Modafinil is a drug developed for the treatment of extreme lethargy. Despite being
proven its effectiveness in the intervention of sleep disorders, there is still controversy
whether it can improve subject performance in higher cognitive processes, such as
memory and executive functions.

This randomized, crossover, double-blind, placebo-controlled clinical trial; it was designed
to evaluate the effect of Modafinil compared to a placebo, on the cognitive functions of
healthy college students. 162 volunteers were recruited, randomly assigned to a group
Modafinil or a placebo consumption group. Both groups were evaluated using
the Stroop Test, the Cognitive Estimation Biber Test and the Digit Span Test
digits). After 15 days, they were assigned to the other intervention

Modafinil (-2-[(difenil)methylsulfinil]acetamide) is a psychostimulant with wakefulness-promoting properties, which was already available for commercial use in France in the 1990s [1]. It has demonstrated particular effectiveness in the treatment of lethargy and sleep disorders [

Some authors state that Modafinil increases performance in tasks associated with cognitive functions such as working memory, visual health care and executive functions. For others, Modafinil improves cognitive performance in healthy sleep deprived adults, but only in regard to attentional and alert functions [8],[9].

Its primary mechanism of action is unknown [15], although its effects have been demonstrated in different neurotransmitter systems

The use of stimulants to improve academic performance has increased in the young population in the United States [22]. More than seven million Americans employ wake-up stimulants, and approximately 1.6 million of these people are students[23],[24]. An online survey of more than 1400 people from sixty countries showed that 20% of respondents had ever used a psychoactive drug to improve their concentration or memory and 44% of them had used Modafinil. Students between the age of 18 and 25 [25] are the population most often associated with the use of stimulants to improve attention and memory.

There are no formal studies reporting the use of Modafinil among students in Chile. However, some media surveys report an increase in stimulant consumption in students between the age of 19 and 25, with the highest levels of consumption concentrated during the final exam periods of the courses [26],[27].

Effect of Modafinil on attention
Most of the research conducted on healthy adults to assess whether stimulants improve cognitive performance has produced conflicting or inconclusive results [28]. Although Modafinil plays a key role in certain cognitive functions such as attention [29],[30] and tasks that demand a certain level of performance, it seems to have little effect when a higher demand is added [31].

Trials that have evaluated attention in adults demonstrate advantages among those who consume Modafinil compared to those who consume placebo, in terms of attention using the Stop-Signal Task [29], but this result appears to be closely associated with the subject’s IQ.

A study in young volunteers also found evidence of a positive effect on the Attention Shift Task, after intake of Modafinil. It seems to facilitate rapid shifting of care in demanding conditions, although it offers minimal benefit when unpredictable and infrequent care unhook is required to respond to an alternative stimulus in a concurrent task.

A clinical trial with 45 participants without sleep deprivation found no conclusive results regarding attentional performance, possibly due to the small sample size [33]. This finding shows that the evidence in favor of Modafinil as an attentional optimizer is ambiguous.

This is why it becomes relevant to investigate the role that this substance plays in relation to certain attentional phenomena. In particular with regard to selective attention (inhibition of a response to irrelevant information), which is a key process in learning [34]. This dimension of attention has been selected in this research, due to the fact that impairments in selective care among secondary and tertiary students have been shown to be accompanied by low information processing and learning capacity, and therefore poor academic performance [35].

Executive functions and memory
Studies that have aimed to prove that Modafinil can improve performance in higher cognitive processes such as memory and executive function in healthy participants have yielded conflicting results [29],[30],[33],[36]. So far there have been no systematic reviews of its impact.

The ambiguity of these previous findings motivated this research. The goal was to evaluate the effects of Modafinil on the cognitive performance of college students, particularly in terms of short-term memory, executive functions and attention.


This randomized, double-blind, placebo-controlled, crossover-designed trial was designed to evaluate the effect of Modafinil on the cognitive functions of healthy students. It was held at the University of Valparaiso, Chile. The protocol was approved by the Ethics Committee of the Faculty of Medicine of the University of Valparaiso, under authorization code 04/2010 CEFM and was registered on the Clinical Trials ( website under CNT code 01365897.

Eligible participants included health students between the ages of 18 and 29. They were summoned using open notices on a website. Thus, medical and psychology students (No. 180) of both sexes were contacted, recruiting those who met the criteria of inclusion (No. 162). The minimum sample size was 155 subjects considering significance level p.0.05, power of 0.80 (1-beta), expected difference from 19 to 19.15 and a possible loss of 20%.

Significance level of p-0.05.
Power (1-Ī²) of .0.80.
Expected difference from 19 (SD-0.7) to 19.25 (SD-0.7) and a possible loss of 20%.
The inclusion criteria were:

a) Age between 18 and 29 years: This age range was chosen because there is a cognitive impairment of 1% of the total IQ between the ages of 25 and 29 [37]. The purpose of this criterion was to work with a sample without cognitive impairment, as this could modify the performance of the volunteers.

b) Be a student of health careers at the University of Valparaiso.

c) Have a healthy weight. The reason behind this criterion is that all volunteers received the same dose of Modafinil. Therefore, subjects outside this range could have generated different plasma levels.

The exclusion criteria were:

a) Mental disorders. Evaluated according to the subject’s medical history or by obtaining a pathological significance score in the Primary Care Evaluation of Mental Disorders (Prime-MD) questionnaire [38].

b) Current use of psychotropic substances of any kind.

c) Alcohol consumption up to three days before the experiment.

d) History or symptoms of current chronic physical illness.

e) Be pregnant or breast-feeding.

f) Be deprived of sleep.

