Brain Chemistry


Overview

Neurotransmitters (baseball)
Neurotransmitters are molecules that is used to communicate messages from a transmitting nerve cell to a receiving nerve cell. This is kind of like baseball. The pitcher is the transmitting nerve cell, the catcher is the receiving nerve cell, and the baseball is the neurotransmitter molecule. When the ball is thrown and caught, a little message is transmitted. The catcher's mitt is called a "receptor". After the catcher has caught the ball, he or she throws it back to the pitcher to the pitcher so it can be thrown again.

Problems (shortages)
If the receptor is clogged, one will have trouble communicating. If the baseball is missing, one will have trouble communicating. If the leather that is used to make the ball is missing, then the ball will be missing, and one will have trouble communicating. If the train that transports the leather to the ball factory breaks, one will have trouble communicating. If the train that transports the ball from the ball factory to the baseball field breaks, one will have trouble communicating. Easy.

Different Kinds of Neurotransmitters (baseballs)
There are several different neurotransmitters (baseballs). The main ones are called Noradrenaline (NA), which is sometimes referred to as "norepinehprine", Dopamine (DA), Serotonin (5HT), and GABA. One could think of these as different fruit instead of baseballs. Each neurotransmitter molecule could be an apple, orange, pear or watermelon. And then you have pitchers and catchers who are trained in throwing/catching these specific items. A pear catcher can only catch pears. In fact, there are several different kinds of catchers for each neurotransmitter (e.g. different kinds of pear catchers). Imagine 15 catchers next to each other with the numbers 1 through 15 on their shirts. If #1 catches the fruit, he gets on the phone with another pitcher in the neighborhood, and tells him to throw a specific kind of fruit to a specific place. Numbers #2 through #15 have phones too, that go to other places in the neighborhood. All this throwing fruit and chatting on the phone is "thinking".

Noradrenaline (NA) alpha-1 and alpha-2 receptors
With the noradrenaline (NA) neurotransmitter, for example, two of the receptors are called "alpha-1" and "alpha-2" (catcher with #1 on his shirt, and catcher with #2 on his shirt, each with their own special phone line). The Alfa-1-receptors stimulate the conversion of liver molecules to sugar molecules (glucogenolysis), resulting in more glucose in the blood. Alpha-1 also stimulates the consumption of oxygen (O2) by the cells and stimulates the conversion of fatty acid in blood to energy. All of these alpha-1 items result in more energy for the person. If the alpha-1 receptors are clogged (e.g. by a pesky heavy metal molecule), one would feel fatigued. The following things can clog NA alpha-1 receptors: antagonist drugs, lead, mercury, cadmium, sulfur-toxins, over 70,000 manmade chemicals, and several natural toxins. To see examples of studies on noradrenaline receptors, please click here.

Reuptake inhibitors (pitcher glove clogger)
There is a class of drug called a reuptake inhibitor, which clogs the pitcher's glove (or makes it smaller) and makes it hard for him to catch the ball when the catcher throws it back to him. When this happens, the ball hits a wall behind the pitcher and it bounces back to the catcher. It is not exactly sure what happens here, yet we know this has an affect on the amount of communication between the pitcher and catcher using that type of ball (neurotransmitter).

Serotonin Reuptake Inhibitor Drugs
Drugs that clog (or shrink) the serotonin pitcher's glove are called serotonin reuptake inhibitors (SSRI). Popular SSRI's are Prozac, Luvox, Paxil, Zoloft, and Celexa. Other ways to boost serotonin are to take the over the counter supplements L-Triptophan (which is not available in the USA) or 5-HTP. SSRI's are famous for relieving depression, which also means that low levels of serotonin or clogged serotonin receptors can cause depression. Heavy metals and proteins from genes are examples of things that can clog a receptor. There are also some serotonin receptors which are inhibitory, which means that stimulating inhibits feelings (e.g. the serotonin 5-HT1A receptor inhibits worrying). Therefore, it is possible for drugs that increase serotonin can increase (not decrease) depression. Also, if a serotonin receptor is clogged, then increasing the level of serotonin may not help, and one may need a Serotonin Agonist instead to unclog it.

Noradrenaline Reuptake Inhibitor Drugs
Drugs that inhibit noradrenaline reuptake are referred to as noradrenaline reuptake inhibitors (NARI). A popular NARI drug is called Wellbutrin SR (Buproprion). To learn more about Wellbutrin , click here.

