By Audree Evans
Adderall. It’s a drug that has become so familiar since it hit the market in 1977 that most people recognize the name immediately. But why would our culture foster such knowledge of a prescription drug used to treat Attention-Deficit / Hyperactivity Disorder (ADHD)? According to the Attention Deficit Disorder Resource Center, 6.1% of the American population suffers from ADHD. This is a significant number of people, but when compared to other ailments, like cancer, which affects 38.4% of Americans, according to the National Cancer Institute, it’s a wonder why so many people are familiar with Adderall over the various drugs used in the process of treating cancer.
So what is Adderall? It is the d-form of amphetamine, known as dextroamphetamine, which acts as a powerful central nervous system stimulant; the central nervous system is comprised of the brain and spinal cord. Adderall and similar amphetamines work by blocking the reuptake of dopamine and adrenergics, stimulating the release of monoamines, and inhibiting monoamine oxidase (National Center for Biotechnology Information). To understand this description, let’s first look at neurotransmitters and how they work.
Neurotransmitter is just a fancy term for one way in which our neurons, the cells of the nervous system, communicate with one another. Sometimes the neurons use electrical communication, like the wiring in our computers, and sometimes they use chemicals, like in the case of neurotransmitters. Between two neurons is a small gap called a synapse where the neurotransmitters pass from neuron to neuron. In the synapse, the neurotransmitters can either be re-absorbed by the original neuron (we will call this neuron 1 for the rest of the description) that transmitted it or bind to receptors on the second neuron (called neuron 2), potentially resulting in some reaction from the body.
Monoamine is a blanket term describing certain types of neurotransmitters that only have one amine group in their chemistry. Dopamine is a type of monoamine that is known to be involved in pleasure, reward fulfillment, motor function, and compulsion (Klein et al., 2019). Serotonin, another monoamine, is known to regulate mood, appetite and digestion, sleep, memory, and sexual function (Frazer & Hensler, 1999). Epinephrine, more commonly known as adrenaline, and norepinephrine are both monoamines that have similar effects on the body, like increasing heart rate, increasing blood pressure, initiating sweating, decreasing digestion, etc. Adrenergics is a term that encompasses both epinephrine and norepinephrine, two of the main neurotransmitters associated with our fight-or-flight response (Bylund, 2015).
Adderall has such a strong effect because it blocks the reuptake of both dopamine and the adrenergics, meaning the neuron 1 that transmitted these neurotransmitters can no longer re-absorb them. Typically, if there is excess of a neurotransmitter in the synapse, neuron 1 will re-absorb them and then the neurotransmitter can no longer have an effect on neuron 2. However, if the reuptake is blocked, then the neurotransmitter will continue to sit in the synapse and have an effect on neuron 2 until it is broken down by an enzyme known as monoamine oxidase, diffuses out of the synapse, or the Adderall loses its effect (Richardson, 1993).
Adderall also stimulates the release of monoamines, including some of those mentioned above, dopamine and the adrenergics. This means that not only are there more neurotransmitters sitting in the synapses from a lack of re-uptake, but there are also more released from neuron 1. On top of that, Adderall inhibits monoamine oxidase. Monoamine oxidase is the enzyme that breaks down monoamines. When there are excess monoamines within a synapse, monoamine oxidase comes and breaks down the neurotransmitters to be recycled and used in later processes. Since Adderall inhibits this, it acts as another method to increase the amount of dopamine, serotonin, epinephrine, and norepinephrine within the synapses (National Center for Biotechnology Information; Richardson, 1993).
These functions of Adderall have been shown to work well for people with ADHD because with the increase of these neurotransmitters there is an increase in their pleasure and feeling of reward when completing tasks. People with ADHD normally have been found to have a decrease in dopamine within their ventral striatum and prefrontal and temporal cortices within their brains (Lakhan & Kirchgessner, 2012). Adderall is able to increase these levels of dopamine, which effectively brings their dopaminergic system to a similar level of functioning that is present in people without ADHD. Thus, decreasing the inclination to be distracted and bringing them operationally to a level that society has determined to be a normal amount of focus (Volkow et al., 2012).
The brains of people with ADHD have been found to have less amygdala and hippocampal volume than people with a more common morphological phenotype (Saute et al., 2014). In a study looking at chronic low and heavy doses of Adderall given to mice, it was found that hippocampal volume of the mice increased and there was greater proliferation of the cells in these regions of the brain (Dabe, Majdak, Bhattacharya, Miller, & Rhodes, 2013). Although there has not yet been similar studies within humans, there is so much conservation between human and mouse brains that this study gives good insight that the increase in hippocampal volume may be one of the reasons why Adderall is an effective form of treatment for those with ADHD (Strand et al., 2007).
