Brain Health and Function

Paul L. Reller L.Ac. / Last Updated: August 03, 2017

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Some proven herbal medicines for cognitive decline and neurodegeneration

Huperzine A, Vinpocetine, Rosemary extract, and Bacopa monniera are just some of the herbs proven to aid cognitive decline. Huperzine A and B are alkaloid chemicals isolated from the root of the club moss Huperzia serrata, or Lycopodium serratum, a Chinese herb (Qian ceng ta). Huperzine A was developed in China as a selective acetylcholinesterase (AChE) inhibitor for the treatment of neurodegenerative diseases, and was found to be more potent than the pharmaceuticals phytostigmine and galanthamine. An AChE inhibitor decreases the enzymatic rate of degradation of the important neurotransmitter acetylcholine. Huperzine A can penetrate the blood brain barrier rapidly and is highly neuroprotective. In microdialysis studies, Huperzine A was found to be able to increase the levels of acetylcholine, dopamine and norepinephrine in brain tissues while not exerting a significant change in 5HT/serotonin. A synthetic racemic analog was created, but the natural herbal Huperzine A is found to be 3 times as potent. In animal studies, Huperzine A was found to increase the endplate potential and prolong the potential rise time in the neuromuscular junction as well, potentially aiding muscle function in athletics. Clinical human trials in China have shown it to be effective in the treatment of Alzheimer's disease, with no serious adverse events noted, and much milder cholinergic side effects than pharmaceutical anticholinesterase drugs. The NIH National Institute on Aging has completed a phase 2 clinical trial for the treatment of Alzheimer's disease, and Harvard University has investigated its efficacy to treat epilepsy, with a synergistic effect noted with the addition of N-acetyl cysteine to improve glutathione metabolism. Numerous studies in China have affirmed the effectiveness of Huperzine A to improve memory in mild cognitive disorders.

Vinpocetine is a chemical from the periwinkle plant that has been long used in China to treat cerebrovascular disorders, improving blood circulation, dilating blood vessels, improving oxygen utilization, increasing glucose metabolism, and inhibiting platelet aggregation. It has also been shown to inhibit phosphodiesterase to preserve ATP, the source of cellular energy. Rosemary extract has been found to be a potent antioxidant in the brain as well as a Cox-2 inhbitor, decreasing chronic inflammatory symptoms. Together with Huperzine A, this trio of herbal chemicals makes up the formula Vinpurazine by Health Concerns. When combined with alpha-GPC choline (CogniSpark from Health Concerns), these herbs and supplements provide a well rounded and complete treatment for brain function and health, serving both as a treatment and a preventive medicine. Adding the nutrient and herbal formula AGEBlock, by Vitamin Research Products, which includes P5P, L-Carnosine, L-Histidine, R-Lipoic acid, and Yerba Mate extract, forms a trio of medicines that could be play a very significant role in treating or preventing brain dysfunction and ill health. Combining acupuncture with this protocol, with the proven effects of acupuncture stimulation on specific areas of the brain, will work to make this healthy protocol more effective.

Resveratrol, a chemical constituent of the Chinese herb Polygonum cuspidatum (Hu zhang), and found in other herbs and foods (grape skins and wine), has been heavily researched and utilized even in standard medicine. Pharmaceutical companies have applied for patents and FDA approval of forms of resveratrol that may provide a higher dosage reaching the brain. The Chinese developed this chemical, isolating a particular isomer (trans-resveratrol) of the herbal chemical that could be supplied in a sufficient dosage to effect considerable antioxidant and other effects for brain health and function. Much research has been conducted with resveratrol, and more and more surprising data is being found to reveal its effectiveness. A 2011 study at the University of Fribourg, in Switzerland, found that resveratrol improves vascular endothelial function in the aging in part by inhibition of a protein kinase signalling molecule called S6K1, or P70-S6 kinase beta-1, responsible for regulation of growth factors and cell proliferation. S6K1 is overexpressed in aging arterial membranes and the blood brain barrier, leading to increased reactive oxygen species (ROS), such as superoxide dismutase and nitric oxide. A 2011 study at the University of Pais Vasco, in Spain, showed that resveratrol regulated lipolytic activity as well (breakdown of fatty accumulation in the brain), and increased fatty acid release from fat tissues while not affecting glycerol release. This finding could result in further study proving that resveratrol is an effective herbal chemical to reduce beta-amyloid peptide plaque accumulations, and other plaques in the brain. It could also explain how this chemical is able to show profound effect in patients with neurodegenerative disease, since the brain has a high percentage of fatty tissues than other parts of the body, which may generate much of the oxidant stress. A 2011 study at the Keio University School of Medicine in Japan found that resveratrol reduced inflammation, oxidative stress, neoangiogenesis, and extracellular matrix disruption, suggesting that this herbal chemical would prevent arterial aneurysms and improve vascular health. The numerous ways that Resveratrol may serve as a neuroprotective agent, antioxidant, antiinflammatory, and regulating agent makes this herbal therapy important in any treatment protocol concerning brain health and function.

