title: Does Modafinil Enhance Cognitive Performance in Young Volunteers Who Are Not Sleep-Deprived? Cognitive enhancing effects of modafinil in healthy volunteers Functional magnetic resonance imaging neuroactivation studies in normal subjects and subjects with the narcoleptic syndrome. Actions of modafinil. Effect of Modafinil on Learning and Task-Related Brain Activity in Methamphetamine-Dependent and Healthy Individuals Modafinil combined with cognitive training is associated with improved learning in healthy volunteers – A randomised controlled trial Use of illicit and prescription drugs for cognitive or mood enhancement among surgeons Modulatory Effects of Modafinil on Neural Circuits Regulating Emotion and Cognition Effects of modafinil on working memory processes in humans Early markers of cognitive enhancement: developing an implicit measure of cognitive performance Modafinil Alters Intrinsic Functional Connectivity of the Right Posterior Insula: A Pharmacological Resting State fMRI Study The cognitive-enhancing properties of modafinil are limited in non-sleep-deprived middle-aged volunteers Modafinil improves rapid shifts of attention Modafinil affects mood, but not cognitive function, in healthy young volunteers. Motor excitability and motor behaviour after modafinil ingestion – a double-blind placebo-controlled cross-over trial Effects on cognition and mood in postmenopausal women of 1-week treatment with Ginkgo biloba Influence of modafinil on somatosensory input processing in the human brain-stem Comparing the Stimulant Effects of the H1-Antagonist Fexofenadine With 2 Psychostimulants, Modafinil and Methylphenidate Piracetam‐induced improvement of mental performance Behavioral and subjective effects of d-amphetamine and modafinil in healthy adults. A glucose-caffeine ‘energy drink’ ameliorates subjective and performance deficits during prolonged cognitive demand Increase in the power of human memory in normal man through the use of drugs
abstract: Abstract : In a double-blind , parallel groups study , 60 healthy student volunteers ( 29 men and 31 women , aged 19 - 22 years ) were r and omly allocated to receive placebo , 100 or 200 mg modafinil . Two hours later , in the early evening , they completed an extensive cognitive battery . The 3 groups did not differ in self-ratings of sleepiness or tiredness before the testing session , and there were no treatment-associated changes in these or in mood ratings during the tests . Modafinil was without effect in several tests of reaction time and attention , but the 200-mg group was faster at simple color naming of dots and performed better than placebo in the Rapid Visual Information Processing test of sustained attention . Modafinil was without effect on spatial working memory , but the 100-mg group performed better in the backward part of the digit span test . Modafinil was without effect on verbal short-term memory ( story recall ) , but 100 mg improved digit span forward , and both doses improved pattern recognition , although this was accompanied by a slowing of response latency in the 200-mg group . There were no significant effects of modafinil compared with placebo in tests of long-term memory , executive function , visuospatial and constructional ability , or category fluency . These results suggest that the benefits of modafinil are not clearly dose-related , and those from 100 mg are limited to the span of immediate verbal recall and short-term visual recognition memory , which is insufficient for it to be considered as a cognitive enhancer in non-sleep-deprived individuals Abstract Rationale . Modafinil , a novel wake-promoting agent , has been shown to have a similar clinical profile to that of conventional stimulants such as methylpheni date . We were therefore interested in assessing whether modafinil , with its unique pharmacological mode of action , might offer similar potential as a cognitive enhancer , without the side effects commonly experienced with amphetamine-like drugs . Objectives . The main aim of this study was to evaluate the cognitive enhancing potential of this novel agent using a comprehensive battery of neuropsychological tests . Methods . Sixty healthy young adult male volunteers received either a single oral dose of placebo , or 100 mg or 200 mg modafinil prior to performing a variety of tasks design ed to test memory and attention . A r and omised double-blind , between-subjects design was used . Results . Modafinil significantly enhanced performance on tests of digit span , visual pattern recognition memory , spatial planning and stop-signal reaction time . These performance improvements were complemented by a slowing in latency on three tests : delayed matching to sample , a decision-making task and the spatial planning task . Subjects reported feeling more alert , attentive and energetic on drug . The effects were not clearly dose dependent , except for