Modafinil in healthy adults: study-by-study evidence review

Key points

• In rested, healthy adults the pooled effect of a single modafinil dose is small: g = 0.10 across 19 trials (Kredlow 2019) and SMD 0.12 across 14 studies (Roberts 2020) [5][6].
• Roberts found a statistically significant effect in only one of eight cognitive domains, memory updating (5 studies). Most domains rest on 2 to 8 studies with wide intervals [6].
• Several trials found nothing. In a 2021 trial of 48 men, modafinil had no significant effect on any test in the battery [15]. Creativity results were inconsistent or lower, and in chess players all three stimulants tested increased games lost on time [4][13][14][17].
• Almost every trial gave one dose to young volunteers and tested a few hours later. We found no trial of repeated daily use and none in adults over 67 [6][9].

Scope and method

This article expands one section of the modafinil guide. Sleep-deprived volunteers are covered in modafinil and sleep deprivation studies, and caffeine comparisons in modafinil vs caffeine.

On 8 November 2026 we searched PubMed (through NCBI’s public API, because its web pages blocked automated reading) for reviews and for placebo-controlled trials of modafinil in healthy adults. We read the full text of Roberts 2020 (accepted manuscript), Müller 2013, Repantis 2021 and Becker 2022. For the others only the PubMed abstract was available; publisher sites refused automated access. Where a figure is not in an abstract, the tables say so. A 2000 working-memory paper by Mehta and colleagues tested methylphenidate, not modafinil, and is excluded [19].

The four reviews

Review	Scope	Headline	Funding
Repantis 2010 [3]	Systematic review with meta-analysis, modafinil and methylphenidate, healthy people	Expectations “exceed their actual effects”; modafinil improved attention in well-rested people. Effect size and study count not in abstract	Not verified
Battleday and Brem 2015 [4]	Systematic review, MEDLINE, English studies Jan 1990 to Dec 2014, non-sleep-deprived humans; no pooled estimate	Simple tests: executive function improved in most studies, attention and learning/memory in about half, divergent creative thinking impaired in a few. Complex tests: more consistent gains. No excess side effects or mood change	Not verified
Kredlow 2019 [5]	Meta-analysis, 19 single-dose placebo-controlled trials, 67 effect sizes	g = 0.10 (95% CI 0.05 to 0.15). No difference between domains, no moderation by dose (100 vs 200 mg) or psychiatric status	Not verified
Roberts 2020 [6]	Meta-analysis, 14 modafinil studies, 64 effect sizes; 572 participants (260 crossover, 312 in between-group designs); searches November 2019	SMD 0.12 (95% CI 0.02 to 0.21), I² = 72%	No statement found in the manuscript; the PubMed record carries one conflict-of-interest sentence

We found no newer systematic review of modafinil in rested healthy adults in PubMed after Roberts 2020. That search was ours and could have missed something.

Effect sizes by cognitive domain

Roberts 2020 is the only review whose domain-level numbers we could read [6].

Domain	Studies	SMD (95% CI)
Memory updating	5	0.28 (0.02 to 0.54)
Inhibitory control	8	0.27 (-0.04 to 0.57)
Spatial working memory	6	0.21 (-0.03 to 0.44)
Access to long-term/semantic memory	2	0.15 (-0.48 to 0.79)
Recall	7	0.09 (-0.02 to 0.19)
Switching	5	-0.02 (-0.16 to 0.12)
Selective attention	5	-0.01 (-0.16 to 0.15)
Sustained attention	8	-0.13 (-0.52 to 0.26)

Only memory updating excluded zero. The test for differences between domains was not significant (p = 0.25), so the pattern should not be read as “modafinil helps working memory but not attention” [6]. Kredlow likewise found no difference between domains [5]. The authors treated d = ±0.2 as the smallest effect of interest and reported the overall estimate as statistically within that band (p = 0.05) [6].

Trials in healthy, rested adults

All trials gave a single dose unless noted. Effect sizes are given where the abstract or full text states them.