A wide array of Chinese herbal chemicals have demonstrated neuroprotective effects, though. Berberine, an active metabolite in Coptis chinensis (Huang lian) and other Chinese herbs, has demonstrated neuroprotective effects by a block of potassium ATP channels in the substantia nigra, a brain nuclei responsible for many of the symptoms of Parkinson's disease, exerting an excitatory effect on this area of the brain that is inhibited in this disease by poor dopamine effects. Berberine has also shown potential to inhibit platelet aggregration and thromboxane B2 to aid blood circulation in the brain, and to inhibit cholinesterase activity as well, increasing neurotransmitter function. Berberine is primarily used as an antibacterial agent in Chinese medicine, and shows good antiviral and antifungal activity as well, which may serve to clear chronic inflammatory problems in the CNS. Chronic inflammatory cytokines, such as TNF-alpha, are now known to be intricately tied to neurodegenerative disorders, and berberine and other herbal chemicals are well studied as inhibitors of TNF-alpha, and other problematic overexpressed cytokines. In studies we see these herbal chemicals acting in an evolved modulatory manner, preserving normal homeostasis. Pharmaceutical drugs do not display such modulatory effects. Various alkaloids in Coptis chinensis have also shown potent antioxidant activity and the ability to inhibit beta-amyolid plaque formation. A single herb has this much potential to benefit brain function and health. A formula of herbs containing berberine has tremendous potential to benefit the patient. These formulas may be used as a preventive medicine as well as treatment for more severe conditions.

Adaptogenic Chinese herbs, such as ginseng, Siberian ginseng (Eleutherococcus), and Rhodiola rosea (Hong jin tian) have also shown value as antioxidants and neuroprotective herbs. These various herbs may be combined in formulas in Traditional Chinese Medicine to exert a variety of effects to benefit brain function and health, treating other aspects of the health as well. Ashwagandha (Withania somnifera), an ayurvedic adaptogen has also been extensively studied and proven to exert significant neuroprotective effects and to speed growth and recovery of both neurons and support glial cells. These studies, some of which are cited below, have been conducted both on laboratory animals and in human clinical trials (in vitro and in vivo), and are proceeding through the 3 stage clinical trial processes created for pharmaceutical drugs even though this is unnecessary to prove effectiveness. This FDA staging of human clinical trials was created to judge the safety of harsh pharmaceutical medicines, and these herbs are proven safe by thousands of years of use and clinical record. The array of treatment options in Chinese medicine is extensive in this regard.

Bacopa monnieri (Water hyssop) is an Ayurvedic herb that has long been used to treat neurological disorders, such as epilepsy, and is now much studied for its positive effects treating neurodegenerative disorders. This herb has strong antioxidants and anxiolytic effects, and is considered a nootropic, or enhancer of cognitive ability. It is shown to inhibit lipoxygenase and reduce beta-amyloid plaques in Alzheimer's disease. This plant is used in traditional Vietnamese cuisine, and normal dosage is very safe and nontoxic. A tincure of the leaf provides many of the important glycosides and flavonoids.