those seen with the stop-signal paradigm . In contrast to previous findings with methylpheni date , there were no significant effects of drug on spatial memory span , spatial working memory , rapid visual information processing or attentional set-shifting . Additionally , no effects on paired associates learning were identified . Conclusions . These data indicate that modafinil selectively improves neuropsychological task performance . This improvement may be attributable to an enhanced ability to inhibit pre-potent responses . This effect appears to reduce impulsive responding , suggesting that modafinil may be of benefit in the treatment of attention deficit hyperactivity disorder Functional magnetic resonance imaging ( fMRI ) can be used to detect regional brain responses to changes in sensory stimuli . We have used fMRI to determine the amount of visual and auditory cortical activation in 12 normal subjects and 12 subjects with the narcoleptic syndrome , using a multiplexed visual and auditory stimulation paradigm . In both normal and narcoleptic subjects , mean cortical activation levels during the presentation of periodic visual and auditory stimulation showed no appreciable differences with either age or sex . Normal subjects showed higher levels of visual activation at 10:00 hours than 15:00 hours , with a reverse pattern in narcoleptic subjects ( P = 0.007 ) . The group differences in spatial extent of cortical activation between control and narcoleptic subjects were small and statistically insignificant . The alerting action , and imaging response , to a single oral dose of the sleep-preventing drug modafinil 400 mg were then determined and compared with placebo in both the 12 normal ( 8 given modafinil , 4 placebo ) and 12 narcoleptic subjects ( 8 modafinil , 4 placebo ) . Modafinil caused an increase in self-reported levels of alertness in 7 of 8 narcoleptic subjects , but there was no significant difference between mean pretreatment and post-treatment activation levels as determined by fMRI for either normal or narcoleptic syndrome subjects given modafinil . However , in the modafinil-treated group of 8 normal and 8 narcoleptic subjects , there was a clock time independent correlation between the initial level of activation as determined by the pretreatment scan and the post-treatment change in activation ( visual , P = 0.002 ; and auditory , P = 0.001 ) . No correlation was observed in placebo-treated subjects ( P = 0.99 and 0.77 , respectively ) . Although limited by the small number of subjects , and the lack of an objective measure of alertness , the findings of this study suggest that low cortical activation levels in both normal and narcoleptic subjects are increased following the administration of modafinil . Functional magnetic resonance imaging may be a valuable addition to established studies of attention Methamphetamine (MA)-dependent individuals exhibit deficits in cognition and prefrontal cortical function . Therefore , medications that improve cognition in these subjects may improve the success of therapy for their addiction , especially when cognitive behavioral therapies are used . Modafinil has been shown to improve cognitive performance in neuropsychiatric patients and healthy volunteers . We therefore conducted a r and omized , double-blind , placebo-controlled , cross-over study , using functional magnetic resonance imaging , to examine the effects of modafinil on learning and neural activity related to cognitive function in abstinent , MA-dependent , and healthy control participants .  Modafinil ( 200 mg ) and placebo were administered orally ( one single dose each ) , in counterbalanced fashion , 2 h before each of two testing sessions . Under placebo conditions , MA-dependent participants showed worse learning performance than control participants . Modafinil boosted learning in MA-dependent participants , bringing them to the same performance level as control subjects ; the control group did not show changes in performance with modafinil . After controlling for performance differences , MA-dependent participants showed a greater effect of modafinil on brain activation in bilateral insula/ventrolateral prefrontal cortex and anterior cingulate cortices than control participants . The findings suggest that modafinil improves learning in MA-dependent participants , possibly by enhancing neural function in regions important for learning and cognitive control . These results suggest that modafinil may be a suitable pharmacological adjunct for enhancing the efficiency of cognitive-based therapies for MA dependence Improving cognition in people with neuropsychiatric disorders remains a major clinical target . By themselves pharmacological and non-pharmacological approaches have shown only modest effects in improving cognition . In the present study we tested a recently-proposed methodology to combine CT with a ' cognitive-enhancing ' drug to improve cognitive test scores and exp and ed on previous approaches by delivering combination drug and CT , over a long intervention of repeated sessions , and used multiple tasks to reveal the cognitive processes being enhanced . We also aim ed to determine whether gains from this combination approach generalised to untrained tests . In this proof of principle r and omised-controlled trial thirty-three healthy volunteers were r and omised to receive either modafinil or placebo combined with daily cognitive training over two weeks . Volunteers were trained on tasks of new- language learning , working memory and verbal learning following 200 mg modafinil or placebo for ten days . Improvements in trained and untrained tasks were measured . Rate of new- language learning was significantly enhanced with modafinil , and effects were greatest over the first five sessions . Modafinil improved within-day learning rather than between-day retention . No enhancement of gains with modafinil was observed in working memory nor rate of verbal learning . Gains in all tasks were retained post drug-administration , but transfer effects to broad cognitive abilities were not seen . This study shows that combining CT with modafinil specifically elevates learning over early training sessions compared to CT with placebo and provides a proof of principle experimental paradigm for pharmacological enhancement of cognitive remediation Background Surgeons are usually exposed to high workloads leading to fatigue and stress . This not only increases the likelihood of mistakes during surgery but also puts pressure on surgeons to use drugs to counteract fatigue , distress , concentration deficits , burnout or symptoms of depression . The prevalence of surgeons taking pharmacological cognitive enhancement ( CE ) or mood enhancement ( ME ) drugs  has not been systematic ally assessed so far . Methods Surgeons who attended five international conferences in 2011 were surveyed with an anonymous self-report question naire ( AQ ) regarding the use of prescription or illicit drugs for CE and ME and factors associated with their use . The R and omized Response Technique ( RRT ) was used in addition . The RRT guarantees a high degree of anonymity and confidentiality when a person is asked about stigmatizing issues , such as drug abuse . Results A total of 3,306 question naires were distributed and 1,145 entered statistical analysis ( response rate : 36.4 % ) . According to the AQ , 8.9 % of all surveyed surgeons confessed to having used a prescription or illicit drug exclusively for CE at least once during lifetime . As one would expect , the prevalence rate assessed by RRT was approximately 2.5-fold higher than that of the AQ ( 19.9 % ; 95 % confidence interval ( CI ) , 15.9 % to 23.9 % , N = 1,105 ) . An even larger discrepancy between the RRT and AQ was observed for the use of antidepressants with a 6-fold higher prevalence ( 15.1 % ; 95 % CI , 11.3 % to 19.0 % , N = 1,099 ) as compared to 2.4 % with the AQ . Finally , logistic regression analysis revealed that pressure to perform at work ( odds ratio ( OR ) : 1.290 ; 95 % CI , 1.000 to 1.666 ; P = 0.05 ) or in private life ( OR : 1.266 ; 95 % CI , 1.038 to 1.543 ; P = 0.02 ) , and gross income ( OR : 1.337 ; 95 % CI , 1.091 to 1.640 ; P = 0.005 ) , were positively associated with the use of drugs for CE or ME . Conclusions The use of illicit and prescription drugs for CE or ME is an underestimated phenomenon among surgeons which is generally attributable to high workload , perceived workload , and private stress . Such intake of drugs is associated with attempts to counteract fatigue and loss of concentration . However , drug use for CE may lead to addiction and to overestimation of one ’s own capabilities , which can put patients at risk . Coping strategies should be taught during medical education Modafinil differs from other arousal-enhancing agents in chemical structure , neurochemical profile , and behavioral effects . Most functional neuroimaging studies to date examined the effect of modafinil only on information processing underlying executive cognition , but cognitive enhancers in general have been shown to have pronounced effects on emotional behavior , too . We examined the effect of modafinil on neural circuits underlying affective processing and cognitive functions . Healthy volunteers were enrolled in this double-blinded placebo-controlled trial ( 100 mg/day for 7 days ) . They underwent BOLD fMRI while performing an emotion information-processing task that activates the amygdala and two prefrontally dependent cognitive tasks — a working memory ( WM ) task and a variable attentional control ( VAC ) task . A clinical assessment that included measurement of blood pressure , heart rate , the Hamilton anxiety scale , and the profile of mood state ( POMS ) question naire was also performed on each test