Agonists (catchers glove stimulators)
There is another class of drug called an Agonists. These stimulate specific receptors to make them think they just received a neurotransmitter molecule (i.e. a specific catcher thinks he just caught a piece of fruit, and he subsequently gets on the phone). If the catcher glove had been clogged, an Agonists can help unclog it by stimulating it. Agonists are often selective, in that they accelerate the activity of a specific kind of receptor for one neurotransmitter (e.g. catcher #5 that catches Pears). NA-Agonists are sometimes referred to as "Noradrenergic Agonists", and Agonists for serotonin called "Serotonin Agonists". Serotonin has several important receptors called 5-HT1A, 5-HT2, 5-HT3.

The Famous Serotonin 5-HT2 Receptor
Did you know that over eating, heavy metal, LSD, cocaine, and sugar cravings are all related? They are, via the serotonin 5-HT2 receptor. LSD and cocaine are 5-HT2 Agonists. Fenfluramine and PhenFen (DexFenfluramine) are also 5-HT2 Agonists, yet were taken off the market when PhenFen, the weight loss drug, was found to be harmful. Is 5-HT2 related to addiction? Yes, addiction, on a chemical level, is when the body wants a specific receptor to be stimulated, over and over. It is as though stimulating causes the receptor to get on the phone to another part of the brain and say, "Hey, feeling goooood! Yea Baby !". Serotonin 5-HT2 is one of those addictive receptors (the Doc's sometimes refer to this as "habit forming"). Another habit forming receptor is the opiod receptors, which are stimulated with heroin.

When one eats food, the 5-HT2 receptors are stimulated due to increased serotonin from increased sugar and Triptophan in the blood. In some cases, it is believed that some people eat because they are addicted to this stimulation of 5-HT2. This is why PhenPhen, the 5-HT2 receptor drug, was used to encourage weight loss. By stimulating it with a drug, the person would feel satisfied, like they had just eaten a big meal, when they had only had 2 crackers 3 hours ago. This is one reason that people sometimes crave sweets. They want to stimulate their 5-HT2. If the 5-HT2 receptors gets clogged (for example, with heavy metal molecules), then one may want sweets, even when there is much sugar in the blood since. Folks with heavy metal issues often cannot keep their hands off sweets after dinner -- they've got to have them. Is there anything one can do about this? Not really, since the 5-HT2 Agonists are habit forming, and unclogging the receptors is not easy with heavy metals that have 15year half lives in the brain. There is much research on 5-HT2, and someday there maybe some safe meds for it. Also, the world needs a better drug that will pull heavy metals out of brain, and out of the insides of cells.

Other Serotonin Agonists
Another Serotonin Agonists is BuSpar (Buspirone). BuSpar stimulates the serotonin 5-HT1A receptor big-time, and the Dopamine D2 receptor moderately. Dopamine D2 is used for motor control, and 5-HT1A is used to inhibit worrying about things (sometimes referred to as "inhibitory"). This inhibitory action has a calming affect, and BuSpar is therefore used as an "anti-anxiety" drug. If one has clogged 5-HT1A receptors and this is causing anxiety, BuSpar could be very helpful. To learn more about BuSpar, click here.

Noradrenaline Agonists
Provigil (Modafinil = Modiodal) is an example of an NA-Agonists that is FDA approved. It stimulates the noradrenaline alpha-1 receptor, and subsequently increases glucose (sugar) in blood (due to increase glucogenolysis) and increases oxygen to cells, which results in more biochemical energy (i.e. less fatigue). Several NA-Agonists have been used extensively in Europe, including Ordinal Forte, and Adrafinil (Omifon) and Modafinil. To learn more about Provigil, click here. The NA-Agonists tend to not be habit forming, unlike some of the serotonin Agonists.

Antagonists (catchers glove cloggers)
There is another class of drug called an Antagonists. These make it harder for the catcher to catch the ball by clogging it up a little. Subsequently, the ball bounces into the space between the pitcher and catcher and then bounces around a bit. Examples of drugs that do this with serotonin are called Serzone and Desyrel.