Passiflora incarnata (Passionflower) is an herb that has been much studied in relation to neurological disorders, and has proven effects that are significant in the treatment of insomnia, depression and anxiety. This plant contains many beneficial chemicals that exert significant antioxidant and antiinflammatory effects, as well as neuroprotective effects. Apigenin, kaempferol, luteolin, and quercetin are the main active chemicals. These are all neuroprotective, estrogenic, may increase bioavailability of tyrosine, and inhibit nitric oxide. Other chemicals, such as harmane, harmalol, and harmaline, have shown potent antiparkinsonism effects, and may act as a mild MAO inhibitor and dopaminergic. Passiflora has been found to potentiate some of the effects of St. John's Wort as well.

Periodic use of these various Chinese herbal formulas and specifics could be vitally important to a great percentage of the population, since studies show that a majority of the population will now suffer from some neurodegenerative dysfunction in life. Whether this is a mild disease, such as attention deficit and hyperactivity disorder, a nagging chronic problem such as fibromyalgia (myoencephalopathy), or a potentially serious problem such as the advance of mild congitive dysfunction to Alzheimer's dementia, preventive medicine is a smart choice. Acupuncture plays a synergistic role in a well designed holistic treatment protocol that is individualized and inexpensive.

The role of acupuncture stimulation in improving or restoring brain function and health

Since 1998, when groundbreaking functional MRI (fMRI) studies were performed at the University of California under the direction of the inventor of the PET scan, numerous studies around the world have documented the direct effects of acupuncture stimulation on specific areas of the brain and the resulting cascade of chemical, hormonal and physiological effects. It has been surmised that much of the positive effects of acupuncture, in fact, occur because of this stimulation of the brain. It is not difficult to understand that if one is taking nutrient and herbal medicines to improve brain function and health that stimulation of the brain with acupuncture will enhance these effects.

The original studies with fMRI showed that acupuncture points specific to visual and auditory pathology did in fact significantly increase brain activity in the corresponding areas of the brain devoted to vision and hearing. These points were chosen at the ends of the acupuncture meridians most corresponding to the brain at the feet and hands or wrists. Subsequent studies are revealing more and more specific information about how this acupuncture stimulation actually affects brain function. For example, it has been demonstrated that much of the effects of acupuncture on pain analgesia occur in the hypothalamus, the neurological seat of command of the endocrine and autonomic nervous systems. A further study in 1999, published in the medical journal Radiology (Radiological Society of North America, Inc.), found that acupuncture stimulation not only affected the hypothalamus, the nucleus accumbens, the raphe nucleus and periaqeductal gray matter, but that acupuncture stimulation at specific points also decreased signal intensity in the limbic system, the area of the brain associated with emotion and pain perception. In this study, the limbic system was the only area of the brain showing a decrease in signal intensity with stimulation of the acupuncture points LI4 and ST36. The limbic system is acknowledged as an area of the brain most important in formation of the cognitive and affective aspects of pain sensation, meaning that patients with chronic pain often experience excess pain sensation that is associated with memory and emotional triggers. Specific areas of the limbic system were found to be deactivated, or calmed, with this treatment, namely the amygdala, hippocampus and rostral part of the anterior cingulate cortex. Stimulation with minimal acupuncture and sham acupuncture on the human subjects had little and no effect on these areas of the brain (Ming-Tung Wu MD, Bruce R. Rosen MD PhD et al, July 1999, 212, 133-141; cited below with a link). The authors of this study noted: "Activation of the hypothalamus and nucleus accumbens of the descending antinociceptive system and deactivation of the limbic areas, which are associated with pain perception, provide a neurophysiologic mechanism for the analgesia effect of acupuncture. Given that the hypothalamus and limbic system provide multidimensional integration of neuroendocrinal and autonomic homeostasis, our finding that acupuncture activates the hypothalamus and limbic system also provide a basis for the versatility of acupuncture for use in conditions other than pain disorders, such as management of nausea and vomiting, asthma, and substance addiction."