day . BOLD fMRI revealed significantly decreased amygdala reactivity to fearful stimuli on modafinil compared with the placebo condition . During executive cognition tasks , a WM task and a VAC task , modafinil reduced BOLD signal in the prefrontal cortex and anterior cingulate . Although not statistically significant , there were trends for reduced anxiety , for decreased fatigue-inertia and increased vigor-activity , as well as decreased anger-hostility on modafinil . Modafinil in low doses has a unique physiologic profile compared with stimulant drugs : it enhances the efficiency of prefrontal cortical cognitive information processing , while dampening reactivity to threatening stimuli in the amygdala , a brain region implicated in anxiety Rationale Modafinil is a well-tolerated psychostimulant drug with low addictive potential that is used to treat patients with narcolepsy or attention deficit disorders and to enhance vigilance in sleep-deprived military personal . So far , underst and ing of the cognitive enhancing effects of modafinil and the relevant neurobiological mechanisms are incomplete . Objectives The aim of this study was to investigate the effects of modafinil on working memory processes in humans and how they are related to noradrenergic stimulation of the prefrontal cortex . Methods Sixteen healthy volunteers ( aged 20–29 years ) received either modafinil 200 mg or placebo using a double blind crossover design . Two computerized working memory tasks were administered , a numeric manipulation task that requires short-term maintenance of digit-sequences and different degrees of manipulation as well as delayed matching task that assesses maintenance of visuo-spatial information over varying delay lengths . The battery was supplemented by st and ardized paper pencil tasks of attentional functions . Results Modafinil significantly reduced error rates in the long delay condition of the visuo-spatial task and in the manipulation conditions , but not in the maintenance condition of the numeric task . Analyses of reaction times showed no speed-accuracy trade-off . Attentional control tasks ( letter cancellation , trail-making , catch trials ) were not affected by modafinil . Conclusions In healthy volunteers without sleep deprivation modafinil has subtle stimulating effects on maintenance and manipulation processes in relatively difficult and monotonous working memory tasks , especially in lower performing subjects . Overlapping attentional and working memory processes have to be considered when study ing the noradrenergic modulation of the prefrontal cortex There is intense interest in the development of effective cognitive enhancing drugs which would have therapeutic application across a number of neurological and psychological disorders including dementia , schizophrenia and depression . However , development in this area has been limited by the absence of sensitive biomarkers which can be used to detect and refine therapeutic-like action in phase 1 clinical studies . The aim of the present study was therefore to develop a measure of cognition relevant to the action of c and i date cognitive enhancers which might be sensitive to pharmacological manipulation in healthy volunteers . Healthy volunteers ( n = 34 ) were r and omised to receive a single dose of modafinil ( 100 mg ) or placebo . Five hours post dose , attentional flexibility in learning was assessed using a novel implicit learning task . Volunteers also completed an auditory digit span task and visual analogue scales ( VAS ) . Modafinil increased alertness as measured by the VAS . In the implicit learning task , modafinil enhanced learning rates in terms of both accuracy and reaction time , suggesting an increase in implicit rule learning . These results suggest that the novel learning task should be explored as a biomarker of early cognitive improvement which could be more sensitive than conventional measures Background Modafinil is employed for the treatment of narcolepsy and has also been , off-label , used to treat cognitive dysfunction in neuropsychiatric disorders . In a previous study , we have reported that single dose administration of modafinil in healthy young subjects enhances fluid reasoning and affects resting state activity in the Fronto Parietal Control ( FPC ) and Dorsal Attention ( DAN ) networks . No changes were found in the Salience Network ( SN ) , a surprising result as the network is involved in the modulation of emotional and fluid reasoning . The insula is crucial hub of the SN and functionally divided in anterior and posterior subregions . Methodology Using a seed-based approach , we have now analyzed effects of modafinil on the functional connectivity ( FC ) of insular subregions . Principal Findings Analysis of FC with resting state fMRI ( rs-FMRI ) revealed increased FC between the right posterior insula and the putamen , the superior frontal gyrus