malabsorption such as with cystic fibrosis & other pancreatic deficiency syndromes. DETOXIFICATION: Taurine conjugates & detoxifies various internal & external toxic compounds & may help chemical sensitivities. ANTIOXIDANT: Taurine plays a major role in protecting cell membranes from oxidative attack. STRESS: It can inhibit the release of adrenalin & thus help with anxiety in this way, as well as protecting from other adverse effects of too much adrenalin. MISC: Acts as an immune stimulant to increase Natural Killer Cell Activity & Interleukin 2. Controls cell volume & osmolality. Is involved in the regulation of iron metabolism. Modulates levels of serum copper. TAURINE CAN ALSO STIMULATE RELEASE OF STOMACH ACID SO YOU SHOULD AVOID IF YOU HAVE ULCERS OR GASTRITIS. BE HAPPY!! Priscilla Slagle M.D.

Urinary neutotransmitters

Neurorelief.com * Increased glutamate, epinephrine, norepinephrine, or PEA levels are observed in patients with anxiety disorders. * Anxiety may result from inefficient GABA or Glycine receptors. * High GABA, Glycine, and frequently Taurine levels are observed in patients with anxiety disorders. * Neurotransmitter tests can help identify chemical imbalances that underlie anxiety. * Reducing excitatory neurotransmitters glutamate, norepinephrine, PEA, epinephrine etc., will reduce anxiety and GABA and Glycine levels. * Patients with high GABA levels need GABA support.

Neurotransmitters and alcoholism (levels similar to our kids)