What Medication To Take?
Reuptake inhibitors increase the level of a neurotransmitter both in the Central Nervous System (CNS) and in blood, and therefore can have far reaching affects. For this reason, if there is a problem with one, or a few receptors, Agonists are often desirable since they more specifically address the problem area, whereas the reuptake inhibitor may have many side effects. Sometimes, however, it can be difficult to identify which receptor is in trouble since there are so many receptors, or the problem receptor may not have been discovered yet, or an Agonist for the problem receptor may not exist. If a neurotransmitter level is low on the other hand, a reuptake inhibitor may be the perfect medication for the job.

The Chemistry Behind Sex
The orgasm pleasure is fascillitated through stimulation of the endorphins/opiate receptors. The libido itself is stimulated by dopamine and noradrenal receptors (Provigil boosts libido) and inhibited with serotonin receptors (SSRI's can inhibit libido). Things that can increase libido are NA-Agonists, Zinc, P5P and B12. Things that can reduce libido are SSRI's and anything that can clog NA receptors such as heavy metals and H2S (hydrogen sulfide caused by fermentation of sugar in gut by bad yeast or bacteria). Things that make H2S worse and therefore reduce libido are bad bacteria or yeast in gut, and the sugar they ferment. Therefore, less sugar consumption, in some people with this condition, boosts libido.

All Other Neurotransmitters
For a summary of all neurotransmitters, please click here.


Noradrenaline Chemistry Tutorial

Click here to learn about the chemistry behind the Noradrenaline neurotransmitter.

Click here to learn about how to test for a NA problem, and how to respond if a problem is found.


Rx Noradrenaline Drugs

Provigil
Provigil (Modafinil = Modiodal) is an NA-Agonists that stimulates the NA alpha-1 receptor. In doctor lingo, it is a CNS (central nervous system) alpha-1 adrenergic Agonist. It is FDA approved and is used to effectively reduce sleepiness for people with narcolepsy. Sleepiness? Is that like fatigue? Yes. NA-Agonists have been used in Europe during the 1990's, and are just beginning to become popular in the USA. For details on the Rx drug Provigil, please click here. For an example of a study that found that Provigil is not harmful (e.g. not habit forming) over a long period of time and helped people with narcolepsy, please see REFERENCE #10. For a study that found that Provigil does not hurt one's hormones, please see REFERENCE #11. For a study that looked at the noradrenic properties of Provigil, please see REFERENCE #12. For a paper on the use of Provigil (Modafinil) for Idiopathic Hypersomnia (a term that sleep researchers use for chronic fatigue), please click here. To learn about the pitfuls of long term use, please click here. To learn more about studies involving Provigil, search "Modafinil" at Medline after 1990.

Wellbutrin SR
Wellbutrin SR (also called "Buproprion") is a noradrenaline reuptake inhibitor (NARI), and decreases the amount of noradrenaline (NA) absorbed by the transmitting nerve cell when it is recycled back for another pitch of the ball (neurotransmitter) from the pitcher to the catcher (tranmsitting nerve cell to receiving nerve cell). The end result is you end up with excess noradrenaline in the space between the transmitting and receiving nerve cell. Wellbutrin is an FDA approved Rx drug and has been used extensively in the USA during the 1990's. For details on Wellbutrin, please click here. To learn about the pitfuls of long term use, please click here. To learn more about studies involving Wellbutrin, search "Buproprion" at Medline after 1990.


Depression and Fatigue

There are many different feelings that one can experience, and each can correspond to a specific neurotransmitters or a specific receptor. Two big feelings are fatigue and the more classical form of depression, which is marked by disinterest and feelings of sadness. Fatigue is when one feels tired, like they have been up for 48hrs, and they want to sleep. They are thinking about how wonderful it would to be to get into bed and fall asleep. These people may be extremely happy and may be very interested in life. Imagine a medical intern that is a happy and interested, yet has been up for 36hrs, and feels tired. Not "depressed", yet "fatigued". There is a huge difference between the two.

Classical depression is associated with feelings of melancholy, disinterest in life, boredom, a lack of enjoyment in life, and self doubt. These folks may not be interested in sleeping. In fact, if they get into bed during the day, they may feel like they need to get out of bed, since it is daytime, and they cannot sleep at that time. These people are not fatigued, they are "depressed".