These studies of acupuncture show that brain function may indeed be stimulated and improved with acupuncture, especially if the brain is supplied with specific nutrient aids, and problems affecting the brain function, such as chronic inflammation and metabolic dysfunction are simultaneously treated with specific herbal chemistry. These studies proved that different effects occur with the type of stimulation by the physician as well. Given the complexity of the brain and central nervous system, and the complexity of the pathologies involved in cognitive dysfunction and decline, such a thorough and comprehensive holistic approach is obviously the best type of therapy to integrate into standard medical care to both treat and prevent cognitive dysfunction, central neurological disorders, and even advanced dementias. Simple searches on the internet provide the physician and patient with ever increasing proof of the efficacy of these acupuncture treatments, and provide ever more specific guidance for the acupuncturist in treatment.

In 2000, Harvard Medical School's Department of Radiology and the MGH-NMR Center demonstrated that acupuncture stimulation at a single point, LI4, with manual manipulation, "produced prominent decreases of fMRI signals in the nucleus accumbens, amygdala, hippocampus, parahippocampus, hypothalamus, ventral tegmental area, anterior cingulate gyrus, caudate, putamen, temporal lobe, and insula in all 11 subjects who experienced acupuncture sensation. In marked contrast, signal increases were observed in all 11 subjects primarily in the somatosensory cortex. The two subjects who experienced pain instead of acupuncture stimulation to the same area elicited signal increases instead of decreases in the anterior cingulate gyrus, caudate, putamen, anterior thalamus, and posterior insula. Superficial tactile stimulation (acupressure) to the same area elicited signal increases in the somatosensory area as expected, but no signal decreases in the deep structures. These preliminary results suggest that acupuncture needle manipulation modulates the activity of the limbic system and subcortical structures. We hypothesize that modulation of subcortical structures may be an important mechanism by which acupuncture exerts its complex multisystem effects." This study, and many more that followed, demonstrated clearly in all human subjects, that expert manipulation of the needle and clearly felt or observed stimulatory effects, exerts profoundly different effects on the central brain, the regulatory center of our body. The different effects felt at the needle, including the pain sensation, produced different effects on brain function, and did so in a modulatory manner cosistent with natural endogenous homeostatic mechanisms.

In 2004, the National Institutes of Health of the U.S. government, through the National Center for Complementary and Alternative Medicine, started clinical human trials mapping the effects of acupuncture on parts of the brain and assessing modulatory effects of acupuncture stimulation. This study was completed, and last updated in 2008 (trial NCT00079898), and affiliated with Massachusetts General Hospital and Dr. Kathleen Hui MD. Such studies are providing a wealth of information to researchers, who are busy mapping the objective scientific data on specific acupuncture points and types of stimulation on areas of the brain and subsequent physiological effects. A Harvard Medical School neuroscientist, Vitaly Napodow PhD LAc (yes, acupuncturists are employed as researchers and teachers at our most prestigious standard medical universities), states that he is measuring gene expression and molecular changes in the nervous and immune systems in response to stimulation of the brain. These researchers are also clearly measuring how the placebo effect, or treatment expectation, modulates brain activity in a different manner than the acupuncture stimulation. Treatment expectation, a powerful tool in Traditional Chinese Medicine and acupuncture that falls within the traditional category of Qi Gong, is also a means by which a skilled acupuncturist is able to exert profound effects on the brain to modulate both perception and actual chemical and motor responses by working with the patient, as a team, during treatment. We see from such studies that the thorough education and training received by Licensed Acupuncturists at the best medical colleges is superior to short courses on acupuncture techniques that Medical Doctors use to learn how to perform acupuncture needle stimulation. Links to these studies are available below in additional information.

Ongoing research into the measurable effects of acupuncture and electroacupuncture has been published by experts in a collaboration between The University of Texas Medical School, at Houston, Texas, U.S.A., Shanghai Medical College of Fudan University, Shanghai, China, and the Shanghai Research Center for Acupuncture and Meridians, Fudan University, Shanghai, China, headed by Ying Xia, Guanghong Ding, and Gen-Cheng Wu, and published as Current Research in Acupuncture. Contributing scientists include Dr. Tetsuya Asakawara MD, Hamamatsu University School of Medicine, Shizuoka, Japan, Dr. Henry Johannes Greten MD, Heidelberg School of Chinese Medicine, Heidelberg, Germany, Dr. Peng Li MD and Dr. John C. Longhurst MD, University of California-Irvine Susan Samueli Center for Integrative Medicine, Los Angeles, California, U.S.A., and Dr. Elisabet Stener-Victorin Ph.D., of the University of Gothenburg Sahlgrenska Academy Institute of Neuroscience, Gothenburg, Sweden. In this ongoing series of books, the various researchers note that in recent years the body of literature on measurable effects of acupuncture and electroacupuncture on the brain has grown exponentially, as technical developments, such as the use of functional MRI, PET scans, and other measuring devices, have been utilized.