The HPA Axis The “Home” of Alcoholism in the Body and Mind Research has concluded that the “home” of alcoholism resides in the HPA (hypothalamus, pituitary, adrenal) axis of the neuroendocrine system. Now that we have the well-defined markers of addictive chemistry and we know where they live, scientists have developed extremely sophisticated tests which monitor the performance of this axis under various conditions by measuring dopamine, serotonin, GABA, glutamate, epinephrine (adrenaline), norepinephrine (noradrenalin), cortisol and DHEA which are the six big neurotransmitters and two key hormones which define either the health of the neuroendocrine system or its state and depth of illness. In Alcoholism: The Cause & The Cure you learn that addictive or addicted biochemistry is essentially the body's inability to adequately self-medicate with the natural, feel-good transmitters such as serotonin, GABA, dopamine and endorphins (as well as enkephalins) which predisposes an individual to “seek” relief in external ways such as alcohol. Addictive biochemistry is intricately associated with an upregulated (in excess) sympathetic nervous system where, due to low GABA, serotonin, and endorphins; excitatory neurotransmitters such as glutamate, norepinephrine and epinephrine are overexpressed which cause the many symptoms problem drinkers are known to self-medicate. It is also the bedrock of the progression of alcoholism in active drinkers because the longer one drinks, the more damage is done to the neuroendocrine system rendering it progressively unable to medicate the body naturally which intensifies symptoms which then causes one to drink more. To help you understand the root of this phenomenon I will go into a little more detail regarding genetic addictive biochemistry and active addiction and how they affect the HPA axis. The endocrine system is the network of glands in the body comprised of the hypothalamus, pituitary, pineal, adrenals, thyroid, parathyroid and the sex glands; ovaries and testes. These glands secrete hormones throughout the body to each and every organ via the blood which are received by their complimentary receptors. Hormones are “messengers” which carry messages coded by our DNA with the intention of keeping an organ regulated and healthy, essentially functioning as it should. A hormone's message will stimulate, suppress or maintain functional cell or tissue activity of the organ it is received by. The hypothalamus is the center piece of the endocrine system and is located in the middle of the base of the brain. The hypothalamus' ultimate purpose is to establish and maintain homeostasis; balance within the body. It regulates all the functions of the autonomic system of breathing, heart rate, etc… but also hunger, thirst, sexual drive, sleep urination and metabolism which includes blood sugar control. Although technically the hypothalamus is part of the endocrine system it is really central to both the endocrine and nervous system; in fact, it is in the hypothalamus that these two extremely complex systems of the body intersect. As the Master Accountant, the hypothalamus performs checks and balances and responds to chemical messages of deficient or excess by sending various hormones and neurotransmitters to “adjust” to the requirements of your internal and / or external environments to maintain status quo. The hypothalamus is able to do this because it houses receptor sites for both hormones from the endocrine system and neurotransmitters from the nervous system and it utilizes the information it receives from those sites to do its job of not only controlling the entire endocrine system, including having a profound influence on the liver, heart and kidneys, but establishing healthy brain chemistry and nervous system performance by correcting neurotransmitter imbalances by either slowing production of what is in excess, ingesting or degrading them faster, or in cases of deficiency, producing and releasing them as required. The door to addictive biochemistry opens when either the hypothalamus or one of the organs which serve the hypothalamus in accomplishing this job is injured, or if the nutrients required are not available. In any one of these conditions the entire system will fall off the “point zero” (homeostasis) that the HPA system tries to maintain, and the door for addictive biochemistry is opened. It is a well known fact that addictive biochemistry and full out alcoholism are associated with over expression of the sympathetic nervous system; low serotonin, GABA, dopamine, endorphins and enkephalins and it is in the hypothalamus where the delicate job of balancing this network of hormones and neurotransmitters to achieve physical and mental health is supposed to be done - whether it be directly from the hypothalamus or via the pituitary and adrenals under the control of the hypothalamus. The only difference between addictive biochemistry and full out alcoholism is that addictive biochemistry becomes aggravated, meaning that the deficient condition within the hypothalamus, pituitary or adrenals is made more profound by the damaging effects of alcohol toxicity and the medicating effects which, while drinking, overexpress serotonin, endorphins and dopamine which magnifies the negative impact of an already upregulated brain chemistry. The symptoms the problem drinker experiences intensify in direct relationship to the diminishing health of the neuroendocrine system which further encourages the person to drink more thus causing even more damage. This cycle progressively intensifies until intervention which discontinues and heals the damage is required to stop it. The pituitary gland is located below the hypothalamus and is directly connected to it via nerve and circulatory pathways. The hypothalamus regulates the function of the pituitary gland which in turn controls hormonal secretions of all other glands; however, specific to alcoholism we are concerned with the function of the adrenals and the secretion of cortisol which is under control of ACTH (adrenocorticotrophin) secreted by the pituitary, and epinephrine and norepinephrine which is also released by the adrenals due to a rise in CRH and/or signals from the sympathetic nervous system. In the case of cortisol release, when the hypothalamus registers low blood sugar it will send CRH (corticotrophin releasing hormone) to the pituitary which then releases ACTH which will cause cortisol to be secreted from the adrenals. This chain of events will also cause the release of epinephrine and to a lesser degree norepinephrine. Prolonged increased levels of epinephrine will block insulin receptors which leads to insulin resistance and lowered serotonin, endorphin, enkephalin and GABA levels which impairs HPA functions and increases compulsive / addictive behavior. The adrenals sit on top of the kidneys and are directly controlled by the pituitary gland. The adrenals are comprised of two sections; one is the medulla which is the inner core and the second is the adrenal cortex which is the outer layer. The medulla relates to the sympathetic nervous system and produces the catecholamines epinephrine and norepinephrine. The adrenal cortex produces sex hormones, aldosterone, and what we're most concerned with cortisol. The adrenals receive chemical messengers (hormones) from the pituitary and signal from the sympathetic nervous system which determines how much of its hormones it will release. However, if they are injured, diseased or fatigued they will not be able to keep up with the demands from the hypothalamus to maintain homeostasis and mild to severe mental disorders will surface as symptoms of compromised adrenal health. Although it is hard to imagine because they are docked on our kidneys, adrenal health is fundamental to our mental health. Proper levels of cortisol, epinephrine and norepinephrine are crucial to our mental well-being so concentrated focus needs to be applied to their health when healing addictive biochemistry and alcoholism. How They All Work Together I will use stress as an example of how the organs of the HPA work together and then we will take a look at how excessive alcohol use causes alcoholism and how to correct the metabolism so the addictive biochemistry and conditions for alcoholism are no longer present. During periods of acute stress special serotonin receptors on the hypothalamus are stimulated which cause the hypothalamus to produce CRF (corticotrophin release factor). The CRF is sent directly to the pituitary which causes ACTH to be sent to the adrenals which triggers release of cortisol. Cortisol is sent throughout the body on a number of different missions with the primary one to reduce the stress by stimulating serotonin (inhibitory neurotransmitter) in the amygdala which has an inhibitory effect on amygdala glutamate (excitatory neurotransmitter) which helps to calm the person down. The amygdala is directly connected to the hypothalamus and is a component of the limbic area of the brain where processing of emotions, fear, panic and long term memories occur. Many forms of depression, anxiety and panic disorders originate in the amygdala due to low serotonin and its inhibitory effects on the glutamate pathways of the amygdala. The HPA and Addictive / Addicted Biochemistry The genetic markers in the brain chemistry which spell alcoholism are the same for those that earned the condition through alcohol abuse; they are low endorphin, enkephalin, GABA, serotonin and dopamine expression which results in the over expression of the sympathetic nervous system; glutimate, epinephrine and norepinephrine. It doesn't necessarily have to be all of these; it could be just one or two that can engage the practice of self-medicating once a person, regardless of age, is exposed to a substance that helps balance their deficiencies. Albeit for a short time with known ramifications but it seems to be worth it because they will continue the habit until they find a way to stop the mild to severe symptoms they suffer through another means. The symptoms those with inherited capacity for addictive biochemistry are not as pronounced as the active drinker, however they are indeed debilitating and extremely mentally and physically uncomfortable. These symptoms can vary depending on the exact deficiencies of these neurotransmitters combined but they can include everything from depression, mental / physical fatigue and cravings for simple carbs to low self-esteem / confidence and low grade anxiety or restlessness. Alcohol can fix all of these in one fell swoop because it immediately raises all of the deficient neurotransmitters. The price to pay is high though, because on the other end comes the bottoming out of the already inherently low levels of neurotransmitters. Long-term drinking causes exaggerated over expression of the sympathetic nervous system due to overexpression of excitatory neurotransmitters glutamate, epinephrine, and norepinephrine; and underexpression of the inhibitory neurotransmitters; serotonin, GABA and dopamine, and the opioids endorphins and enkephalins during periods of sobriety which cause the “excitatory” symptoms I mentioned earlier which the individual is encouraged to self medicate. They will suffer their own combination of these now magnified symptoms due to the similar, now magnified neurotransmitter deficiencies. Due to the continual extreme demands on the adrenals, problem drinking invariably fatigues the adrenals and brings the problem drinker to a serious stress syndrome due depletion of cortisol, epinephrine and DHEA in concert with the depressive effects of low serotonin. Due to low cortisol / epinephrine, they will suffer from overexpression of norepinephrine which is known to cause irritability, anxiety, aggression, hypertension, and bipolar disorder. What happens within the body of those that have been abusing alcohol for a while and have damaged their neuroendocrine system is this: while the person is drinking, GABA, endorphins, dopamine and serotonin are overexpressed and literally emptied out from the CNS and hypothalamus which gives them the relaxation and medication for their symptoms they desire (which causes one to drink even more to achieve relief they found with far less alcohol early in their habit). This extreme depletion of inhibitory neurotransmitters leaves stores “empty” the next morning when they wake up which causes the overexpression of glutamate and the catecholamines. The symptoms of this condition are any of those I've mentioned including anxiety, restlessness, worry, short attention span, inability to focus, can't sit in one place for long, jitters, insomnia; basically most any feeling that is associated with being too “amped” up internally - this doesn't necessarily mean you feel like running a marathon; you don't. It means you are internally overexcited. Your endorphins and enkephalins were also over produced and emptied out so you won't have much of your natural pain killers available to mediate the condition you're in; ergo, soon you will have another drink. The internal scene with most people who rarely drink excessively is quite different; they have ample healthy stores of serotonin, dopamine, GABA, endorphin and enkephalin and they will immediately rise to the job of balancing the overexpressed glutamate and catecholamines. In the long-term drinker this is impossible because their body's ability to manufacture and replenish healthy levels of these neurotransmitters has been diminished from the damage of alcohol toxicity and the resulting malnutrition. The possible genetic handicap of not being able to naturally balance the autonomic sympathetic and parasympathetic nervous system by producing ample amounts of inhibitory neurotransmitters may also be involved which means there was a precondition of low levels of the natural feel-goods which will serve to accelerate the progression of alcohol abuse. Once the damage is established in the HPA by long-term drinking the cycle becomes deeply embedded in the person's biochemistry because this condition renders them entirely dependent on alcohol to achieve peace, relaxation and the natural euphoria of life because they can't feel good inside their own skin naturally anymore within a reasonable amount of time, and not without a bout of severe withdrawal which they are not inclined to endure. Inherited and acquired imbalanced, upregulated sympathetic neuroendocrine hormones and neurotransmitters are predominately caused by weakened or injured organs of the HPA caused by extreme blood sugar fluctuations over a considerable period and / or malnutrition. Alcohol metabolites such as acetaldehyde will also injure all of these organs in variable degrees making a considerable contribution to the addiction. A family history of unmet need for brain sugars due to a number of reasons such as famine or dietary restrictions due to location or climate which caused an excess of grains to be consumed over protein has been identified as contributing factors for weakened adrenals and injury to the hypothalamus and pituitary which can result in inheriting the predisposition to seek alcohol, other simple sugars and stimulants to self medicate. Another contributor to a genetic predisposition to addictive biochemistry is an early adoption of the industrialized food craze which began in the 40s and 50s which has now manifested in nearly 95% of what is at your supermarket being adulterated with sugars, hydrogenated fats, or foods so processed that there really isn't any food in the product anymore. These so called “foods” cause malnutrition and also damage the delicate workings of the HPA axis. Excessive dietary sugars, OTC, prescription and street drugs, malnutrition, disease and environmental toxins (especially acetaldehyde) can create a deficiency of neurotransmitters and imbalance or even damage the neuroendocrine system, creating an immediate requirement to replete and balance them before illness and possibly disease sets in. Alcoholism is extremely responsive to neurotransmitter repletion since it is their deficiencies and imbalance that is at the very root of alcohol addiction. In the Brain - a drink in a long time problem drinker (simplified) ? serotonin, GABA, endorphins and dopamine > hypothalamus produces ? CRF > pituitary produces ? ACTH > adrenals produce ? Cortisol. Sympathetic nervous system produces ? norepinephrine and epinephrine. 20 to 30 min. later, sharp drop in blood sugar, serotonin, endorphins and dopamine. Individual begins to feel “excitatory” symptoms. Has another drink, cycle begins again. Next day: Individual experiences symptoms of low levels of the feel-good neurotransmitters: serotonin, GABA, dopamine, endorphins, enkephalins and GABA. Concurrently, he/she will suffer symptoms of high cortisol (due to low blood sugar this time), glutamate, norepinephrine and epinephrine. The “tank” for the parasympathetic, feel-good neurotransmitters is emptied out and mental and physical capacities are diminished while the person suffers resulting symptoms. The individual begins to cultivate his/her habits around repletion of these neurotransmitters through the use of alcohol which progressively damages the person's ability to produce them and an addiction is born. The biochemistry of alcohol related symptoms exposed: Symptoms of long-term alcohol abuse directly related to HPA function: Stress Disorder There are possibly a hundred pathways for the various symptoms caused by alcohol toxicity and damage. I am provided a simplified one to demonstrate the very real fundamental message of this section: that alcohol toxicity and the results of its metabolism in the brain cause the psychological symptoms they suffer which triggers the survival mechanism to reduce pain and since they can't do it naturally, will seek it relief in alcohol. Due to alcohol toxicity damage and malnutrition, adrenal fatigue causes low cortisol output which leads to high norepinephrine levels (overexpressed). I've mentioned the debilitating symptoms of this condition earlier. The cause is because cortisol is required (along with SAMe) to produce epinephrine from norepinephrine. When this doesn't occur, norepinephrine is overexpressed while epinephrine and cortisol are diminished. Note here that cortisol is required in some areas of the brain to activate serotonin so when it is low it can also inhibit serotonin expression. This condition delivers one to the “alarm” stage of stress disorder due to the profound states of mind that can result from elevated norepinephrine including extreme anxiety, panic attacks, exaggerated fear (paranoia), insomnia, aggression, irritability, hypertension and even bipolar disorder. All of these conditions center on the deregulation of the HPA axis. How The 101 Program Corrects Addictive Biochemistry (simplified) Through the use of HPA axis testing, measuring the key neurotransmitters known to facilitate addictive biochemistry: dopamine, serotonin, GABA, glutamate, epinephrine, and norepinephrine. Cortisol and DHEA levels are also tested to establish the degree to which the adrenals are damaged so that an appropriate treatment for the adrenals can be developed. Once the neurotransmitter deficiencies are exposed, the practitioner can develop a personalized, targeted nutritional therapy (TNT) and aggressive nutriceutical protocol to bring the neuroendocrine system back into balance, optimizing the HPA axis and relieving the individual of the symptoms they self-medicate. Other contributing factors such as liver and GI damage are considered and addressed as well to provide the system with the best possible environment to heal and correct the “broken” metabolism.

