So your body has MAO A and MAO B for neurotransmitters in too high of quantities in specific body and brain areas are toxic. This includes dopamine, norepinephrine, serotonin, and the trace amines such as the Phenethylamines compounds. Amphetamine is a modified form of Phenethylamine, which is your body's natural amphetamine. Your body releases phenethylamine during specific triggers such as exercise to cause the purposeful release of dopamine and norepinephrine. Phenethylamine is also released when your body experiences many positive sensory or emotional experiences. Whenever you have an intense emotion which is "useful" in its intensity most likely it is caused by the release of Phenethylamine for a brief period, and then the other neurotransmitters that Phenethylamine causes the release of is the feeling that lasts longer than a few seconds. Aka the electric touch of you being in puppy love with your hear fluttering, the intital intensity of a few seconds is phenethylamine, the rest is the after effects where phenethylamine causes the release of other neurotransmitters.

Phenethylamine in the area of the neuron that is inside the neuron and not the synaptic vesicles only lasts 30 seconds for MAO breaks it down to protect very important cellular structures the main one is the cell's energy factory called mitochondria. If a single neurotransmitter gets too close to the mitochondria and there is not enough MAO to prevent it, it steals an electron from the mitochondria which then causes a chain reactions for that atom tries to steal an electron from its neighbors. This is called oxidation, aka the stuff antioxidants are supposed to prevent but in this specific area of the body it is MAO that plays this important role wikipedia on oxidative stress. If a chain reaction occurs, your body purposefully releases chemicals that purposefully cause that cell to specifically self destruct in a fashion so it can't spread to nearby neurons, or mutate in a way that cancer is a possibility, wikipedia on preprogramed cell death called Apoptosis.

But too much MAO-A or MAO-B is bad for it means your body destroys neurotransmitters too fast, faster than your body can make them. This can lead to anxiety or depression.

Amphetamine is a modified form of Phenethylamine. The difference between Phenethylamine vs Amphetamine is a couple of atoms that makes it harder but not impossible for Amphetamine to be broken down by MAO-A and MAO-B. Thus you want to be really really careful with anything that inhibits MAO-A or MAO-B when you are using a substance that acts like Phenethylamine but is much harder for your body to stop. Thus with amphetamines you actually need more MAO-A or MAO-B to be in the safe zone.

Effectively your body is a big huge chemcial reaction, that consists of trillions of chemical reactions per second. Your body has to keep everything in balance, causing a purposeful imbalance of just a little to cause change such as the conduction of electrical discharge via nerve cells, but make sure that imbalance does not threaten the system.

 

 

How your nerve cells work on a simplistic level is this. Your neurotransmitters should be in one of three places at all times.

1) In synaptic vesicles storage closets inside the nerve when the neurotransmitters are not supposed to be used.

2) The synaptic vesicles are sent to the end of the cell membrane and forced out of the original nerve cell and into the space between two nerve cells, this space is called the synapse, the original nerve cell is the presynapse, and the receiving nerve cell is the post synapse. The post synaptic receptors when turned on by neurotransmitters such as dopamine tell the cell to do things, as well as getting their synaptic vesicles read to fire. It also tells the cell to change stuff inside the cell to increase the electrical conductivity between the original and receiving nerve cell and then their is an electrical arc which cause the 2nd nerve cell to release its neurotransmitters from the synaptic vesicle to talk to the third nerve cell.

3) The neurotransmitters are "stopped being released" by little neurotransmitter indicators called presynaptic receptors, they are in the space between two nerve cells and are on the firing nerve cell to indicate the current amount of neurotransmitters between these two nerve cells and once the desired stimulation occurs to stop releasing even more. At the same time reuptake transporters suck back up the neurotransmitters in the space between the nerve cells and the neurotransmitters are now inside the nerve cell but not inside the synaptic vesicles yet. This is the time that they can damage very important things. Thus your body uses its synaptic vesicles and the VMAT2 reuptake transporters on those little storage closets that look like orbs and place the neurotransmitters back into storage so they can't damage anything.

 

 

So amphetamine has many ways it works, but the end results is that it increases dopamine and norepinephrine both between the two nerve cells within the synapse but it also increases dopamine and norepinephrine inside the nerve cell but not inside the synaptic vesicles, this is because the amphetamine is instead placed in the synaptic vesicles by design, for amphetamine is very similar to phenethylamine and phenethylamine is done by designed to be inside the synaptic vesicles first, and dopamine and norepinephrine are less important in the synaptic vesicles compared to phenethylamine. This is because phenethylamine is more toxic than dopamine and norepinephrine and thus your body purposefully puts the most toxic thing inside the synaptic vesicles.

Now your body has a second defense mechanism to protect essential cellular parts from being damaged from neurotransmitters. It has a specific receptor inside the nerve cells called the trace amine receptor, receptors that are turned on by phenethylamine as well as amphetamine and rarely turned on by dopamine and norepinephrine. Wikipedia on TAAR1 When your phenthylamine level is very high inside the nerve cell but not in the synaptic vessicles, it turns on a warning switch that tells your nerve that you have way too many toxic phethylamine inside the nerve cell and it can damage stuff if MAO can't keep up. Thus your body actually reverses the direction of the dopamine and norepinephrine reuptake transporters so instead of sucking neurotransmitters inside the nerve cell they flush the contents of the neurotransmitters into the synapse so you have less possibly dangerous neurotransmitters that can damage things. It is like playing a tower defense game and you have too many enemies near the castle gate, thus you have a special item that has limited charges which you use when enemies are way too close that destroys all the enemies temporarily and they have to regather their numbers to be threatening. Well by flushing the neurotransmitters out you are very likely to activate the next nerve cell in the line for if enough neurotransmitters are released it triggers the next nerve cell. Thus how lightly or heavily you activate TAAR1 makes a big difference and this is why amphetamines can be very addictive if used at too high of doses or if you smoke or inhale them which causes the nerve cells to absorb the artificial phenethylamine all at once which activates this TAAR1 not just occasionally but very heavily.

At the same time remember those presynaptic receptors that monitor those neurotransmitters. There are 3 versions of the DRD2 receptor, 1 is a postsynaptic receptor that sends the next nerve cell in line, another is a presynaptic receptor that monitors the levels of neurotransmitters. Your body has these presynaptic receptors to turn off the release of neurotransmitters. Your body also can form combination presynaptic receptors with TAAR1 and the DRD2 (short aka presynaptic receptor) and these receptors are much more sensitive than DRD2 short presynaptic by itself. (Combination receptors are known as heterodimers) Thus having these DRD2+TAAR1 combination receptors on the outside of the nerve cell on the synapse actually prevent the over release of dopamine by telling your body to stop releasing dopamine from the synaptic vesicles unless the TAAR1 inside the nerve cell tells it to activate. Literally it is a push and pull system that forms a complete cycle, a circle to keep everything balanced. We now know via purposefully modifying the TAAR1 gene in rodents that if you are lacking it you are going to get a rat which becomes super hyperactive via amphetamine or meth, but give it to a rat that has the correct genes in the right amount and you calm it down. We also having evidence that taar1 activating drugs not necessary amphetamines but others have benefits in treating schizophrenia and various forms of addiction. How you activate TAAR1 causes excess release or prevents over release of neurotransmitters.

See followup post for reddit says it is too long for 1 reply