Study	Design and population	Headline result	Funding
Turner 2003 [7]	60 young men; double-blind, three parallel groups (placebo, 100, 200 mg)	Better digit span, pattern recognition, spatial planning, stop-signal; slower responses on three tests; no effect on spatial working memory, rapid visual information processing, set-shifting, paired associates. Effect sizes not in abstract	Not verified
Randall 2003 [8]	30 students, 19-23; parallel, three groups	No difference on any cognitive test; more somatic anxiety ratings, mainly in the 100 mg group	Not verified
Randall 2004 [9]	45 volunteers aged 50-67; parallel	Most tests unchanged; faster colour naming and better clock drawing at 200 mg, but more set-shifting errors	Not verified
Randall 2005 [10]	60 students, 19-22; parallel	Mixed small gains (sustained attention, digit span, pattern recognition); no effect on long-term memory, executive function or fluency. Authors: insufficient to call it a cognitive enhancer	Not verified
Müller 2004 [12]	16 volunteers, 20-29; crossover	Fewer errors on long-delay spatial and manipulation tasks; attention tests unaffected	Not verified
Müller 2013 [13]	64 volunteers (32 per arm), 19-36; parallel	Better spatial working memory, planning and decision-making at the hardest levels, and higher task enjoyment; creativity inconsistent, not significant	MRC and Wellcome Trust; no competing-interest statement found in the text
Franke 2017 [14]	39 male chess players; four-way crossover vs methylphenidate, caffeine, placebo	No effect on performance across 3,059 games; all drugs raised thinking time and games lost on time; modafinil scored higher only after controlling for game duration and excluding games lost on time	Not verified
Repantis 2021 [15]	48 men, 21-36; three arms (modafinil, methylphenidate, caffeine), each against placebo	No significant effect of modafinil on any test	DFG, ERC, Jacobs and Volkswagen Foundations; no competing interests
Becker 2022 [16]	Secondary analysis of the same 48 men, with resting-state fMRI	Stimulants pooled enhanced memory; not modafinil-specific in the abstract	Volkswagen Foundation and others
Ang 2022 [17]	19 healthy adults, mean age 23.2; three-dose crossover	At 200 mg, option generation was less unique (partial η² = 0.16) and less diverse (0.19)	NIMH grants

A 2025 imaging study of 50 people (25 per arm) reported altered thalamic connectivity after one dose and, in the abstract, connectivity outcomes only [21]. A 2022 EEG study of 30 adults found modafinil-related changes that were not associated with changes in flanker-task behaviour [22].

Where results were null or negative

Randall’s three trials in students and middle-aged volunteers (n = 30, 45, 60) found few or no effects [8][9][10]. A retrospective pooling of two of them (n = 89) found improved sensitivity on a sustained-attention test only in participants with lower IQ scores, which suggests ceiling effects may hide benefits in high performers [11].

Creativity: Battleday and Brem counted “a few” studies with impaired divergent thinking [4]. Müller 2013 found inconsistent, non-significant effects [13]. Ang 2022 found less unique and less diverse self-generated options at the higher dose [17].

Complex tasks are described as the best case for modafinil, yet the chess trial found that gains appeared only after controlling for game duration and excluding games lost on the clock [4][14]. We did not find a placebo-controlled trial of risk-taking in rested healthy adults.

Publication bias and tests built for patients

Roberts reported asymmetric funnel plots for modafinil and methylphenidate, then ran Egger’s test, which was not significant for modafinil (p = 0.19) [6]. The review used published studies only, and 22 papers across all three drugs were excluded because needed statistics were missing and not supplied on request [6]. We could not confirm bias tests in the other three reviews, whose full texts were closed.

Battleday and Brem point out that many studies used psychometric tests “designed to detect cognitive effects in ill rather than healthy populations” [4]. Repantis 2021 suggested future work use “more demanding” tasks [15].

