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Adderall Abuse and its Implications for the College Academic Community

By Nahel Kapadia

Published on February 8, 2012

FtWashGuy/Wikimedia Commons

Figure 1: Adderall XR extended release pills with amphetamine salts.

Background

Adderall is a psychostimulant used in the treatment of attention-deficit hyperactive disorder (ADHD) and narcolepsy. Although it has been approved for medical use, Adderall is increasingly being abused among college students as a "study drug" to increase mental concentration and alertness [1].

Medical Uses of Adderall

Adderall is commonly prescribed to patients who have difficulty controlling their actions, maintaining focus, or staying awake. It contains the active ingredients dextroamphetamine and levoamphetamine, both of which are psychostimulant amphetamine molecules. Adderall was first introduced into the public in 1996 as an instant-release (IR) drug by Shire Pharmaceuticals. In 2006, a new version, Adderall extended release (XR), was made available as well (see Figure 1) [2]. While the instant-release drug requires 3 hours to reach its maximum plasma concentration after consumption, the extended release version takes 7 hours to do so [3]. Known side effects of Adderall include insomnia, loss of appetite, nausea, and hallucination. Adderall has been found to be addictive and dangerous to the health of some patients. Several withdrawal symptoms include panic attacks, seizure, fatigue, and depression [2].

The Chemistry and Mechanisms Behind Adderall

The structure and action of Adderall resembles that of recreational drugs such as methamphetamine (also known as crystal meth) and MDMA (3,4-Methylenedioxymethamphetamine) (also known as ecstacy). Adderall is a phenylalkylamine, consisting of a phenyl ring and nitrogen group. The molecular resemblance of Adderall to catecholamine neurotransmitters (epinephrine, norepinephrine, and dopamine) underlies the similarities in physiological function between Adderall and these natural neurotransmitters [4].

Sarah Waliany/USCience Review

Figure 2: The amphetamine salts in Adderall have the ability to directly stimulate catecholamine receptors. They also can increase concentration of catecholamines in the synapse by blocking monoamine transporters to prevent reuptake of catecholamine back into the presynaptic neuron and by participating in a "reverse-transport" reaction with the monoamine transporters.

The amphetamines in Adderall can bind to receptors that are normally activated by specific catecholamines produced by different glands in the body (including the hypothalamus and adrenal medulla). Amphetamine can also result in the release of more neurotransmitters that can activate sensory regions throughout the nervous system. When these psychostimulants activate receptors in the brain, the emotional response consists of euphoria, insomnia, increased alertness, and, sometimes, anxiety or psychosis. Peripherally, the binding of amphetamine compounds to catecholamine receptors can result in a physical response that may include the vasoconstriction of blood vessels, tachycardia, and hypertension [4, 5].

In addition to stimulating the release of catecholamines, the amphetamines in Adderall also inhibit the function of monoamine transporters, which function in the re-uptake and recycling of catecholamine neurotransmitters in order to terminate the neural signal by removing the neurotransmitters from the synapse. In effect, Adderall stimulates sensory systems by maintaining the concentration of neurotransmitter in the synapse. Adderall also partakes in a "reverse-transport" or efflux process in which the amphetamines are transported from the synapse through the transporters into the presynaptic neurons and the catecholamines are simultaneously transported from the presynaptic neurons through the transporter into the synapse (see Figure 2). This leads to an increased concentration of neurotransmitters in the synapse, allowing them to trigger receptors and activate the neuropsychological effects mentioned above. Finally, amphetamine and its analogs also enhance the synaptic neurotransmitter concentration by acting as competitive inhibitors of monoamine oxidase (MAO), an enzyme that breaks down monoamine neurotransmitters [4].

Potential for Abuse

As a Schedule II drug, Adderall has high risk for dependence and addiction. It is hypothesized that the addictive characteristics of Adderall are due to the activation of the mesolimibic dopaminergic pathway, in which the amphetamine in the drug binds to the transporter of the neurotransmitter dopamine to prevent removal of dopamine from the synaptic cleft [6]. By prolonging the presence of dopamine in the synapse, amphetamine produces the long-lasting side-effects of euphoria, pleasure, and concentration. In addition, the highly connected neural circuits in the central nervous system can transport dopamine from one part of the brain to another, resulting in the proliferation of the chemical signal [7].

Adderall abuse can also cause dangerous physiologic effects such as hypertension, seizures, and mydriasis (dilation of the pupil). Increase in blood pressure is thought to be caused by the continued release of norepinephrine. The constant stimulation of nerve receptors is the mechanism behind Adderall addiction. With continued use over time, a tolerance is developed to Adderall, as seen with other addictive drugs as well – the more frequently these drugs, including Adderall, are used, the greater the amount that is needed to supply a response [2]. The reinforcement behavior produced by Adderall can eventually cause long-term dependence.