It is estimated that approximately 60% of children in the United States with an ADHD diagnoses receive pharmacological treatment (CDC, 2010). Usually they are prescribed either Adderall or Ritalin, but in the past 20 years the prescription rate of Ritalin declined by 2.7% and Adderall increased by 7.6%, making Adderall the most commonly prescribed stimulant for ADHD in the United States (Saute et al., 2014).
However, people with a normal level of focus and normal brain structures experience similar effects when ingesting Adderall. Elevating their feeling of pleasure, rather than purely stabilizing it, like in ADHD, can result in a euphoric and high feeling that can cause many to become addicted and seek out the drug without a prescription or physiological need. Moreover, Adderall can increase pleasure during tasks like schoolwork, so the drug has become increasingly popular to students in high school, undergraduate, and graduate programs. For example, a survey administered to medical students from a public medical university found that 10% of the medical students reported using stimulants to improve their academic performance. Of this population, only 5.5% were diagnosed with ADHD and 72.2% of that population was diagnosed after the age of 18, whereas the normal onset and diagnostic age for ADHD is in early childhood (Tuttle, Scheurich, & Ranseen, 2010). Some healthy students are going to psychiatrists and mimicking the signs of ADHD in order to be prescribed stimulant medication, which has led to a shortage of ADHD drugs such as Adderall (Mitchell, 2012). Interestingly enough, when testing the drugs on individuals without ADHD, they found that people felt they had a sustained attention span only when they anticipated taking Adderall regardless if they ingested any of the drug or purely a glucose tablet (Looby & Earleywine, 2011).
The placebo effect seen here is especially interesting because, as previously stated, subjects report feeling an enhanced ability to focus regardless of if Adderall is in their system. However, a study that reviewed data collected on prescription stimulants working as neuroenhancers only found a slight correlation with rote memory tasks and no benefit to complex memory, which is much more likely to appear on university exams and be encountered on normal workdays (Smith & Farah, 2011). Unfortunately, the fact that Adderall only improves rote memorization for limited periods of time is not the information that is normally provided about such stimulants. Most people tend to think of Adderall as a “super” or “smart” pill that enhances cognition even though this is in inaccurate. This may be because media tends to support the idea that Adderall, and similar stimulants, will work as a neuroenhancer. In fact, a study looking at multiple reports on Adderall found that 95% of media articles mentioned at least one possible benefit of using a prescription stimulant as a neuroenhancer and only 58% mentioned any risks involved in this behavior or possible side effects (Partridge, Bell, Lucke, Yeates, & Hall, 2011). Moreover, the research has not even shown that Adderall plays a significant role in cognition. Adderall may be useful with rote memory tests, but it does not act as a neuroenhancer; it just increases enjoyment of normally mundane tasks so people feel like they are performing at a higher level.
The long term effects Adderall has on the brain are largely unknown, which is alarming considering the high number of people who take this drug daily. Due to the neuroplasticity of our brains, which essentially means our brains are able to adapt to various changes throughout our lifetime, those who take Adderall become accustomed to higher levels of the neurotransmitters. If people stop taking Adderall, then they will lower the levels of dopamine, serotonin, epinephrine, and norepinephrine within their brains (Proebstl et al., 2019). This then leads to a need for more of these neurotransmitters to produce the same effect, which leads to dependency and addiction. The wrong levels of dopamine and serotonin alone have been implicated in depression, anxiety, schizophrenia, and other such mental disorders. Moreover, there have been recent studies looking at cardiac health related to Adderall use. It has been found that, due to the elevated epinephrine and norepinephrine levels, there have been heart attacks, sudden cardiac death, and other cardiac issues associated with the ingestion of Adderall (Gandhi, Ezeala, Luyen, Tu, & Tran, 2005).
Due to Adderall only hitting the market in 1977 and not being widely prescribed until recently, the research about the long-term effects for chronic users, unfortunately, is extremely minimal. As previously mentioned, there is much concern over the effect on cardiac tissue and there is a link between Adderall use and cardiac tissue death (Gandhi et al., 2005). However, the effects on brain tissue has either not been previously studied due to the short-term nature of chronic users or because there hasn’t been significant findings in alterations to brain tissue. The main findings revolve around the changes in neurotransmitter levels and that has been found to have an increase in psychosis and abuse of other drugs in the future (Berman, Kuczenski, McCracken, & London, 2009). As for physical changes within the brain, there has not been any findings that indicate long-term ingestion of Adderall causes significant variations within brain structures. It is possible that chronic use has no impact on brain tissue, which would be astounding, but future research is needed to fully determine if this is the case or not.
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