Lab results versus everyday performance

Most modafinil trials tested volunteers 90 to 150 minutes after a single dose; mean age was about 24 to 25 [6]. Roberts concluded the experiments “do not accurately reflect their actual use in the wider population” and that user belief in efficacy is not supported so far [6]. Müller 2004 and Müller 2013 found gains mainly in difficult or monotonous tasks, and Müller 2004 saw them mainly in lower performers [12][13]. No study we read measured grades, work output or error rates in daily life.

Regulatory status

United States (FDA, label revised February 2025): indicated to improve wakefulness in adults with excessive sleepiness from narcolepsy, obstructive sleep apnea or shift work disorder; Schedule IV; the label does not say effectiveness is established in healthy people [1]. European Union: after a referral, the CHMP opinion of 18 November 2010 and Commission decision of 27 January 2011 restricted use to narcolepsy [2]. UK and Germany: not re-checked here; see the guide. It is a prescription medicine, so “research use only” does not apply. Use for cognition in healthy people is off-label.

Risks and unknowns

Adverse events reported in these trials. Reports are sparse and mostly mild. Repantis 2021 recorded 12 adverse events in 48 men: two headaches after placebo, two cases of sleep-onset insomnia after modafinil, four events each after methylphenidate and caffeine [15]. Müller 2013 recorded one headache among 32 modafinil participants [13]. Randall 2003 found raised ratings of shaking, palpitations, dizziness and restlessness mainly at 100 mg, while Randall 2004 and 2005 found no mood changes [8][9][10]. A single 200 mg dose caused no vestibular impairment in a 10-man crossover study [20]. In the chess trial, slower play cost games on time [14]. Expectation matters: in a sham trial of 201 students, those told they had received modafinil (but given placebo) reported more symptoms (mean 2.65) than those given no placebo (1.68) [18]. Rates from patient trials are in the guide.

Not studied, as far as we found. Repeated or daily use and long-term use in healthy people; adults over 67 (the oldest trial covered ages 50 to 67, with 45 people) [9]; women (Turner 2003, Franke 2017 and Repantis 2021 enrolled only men); real-world outcomes; and effects of modafinil on risk-taking in rested adults.

Frequently asked questions

How large is modafinil’s effect in healthy adults?

Small. Two meta-analyses put it at g = 0.10 (19 trials) and SMD 0.12 (14 studies) after single doses [5][6]. Roberts’s authors judged the estimate within a band they considered negligible [6].

Did any trial find no benefit?

Yes. Randall 2003 found no difference on any cognitive test, and Repantis 2021 found no significant effect of modafinil on any instrument [8][15].

Are the results affected by publication bias?

Roberts saw funnel-plot asymmetry but a non-significant Egger test (p = 0.19). We could not verify bias tests in the other reviews [6].

Has long-term use been studied in healthy people?

We found no placebo-controlled trial of repeated or long-term use in healthy adults. The evidence base is single-dose laboratory studies [5][6].

Sources

PubMed records were read through NCBI’s E-utilities API because pubmed.ncbi.nlm.nih.gov showed a cookie wall to automated requests. Publisher sites for paywalled papers were not opened.