In a study conducted by Surles et al., it was found that under some circumstances, Adderall can induce psychosis in adolescents comparable to schizophrenia. Though the precise mechanism is not clear, it is possible that this effect is due to an increased amphetamine-induced dopamine release. The symptoms cleared in patients who withdrew from using Adderall [8].

The chemical similarity between natural neurotransmitters in the body and Adderall increases both the likelihood and degree of abuse. Thus, until the risks of psychostimulants are understood in more detail, it is advisable to remain cautious about prescribing Adderall to those with ADHD.

Adderall in Academia

Given the effectiveness of Adderall as a “study drug,” the stimulant is becoming increasingly common in collegiate lifestyles. The National Survey on Drug Use and Health (NSDUH) reports that 15% of college students have admitted to using some form of psychotherapeutic drugs for non-medical use. Of those 15%, 7% have claimed to use Adderall to either increase attention span, party, or improve grades. The survey found that college students most likely to abuse Adderall were male, Caucasian, fraternity and sorority members, and students with lower grade point averages [9].

Between 1993 and 2003, the number of prescriptions given for Adderall has more than tripled [10]. However, not all of the Adderall obtained by college students is prescribed. In fact, about 14% of students note that they have been asked to sell, trade, or distribute Adderall, while only 2% actually have a prescription from their doctor [10]. The relative ease with which students are able to obtain Adderall has played a major role in reinforcing this “epidemic.” For example, physicians and psychiatrists ask a series of questions before providing a prescription for Adderall. These questions (for instance, “How well do you do in your college courses?”) are fairly straightforward, and the answers are obvious. In one study, about 95% of students “were able to obtain a false diagnosis of ADHD by faking symptoms on one of the most commonly used self-reporting scales” [11]. The guidelines for prescribing psychostimulants such as Adderall, therefore, should be practically assessed and improved.

Student Justifications for Adderall Abuse

A study conducted in 2007 with 175 undergraduate students found that some view the continued, unprescribed use of Adderall as not only morally acceptable but also harmless [12]. Researchers cite four recurring arguments made by students who justify the nonmedical use of Adderall. First, students say claim that since Adderall is not illegal such as more deleterious drugs such as cocaine, methamphetamine, and ecstasy, its use must be relatively harmless. The second cited reason is that Adderall used in moderation does not pose any significant danger to health. The third justification is the self-medicating argument these students self-diagnose themselves with ADHD when they experience its known symptoms, such as difficulty concentrating, propensity to daydream, and boredom. Since these symptoms cease when they use Adderall, they believe must have ADHD. The fourth argument is the cultural minimization of the risk that Adderall poses. For example, students reduce the "serious nature of amphetamines by framing them as harmless, benign, and socially acceptable antifatigue aid." As per this argument, Adderall is comparable to coffee or energy drinks [12].

Students also commonly believe that the risks of prescription drug use are low to nonexistent [12]. In a study conducted by 'The Partnership for a Drug-Free America,' it was found that 40% of teens believed that prescription drugs are "much safer" to use than illegal drugs; 31% viewed "nothing wrong" with occasionally using a drug without a prescription; and 29% believed that prescription medications are not addictive. This lack of education and understanding of the dangers of abusing prescription drugs illustrates the relevancy and significance of the issue [13].

The Implications of Adderall Abuse

Despite students' attempts to justify use of Adderall, medical professionals have recognized and are alarmed by the dangerous effects of this drug even with patients with a correct ADHD diagnosis and legally acquired prescription. Between 2000 and 2005, the FDA found that Adderall and other similar drugs caused mania and psychosis with symptoms of hallucinations in about 1000 patients. In fact, physicians have been alerted to prescribe Adderall sparingly and are required by the FDA to give their patients a medication guide with warnings regarding the dangers of the drug's use [14].

NEUROtiker/Wikimedia Commons

Figure 3 (Click here to see enlarged image): Metabolism of dopamine by monoamine oxidase (MAO) takes place when monoamine transporters are able to reuptake dopamine into the presynaptic neuron. Since amphetamines block reuptake, this process does not take place in the presence of Adderall, thereby leading dopamine to be washed out out of the synapse and lowering the amount of available dopamine.