and the anterior cingulate cortex in the modafinil-treated group . Conclusions Modafinil is considered a putative cognitive enhancer . The rs-fMRI modifications that we have found are consistent with the drug cognitive enhancing properties and indicate subregional targets of action . Trial Registration Clinical Trials.gov Modafinil is a selective wakefulness-promoting agent that has been shown to enhance cognitive performance under conditions of sleep deprivation but which has equivocal effects in normal young volunteers . In a double-blind parallel group design study , 45 non-sleep-deprived middle-aged volunteers ( 20 men and 25 women , aged 50 - 67 years ) were r and omly allocated to receive two capsules containing placebo , 100 or 200 mg modafinil , and 3 h later they completed  100 mm visual analogue scales of mood and bodily symptoms  , before and after an extensive battery of cognitive tests [ pen and paper and the Cambridge Neuropsychological Test Automated Battery ( CANTAB ) ] . There were no significant treatment-associated changes in ratings of mood or bodily symptoms and no significant effects on most of the cognitive tests used in this study . The group treated with modafinil ( 200 mg ) was significantly faster in a simple colour naming of dots and also significantly better in a test of constructional ability ( Clock Drawing Test ) compared with the placebo group . However , subjects in the 200-mg group also made significantly more total errors in the Intra/Extradimensional Set Shift ( ID/ED ) task than both the other groups . Thus , this study found limited evidence of cognitive-enhancing properties of modafinil in healthy middle-aged volunteers Rationale The majority of studies investigating the cognitive effects of modafinil , a wake-promoting compound , demonstrate some improvements in attention . The potential of the drug to selectively benefit distinct components of attention has yet to be fully explored in healthy adults . Objective The present study was conducted to investigate modafinil ’s effect on specific cognitive tasks that tax components of attention switching . One required the rapid switching of attention between stimuli , and another contained an embedded working memory component on top of the attentional shift requirements . Additionally , prospect i ve memory was examined , which requires the interruption of an ongoing activity to retrieve and act upon a previously formed intention . Material s and methods Healthy non-smoking volunteers , matched on age , intelligence , and baseline cognitive ability , received either a capsule that contained 200 mg modafinil or placebo .  Subjective measures of mood and physiological response were taken throughout the experimental session , and the tasks were completed between 2 and 3 h post-dosing . Results Two hundred milligrams modafinil improved accuracy without a reaction time trade-off , in both conditions of the attention-shifting task , but only when re sources were most challenged . In contrast , the drug afforded no improvement in prospect i ve remembering or in the ongoing task that was interrupted . Conclusion Modafinil appears to promote rapid switching of attention in conditions that are most dem and ing , whilst it offers no benefits in a task that requires unpredictable and infrequent disengagement of attention from an ongoing task in order to act upon an alternative task Modafinil is a selective wakefulness-promoting agent with beneficial effects in narcolepsy and conditions of sleep deprivation . In a double-blind study we examined its effects in 30 healthy , non sleep-deprived students ( 19 men and 11 women , aged 19 - 23 years ) , who were r and omly allocated to placebo , 100 or 200 mg modafinil and 3 h later completed 100 mm visual analogue scales relating to mood and bodily symptoms , before and after an extensive battery of cognitive tests ( pen and paper and CANTAB ) . There were no significant differences between the three treatment groups on any of the cognitive tests used in this study . There was a significant post-treatment change in the factor measuring ' somatic anxiety ' and in individual ratings of ' shaking ' , ' palpitations ' , ' dizziness ' , ' restlessness ' , ' muscular tension ' , ' physical tiredness ' and ' irritability ' , which was mainly due to significantly higher ratings of somatic anxiety in the 100 mg group compared with the other two groups . Further changes in mood were revealed after the stress of cognitive testing , with the 100 mg group showing greater increases in the ' psychological anxiety ' and the ' aggressive mood ' factors ( as measured from the Bond and Lader scales ) Summary .Modafinil is a novel vigilance-enhancing agent . We were interested if modafinil would also enhance motor excitability and improve motor performance and attention in healthy subjects . Ten volunteers received either a single oral dose of placebo or 