These researchers note that acupuncture can induce healthy regulation of neurotransmitters, endogenous opioids such as endorphins, monoamine substance P, and other modulators of CNS disease, can increase the genetic mRNA expression of brain-derived growth factors and their receptors, downregulate inducible nitric oxide levels in the brain while elevating it in blood plasma and vascular organs, suppress the activity of acetylcholinesterase to degrade acetylcholine neurotransmitter (acetylcholinesterase inhibition), enhance 5-HT (serotonin) metabolism, decrease glutamate NMDA expression, and increase the concentration or prostaglandins (inflammatory mediators) in some diseased states. This array of effects is impressive. The researchers noted that most of the available scientific studies in print were not found in English-language medical journals, but are of high quality, suggesting a bias against printing acupuncture studies in Western Medical Journals that is ongoing in 2012. These researchers noted that most of the above effects of acupuncture stimulation are modulatory, enhancing homeostatic mechanisms. In electroacupuncture, a lower frequency, such as 15 hertz, is shown to upregulate specific kinds of opioid neurotransmitters, while a higher frequency, such as 100 hertz, elevates dynorphin only, proving that the traditional views that this slower stimulation is benefiting a tonic effect, while the faster stimulation a reducing effect. The array of beneficial effects measured in studies on most of the important neurotransmitters, inflammatory modulators, and neurohormonal effects, is impressive in this published review of study.

In recent years, a number of sound scientific studies have also demonstrated that acupuncture and electroacupuncture may also stimulate and regulate the creation and utilization of mesenchymal stem cells to aid repair and regeneration of the central nervous system, the brain, brain stem and spinal cord. Stem cells originate and hibernate in the bone marrow, and a complex cascade of signals stimulate their release into circulation and growth in specific areas of the body. While stem cells can be grown or removed from the bone marrow and transplanted, the success of stem cell therapy so far has not been dramatic. Studies at Chinese and Korean Universities have shown that specific acupuncture and electroacupuncture stimulations provide an array of effects that may even enhance stem cell therapy, significantly improving the taking of stem cells transplanted onto injured areas of the spinal cord, as well as stimulating the differentiation and function of these stem cells (see research links below in Additional Information). Universities in the United States have taken up this study and found that there is ample proof that acupuncture and electroacupuncture may stimulate the bone marrow and stem cells with a variety of neurohormonal and immunological mechanisms. This tactic may prove to be very useful in regeneration and repair of CNS tissues, as the body needs an array of coordinated actions to occur to make this work. Further study, at UCLA and the University of Pittsburgh, has shown that this application of acupuncture may also be important in anticancer therapy, stimulating the production of specialized immune cells to attack cancer in the body. It is curious that in Traditional Chinese Medicine (TCM) that ancient Daoist physicians theorized that the brain and nervous system was intricately tied to the system of the Bone Marrow. Points indicated to stimulate the Marrow are still frequently used in cases of brain injury, such as stroke recovery.

The role of neurotransmitter/hormones in brain function and health

Standard medicine has long persisted in classification of chemicals in our bodies as distinct entities with specific functions, an attitude that lends itself to an allopathic approach in medicine. The public now believes, for the most part, that each chemical in the body is a distinct entity with a single specific function. In the case of neurotransmitters this is certainly not the case, and we have known this for many decades. While a chemical that we call a neurotransmitter has a specific function in neurotransmission in a specific part of the brain, the same chemical may have an opposite function in another part of the brain, and exert effects at hormonal receptors, nociceptors, and nerve plexuses in other parts of the body. The production of neurotransmitters is also very fluid in many cases, as these molecules may undergo frequent transformations in local tissues depending on the need of the body and the array of chemicals surrounding the molecule. A good example is serotonin, which is also called 5-hydroxytryptamine (5HT). This molecule is derived from the amino acid tryptophan, and 80-90 percent of the serotonin in the body is produced and functions outside of the brain. The array of effects of this simple molecule are extremely varied and dependant more on the cell receptors than the serotonin itself. While serotonin, or 5HT, is given nicknames like the "happiness hormone", this only serves to simultaneously oversimplify the roles of this neurohormone, and to confuse the public.