1. Apotex Corp., “PROVIGIL (modafinil) tablets, prescribing information”, DailyMed (revised February 2025; page updated 27 Aug 2025). https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0391f182-1958-9fef-a944-53b229ce99e7
2. EMA, “Modafinil - referral” (CHMP opinion 18 Nov 2010; Commission decision 27 Jan 2011). https://www.ema.europa.eu/en/medicines/human/referrals/modafinil
3. Repantis D et al., “Modafinil and methylphenidate for neuroenhancement in healthy individuals: a systematic review”, Pharmacol Res 2010 (abstract). https://pubmed.ncbi.nlm.nih.gov/20416377/
4. Battleday RM, Brem AK, “Modafinil for cognitive neuroenhancement in healthy non-sleep-deprived subjects: a systematic review”, Eur Neuropsychopharmacol 2015 (abstract). https://pubmed.ncbi.nlm.nih.gov/26381811/
5. Kredlow MA et al., “The efficacy of modafinil as a cognitive enhancer: a systematic review and meta-analysis”, J Clin Psychopharmacol 2019 (abstract). https://pubmed.ncbi.nlm.nih.gov/31433334/
6. Roberts CA et al., “How effective are pharmaceuticals for cognitive enhancement in healthy adults?”, Eur Neuropsychopharmacol 2020;38:40-62 (PubMed record and accepted manuscript, Liverpool John Moores University repository). https://pubmed.ncbi.nlm.nih.gov/32709551/
7. Turner DC et al., “Cognitive enhancing effects of modafinil in healthy volunteers”, Psychopharmacology 2003 (abstract). https://pubmed.ncbi.nlm.nih.gov/12417966/
8. Randall DC et al., “Modafinil affects mood, but not cognitive function, in healthy young volunteers”, Hum Psychopharmacol 2003 (abstract). https://pubmed.ncbi.nlm.nih.gov/12672167/
9. Randall DC et al., “The cognitive-enhancing properties of modafinil are limited in non-sleep-deprived middle-aged volunteers”, Pharmacol Biochem Behav 2004 (abstract). https://pubmed.ncbi.nlm.nih.gov/15006466/
10. Randall DC et al., “Does modafinil enhance cognitive performance in young volunteers who are not sleep-deprived?”, J Clin Psychopharmacol 2005 (abstract). https://pubmed.ncbi.nlm.nih.gov/15738750/
11. Randall DC et al., “Cognitive effects of modafinil in student volunteers may depend on IQ”, Pharmacol Biochem Behav 2005 (abstract). https://pubmed.ncbi.nlm.nih.gov/16140369/
12. Müller U et al., “Effects of modafinil on working memory processes in humans”, Psychopharmacology 2004 (abstract). https://pubmed.ncbi.nlm.nih.gov/15221200/
13. Müller U et al., “Effects of modafinil on non-verbal cognition, task enjoyment and creative thinking in healthy volunteers”, Neuropharmacology 2013 (full text). https://pmc.ncbi.nlm.nih.gov/articles/PMC3485563/
14. Franke et al., “Methylphenidate, modafinil, and caffeine for cognitive enhancement in chess”, Eur Neuropsychopharmacol 2017 (abstract). https://pubmed.ncbi.nlm.nih.gov/28119083/
15. Repantis D et al., “Cognitive enhancement effects of stimulants: a randomized controlled trial testing methylphenidate, modafinil, and caffeine”, Psychopharmacology 2021 (full text). https://pmc.ncbi.nlm.nih.gov/articles/PMC7826302/
16. Becker M et al., “Cognitive enhancement: effects of methylphenidate, modafinil, and caffeine on latent memory and resting state functional connectivity in healthy adults”, Hum Brain Mapp 2022 (full text). https://pmc.ncbi.nlm.nih.gov/articles/PMC9435011/
17. Ang et al., “A multi-pronged investigation of option generation using depression, PET and modafinil”, Brain 2022 (abstract). https://pubmed.ncbi.nlm.nih.gov/35150243/
18. Heller et al., “Beliefs about medicines predict side-effects of placebo modafinil”, Ann Behav Med 2022 (abstract). https://pubmed.ncbi.nlm.nih.gov/35512392/
19. Mehta et al., “Methylphenidate enhances working memory by modulating discrete frontal and parietal lobe regions in the human brain”, J Neurosci 2000 (abstract; methylphenidate, so excluded). https://pubmed.ncbi.nlm.nih.gov/10704519/
20. Liu et al., “Equilibrium and vestibular safety of modafinil in healthy volunteers”, Aerosp Med Hum Perform 2022 (abstract). https://pubmed.ncbi.nlm.nih.gov/35729759/
21. Delli Pizzi et al., “Modafinil alters the functional connectivity of distinct thalamic nuclei with the neocortex”, Neuroimage 2025 (abstract). https://pubmed.ncbi.nlm.nih.gov/40288703/
22. Linton et al., “Effects of modafinil on electroencephalographic microstates in healthy adults”, Psychopharmacology 2022 (abstract). https://pubmed.ncbi.nlm.nih.gov/35471613/

This article is information, not medical advice.