200 mg modafinil . A r and omized double-blind crossover design was used . Transcranial magnetic stimulation was employed to test intracortical inhibition , intracortical facilitation , the cortical silent period and to obtain stimulus-response curves . In addition , M responses and F waves were recorded . Reaction time tasks , the nine-hole-peg test and the d2 attention test were also applied . These studies were performed prior to and 3 and 24 hours after drug ingestion . Modafinil did not change excitatory or inhibitory properties in the motor cortex . It did not alter corticospinal excitability and alpha motoneuronal excitability . In the modafinil group and in the placebo group , performance of the nine-hole-peg test and the d2 test improved to a similar extend over time . Thus , this study does not demonstrate significant differences between a single dose of modafinil and placebo in healthy subjects In a double-blind , placebo-controlled study , postmenopausal women ( 53 - 65 years old ) were r and omly assigned to 7-day treatment with Ginkgo ( 120 mg/day , n=15 ) or matched placebo ( n=16 ) . They were given a battery of cognitive tests and measurements of mood and menopausal symptoms at baseline ( before treatment began ) and at the end of 7 days . The group treated with Ginkgo was significantly better than the placebo group in a matching-to- sample test of nonverbal memory , but the groups did not differ in immediate or delayed paragraph recall or in delayed recall of pictures . In a test of frontal lobe function ( rule shifting ) and in the Paced Auditory Serial Addition Test ( PASAT ) ( which measures sustained attention but also involves frontal lobe function ) , the group treated with Ginkgo performed significantly better than the placebo group . However , the groups did not differ in a test of planning . The treatments did not differ in their effects on the volunteers ' ratings of menopausal symptoms , sleepiness , bodily symptoms or aggression . The benefits of Ginkgo on memory and frontal lobe function found in this study are modest but are unlikely to be secondary to major mood changes OBJECTIVE Since high frequency oscillations ( HFOs ) evoked by upper limb stimulation are susceptible to arousal fluctuation , we verified whether administration of modafinil , a vigilance promoting drug , modifies such responses at different levels of the somatosensory system . METHODS HFOs were obtained in 6 healthy volunteers by 500 - 700 Hz filtering of right median nerve somatosensory evoked potentials , before and 2 hours after the administration of 100 mg modafinil . Raw data were further su bmi tted to brain electrical source analysis . RESULTS Modafinil significantly increased subcortical HFOs , as well as the strength of a dipolar source at the base of the skull . CONCLUSIONS Our data suggest that modafinil exerts its action also at the level of the brain-stem , where it interferes with the processing of somatosensory ascending inputs Background Although antihistamines are known for their sedative adverse effects , fexofenadine was previously shown to have stimulating effects . These stimulant effects were rather mild in magnitude and were only demonstrated in tasks with a high workload . Aim The present study was set up to compare the magnitude of the stimulant effect of fexofenadine with those of 2 psychostimulants , modafinil and methylpheni date . Method Sixteen healthy volunteers ( 5 males and 11 females ; mean age , 21.8 years ) participated in a 4-way , placebo-controlled , crossover study . The effects of fexofenadine ( 360 mg ) , modafinil ( 200 mg ) , methylpheni date ( 20 mg ) , and placebo were compared in a critical tracking , divided attention , motor impulsivity , and vigilance task . Results In this study , no significant stimulant effects of fexofenadine were found in any of the tasks . Modafinil only improved reaction time in the vigilance task , whereas methylpheni date improved performance in the divided attention and vigilance tasks . In addition , performance after methylpheni date treatment was also better than after fexofenadine in the divided attention and vigilance tasks . Conclusion From the results , it can be concluded that the stimulating effects of methylpheni date are confirmed , whereas the stimulating effects of fexofenadine were not demonstrated in this study . It is evident that the stimulating effects of fexofenadine , which were apparent in previous studies , are not of the same magnitude as the effects of known psychostimulants such as methylpheni date A double‐blind , intra‐individual cross‐over comparison of the mental performance of 18 aging , non‐deteriorated individuals during two 4‐week periods of piracetam ( 1‐acetamide‐2‐pyrrolidone ) and placebo administration was performed using conventional and computerized perceptual‐motor tasks . In a majority of these tasks the subjects did significantly