It's time we started calling most of the molecules that we have classified as neurotransmitters neurohormones. The idea that these molecules simply transmitted neural signals is long outdated. Like hormones, these simple monoamino neuromodulators are constantly being synthesized by cells, converted to other neurotransmitters as needed, and dependent upon a complex feedback cycle to determine their quantity and form. Like hormones, these neuromodulators work by simply triggering a wide variety of neuroreceptors, as well as hormone receptors and immune receptors. A monoamine is a signaling peptide that contains a single amino acid group, connected to an aromatic ring, and are derived from amino acids such as tryptophan, tyrosine, phenylalanine, as well as thyroid hormones. While drugs that block the reuptake cycle of these neurohormones do affect depression, this does not restore the complex feedback cycle of neuromodulation, and the homeostasis that we need to function at our best mentally and emotionally. Modern phamaceutical psychotherapy has utilized monoamine oxidase inhibitors to maintain higher levels of these neuromodulators as well, but our brains adapt to these pharmacological inhibitors, and they often supply temporary effects. There are ways to restore neuromodulator homeostasis and production with Complementary Medicine, perhaps providing a better treatment in the long run.

Examples of monoamine neuromodulators include the catecholamines dopamine, norepinephrine, and epinephrine (adrenalin), the tryptamines serotonin and melatonin, the trace amines phenylethylamine, tryptamine, 3-iodothyronanime, thyronamine, tyramine, and even histamine. Catecholamines are derived from the amino acid tyrosine, tryptamines are derived from the amino acid tryptophan, and histamine is derived from the amino acid histidine. We are learning that these amino acids are the building blocks of a holistic treatment protocol to restore neuromodulator, or neurohormonal, homeostasis. L-tyrosine, L-phenylalanine, N-acetyl cysteine, and L-tryptophan, or the precursor to L-tryptophan, 5HTP, are important parts of these neuromodulating prescriptions, as well as melatonin. Enzymes such as monoamine oxidase (MOA) are also very important, and depend upon a variety of factors to achieve a constant homeostasis. Monoamine oxidase enzymes break down serotonin, melatonin, norepinephrine, adrenalin (epinephrine), phenethylamine, dopamine, tryptamine, and tyramine, and improper homeostasis, or imbalance of the changing levels of MOAs, are thought to be highly associated with depression, attention deficit and hyperactivity disorders, migraines, addiction, and schizoid affective disorders.

Herbs such as St. John's Wort and Paeonia lactiflora (Bai shao) have been shown to affect monoamine oxidase metabolism, but indirectly. St. John's Wort (Hypericum perforatum) has also been accused of being a serotonin reuptake inhibitor, but studies have shown that its action on the serotonin metabolism is modulating, not inhibiting. A 2000 study at the University of Saskatchewan, Saskatoon, Canada (see study link below) showed that Hypericum extract exerted weak monoamine oxidase inhibition, and increased the 5-HT (hydroxytryptophan) levels in the hypothalamus and hippocampus, and significantly reduced the blood plasma levels of tryptophan, showing that St. John's Wort increased the levels of 5-HT, the serotonin precursor, but did not act like a serotonin reuptake inhibitor. In addition, this study showed that St. John's Wort increased the chemical that serotonin breaks down to, 5-HIAA in the hypothalamus, hippocampus and cortex, in the first few hours after administration, with just a low dose of Hypericum extract administered, but did not further alter these levels with chronic use. Obviously, St. John's Wort both stimulated breakdown, or utilization, of serotonin, and stimulated increased bioavailability of this neurotransmitter. This is called neuromodulation, and is a gentle and safe method of gradually righting the ship, or restoring homeostasis. Studies have also noted the ability of St. John's Wort extracts to modulate a number of neurohormonal receptors, including GABA, glutamate and adenosine, and to affect the cell receptor uptake of not only serotonin, but also dopamine and norepinephrine. Initital use of this extract showed more dramatic effects, but levels of neurotransmitters and their metabolities appeared to level off and not continue to be further effected with chronic use. All of this study shows the potential of St. John's Wort to gently modulate neurotransmitter, or neurohormonal, homeostasis. It is no wonder that a large effort was made by the pharmaceutical industry to deter usage of this safe and simple herbal extract, stimulating thousands of warnings in print of the potential adverse effects and contraindications of Hypericum, that have since all been discounted by studies, with St. John's Wort now the most studied herb in the world.