Four Major Transmitters

Neurotransmitters are powerful chemicals that regulate numerous physical and emotional processes such as mental performance, emotional states and pain response. Virtually all functions in life are controlled by neurotransmitters. They are the brain's chemical messengers.Interactions between neurotransmitters, hormones, and the brain chemicals have a profound influence on overall health and well-being. When our concentration and focus is good, we feel more directed, motivated, and vibrant. Unfortunately, if neurotransmitter levels are inadequate these energizing and motivating signals are absent and we feel more stressed, sluggish, and out-of-control. Proteins, minerals, vitamins,carbohydrates, and fats are the essential nutrients that make up your body. Proteins are the essential components of muscle tissue, organs, blood, enzymes, antibodies, and neurotransmitters in the brain. Your brain needs the proper nutrients everyday in order to manufacture proper levels of the neurotransmitters that regulate your mood. Neurotransmitter Effects: Control the appetite center of the brain Stimulates Corticotropin Releasing Factor, Adrenalcorticotropic Hormone, & Cortisol Regulate male and female sex hormone Regulates sleep Modulate mood and thought processes Controls ability to focus, concentrate, and remember things The Mind Body Connection The chemistry of our bodies can alter, and be altered by our every thought and feeling. Our bodies and our minds are truly interconnected, the health of one depends on the health of the other. There are many biochemical neurotransmitter imbalances that result in mental health symptoms such as: *Adrenal dysfunction *Blood sugar imbalance *Food and Chemical allergy *Heavy Metal Toxicity *Hormone imbalance *NutritionalDeficiency *Serotonin/Dopamine/Noradrenalin imbalance *Stimulant and drug intoxication *Under or overactive thyroid >Neurotransmitter Imbalances Disrupted communication between the brain and the body can have serious effects to ones health both physically and mentally. Depression, anxiety and other mood disorders are thought to be directly related to imbalances with neurotransmitters. The four major neurotransmitters that regulate mood are Serotonin, Dopamine, GABA and Norepinephrine. The Inhibitory System is the brains braking system, it prevents the signal from continuing. The inhibitory system slows things down. Serotonin and GABA are examples of inhibitory neurotransmitters. GABA (Gamma amino butyric acid) GABA is the major inhibitory neurotransmitter in the central nervous system. It helps the neurons recover after transmission, reduces anxiety and stress.It regulates norepinephrine, adrenaline, dopamine, and serotonin, it is a significant mood modulator. Serotonin imbalance is one of the most common contributors to mood problems. Some feel it is a virtual epidemic in the United States. Serotonin is key to our feelings of happiness and very important for our emotions because it helps defend against both anxiety and depression. You may have a shortage of serotonin if you have a sad depressed mood, anxiety, panic attacks, low energy, migraines, sleeping problems, obsession or compulsions, feel tense and irritable, crave sweets, and have a reduced interest in sex. Additionally, your hormones and Estrogen levels can affect serotonin levels and this may explain why some women have pre-menstrual and menopausal mood problems. Moreover, daily stress can greatly reduce your serotonin supplies.