better when on piracetam than on placebo , a finding consistent with ratings completed by two independent observers . The findings indicate new avenues for the treatment of individuals with reduced mental performance  possibly related to disturbed alertness — a neglected group of psychiatric conditions Modafinil is indicated for the management of excessive daytime sleepiness ; however , recent studies have examined a broad range of potential uses . Given that clinical uses of modafinil may be exp and ing , this study compared modafinil and d-amphetamine effects on subjective and performance measures . Across 11 sessions , 11 healthy adults were tested after oral doses of placebo ( 5 sessions ) , modafinil ( 1.75 mg/kg , 3.50 mg/kg , or 7.00 mg/kg ) , and d-amphetamine ( 0.035 mg/kg , 0.070 mg/kg , 0.140 mg/kg ) under double-blind , r and omized conditions . Assessment s of cognitive performance and subjective effects were completed before drug administration , 30 min after drug administration , and at hourly intervals after drug administration for 5 hr . Modafinil increased ratings on the Amphetamine and Morphine Benzedrine Group scales of the Addiction Research Center Inventory ( ARCI ) and increased ratings on the Vigor and Total Positive scales of the Profile of Mood States .  d-Amphetamine increased visual analog ratings of feeling stimulated and liking the drug and increased ratings on the Morphine Benzedrine Group scale of the ARCI . Both medications significantly reduced visual analog scale ratings of feeling sleepy , and modafinil decreased ratings on the ARCI Pentobarbital-Chlorpromazine-Alcohol Group scale . Both medications sustained performance that deteriorated across time on the Sternberg Number Recognition Test . Modafinil also enhanced performance rate on the Digit-Symbol Substitution Task above baseline levels and increased response rate on the Repeated Acquisition of Response Sequences Task . These results suggest that modafinil engenders alerting effects and increases performance in healthy non-sleep-deprived individuals comparable with that of d-amphetamine Effects of a combination of caffeine and glucose were assessed in two double-blind , placebo-controlled , cross-over studies during extended performance of cognitively dem and ing tasks . In the first study , 30 participants received two drinks containing carbohydrate and caffeine  ( 68 g/38 mg ; 68 g/46 mg , respectively ) and a placebo drink , in counter-balanced order , on separate days . In the second study 26 participants received a drink containing 60 g of carbohydrate and 33 mg of caffeine and a placebo drink . In both studies , participants completed a 10-min battery of tasks comprising 2-min versions of Serial 3s and Serial 7s subtraction tasks and a 5-min version of the  Rapid Visual Information Processing task ( RVIP ) , plus a rating of ' mental fatigue ' , once before the drink and six times in succession commencing 10 min after its consumption . In comparison to placebo , all three active drinks improved the accuracy of RVIP performance and both the drink with the higher level of caffeine in first study and the active drink in the second study result ed in lower ratings of mental fatigue . These results indicate that a combination of caffeine and glucose can ameliorate deficits in cognitive performance and subjective fatigue during extended periods of cognitive dem and Nootropyl ( Piracetam ) a drug reported to facilitate learning in animals was tested for its effect on man by administering it to normal volunteers . The subjects were given 3 × 4 capsules at 400 mg per day , in a double blind study . Each subject learned series of words presented as stimuli upon a memory drum . No effects were observed after 7 days but after 14 days verbal learning had significantly increased
target: We found that whilst most studies employing basic testing paradigms show that modafinil intake enhances executive function , only half show improvements in attention and learning and memory , and a few even report impairments in divergent creative thinking .
  In contrast , when more complex assessment s are used , modafinil appears to consistently engender enhancement of attention , executive functions , and learning .
  Importantly , we did not observe any preponderances for side effects or mood changes .
background: Modafinil is an FDA -approved eugeroic that directly increases cortical catecholamine levels , indirectly upregulates cerebral serotonin , glutamate , orexin , and histamine levels , and indirectly decreases cerebral gamma-amino-butrytic acid levels .
  In addition to its approved use treating excessive somnolence , modafinil is thought to be used widely off-prescription for cognitive enhancement .
  However , despite this popularity , there has been little consensus on the extent and nature of the cognitive effects of modafinil in healthy , non-sleep-deprived humans .