Serotonin (5HT) is considered to be an important neurohormonal chemical in the regulation of mood, short term memory, sleep cycling, and cognition, as well as appetite, sexual function, libido, temperature regulation, and vasoconstriction (as in vascular headaches). In the midbrain and frontal cortex, there is much interaction between serotonin and dopamine, which is considered to an important neurohormonal chemical in the regulation of feelings of motivation, reward, pleasure, euphoria, compulsion, perseveration, and fine motor function. Dopamine also may convert to norepinephrine, a neurohormonal chemical affecting attention span, alertness, oxygen utilization, and neuroinflammation, or may convert to the more active epinephrine (adrenaline) which may more strongly stimulate the sympathetic nervous system, create anxiety, and affect the insulin system. All of these neurohormonal chemicals may affect the seat of hormonal regulation, the hypothalamus. The amount of local conversion of these neurotransmitters, affects of concentrations of one neurotransmitter on the functions of another, and the effects of substrates on the functions of the neurotransmitters make the whole array of chemicals, and the homeostatic balance, more important than a particular level of just one of these chemicals. For example, norepinephrine may affect receptors on the synapses of the neurons or on the cell membranes of non-neuronal cells. Substrates of the uptake into non-neuronal cells include dopamine, serotonin (5HT), and histamine, all of which will affect the chemical responses triggered by the norepinephrine. Keeping these neurohormonal chemicals available and in a homestatic balance is very important for brain function and health.

Receptors for these neurohormonal chemicals vary according to the need for various neural effects, and a number of types of cell receptors may be primarily stimulated by a single neurotransmitter. The balance between expression of one type of receptor versus another often has a profound effect on brain function, and the amount of stimulation of these receptor types determines the rate of expression of the receptor proteins on neural cell membranes and synapses. Imbalances of receptor types has become more of an issue in many disease pathologies than the levels of neurotransmitters themselves. These receptors for neurotransmitters are also stimulated by different neurotransmitters, as well as different hormones and inflammatory cytokines, albeit with different degrees of affinity for specific receptors types. Not only imbalances of neurotransmitters, but imbalances of hormones and inflammatory cytokines may cause adverse effects related to receptor stimulation, balance of receptor expression, and decreased effects from the primary neurotransmitter affecting the receptor. This is what makes neurological diseases so difficult to understand, and why research is still unclear on the mechanisms of well-studied diseases such as Parkinson's and Alzheimer's disease.

GABA, or gamma-aminobutyric acid, is the chief inhibitory neurotransmitter in the brain, although it may exert stimulation in some circumstances, depending on the receptors involved and the chemical balance around it. It is well known for its function to inhibit excess neuronal activity and to stop frequent or quick mood changes. At the nerve synapse, GABA works synergistically with glutamate and glutamine. GABA is able to be synthesized and taken as a supplement, but does not cross the blood brain barrier, so L-Glutamine is the preferred nutrient medicine used to have a direct effect on GABA, although a number of herbs are also effective in this regard. P5P is also needed, along with L-Glutamine, to effectively stimulate increased neuronal production of GABA. A combination of L-Glutamine, P5P and inositol hexacotinate will have the greatest effect of increasing GABA potential. A dysfunction in GABA inhibitory effects and neuromodulation may occur with an excess stimulation of the neurotransmitter glutamate. This often occurs when unhealthy types of glutamate receptors (NMDA) are expressed due to glutamate chemicals in our food and now our water stimulating these receptor expressions. There are now many types of glutamate additives, such as monosodium glutamate, that induce increased food addiction, and these may have created new types of glutamate receptors that result in excess glutamates but deficient bioavailability for the production of GABA. Since dysfunction in the glutamate metabolism in the brain and brainstem is now linked to a number of diseases, including sleep disorders, nocturnal bruxism, ADHD, and even schizophrenia, a holistic protocol to help restore homeostatic glutamate function and metabolism is an important consideration. This glutamate system is complex and thus still poorly understood, but holistic approaches to health correction seem sensible, while in complex pathological mechanisms, the potential that a simplified allopathic approach with one chemical block or biologic mechanism seems unlikely to work by itself. To better understand the subject of glutamate dysfunction and toxicity, read below.