Students may mistakenly believe that they could revert to their normal lifestyle and neural function by stopping Adderall use. However, studies have shown that misuse of Adderall and long-term use can permanently alter and damage the brain [14]. Since the amphetamines are able to prevent the reuptake of catecholamines such as dopamine back into the presynaptic neuron, dopamine is able to remain in the synapse for some time and lead to increased activation of the receptors on the postsynaptic neuron. However, reuptake is necessary to metabolize dopamine back into its components so that they can be recycled into making dopamine again. Without this reuptake, the dopamine gets washed away, thereby eliminating its components from the neurons and lowering the concentration of this catecholamine in the neural system [15]. Thus, Adderall "tricks the brain that it doesn't need to make dopamine, and dopamine is the only chemical in the brain that once it is damaged, you never get it back," said Fallon Schultz, a licensed clinical social worker from New Jersey. Since dopamine is needed to control emotions and prevent aggression, "that results in severe depressions and mood dysregulation," which has caused high rates of aggression, psychosis, and suicide for many long-term users of Adderall, as shown by studies at UCLA [14, 15].

While opponents of Adderall use in an academic setting argue that the illicit usage of psychostimulants is equivalent to cheating and is unfair to students who do not rely on prescription drugs, one scientist proposes that "access to and [the] performance-enhancing use of Adderall merely reflects class disparity, and does not cause it" [16].

Many educators and researchers acknowledge the popularity of Adderall and other stimulant drugs among college students and believe that the best course of action would be to create a comprehensive drug abuse prevention program that both educates the college community and aims to decrease abuse in the long-term [17].

Works Cited

1. "Adderall." The American Society of Health-System Pharmacists. Available: http://www.drugs.com/monograph/adderall.html.

2. M. Collier. "Adderall: History, Uses, Side Effects, and Withdrawal." 2008.

3. Drug Information Online: Drugs.com. (2011.) "Adderall XR." Available: http://www.drugs.com/pro/adderall-xr.html.

4. K. Foley. (2005.) "Mechanism of Action and Therapeutic Uses of Psychostimulants." Clinical Laboratory Science. 18(2): pp. 107-13.

5. PubMed Health [Internet]. Dextroamphetamine and Amphetamine. Bethesda (MD): National Library of Medicine (US); [updated 2010 Aug 1; cited 2011 Nov 11]. Available from: http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000166/.

6. Genetic Science Learning Center, "Beyond the Reward Pathway," Learn.Genetics, 24 January 2011, [11 November 2011].

7. C. Teter, et al. (2006.) "Illicit Use of Specific Prescription Stimulants Among College Students: Prevalence, Motives, and Routes of Administration." Pharmacotherapy. 26(10): pp. 1501-10.

8. L. Surles, et al. "Adderall-induced psychosis in an adolescent." Journal of the American Board of Family Medicine. 15: pp. 498-500 (2002).

9. T. Workman, and G. Eells. (2010.) "Assessing the Risks and Issues: Prescription Drug Abuse on Campus." National Conference for Law and Higher Education. http://www.law.stetson.edu/conferences/highered/archive/media/higher-ed-archives-2010/assessing-the-risks-and-issues.pdf.

10. R.A. Sansone and L.A. Sansone. (2007.) "Prescription Psychostimulant Abuse." Psychiatry. 4(9): pp. 18-19.

11. S. Sweeny. (2010.) "The Use of Prescription Drugs for Academic Performance Enhancement in College Aged Students." Social Work Student Papers. http://digitalcommons.providence.edu/socialwrk_students/48.

12. A.D. Desantis and H. Audrey .(2010.) "Adderall is Definitely Not a Drug:" Justifications for the Illegal Use of ADHD Stimulants." Substance Use and Misuse. 45(1-2): pp. 31-46.

13. L. Manchikanti. (2006.) "Prescription Drug Abuse: What is Being Done to Address this New Drug Epidemic? Testimony before the Subcommittee on Criminal Justice, Drug Policy and Human Resources." Pain Physician. 9: pp. 287-321.

14. S.D. James. (2010.) "Adderall Abuse Alters Brain, Claims a Young Life." Available: http://abcnews.go.com/Health/MindMoodNews/adderall-psychosis-suicide-college-students-abuse-study-drug/story?id=12066619&singlePage=true#.TwKv-WDWZ97.

15. M. Coker. "This is your brain on Adderall." Available: http://www.ocweekly.com/2008-08-28/news/this-is-your-brain-on-adderall/, August 28, 2008 [December 28, 2011].

16. A. Radu. "Competitive Academic Culture and Cognitive Enhancement with Psychostimulants." UPenn Center for Bioethics Program. 2009.

17. J. Schiffner. "Harder, Better, Faster Stronger: Regulating Illicit Adderall Use Among Law Students and Law Schools." ExpressO. 2010. http://works.bepress.com/jennifer_schiffner/1.

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