The Excitatory Neurotransmitter System can be related to your car's accelerator. It allows the signal to go. When the excitatory neurotransmitter system is in drive your system gets all reved up for action. Without a functioning inhibitory system to put on the brakes, things (like your mood) can get out of control Epinephrine also known as adrenaline is a neurotransmitter and hormone essential to metabolism. It regulates attention, mental focus, arousal, and cognition. It also inhibits insulin excretion and raises the amounts of fatty acids in the blood. Epinephrine is made from norepinephrine and is released from the adrenal glands. Low levels have been can result in fatigue, lack of focus, and difficulty losing weight. High levels have been linked to sleep problems, anxiety and ADHD. Dopamine is responsible for motivation, interest, and drive. It is associated with positive stress states such as being in love, exercising, listening to music, and sex . When we don’t have enough of it we don’t feel alive, we have difficulty initiating or completing tasks, poor concentration, no energy, and lack of motivation. Dopamine also is involved in muscle control and function. Low Dopamine levels can drive us to use drugs (self medicate), alcohol, smoke cigarettes, gamble, and/or overeat. High dopamine has been observed in patients with poor GI function, autism, mood swings, psychosis, and children with attention disorders. Glutamate is the major excitatory neurotransmitter in the brain. It is required for learning and memory. Low levels can lead to tiredness and poor brain activity. Increased levels of glutamate can cause death to the neurons (nerve cells) in the brain. Dysfunction in glutamate levels are involved in many neurodegenerative diseases such as Alzheimer's disease, Parkinson's, Huntington's, and Tourette's. High levels also contribute to Depression, OCD, and Autism. Histamine is most commonly known for it's role in allergic reactions but it is also involved in neurotransmission and can affect your emotions and behavior as well. Histamine helps control the sleep-wake cycle and promotes the release of epinephrine and norepinephrine. High histamine levels have been linked to obsessive compulsive tendencies, depression, and headaches.Low histamine levels can contribute to paranoia, low libido, fatigue, and medication sensitivities. Norepinephrine also known as noradrenaline is a excitatory neurotransmitter that is produced by the adrenal medulla or made from dopamine. High levels of norepinephrine are linked to anxiety, stress, high blood pressure, and hyperactivity. Low levels are linked to lack of energy, focus, and motivation. PEA is an excitatory neurotransmitter made from phenylalanine. It is important in focus and concentration. High levels are observed in individuals experiencing "mind racing", sleep problems, anxiety, and schizophrenia. Low PEA is associated with difficulty paying attention or thinking clearly, and in depression. Neurotransmitter Levels Neurotransmitter levels can now be determined by a simple and convenient urine test collected at home. Knowing your neurotransmitter levels can help you correct a problem today or prevent problems from occuring in the future. Find out more about the Neurotransmitter Testing that is available! For many years, it has been known in medicine that low levels of these neurotransmitters can cause many diseases and illnesses. A Neurotransmitter imbalance can cause: Depression Anxiety Attention deficit/ADHD Panic Attacks Insomnia Irritable bowel PMS/ Hormone dysfunction Fibromyalgia Obesity Eating disorders Obsessions and Compulsions Adrenal dysfunction Psychosis Early Death Chronic Pain Migraine Headaches What causes a neurotransmitter imbalance? Prolonged periods of stress can deplete neurotransmitters levels. Our fast paced, fast food society greatly contributes to these imbalances. Poor Diet. Neurotransmitters are made in the body from proteins. Also required are certain vitamins and minerals called “cofactors”. If your nutrition is poor and you do not take in enough protein, vitamins, or minerals to build the neurotransmitters, a neurotransmitter imbalance develops. We really do think and feel what we eat. Genetic factors, faulty metabolism, and digestive issues can impair absorption and breakdown of our food which reduces are ability to build neurotransmitters. Toxic substances like heavy metals, pesticides, drug and alcohol use, and some prescription drugs can cause permanent damage to the nerve cells that make neurotransmitters. Certain drugs and substances such as caffeine, alcohol, nicotine, NutraSweet, antidepressants, and some cholesterol lowering medications deplete neurotransmitter levels leading to neurotransmitter imbalances. Hormone changes such as thyroid, adrenal, male and female sex hormones, can cause neurotransmitter imbalances. Medical conditions such as food and chemical allergy, blood sugar imbalance, inflammatory conditions, GI disorders, and head injury.

Lead inhibits the formation of GABA and increases the concentration of Glutamate/glutamine in the synapse.

Pubmed Laboratory of Pathobiochemistry of the Central Nervous System, Department of Neurochemistry, Medical Research Centre, Polish Academy of Sciences, 5 Pawinskiego str., 02-106 Warsaw, Poland. lidkas@cmdik.pan.pl

Glutamine (Gln), glutamate (Glu) and gamma-amino butyric acid (GABA) are essential amino acids for brain metabolism and function. Astrocytic-derived glutamine is the precursor of the two most important neurotransmitters: glutamate, an excitatory neurotransmitter, and GABA, an inhibitory neurotransmitter. In addition to their roles in neurotransmission these neurotransmitters act as alternative metabolic substrates that enable metabolic coupling between astrocytes and neurons. The relationships between Gln, Glu and GABA were studied under lead (Pb) toxicity conditions using synaptosomal fractions obtained from adult rat brains to investigate the cause of Pb neurotoxicity-induced seizures. We have found that diminished transport of [(14)C]GABA occurs after Pb treatment. Both uptake and depolarization-evoked release decrease by 40% and 30%, respectively, relative to controls. Lower expression of glutamate decarboxylase (GAD), the GABA synthesizing enzyme, is also observed. In contrast to impaired synaptosomal GABA function, the GABA transporter GAT-1 protein is overexpressed (possibly as a compensative mechanism).

Furthermore, similar decreases in synaptosomal uptake of radioactive glutamine and glutamate are observed. However, the K(+)-evoked release of Glu increases by 20% over control values and the quantity of neuronal EAAC1 transporter for glutamate reaches remarkably higher levels after Pb treatment. In addition, Pb induces decreased activity of phosphate-activated glutaminase (PAG), which plays a role in glutamate metabolism. Most noteworthy is that the overexpression and reversed action of the EAAC1 transporter may be the cause of the elevated extracellular glutamate levels. In addition to the impairment of synaptosomal processes of glutamatergic and GABAergic transport, the results indicate perturbed relationships between Gln, Glu and GABA that may be the cause of altered neuronal-astrocytic interactions under conditions of Pb neurotoxicity.

Neurotransmitter Levels Predict Post-Traumatic Stress

TUESDAY, Aug. 29 (HealthDay News) -- Blood levels of the neurotransmitter gamma-aminobutyric acid, or GABA, in trauma patients may predict the development of post-traumatic stress disorder (PTSD), according to the results of a study of car-accident victims published in the August issue of the American Journal of Psychiatry.

Guillaume Vaiva, M.D., Ph.D., of the University of Lille II, School of Medicine in France, and colleagues measured GABA blood levels in 78 car-accident victims who had been admitted to trauma centers and hospitalized for at least three days.

After one year, the researchers found that 80 percent of patients whose post-trauma GABA levels were below 0.2 mmol/ml met all or most of the criteria for PTSD and that two-thirds of them also met criteria for major depressive disorder. Among patients who met all or most of the criteria for PTSD at six weeks, they also found that 75 percent of those whose post-trauma GABA levels were above 0.2 mmol/ml no longer met criteria for PTSD after one year.

"From a clinical perspective, it would be extremely helpful to predict with reasonable accuracy which trauma patients are at risk of having chronic PTSD," the authors conclude. "Our results, if replicated, would suggest that a plasma GABA level greater than 0.2 mmol/ml may protect against chronic PTSD and may represent a marker of recovery among patients who have suffered trauma."

This article: Copyright © 2006 ScoutNews, LLC. All rights reserved.