To address the subject of neurotransmitters with Complementary and Integrative Medicine, the role of this approach should be to restore the homeostatic balance and bioavailability and let the body do what it is genetically programmed to do, namely function in a healthy manner if given a chance. The affects of this approach may not be as quickly felt as with a pharmaceutical drug, but the overall effect will eventually be much better, and should be sustained without continuing need for therapy. Restoration of health is the sensible goal, and this may be accomplished in an integrative fashion with standard medicine. In addition, a restoration of hormonal balance, and resolution of chronic inflammatory problems may also need to be addressed with this holistic approach.

Herbal medicine and studied effects on neurotransmitters

Effects on neurotransmitters of herbal chemicals has been well studied. The USDA website entitled Dr. Duke's Phytochemical and Ethnobotanical Databases provides a substantial documentation of such study. Herbs with dopaminergic activity include Uncaria Tomentosa (Cat's Claw), Alisma plantago (Ze xie), and Euphorbia lathyris. The dopaminergic chemicals in Cat's Claw are also found in the analagous Chinese herb Uncaria rhynchophylla (Gou teng), namely hirsutine and rhynchophylline. One of these dopaminergic chemicals is pyridoxine, or Vitamin B6, which is the precursor to pyridoxal phosphate (P5P), which is required for the production of dopamine, serotonin, norepinephrine and epinephrine. Other dopaminergic herbs include Mucuna pruriens and Muira puamens, two Ayruvedic and South American herbs that have traditionally been used to stimulate libido due to their dopaminergic chemicals. Diet also may mildly stimulate dopamine production, and whole oats, soy, barley, lentil, rice, pea, wheat, fenugreek, avocado, cacao, mate, and alfalfa all contain chemicals considered dopaminergic. St. John's Wort (Hypericum perforatum) and Psoralea corylifolia are two herbs with known effects as dopamine reuptake inhibitors. The Uncarias and Mucuna pruriens are also serotonergic, explaining their value in the treatment of various neurological disorders.

The herbs listed on Dr. Duke's database as serotoninergic includes Fennel, Aged Garlic, Arctium lappa (Niu bang), and Piper nigrum (Hu jiao). Diet may also provide serotonergic chemicals, found in whole oats, peanut, fennel, okra, onion, chives, cashew, celery, carrot and blueberry. The Griffonia seed, though, contains actual 5HTP, the serotonin precursor, and the amino acid tryptophan is also available as a supplement. These products are very effective to afford serotonin bioavailability. St. John's Wort (Hypericum perforatum) is also shown to be effective in stimulating serotonin, so much so that contraindications with SSRI medications are frequently seen, although the dosage in standard treatment is so low that inducing a serotonin syndrome with concurrent use is very rare. Clinical cases of serotonin syndrome induced by taking Hypericum with an SSRI are virtually nonexistent. Passiflora incarnata (Passionflower) is an herb that has been shown to potentiate the effects of St. John's Wort, though, and itself has significant effects proven to treat insomnia, depression and anxiety. Passiflora contain rutin, though, which is a 5-HT (serotonin) inhibitor, and is unlikely to increase the serotoninergic effects of St. John's Wort. This array of herbal chemicals now proven to modulate neurotransmitter metabolism in the brain is now supported by much scientific study, some of which is presented in the section of the article entitled Additional Information, with links to the studies.