Something about Adderall, Neuropharmacology of Amphetamine

Published April 26, 2020, 1:04 a.m. by Admin


Amphetamine, or more commonly known as Adderall, is a medication used to treat Attention Deficit Hyperactivity Disorder (ADHD), narcolepsy, and obesity. It was first synthesized in 1887 and is by far one of the most researched drugs ever. The drug functions by acting as a Central Nervous System (CNS) stimulant and is administered via ingestion.

This article will focus on the underlying bio chemistry and neuropharmacology of amphetamine, I will also briefly address its viability as a study drug.

Brief Comparison
Because of amphetamine's maturity it has a relative advantage over newer alternatives such as Modafinil in the sense that the chances of unknown adverse effects are somewhat lower. However, it is important to note that drug testing in North America is fairly rigorous and generally, fairly thorough. Additionally, amphetamine is far more common, doctors and pharmacists understand it better and can anticipate symptoms easily.

Amphetamine is essentially a benzene ring attached to a 3 carbon chain with an amino group on the 2nd carbon.

Essential Information

What are monoamines?
The following is a gross oversimplification of monoamines and their functions but will be sufficient in helping you understand concepts that will be discussed later.

Monoamines are neurotransmitters such as dopamine (I bet that one sounds familiar), serotonin, norepinephrine, and epinephrine. Each of these chemicals are used within your brain to stimulate a certain type of reaction. Most monoamines share a very similar structure and play essential roles in certain neural pathways within the brain. Even though monoamines are mostly synthesized and used in the brain where they are mostly used as neurotransmitters, they can also be synthesized in the kidneys and are also used as hormones. For example, dopamine is synthesized in your kidneys and can function as a hormone.

In this article we will mostly be focusing on dopamine and norepinephrine as they play the most significant roles during amphetamine usage.

Dopamine plays an important role in motivation and is essential to your bodies reward-motivated behavior. Whenever you do something that you like dopamine is released as a reward which feels nice, this gives you an incentive to repeat this behavior so that you can receive another dopamine rush. The reason this occurs is due to an evolutionary mechanic our brains have developed. By releasing dopamine to reward us for things such as hunting prey, eating good food, and having sex, (all of which are essential to a species survival and my Tuesday), an organism becomes more motivated to repeat those actions. As organisms become more and more motivated, they become more and more competitive improving their chances at survival. What a great concept.

Norepinephrine or noradrenaline / noradrenalin (pay close attention to that 2nd half of the name) plays an essential role in your brain and body's ability to mobilize. Norepinephrine is released the least while you are asleep and slowly rises as you become more awake. In high intensity situations where you might feel threatened or stressed norepinephrine release is significantly higher. Norepinephrine will increase feelings of arousal, alertness, and generally promote vigilance. Additionally, higher levels of norepinephrine release have even been associated with enhanced ability for memory formation and recollection as well as improvements in focus / attention. However, norepinephrine also increases restlessness, anxiety, heart rate, and blood pressure.

The Basics
Amphetamine binds to the transporter proteins outside of neurons along the synaptic cleft. These transporter proteins are responsible for binding to monoamines such as dopamine, norepinephrine, and serotonin so that they may be absorbed by the neuron and/or moved across the synapse. Amphetamine and most methyl-amphetamines share a very similar chemical structure to dopamine giving them the ability to bind to these transporter proteins, which allows them to enter the neuron.

Once amphetamine enters the neuron it disrupts the storage of the monoamines discussed above within the synaptic vesicles. One way this is done is by inhibiting the vesicular monoamine transporter 2 protein (VMAT2). VMAT2’s primary responsibility is to transport monoamines in synaptic vesicles. Inhibition of VMAT2 results in higher levels of these neurotransmitters in the neuron.

Diagram of amphetamine interacting with neurotransmitters in a synapse

Although some of the following is still not fully understood, amphetamine is then able to cause the monoamine transporter proteins to run in reverse. This somehow results in the increased release of dopamine, norepinephrine, and a few other monoamines as well as the increased release of their correspondent neurotransmitters in the synaptic cleft, these elevated mono amine levels give rise to the observable traits of amphetamine on the CNS discussed above.

Amphetamine also increases monoamine levels within neurons and correspondent synaptic clefts by inhibiting monoamine re-uptake. The way this works is by directly competing with monoamines for re-uptake. Lastly, various methyl-amphetamines and amphetamine have been observed to inhibit the activity of another enzyme, monoamine oxidase, which is responsible for metabolizing monoamines.

The key takeaway is that amphetamine shares a very similar structure to monoamines such as dopamine. Its similar structure allows the drug to be treated similarly to monoamines which results in inhibition of the normal metabolic pathways of monoamines. This leads to an increase in certain monoamines which finally result in the heightened CNS activity we observe.

The heightened CNS activity we observe is what makes Adderall an effective cognitive enhancer. However, it is important to note that amphetamine is not a miracle drug. There are still adverse side effects and long-term side effects that could be incredibly severe not only to an individual's physical health, but also to their mental health. The irony of it all is that Adderall, a drug people use to study and motivate themselves, will actually reduce dopamine transmission in the long run, making simple tasks such as getting out of bed incredibly difficult to the point where they would need Adderall just to perform basic work. This creates a dangerous dependency.
In conclusion, amphetamine isn't a perfect drug but it can serve excellent short-term usage when prescribed properly.

Now that you the reader are more informed on the matter hopefully you can make improved decisions.