Oxytocin and behavior

http://www.healing-arts.org/children/autism-overview.htm Oxytocin is produced through the influence of the cholecystokinin-A (CCKA) receptor, which requires its substrate, cholecystokinin, to be sulfated (see the free sulfate theory of autism). If there is insufficient ability to sulfate compounds (a finding in some autistic people), the receptor will not work well, and many CCKA mediated functions will be afffected. The presence of opioid peptides and opiate receptors in the hypothalamo-neurohypophysial system, as well as the inhibitory effects of enkephalins and beta-endorphin on release of oxytocin and vasopressin has been well documented 6. Opioid peptides inhibit oxytocin release and thereby promote the preferential secretion of vasopressin when it is of functional importance to maintain homeostasis during dehydration and hemorrhage. Both neuromodulators and a neurohormones co-exist in the same neuron, as demonstrated for vasopressin with dynorphin or leucine-enkephalin, which serves to regulate the differential release of two biologically different, yet evolutionarily-related, neurohormones, e.g. oxytocin and vasopressin, from the same neuroendocrine system. Stress: Human immune function is mediated by the release of cytokines, nonantibody messenger molecules, from a variety of cells of the immune system, and from other cells, such as endothelial cells. There are Th1 and Th2 cytokines. Autoimmune and allergic diseases involve a shift in the balance of cytokines toward Th2. The autoimmune aspect of autism has been related to excessive Th2 cytokines resulting, in part, from vaccination. Gulf War syndrome and asthma have been similarly linked to excess immunization in the presence of increased environmental toxins and pollutants (high antigenic load). http://www.healing-arts.org/children/index.htm Please also see our new article, "Imaging Children with ADHD: MRI Technology Reveals Differences in Neuro-signaling". In this report, it was found that children with attention deficit-hyperactivity disorder (ADHD) may have significantly altered levels of important neurotransmitters in the frontal region of the brain, according to a study published in the December 2003 issue of the Journal of Neuropsychiatry and Clinical Neurosciences. "Our data show children with ADHD had a two-and-half-fold increased level of glutamate, an excitatory brain chemical that can be toxic to nerve cells," said lead author Helen Courvoisie, M.D., assistant professor, division of child and adolescent psychiatry, department of psychiatry and behavioral sciences at the Johns Hopkins Medical Institutions, Baltimore. "The data also suggest a decreased level of GABA, a neuro-inhibitor. This combination may explain the behavior of children with poor impulse control." Environmental factors associated with ADHD include low birth weight, hypozia (too little oxygen) at birth, and exposure in utero to a number of toxins including alcohol, cocaine, and nicotine. Other studies have found correlations between certain toxic agents / nutrient deficiencies and learning disabilities. These include: * Calcium deficiency * High serum copper * Iron deficiency can cause irritability and attention deficits * Magnesium deficiency, which is characterized by fidgeting, anxiousness, restless, psycho- motor inability, and learning difficulties * Malnutrition in general is related to learning disabilities; the child does not have to look malnourished, a fact forgotten in affluent countries * Dyslexic children seem to have abnormal zinc and copper metabolism - low zinc and high copper * Iodine deficiencies have been linked to learning difficulties http://osiris.sunderland.ac.uk/autism/owens.htm CHOLECYSTOKININ Lack of availability of sulfate would also seriously effect the performance of the major gut hormone and neurotransmitter called cholecystokinin. Two types of CCK receptors have been described: the first one, the CCKA receptor, is predominant in the alimentary canal; and the second, the CCKB receptor, is more abundant in the brain. Both receptors are found in both systems, however, and can be co-localized. (95,70) Many forms of CCK are active, but the octapeptide form of CCK which is a chain of eight amino acids, is able to promote the same degree of signal at the CCKB receptor regardless of whether sulfate has attached to it or not. On the other hand, the CCKA receptor is a thousand times more responsive to sulfated octapeptide than it is to the octapeptide's unsulfated form. (44,23) In a condition of low sulfate, CCK's maturation might be affected (24), and the delivery of its signal at the CCKA receptor would be unreliable.When one looks at the function of the CCKA receptor, the possible relevance to autism begins to become clear. Though it is clear there are some regions where the CCKA receptor does not regulate the production of serotonin, it clearly does have effects in the hypothalamus (34,56), and it is also clear that CCK has very powerful effects on serotonin in other regions where the receptor has not been differentiated. It may consequently have effects on serotonin's metabolite, melatonin, in the pineal gland. The CCKA receptor powerfully regulates dopamine(23,92,117); and also intrinsic factor (114), a substance in the digestive system which allows the body to absorb B12. When B12 is lacking it will result in elevations in methylmalonic acid in the urine (31), which was found to be consistently elevated in the children in Wakefield's recent study.(119) Dysregulation of these pathways in autism have been described by others. (7,82) The CCKA receptor also governs the release of oxytocin (64), dubbed "the social hormone" whose inadequacy may relate to the social deficits in autism. http://209.85.165.104/search?q=cache:NxDcVeCDi1EJ:www.eas.asu.edu/~autism/Additional/SummaryofDefeatAutismNow.doc+zinc+CCK+oxytocin&hl=en&ct=clnk&cd=3&gl=us Sulfation: Susan Owens substituted for Rosemarie Waring, and presented Dr. Waring's data on sulfate in autism. Basically, people with autism were found to excrete roughly twice as much sulfate in their urine, so that they had only 1/5 the normal level of sulfate in their bodies. Sulfur is an essential mineral, and is needed for many functions in the body. AIDS patients have also been found to exhibit a loss of sulfur in their urine, leading to a loss of extracellular sulfated structures in the brain. This has not yet been investigated in autism, but may be the same. In AIDS patients, treatment with N-acetyl cysteine was found to be beneficial. In autism, TNF (tumor necrosis factor) is elevated, which can inhibit the conversion of cysteine to sulfate. Low sulfur levels could cause many problems. o Sulfur is needed to sulfate the hormone CCK, which stimulates oxytocinergic neurons to release oxytocin. So, a lack of sulfur could explain the low oxytocin levels found in autism, which is important for socialization. o Sulphate is important for detoxification of metals and other toxins. o Sulphation requires activated sulfate, which requires magnesium. o Boys excrete more sulfur than girls, so they may be more susceptible to sulfation problems. o Wakefields group found that the ileum of the intestine lacks sulfur, which would lead to a leaky gut. o Sulphate is needed to release pancreatic digestive enzymes. o Many enzymes would be impaired if sulfur levels were low. o The perineuronal nets around neurons, which modulate their function, are primarily composed of chondroitin sulfur. Low sulfur would thus yield less modulation of neurons o The hepatitis B vaccine was found to inhibit sulphation chemistry for one week in typical people.

