Introduction: What is Adderall used for?
Amphetamines, including Adderall, are central nervous system (CNS) stimulants that have been widely prescribed for the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. However, the widespread use of Adderall has raised concern about its potential side effects, particularly regarding its impact on the brain and body’s nutritional status. In this article, we provide a comprehensive review of the pharmacology of Adderall, its effects on neurochemistry, and the vitamins and minerals that are depleted by its use. We also offer strategies for mitigating its side effects.
Pharmacology
Adderall is a combination of dextroamphetamine and amphetamine salts that work by increasing the levels of neurotransmitters in the brain, including dopamine and norepinephrine. These neurotransmitters play a role in attention, motivation, and arousal, leading to improved focus and decreased impulsiveness in individuals with ADHD (Biederman & Faraone, 2005). Adderall acts as a reuptake inhibitor of the neurotransmitters, preventing their reuptake into presynaptic neurons and thus prolonging their effect on postsynaptic neurons (Volkow et al., 2006).
Adderall works by blocking the reuptake of dopamine and norepinephrine, allowing these neurotransmitters to accumulate in the synaptic cleft and enhance neurotransmission (Brams et al., 2016). Dopamine is involved in the regulation of attention and motivation, while norepinephrine helps to regulate alertness and energy levels. By increasing the levels of these neurotransmitters, Adderall can improve focus and attention, and reduce fatigue (Brams et al., 2016).
However, this mechanism of action can also lead to a number of side effects, including decreased appetite, insomnia, increased heart rate, and increased blood pressure (Brams et al., 2016). In addition, long-term use of Adderall can deplete the levels of certain vitamins and minerals in the body, leading to deficiencies that can contribute to a number of health problems (Zimmerman & Cerda, 2018).
Effects on Neurochemistry
Adderall’s effects on the brain’s neurochemistry are well documented. By increasing the levels of dopamine and norepinephrine, it leads to improved focus and motivation. However, excessive use of Adderall can lead to changes in the brain’s reward system, leading to addiction and decreased sensitivity to natural rewards (Volkow et al., 2011). Adderall has also been shown to have negative effects on the brain’s ability to regulate emotion, leading to increased anxiety and irritability (Schreiner & Dunn, 2011).
In addition to its effects on dopamine and norepinephrine, Adderall can also affect other neurotransmitter systems in the brain, including the serotonergic and glutamatergic systems (Brams et al., 2016). Serotonin is involved in the regulation of mood and appetite, while glutamate is involved in learning and memory (Brams et al., 2016). By affecting these neurotransmitter systems, Adderall can also contribute to the side effects of decreased appetite, insomnia, and anxiety (Brams et al., 2016).
Use of Adderall in Chronic Fatigue Syndrome (CFS), Myalgic Encephalomyelitis (ME), and Post-Viral Fatigue
Chronic Fatigue Syndrome (CFS) and Myalgic Encephalomyelitis (ME) are conditions characterized by persistent fatigue, headaches, and muscle pain, among other symptoms. While the exact cause of these illnesses remains unknown, they are thought to be related to a combination of genetic, environmental, and viral factors (Carruthers et al., 2011).
Individuals with CFS and ME often experience post-viral fatigue, in which the body’s ability to produce energy is diminished (Nijs et al., 2016). Post-viral fatigue is a condition characterized by persistent fatigue and decreased energy levels following a viral infection. While the exact mechanisms behind post-viral fatigue are not well understood, several factors have been proposed to contribute to this condition.
One theory suggests that post-viral fatigue is related to alterations in the immune system and chronic low-grade inflammation (Lloyd et al., 2004). Following a viral infection, the immune system mounts a response to clear the virus, but this response can be prolonged in some individuals, leading to ongoing inflammation and fatigue.
Another theory involves alterations in the central nervous system, including changes in neurotransmitter levels and activity (Nijs et al., 2016). For example, some studies have found that individuals with post-viral fatigue have decreased levels of neurotransmitters such as serotonin and norepinephrine, which play a role in regulating energy levels and mood (Lloyd et al., 2004).
In addition, changes in the levels of hormones such as cortisol, which helps regulate the stress response, have been observed in individuals with post-viral fatigue (Lloyd et al., 2004). It is possible that these changes contribute to the persistent fatigue and decreased energy levels seen in post-viral fatigue.