Outcome measures
The main result was the attention score, expressed according to the proportion of correct stroop test responses. Additional analyses were conducted that compared the percentage of correct responses and response latency in this test, in the digit amplitude task, and in the Biber Cognitive Estimation Test (BCET) between the two groups.

Participants were recruited from several cohorts of the aforementioned races, without receiving financial compensation. They signed the corresponding informed consent and answered the Primary Care Evaluation of Mental Disorders, a self-administered questionnaire used to assess possible psychiatric conditions. Subsequently, they were briefly interviewed to check for the presence of any other exclusion conditions related to sleep deprivation and substance intake (psychotropic drugs or alcohol use). Those who did not meet any exclusion criteria were deemed eligible to participate in the investigation.

Once the final sample was defined, the volunteers were quoted in randomly formed groups in shifts of twenty people to perform the tests simultaneously. This is intended to ensure that the tests were properly applied, according to the conditions and capacity of the computer room of the School of Psychology of the University of Valparaiso, and to achieve adequate plasma levels of Modafinil during the administration of the tests [39].

The assignment of participants to each arm (group that received one of the two substances) was done randomly through a computer program and the sequence was hidden by the principal investigator. On the first day, participants received substance A or substance B, which corresponded to 200 mg of Modafinil or placebo (placebo grageas that were manufactured at the University School of Chemistry and Pharmacy with the same shape and color of Modafinil gragea used in the experiment).

Volunteers were evaluated with the instruments 120 minutes after administration of the graph to reach the highest possible plasma level [39]. The first experimental phase evaluated attention and executive functions using the Stroop Test and the Biber Cognitive Estimation Test, respectively. Short-term memory was then evaluated using the Digit Span test. These tests were administered on computers using the MediaLabĀ© (New York, United States) program. After a seven-day period of wash out to allow plasma clearance of Modafinil, participants returned and were assigned to the other group [39]. Thus, each person received both Modafinil and placebo during the trial.

Stroop Test [40]: The Iowa Stroop Test was used in a computerized adaptation through the Medialab program. This test requires participants to read color names (blue, green, red, and yellow) that are displayed in different colors (blue, green, red, and yellow). Your task is to identify the color of the word by neglecting the meaning of the word. There are two conditions: a congruent, in which the name of the color and the color of the letters match; and an incongruous one, in which the name of the color and color of the letters are different. The recorded variables were response accuracy (correct color identification) and response latency (in milliseconds). This logging method delivered two types of measures: precision and latency, both for the congruent and incongruous conditions.

The Stroop Test primarily evaluates selective attention, since the subject must ignore the distracting stimulus in the incongruous situation. According to a systematic review [41], the Stroop Test has been the most widely used instrument to evaluate this cognitive function.

Digit Span in normal and inverted order [37]: This test consists of a series of digits presented to the volunteer that measures short-term memory amplitude, attention, and the ability to form sequences. The test consists of two sections: normal and inverted. In the normal section, the stimulus should be repeated in sequence. In the reversed section, the stimulus must be repeated in reverse order. The maximum rating for the first section is 8 points and the maximum of the second section is 7, which yields a total maximum score of 15. This measurement has a high split-half reliability (r-0.89) [42] and acceptable test-retest reliability (r-0.80) [43].

The Biber Cognitive Estimation Test (BCET) [44]: consists of twenty items, five of each of the following categories: time/duration, quantity, weight and distance/length. The test requires participants to submit values to questions for which they have no answers prepared. For example, the question “What is the length of an average man’s spinal cord?” requires the participant to select an appropriate answer and estimate its plausibility, but does not require a complex calculation [45]. Each response that falls within a preset range receives a point. The maximum score for this test is 20 points.

Data design and analysis
A randomized crossover design was chosen, which is based on the advantage of each participant acting as their own control. The mapping sequence was hidden by the lead researcher from volunteers, executors, and data analysts.

Based on the methodological design used, Student’s t-test was used to compare paired sample means. Specifically, the analysis compared the means obtained for each item in the experimental condition and in the placebo condition. Statistical analyses were conducted with the Stata 12.0 program (Statacorp, College Station, Texas, United States). The level of significance considered was p<0.05.

Papers and Bibliography:

Randall DC, Viswanath A, Bharania P, Elsabagh SM, Hartley DE, Shneerson JM, et al. Does modafinil enhance cognitive performance in young volunteers who are not sleep-deprived? J Clin Psychopharmacol. 2005 Apr;25(2):175-9. Info here.

Randall DC, Shneerson JM, File SE. Cognitive effects of modafinil in student volunteers may depend on IQ. Pharmacol Biochem Behav. 2005 Sep;82(1):133-9. Info here.

Spitzer RL, Kroenke K, Williams JB. Validation and utility of a self-report version of PRIME-MD: the PHQ primary care study. Primary Care Evaluation of Mental Disorders. Patient Health Questionnaire. JAMA. 1999 Nov 10;282(18):1737-44. Info here.

Turner DC, Robbins TW, Clark L, Aron AR, Dowson J, Sahakian BJ. Cognitive enhancing effects of modafinil in healthy volunteers. Psychopharmacology (Berl). 2003 Jan;165(3):260-9. Info here.