GABA Potentiators

Neurosciences Newsletter on GABA GABA is a true neurotransmitter and is involved in many clinical conditions. These include anxiety disorders such as panic attacks, seizure disorders like epilepsy, and numerous other conditions including addiction, headaches, Parkinson's Syndrome, and cognitive impairment. GABA's role is that of the primary inhibitory neurotransmitter and functions by down-regulating neurotransmission. Neurons are electrically charge cells. Ion pumps actively transfer Na+ ions out of the neuron and a overall negative charged known as the cells resting potential is attained. Two opposing forces work to alter the neurons electrical potential. The neurotransmitter glutamate increases the flow of positively charged Na+ ions into the neuron and reduce the neurons electrical charge. If the electrical potential is reduced to a critical point , called the action potential, the neuron will fire. In contrast, the neurotransmitter GABA opposes the effects of glutamate and prevents the neuron from firing. GABA achieves this by effecting the actions of the GABA receptor, a 5 subunit ion transporter. When GABA binds to the GABA receptor, the subunits of the receptor "open" and there is an influx of chloride ions. This influx restores the electrical potential of the neuron and thereby decreases the likelihood that the neuron will depolarize and relay the incoming signal. Essentially, weak or irrelevant signals are more likely to be terminated or "ignored." GABA receptor and the putative binding site for a number of agents that affect GABA function. This diagram shows the GABA-A receptor and the putative binding site for a number of agents that affect GABA function. The GABA receptor is a relatively large molecule and has binding sites not only for GABA but also for many modulatory compounds. Many of these modulatory compounds are useful therapeutic agents. Positive GABA modulators, like the benzodiazepines, do not cause the ion channel to open and an influx of chloride ions to occur on their own. They only enhance the activity of naturally occurring GABA by potentiating its function and therefore have vastly reduced potential for overdose or side effects than receptor agonist compounds, like barbiturates. While much safer than barbiturates benzodiazepine use frequently leads to dependence and withdrawal syndrome effects. This limits their utility for mild/moderate symptoms as well as for long-term therapy. Because of the important role for GABA and positive GABA modulators NeuroScience has developed a number of products that address GABA and are beneficial for patients with GABA related disorders. The following ingredients have been found to increase GABA or have a positive GABA modulating effect and have been combined in specific amounts and ratios depending on the results of laboratory tests and the clinical application. Taurine Taurine is an amino acid that is present at significant levels in the CNS and is positive modulator of GABA that does not have any adverse side-effects. Taurine also potentiates glycine - the inhibitory neurotransmitter in the spinal cord. The role of taurine as an inhibitory amino acid has been confirmed in many studies. Not surprisingly, brain tissue and cardiac tissue, which are susceptible to high levels of neurotransmitter stimulation, maintain high levels of taurine. Taurine has been shown to prevent the neuronal damage that can occur when there is an exposure to increased levels of the excitatory neurotransmitter glutamate. Over stimulation by excitatory neurotransmitters is the primary cause of neuron death in ischemic stroke. Taurine has been found to significantly reduce neuron death caused by over stimulation. The calming effects of taurine have been well studied. Other studies of taurine have found that it can reduce epileptic seizures and that low taurine levels are associated with anxiety. Glutamine Significant quantities of glutamine are normally present in the brain to support the complex process of GABA synthesis. Glutamine is an amino acid and a common precursor for the biosynthesis of GABA and glutamate. Glutamine is transported into the presynaptic terminals of inhibitory neurons by the glutamine transporter (GlnT) and is catalyzed by the actions of the enzyme glutamine deaminase to form glutamate. Glutamate in turn is converted into GABA through the actions of glutamic acid decarboxylase (GAD). (NOTE: This biosynthetic route is somewhat more complex than originally thought. Some studies have demonstrated that the glutamate formed from glutamine may enter the tricarboxylic acid (TCA) cycle before being converted to GABA.) 5-HTP Serotonin is a neurotransmitter, or more correctly a neuromodulator, that is widely distributed throughout the brain and generally enhances GABA and therefore has inhibitory activity. Therefore, as a precursor to serotonin, 5-HTP can further increase the activity of GABA. Low serotonin levels are frequently an underlying component of many clinical conditions that are also related to GABA function, e.g. insomnia, depression, & anxiety. Neurotransmitter tests show that GABA needs serotonin to function properly. Normally, GABA increases and acts through a negative feedback mechanism to reduce elevated excitatory neurotransmitters. However, this feedback mechanism requires the neuromodulating effects of serotonin. This is evident in patients with symptoms related to low GABA who have adequate GABA levels but low serotonin. Theanine Theanine is another amino acid that affects GABA. Initial interest in theanine arose due to the seemingly paradoxical calming effect of a caffeine containing drink. Theanine is a naturally occurring amino acid present at significant levels in tea leaves and is the component responsible for this discord. Theanine has been found to alter glutamate transport and actually increase GABA levels. Further studies reveal that theanine reduces hypertension in models of hypertension, increases the effectiveness of some chemotherapy compounds, reduces the stimulatory effect of caffeine, and calms patients.

