1. Introduction

5,6,7,8, Attention-deficit/hyperactivity disorder (ADHD) is a chronic disorder characterized by developmentally inappropriate levels of inattention and/or hyperactivity-impulsivity that affects approximately 3–10% of school age children and adolescents [ 1 ]. Research indicates that increasing numbers of high school students with ADHD are pursuing college and in a recent national survey, 6.4% of male and 3.9% of female freshman reported having ADHD [ 2 ]. College students with ADHD are entitled by the American Disabilities Act to receive educational support services, and approximately 25% of college students receiving disability support services receive services for ADHD. This percentage has increased substantially since 1975 [ 3 ]. The prognosis for college students with ADHD varies across studies, but most suggest that college students with ADHD are at increased risk for academic problems, executive function deficits, lower grade point average, compromised academic coping skills, and higher than average risk for psychological and interpersonal difficulties [ 4 9 ]. A number of non-pharmacological treatments are available for ADHD (e.g., behavioral support therapies, cognitive-behavior therapy, biofeedback) and studies attest to their varying effectiveness. To date, however, the majority of ADHD treatment outcome studies have shown that, in general, the most effective treatment for reducing ADHD symptoms is stimulant medication (e.g., amphetamine, methylphenidate) although questions remain regarding the magnitude of these effects given various methodological problems in the literature [ 10 ]. Questions also remain regarding the extent to which placebo effects and responding contributes to observed improvements in cognitive and behavioral functioning in children and adults. For example, Fageera and colleagues [ 11 ] recently found a significant placebo response in both parents and teachers of children with ADHD during a randomized, placebo controlled clinical trial of methylphenidate with more robust effects observed in parents than teachers. Mateeton et al. [ 12 ] reported that lisdexamfetamine (LDX) is efficacious and well tolerated in the treatment of ADHD in adults, however its acceptability is no higher than placebo. With respect to college students, Weyandt and colleagues [ 13 ] were the first to demonstrate the effectiveness and safety of lisdexamfetmaine dimesylate (LDX; Vyvanse) in college students with ADHD in the context of a double-blind, placebo-controlled crossover study. Specifically, DuPaul and colleagues [ 14 ] and Weyandt et al. [ 13 ] found that lisdexamfetmaine dimesylate was effective at reducing ADHD symptomatology and at improving cognitive skills, including executive functions, in college students with documented ADHD.

Although prescription stimulants are often highly effective in reducing ADHD symptoms, non-medical use of prescription stimulants among college students without the disorder has become increasingly problematic in recent years. Non-medical use, or misuse, of stimulants has been defined as taking stimulants without a valid prescription and/or use of stimulants other than as prescribed [ 13 15 ]. Over a decade ago, Babcock and Byrne [ 16 ] surveyed 283 students regarding misuse of prescription stimulants and found that 16% of the sample reported taking Ritalin for “fun”; yet, less than 2% of the sample had a current prescription for Ritalin. McCabe, Knight, Teter, and Wechsler [ 17 ] found that 6.9% of college students surveyed reported lifetime misuse of prescription stimulants. Further, DuPont et al. [ 18 ] found the most frequently reported motive for misuse of stimulant medication was to “work/study” and to “party.” Similarly, Weyandt et al. [ 19 ] Judson and Langdon [ 20 ], and Bossaer et al. [ 21 ] found that college students who misused prescription stimulants did so to enhance cognitive functioning, such as concentration, and to increase alertness or to stay awake. In a systematic review of 22 studies, Weyandt et al. [ 13 ] found that 5–35% of college students surveyed had misused prescription stimulants primarily for neurocognitive enhancement. Other reasons commonly reported by students include recreational use (e.g., partying, pharming, weight loss) and some students (40%) appear to misuse prescription stimulants for both cognitive enhancement and recreational purposes [ 15 ]. Munro, Weyandt, Marraccini, and Oster [ 22 ] recently studied college students from six public universities located in various regions of the United States and reported that students with clinically significant executive function deficits reported significantly higher rates of prescription stimulant misuse. Prescription stimulant misuse has also been reported among college students in other countries including Germany [ 23 ], Iceland [ 24 ], Switzerland [ 25 ], and the United Kingdom [ 26 ] with rates similar to those found in the USA. Interestingly, and similar to results from studies conducted in the USA, Gudmundsdottir and colleagues [ 24 ] found that ADHD symptomatology and anxiety was significantly associated with prescription stimulant misuse behavior. Other international studies have reported similar findings [ 27 ] underscoring that this behavior is present across cultures.