Nutritional Deficiencies
Adderall can lead to a number of nutritional deficiencies in the body, as it can interfere with the absorption and metabolism of various vitamins and minerals (Wigal, 2009). Some of the key vitamins and minerals that are affected by Adderall use include vitamin B6, magnesium, and iron (Wigal, 2009). These deficiencies can lead to a number of side effects and health problems, including fatigue, weakness, and anemia (Wigal, 2009).
Vitamin B6 is involved in a number of important functions in the body, including the production of neurotransmitters and the metabolism of amino acids (Wigal, 2009). Adderall use can interfere with the absorption and utilization of vitamin B6, leading to deficiencies that can contribute to a range of symptoms, including fatigue, irritability, and insomnia (Wigal, 2009).
Magnesium is another nutrient that is commonly depleted by Adderall use, as it is involved in a number of important processes in the body, including the regulation of muscle and nerve function, the metabolism of energy, and the maintenance of healthy bones (Wigal, 2009). Adderall use can interfere with the absorption and utilization of magnesium, leading to deficiencies that can contribute to a range of symptoms, including muscle weakness, cramps, and fatigue (Wigal, 2009).
Iron is another nutrient that is affected by Adderall use, as it is involved in the production of hemoglobin, the molecule that carries oxygen in the blood (Wigal, 2009). Adderall use can interfere with the absorption and utilization of iron, leading to deficiencies that can contribute to anemia, a condition in which the body does not have enough red blood cells to carry oxygen to the body’s tissues (Wigal, 2009).
Adderall use can also deplete levels of vitamin C. Vitamin C plays a crucial role in maintaining a healthy immune system and is also involved in the absorption of iron. When vitamin C levels are low, iron absorption may be hindered, leading to iron deficiencies and the associated symptoms of fatigue, weakness, and anemia.
Vitamins, Minerals, and Supplements to Mitigate Side Effects
To counteract these deficiencies and mitigate side effects, there are several vitamins, minerals, and supplements that can be taken to support overall health and wellbeing. Some of the key vitamins, minerals, and supplements that may be helpful include:
Vitamin B6:
Vitamin B6 plays a crucial role in brain function, and can help to mitigate some of the neurological effects of Adderall use. Vitamin B6 can be found in foods such as potatoes, bananas, and chicken, and is also available in supplement form.
Magnesium:
Magnesium is an essential mineral that is involved in numerous bodily processes, including muscle and nerve function. Adderall use can deplete magnesium levels, leading to side effects such as anxiety, irritability, and fatigue. Magnesium can be found in foods such as almonds, cashews, and spinach, and is also available in supplement form.
Iron:
Iron is essential for the production of red blood cells, and can help to counteract the fatigue that can occur as a result of Adderall use. Iron can be found in foods such as red meat, poultry, and spinach, and is also available in supplement form.
GABA:
GABA (gamma-aminobutyric acid) is a neurotransmitter that plays a crucial role in regulating mood, anxiety, and sleep. Adderall use can disrupt GABA function, leading to side effects such as anxiety, irritability, and insomnia. GABA is available in supplement form and may help to counteract these effects.
L-Theanine:
L-Theanine is an amino acid that is found in tea leaves and is known for its calming and relaxing effects. Adderall use can lead to increased anxiety and stress, and L-Theanine may help to counteract these effects. L-Theanine is available in supplement form and has been shown to improve mood and cognitive performance.
Omega-3 fatty acids:
Omega-3 fatty acids are essential fatty acids that play a crucial role in brain function, and can help to counteract some of the neurological effects of Adderall use. Omega-3 fatty acids can be found in foods such as fatty fish, flaxseeds, and chia seeds, and are also available in supplement form.
Vitamin C:
Vitamin C is an essential vitamin that is involved in maintaining a healthy immune system, as well as in the absorption of iron. Adderall use can deplete vitamin C levels, which in turn can lead to iron deficiencies. Vitamin C can be found in foods such as citrus fruits, strawberries, and bell peppers, and is also available in supplement form.
Other Implications
With post-viral fatigue on the rise as a result of the pandemic, and the number of ADHD diagnoses steadily increasing, there has been an increased demand for Adderall. This increased demand has been suggested to be one of the causes of the recent Adderall shortage, as manufactures are limited on the amount of the drug they can produce. As a result, patients are making the switch to alternative medications, such as Vyvanse or Ritalin, which function in a similar manner but come with their own unique sets of side effects. Many people have also noticed subtle differences between generic and name brand Adderall, some of which include reactions to the different fillers and dyes, reports of varying levels of effectiveness, and headaches.