GABA

GABA: Gamma-Amino Butyric Acid INTRODUCTION: Gamma-Amino Butyric acid (GABA) is an amino acid which acts as a neurotransmitter in the central nervous system. It inhibits nerve transmission in the brain, calming nervous activity. As a supplement it is sold and promoted for these neurotransmitter effects as a natural tranquilizer. It is also touted as increasing Human Growth Hormone levels and is popular among body builders. The published research supporting any of these promotional claims is weak. Current medical opinion says that GABA taken as a supplement does not reach the brain and has no effect or benefit aside from being a benign placebo. Many websites claim that the neurotransmitter GABA was discovered in Berlin in 1863, which is an outlandish claim. The concept of neurotransmitters had yet to be conceived of. It is more likely that GABA was isolated and identified as an amino acid in 1863. It was 87 years later, in 1950, that Eugene Roberts and J. Awapara discovered that GABA acted as an inhibitory neurotransmitter. NEUROTRANSMITTER REVIEW The nervous system is made up of individual nerve cells called neurons. They serve as the body's wiring. Nerve signals are transmitted through the length of a neuron as an electrical impulse. When a nerve impulse reaches the end of the neuron it can jump over to the next cell using chemical messengers called neurotransmitters. In the central nervous system, which consists of the brain and the spinal cord, neurotransmitters pass from neuron to neuron. In the peripheral nervous system, which is made up of the nerves that run from the central nervous system to the rest of the body, the chemical signals pass between a neuron and an adjacent muscle or gland cell. Glutamate and GABA are the most abundant neurotransmitters in the central nervous system, and especially in the cerebral cortex, which is where thinking occurs and sensations are interpreted. Tiny sacs filled with neurotransmitters are stored at the end of each neuron. When a nerve impulse reaches the cell's end it triggers these sacs to dump the neurotransmitters into the gaps that separate one nerve cell from another. These spaces are called synapses. The neurotransmitters float across the synapse. When they reach the neighboring neuron, the neurotransmitters click into specialized receptor sites much as a key fits into a lock. When enough neurotransmitters attach to the receptors, the neuron ?fires,? sending an electrical impulse down its length. GABA'S ROLE IN THE BRAIN GABA is made in brain cells from glutamate, and functions as an inhibitory neurotransmitter ? meaning that it blocks nerve impulses. Glutamate acts as an excitatory neurotransmitter and when bound to adjacent cells encourages them to ?fire? and send a nerve impulse. GABA does the opposite and tells the adjoining cells not to ?fire?, not to send an impulse. Without GABA, nerve cells fire too often and too easily. Anxiety disorders such as panic attacks, seizure disorders, and numerous other conditions including addiction, headaches, Parkinson's syndrome, and cognitive impairment are all related to low GABA activity. GABA hinders the transmission of nerve impulses from one neuron to another. It has a calming or quieting influence. A good example to help understand this effect is caffeine. Caffeine inhibits GABA release. The less GABA, the more nerve transmissions occur. Think what too much coffee feels like: that is the sensation of glutamate without enough GABA. The reason caffeine does this is that other molecules can bind to the neuron near the GABA binding site and influence GABA's effect. This is how tranquilizing drugs such as Benzodiazepines and barbiturates work. They increase or imitate GABA's effect, inhibiting nerve transmission. Research on GABA In the half century since GABA was identified as a neurotransmitter there has been an enormous amount of research published directed toward its role in both animals and humans. Most of this has focused on the mechanics of GABA action and the drugs and chemicals which affect its action along with GABA's role in various disease states. A search on the term GABA on PubMed today ( October 7, 2004 ) brings up a list of 43,859 published papers. Only a handful of these papers focus on using GABA orally as a nutritional supplement. Some nutritional writers suggest a conspiracy on the part of the drug industry to suppress GABA research so as to promote their drugs such as Valium. [1] A more likely explanation rests in the fact that the common belief among scientists is that GABA will not cross the blood brain barrier. If GABA does not reach the brain, it will have no effect. Although I have found no direct published evidence proving that oral GABA changes brain levels of GABA, some scientists assume that with large enough doses some may cross over. [2] This amount may vary from person to person, their nutritional status, physical conditioning and activity level. This lack of research caught me by surprise. With most nutritional and herbal supplements these days there is ample research to argue in support of their therapeutic use. This is an unusual situation in modern nutritional medicine. Few of the websites which sell GABA list references for the scientifically proven benefits attributed to its use. This is unsatisfactory and discredits the bona fide claims made for other products. Instead of garnering uses directly from clinical research, we are left to look elsewhere. Possible Uses of GABA: The best information I have on clinical use comes from the writing of Eric Braverman and Carl Pfeiffer. [3] Their 1987 book on the clinical use of amino acids is a classic treatise for the practice of nutritional medicine. Anxiety: If oral GABA reaches the brain in any significant amount it should act as a tranquilizer. GABA as a neurotransmitter, blocks nerve impulses and slows neuronal transmission. It should make you feel the opposite of a double espresso. Braverman and Pfeiffer write an anecdotal account of the successful treatment of a forty year old woman suffering from anxiety with 800 mg of GABA a day. They also gave her an undisclosed amount of inositol which we now know is an effective anxiolytic used in treating obsessive compulsive disorder. Was it the GABA or the inositol that helped this patient? Perhaps the combination. Though this anecdote is inconclusive, using GABA to treat anxiety is the most common and reasonable use. Will the brain adapt to supplemental GABA? There are no answers to this as no one has proven GABA reaches the brain. Looking at the brain's capacity to change GABA receptor response and its tendency to build up tolerance to drugs which modify GABA, it is possible that a tolerance to oral GABA might develop and withdrawal symptoms might occur. None are reported in the literature to my knowledge. Depression: There is a well proven tendency for depressed and bipolar patients to have lower levels of GABA in their blood plasma. These low levels are thought to reflect lower brain levels. Both Braverman, Pfeifer and Robert Atkins in their books suggest using GABA to treat depression. The theory is that oral GABA will bring up plasma levels. Unfortunately this theory is too simplistic and possibly dangerous. The current theory of GABA and depression is that low plasma levels of GABA may identify an inheritable tendency for mood disorders such as depression or bipolar disease. [4] Today's view is that things which increase GABA in these people may trigger a depressive episode. It isn't until time or treatment restores GABA to its former low level that these people feel better. [5] This information suggests a situation that is far more complex than what was once thought and certainly argues for caution in using GABA in patients with depressive or bipolar disorders. Will excess GABA from oral supplementation stimulate a depressive episode in susceptible patients? There is no data to answer this question. Until proven safe, GABA should be used with caution in this population. Again recall the biochemistry, GABA is an inhibitory neurotransmitter. Give it to people who look or feel like they've drunk too much coffee, not people who look like they need a cup. Premenstrual Syndrome Women who become depressed with hormonal changes during their menstrual cycle have lower plasma GABA levels than women whose moods are unaffected by menstrual changes. Dr. Atkins suggests that GABA supplementation will ?lift spirits.? [6] The study Dr Atkins cites in support of his suggestion [7] suggests that it is this same inheritable tendency for low GABA levels that underlie their depressive tendencies and their premenstrual depression. More recent research suggests a more complicated interaction between sex hormones and GABA in the brain. In healthy women, brain GABA activity decreases through the menstrual cycle, especially the luteal phase. In women with premenstrual depression, brain GABA activity actually increases during the luteal phase. [8] Giving GABA to women with premenstrual depression may aggravate their problem and drop their spirits. Male Contraceptive Braverman and Pfeiffer suggest GABA as a possible male contraceptive because it decreases sperm motility but don't count on this. The reference they cite is referring to monosodium glutamate, a distant relative of GABA. [9] Newer studies say GABA makes sperm cells hyperactive. [10] In other words GABA might be useful for treating male infertility rather than as a contraceptive No clinical trials have been published but this is not something one would want to make a mistake with. Seizures Dr. Atkin's mentions Taurine's apparent effect of suppressing seizures because it increases GABA effect in the brain. At this time the research on Taurine and epileptic seizures is mixed. The effect of Taurine varies with the time it is administered, sometimes preventing and sometime precipitating seizures. [11] In other carefully designed animal models, no benefit was demonstrated. [12] GABA should thus be used with caution with anyone who has a seizure history. Blood sugar and Diabetes: Braverman and Pfeifer suggest that 2-4 grams of GABA may stimulate insulin production and lower blood sugar levels. [13] This idea is supported by the newer Human Growth Hormone studies which also see an increase in insulin levels with oral GABA. CAN IT WORK? GABA supplements