Contrary to student expectations and beliefs, prescription stimulants may not lead to neurocognitive enhancement and improved academic performance [ 15 ], as stimulant misuse has been found to be negatively correlated with academic functioning [ 13 28 ]. Weyandt and colleagues [ 13 ] emphasized that empirical studies are needed to determine whether stimulants are truly neurocognitive enhancers for college students without ADHD. Ilieva, Boland, and Farah [ 29 ] explored both the objective and subjective effects of amphetamines on cognition among healthy adults and did not find support for significant effects of amphetamine on episodic memory, working memory, inhibitory control, creativity, intelligence and scholastic achievement. Participants, however, did report perceived neurocognitive enhancement suggesting a placebo effect likely accounted for the perceived cognitive enhancement. In contrast, Smith and Farah [ 30 ] conducted a review of studies investigating neurocognitive effects of prescription stimulants in healthy adults and reported that both amphetamine and methylphenidate were associated with overall improvements (accuracy and/or speeded responses) in response inhibition tasks as well as perceptual motor and delay rewards tasks. Interestingly, however, stimulants were found to impair performance on tasks of response inhibition requiring cancellation (i.e., stop signal tasks), cognitive flexibility (i.e., Intra-Extra Dimensional Set-shift Task, Wisconsin Card Sorting Task), trail-making tasks and reversal learning tasks. Amphetamine can induce reductions and increases in incentive-related risk behavior, depending on the individual being tested [ 31 ]. As Marraccini, Weyandt, Rossi, and Gudmundsdottir [ 32 ] (noted, these findings suggest that baseline performance is a crucial moderator and depending on baseline levels, stimulants may result in improvement or worsening of cognitive functioning and those with lower baseline functioning may derive the greatest benefits. Other studies, however, have reported mixed findings with healthy adults, with some supporting positive and large effects of methylphenidate on both immediate and delayed working memory and episodic memory [ 33 ] as well as processing speed [ 32 ]. In summary, some preliminary evidence suggests that healthy adults without ADHD may receive small to moderate cognitive benefits from prescription stimulant medication (e.g., Adderall) in the areas of working memory, response inhibition, processing speed, and delayed memory; however, questions remain regarding the effects of prescription stimulants on measures of attention, executive function (e.g., decision making, verbal fluency, and planning) and other aspects of cognition. A dearth of information exists regarding the potential effects of Adderall on mood and self-perceived cognitive enhancement effects of Adderall.

37, The acute neurocognitive effects of Adderall will be best understood in the larger context of the drug’s concurrent effects on emotion, subjective state, and self-perceived cognitive ability. These domains are readily evaluated by self-report measures such as the Drug Effects Questionnaire, which evaluates subjective ratings of drug liking and drug high [ 34 ]; the Positive Activation scale, which evaluates the presence and intensity of activated emotion such as elation and euphoria [ 35 ]; and the Perceived Drug Effect Self-Report scale, a measure of that evaluates personal perceptions of whether one’s cognitive ability has improved after drug consumption [ 29 ]. Psychostimulant-induced changes in activated positive emotion, subjective drug responses, and autonomic activation are typically large in size [ 36 38 ], with a smaller evidentiary base regarding psychostimulant drug effects on self-perceptions of cognitive functioning [ 29 ]. Very few studies evaluate Adderall effects on neurocognitive function in the context of drug-induced changes in activated emotion, subjective drug experience, autonomic activation, and changes in meta-cognition. Joint assessment of Adderall effects on neurocognition, mood, activation, and perceived cognitive enhancement would thus provide important and highly novel information through which to better understand the potential effects of Adderall on neurocognition as opposed to other outcomes that may affect drug choice behavior.

Given that misuse of prescription stimulants is widely reported on college campuses for the purpose of neurocognitive enhancement, and that students typically view these drugs as safe, research is sorely needed to empirically address the joint neurocognitive and meta-cognitive activational effects of prescription stimulants in college students without ADHD. Therefore, the purpose of the present pilot study was to explore: (a) the potential effects of the prescription stimulant Adderall on the cognitive performance of healthy college students without ADHD in the areas of memory, reading comprehension, sustained attention, impulsivity, and executive function relative to placebo; and (b) concomitant effects of Adderall on autonomic activation, subjective drug responses and activated emotion in healthy college students without ADHD. This approach provides an empirical test of Adderall effects on cognitive function, emotion and autonomic activity, and concurrent estimates of drug impact on each outcome. We hypothesized that participant performance on measures of cognition would be significantly enhanced after ingestion of Adderall compared to placebo. Specifically, we expected enhanced performance after Adderall (30 mg) compared to placebo for (1) reading comprehension; (2) working memory; (3) executive function; and (4) greater self-perceptions of performance on cognitive tasks. Understanding potential effects of stimulants on these outcomes is important for prevention efforts and mitigating prescription drug misuse among healthy college students.