References
Aarts E, Ederveen THA, Naaijen J, Zwiers MP, Boekhorst J, Timmerman HM, Smeekens SP, Netea MG, Buitelaar JK, Franke B, van Hijum SAFT, Arias Vasquez A. Gut microbiome in ADHD and its relation to neural reward anticipation. PLoS One. 2017 Sep 1;12(9):e0183509.
Aizpurua-Olaizola, O., Soydaner, U., Öztürk, E., Schibano, D., Simsir, Y., Navarro, P., and Usobiaga, A. (2018). Evolution of the phenolic content in free and bound forms along the cheese-making process of raw milk from starter cultures with Lactobacillus helveticus and Propionibacterium freudenreichii. Food Chemistry, 241, 454-464.
Baumeister, R. F., & Shams, L. (2010). Is there a hidden source of willpower? Journal of Personality and Social Psychology, 98(2), 517-523.
Biederman, J., & Farone, S. V. (2005). Attention-deficit/hyperactivity disorder in adults. Journal of Clinical Psychiatry, 66 (Suppl. 3), 3-6.
Brams, M., Faries, D. E., Montouris, G., Ades, J., & Kirsh, B. (2016). The Role of Dopamine in the Pathophysiology of Attention-Deficit/Hyperactivity Disorder and the Pharmacology of Stimulant Drugs. CNS Drugs, 30(4), 325–342.
Carabotti, M., Scirocco, A., Maselli, M. A., & Severi, C. (2015). The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems. Annals of gastroenterology, 28(2), 203–209.
Carruthers, B. M., Jain, A. K., De Meirleir, K. L., Peterson, D. L., Klimas, N. G., Lerner, A. M., Goldstein, J. (2011). Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols. Journal of Chronic Fatigue Syndrome, 11(1), 7–115.
DEA. (2021). Controlled Substances – Alphabetical Order.
Kang, J. H., & Leckie, R. L. (2014). Vitamin and mineral supplements in the primary prevention of cardiovascular disease and cancer: An updated systematic evidence review for the US Preventive Services Task Force. Annals of Internal Medicine, 160(12), 806-814.
Lloyd, A. R., Wakefield, D., Boughton, C., Dwyer, J., Carruthers, K. M., & Bleijenberg, G. (2004). Immune System Changes in Chronic Fatigue Syndrome and Their Pathophysiological Significance. Journal of Chronic Fatigue Syndrome, 11(1), 5–20.
Nijs, J., Meeus, M., Moorkens, G., Van Oosterwijck, J., De Meirleir, K., & Duquet, W. (2016). Post-Viral Fatigue Syndrome and Chronic Fatigue Syndrome Are Distinct Clinical Entities. Current Rheumatology Reports, 18(4), 13.
O’Brien, C. S., McCarty, D., & Harrell, P. T. (2016). Nonmedical use of prescription stimulants among US college students: Prevalence and correlates from a national survey. Substance Abuse and Rehabilitation, 7, 9-17.
Schreiner, A. M., & Dunn, D. W. (2011). A review of the literature on the factors associated with prescription stimulant use and misuse among college students. Journal of American College Health, 59(6), 463-471.
Volkow, N. D., Wang, G. J., Telang, F., Fowler, J. S., Logan, J., Ma, Y., … Wong, C. T. (2006). Evaluating dopamine reward pathway in ADHD: Clinical implications. Brain Research Reviews, 51(1), 93-102.
Volkow, N. D., Wang, G. J., Telang, F., Fowler, J. S., Logan, J., Ma, Y., … Wong, C. T. (2011). Methamphetamine exposure decreases dopamine transporters in human brain: Implications for drug-induced neurotoxicity. Synapse, 65(8), 705-710.
Wigal, S. B. (2009). Adderall XR: A Review of the Effects of the Extended-Release Formulation of Amphetamine on Attention Deficit Hyperactivity Disorder Symptoms, Sleep, and Cardiovascular and Gastrointestinal Safety. CNS Drugs, 23(12), 1011–1024.
Yokogoshi, H., & Kimura, K. (1998). The effects of theanine, r-glutamylethylamide, on brain neurotransmitters and neurotransmitter receptors in rats and mice. Neurochemical Research, 23(3), 667–673.
Zimmerman, M., & Cerda, G. (2018). Vitamin and Mineral Deficiencies in Attention Deficit Hyperactivity Disorder. Clinical Psychopharmacology and Neuroscience, 16(3), 250–257.