Serotonin is often associated with the more classical forms of depression, and noradrenaline is often associated with fatigue. If you are fatigued, you may benefit from a noradrenaline medication; and if you are depressed (sad, disinterested), a serotonin medication. Anything that causes a disregulation of the serotonin neurotransmitter, or clogs a seratonin receptor such as 5-HT2, can cause depression. Additionally, one should keep in mind there are many other specific causes of depression, such as impaired Phenylalanine metabolism which inhibits endorphin receptors.

If you understand the above concepts, you are half way to becoming a psychopharmacologist -- congratulations !!!

For details on depression and bipolar disorder, click here; and for details on their treatments, click here. For details on Obsessive Compulsive Disorder, click here.


Healing with Over The Counter Amino Acids

Some people have had success in adjusting their brain chemistry with over the counter, non-Rx, amino acid supplements, such as Phenylalanine. This naturally occuring amino acid is readily available in most food products, particularly meats and milk products, with lower levels found in oats and wheat germ. It is essential for many bodily functions and is one of the few amino acids that can cross the blood-brain barrier (from blood to brain) and thus directly affect brain chemistry. Phenylalanine is the precursor of the amino acid tyrosine and is therefore used to make noradrenaline and other catecholamines (type of neurotransmitter) such as epinephrine, dopamine, and tyramine. Noradrenaline is an important neurotransmitter is apparently important for memory, alertness, and learning. Phenylalanine metabolism requires pyridoxine (P5P or B6), niacin (B3), vitamin C, copper, and iron. Phenylalanine has been used for treatment of depression in the D-, L-, or DL- forms, probably because it increases tyrosine, the excitatory neurotransmitter. Braverman and Pfeiffer, in "The Healing Nutrients Within", suggest that L-phenylalanine works best in bipolar disorders (with manic and depressive states) in doses of 500 mg twice daily (not more than 2-3 grams daily), along with 100 mg vitamin B6 twice daily. They also suggest that D- and DL-phenylalanine works better for affective (lack of positive attitude or emotional enthusiasm for life) depression. Phenylalanine is better absorbed than tyrosine and produces fewer headaches, so may be more useful in depression than taking L-tyrosine directly.

Both DL- and D-phenylalanine are helpful pain relievers in certain musculoskeletal problems, and this is their primary use currently. Aspartame, the new nutrient sweetener, is synthesized from the combination of aspartic acid and phenylalanine. Aspartame is safe, except for pregnant women or people with phenylketonuria (PKU), a genetic problem of phenylalanine metabolism. It probably helps pain because of its function of increasing endorphins (another neurotransmitter that stimulates receptors that make us feel good) in the brain, but it is not really a treatment for the cause of the pain, such as inflammation or spasms. The endorphins are thought to give us a more positive outlook on life, to enhance alertness, and to improve vitality. (This may be a reason why phenylalanine works for depression.) Endorphins are the mysterious substances released when we exercise or when we experience positive emotions. They are also thought to make us less sensitive to or aware of pain. DL-phenylalanine blocks the enkephalinase enzymes that break down the endorphins and enkephalins, the natural pain relievers and mood elevators. However, phenylalanine does not work all the time, nor is it a complete therapy; the underlying cause of the pain or depression should be discovered. Some of the pain problems for which phenylalanine may be helpful are low back pain; neck pain; osteoarthritis; rheumatoid arthritis; menstrual cramps; and headaches, particularly migraines. However, patients suffering from migraines may have elevated phenylalanine levels, in which case supplementation would not help. L-tryptophan may work better in these patients (to increase serotonin). On a trial basis, to see whether it will be helpful for pain, DL-phenylalanine can be taken in a dose of about 500 to 750 mg two to three times daily for a week or two. It really has no common side effects other than occasional headache or jitteriness. However, it may raise blood pressure in some people, so this should be watched. It is recommended by some Doc's that Phenylalanine and other amino acids should not be used for more than three weeks at a time without a break or without the support of the other amino acids.


For more details on brain chemistry and brain meds...

If you want to read more about brain chemistry and brain chemistry meds, please visit www.mdconsult.com/, register for 10 days free of charge, press the "Reference Books" button, scroll down to "Psychiatry", click on "Kaplan: Comprehensive Textbook of Psychiatry, 6th ed", scroll to "32 - BIOLOGICAL THERAPIES", Press the "+" button to expand, and then start reading. Kaplan is serious.


BeatCfsAndFms Home ©Copyright 1999 gsw. All rights reserved.