are promoted as an alternative to these tranquilizing drugs. There's a problem. There is scant evidence that it does anything. Current medical belief is that GABA will not pass the blood brain barrier. The blood brain barrier is a biologic firewall between the body's general blood circulation and the blood circulation that supplies the brain. It prevents many of the chemicals and drugs which circulate in the blood from reaching the brain. GABA can not cross from the body into the brain. If GABA doesn't reach the brain, can it work? Common medical wisdom says it can't. So why are so many people buying and taking GABA insisting that it is helpful for its tranquilizing action? First, it may simply be a placebo. If our thoughts affect our chemistry and physiology, what more susceptible part of our chemistry can there be than the neurotransmitters in our brain that carry thoughts? Second, it may have some affect that hasn't been reported yet. If taking GABA makes a person feel calmer and more relaxed, perhaps some of it crosses into the brain. Studies on Human Growth Hormone suggest that it can. HUMAN GROWTH HORMONE There is evidence that getting extra GABA into the brain increases Human Growth Hormone. Injections of GABA directly into the brain increase Growth Hormone in rats. Baclofin, a drug analog of GABA that does reach the brain, increases HGH [14] so it makes sense that GABA would do the same. Several studies support the notion that taking oral GABA increases Human Growth Hormone (HGH). Two of the studies were published almost 25 years ago. They used a small number of test subjects. Yet they produced significant increases, HGH levels increased 500%. [15] [16] No studies replicated this effect for years bringing the initial results into question. In May of 2003, a new study confirmed the results of the early studies. The new study measured GABA and HGH in body builders. Three grams doses of GABA increased HGH levels, but only if taken just before exercise. Without exercise, the GABA had no effect on HGH. [17] We should clarify the term exercise, test subjects were body builders; we are talking about a strenuous workout. If GABA can raise HGH levels, some of it may cross the blood brain barrier, perhaps only after exhausting exercise. The HGH studies raise some concerns. Oral GABA also affects the pancreas increasing insulin production. [18] Of course with all the concern about Syndrome X and hyperinsulinemia, making more insulin might not desirable. Yet a diabetic might find the insulin stimulating effect contributes to better blood sugar control. Besides increasing insulin and HGH, oral GABA increases prolactin, a finding not emphasized in the promotional literature. Prolactin is the hormone that stimulates the breasts to produce milk. Although body builders want to build up their chest size, they probably don't want to do it this way. Although there is no research on taking GABA during pregnancy or nursing, pregnant or nursing mothers should not take this information to suggest that GABA might increase their milk supply. It might, but it also might stimulate early breast development and lactation in their infants. There are other amino acids besides GABA that increase HGH. [19] Whether they are more effective is unknown. Side Effects: Although the newer studies with body builders report using high doses of GABA with little side effect, these results may not reflect the experience of a more sedentary person. Carl Pfeiffer devotes a full page in his book to describing an unpleasant experience he had after taking a 10 gram dose of GABA: ?About ten minutes after taking the GABA, I started to wheeze and my breath rate increased to 45 a minute. Five minutes later, my heart rate peaked at 140 and my blood pressure at 180/100. I was choking, fidgeting and could not sit still. I had a massive anxiety attack, thinking I was going to die??.I vomited into the waste basket. Over the next half hour, this anxiety attack let up, but I continued to be nauseous for the next two hours. ?This dose of GABA also caused a constant flush sensation, like that of niacin, although my skin was not red. I had a tingling in my hands and over my entire body. This effect occurred even at the lesser dose of 3 g of GABA and is likely neuralgic, unlike the effect of niacin which is primarily vascular??? [20] Home Experimentation: Probably the only way you will figure out if GABA works for you is to try it. GABA is nontoxic and appears generally safe to take. There is nothing stopping you from testing these contradictory claims for yourself. Below are suggested doses for treating various conditions. I personally had never taken GABA before reviewing this research and then stalled experimenting on it until I wrote this article. Once done with the preliminary drafts I experimented using 750 mg. capsules of GABA. I began taking them at 12 hour intervals. After the second dose I began to experience the tingling sensations reported by Pfeifer. I too thought them reminiscent of a niacin flush without the surface heat from vasodilatation. It was very noticeable for about five minutes and then only slightly noticeable if I paid attention and looked for it. I did not feel particularly calm during my normal activity but did wonder if something was different while driving, especially while merging onto the freeway, an experience where I typically notice some agitation. Interesting to note, it was just after getting on the highway while driving that I noticed the tingling. Suggested Dosages: I would consider suggesting GABA to patients who are over anxious or who complain of insomnia due to ?too many thoughts which I can't shut off.? Again I like the coffee analogy: If they look or feel like they drank too much coffee, GABA may help. Research no longer supports using GABA for depression, bipolar disease or PMS: if it looks like they need a cup of coffee, don't use GABA For increasing Human Growth Hormone production the studies used between 3 and 18 grams. Keep in mind that at these doses expect tingling. CAUTIONS GABA may cause sleepiness, that is if it works: Do not operate or drive heavy machinery while taking GABA, at least until you know what effect it has on you. Do not take GABA if you have been diagnosed with bipolar or unipolar depressive disorders. If taking doses greater than 3-4 grams do not be surprised if you experience a flushed tingling sensation; this appears to be a common experience. Caution should also be taken in combining GABA with any drug which affects GABA pathways in the brain. These drugs include but are not limited to barbiturates, benzodiazepines, and alcohol. GABA has not been tested in pregnant or breast-feeding women, children, or people with liver or kidney disease. GHB Gamma-hydroxybutyric acid (GHB) has a similar name but is a different chemical. It is made within the brain from GABA. GHB has been researched for treating alcohol, opiate and other drug dependencies and for treating withdrawal symptoms. [21] [22] [23] [24] GHB unfortunately can also be abused [25] and employed as a ?date rape drug'. [26] It has gone from a promising new treatment for addictions to an addictive and dangerous drug in its own right. [27] Instead of touting potential benefits recent articles focus on how to treat overdoses [28] and the withdrawal syndrome associated with GHB. [29] Don't mix these two names up. Other ways to skin the cat: other ways to increase GABA effect Another approach is to look at substances which change GABA action in the brain. There seems to be more and better clinical research on the use of many of these substances in humans than there is on GABA. There are numerous natural substances which affect GABA. In fact understanding GABA helps explain the action of many commonly used herbs, vitamins and minerals. Valerian root has a long history of use as a tranquilizer and works by increasing the effect of GABA on its receptors [30] American Ginseng also acts on the GABA receptors. [31] So does Kava Kava. [32] All sorts of other unexpected things change GABA activity; the chemicals formed by aging whiskey in oak barrels increase GABA effect. Aging really does make whiskey mellower literally based on what it does to brain neurotransmitters. [33] These chemicals are released from the alcohol as a fragrance and appear to reach the brain by inhalation. [34] The fragrance of Oolong tea has a similar effect, increasing GABA action. [35] Extracts of green tea, black tea and oolong tea elicit a GABA response in test models. [36] Epigallocatechin gallate extracts from tea had the opposite effect, inhibiting the GABA response. Coffee extracts also inhibit GABA response. [37] Magnesium binds to GABA sites and increases effect. [38] Taurine protects against glutamate overstimulation. [39] [40] Its inhibitory effect may act as anxiolytic. [41] Serotonin is another neurotransmitter and it enhances GABA. Therefore, as precursors to serotonin, Tryptophan and 5-HTP increase GABA action. Theanine is an amino acid found in large amounts in tea. It is why a cup of tea can be calming despite the fact it contains caffeine. Theanine may increase glutamate transport [42] and increase GABA levels. The vitamin B6 derivative pyridoxal phosphate is a cofactor in the synthesis of GABA. Some people have trouble converting Vitamin B-6 to pyridoxal phosphate and for those people taking this active B-6 may increase GABA levels. While these other supplements alter or potentiate the GABA receptor, they do not add any GABA to the system. Many companies add one or more of these other materials to capsules containing GABA. The idea may be to amplify the effect of any GABA that crosses the Blood Brain Barrier into the brain. These other ingredients may work independently and be the active ingredient in the product. At this point GABA is more interesting for the understanding it provides of the mechanics of the mind than it is as a nutritional supplement. Although small amounts of orally taken GABA may reach the brain and have a tranquilizing effect in certain individuals, there are many other alternatives which have both a longer history of safe use and better research support for their use. There are unanswered questions about the safety of the long term high doses promoted by some supplement companies. 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