Modafinil.
A prescription wakefulness medicine. It slows dopamine reuptake in wake-regulating circuits, which raises alertness across most of a working day from one morning dose.
Reviewed March 2026
- Category
- Nootropic
What Modafinil is, and what it does.
- Does it work
- It's a prescription-only medicine rather than a supplement ingredient, so it belongs in a conversation with a doctor. Formulators care because of how it shifts liver enzyme clearance.
- How much to take
- Prescribing sits at 100 to 200mg once in the morning, and 400mg appears in research arms. There's no supplement amount, because dosing this belongs with a prescriber.
- Time to feel it
- Wakefulness builds within about an hour of an oral dose and holds for most of the working day, because the parent compound clears slowly.
- The first dose
- Alertness builds over about an hour and holds through the day. Headache, dry mouth, lower appetite and trouble falling asleep that night are the common first-day reports.
- With regular use
- Weeks of daily use shift sleep timing and can build psychological reliance. It also induces one liver enzyme and inhibits another, so co-taken medicines drift in exposure.
- How well tolerated
- Prescription-only and needs medical supervision. It induces one liver enzyme and inhibits another, so hormonal contraception and other medicines can shift in exposure.
- How it feels
- Many describe steady alertness without a stimulant buzz. Others get edginess, dry mouth and a headache. It is prescription-only and not a dietary supplement ingredient.
- The overlooked benefit
- The part that matters to a formulator is pharmacokinetic. It inhibits CYP2C19 and induces CYP3A4, so anything sharing those routes needs checking rather than combining.
100 to 200mg a day is where Modafinil works.
Source: Battleday & Brem, Eur Neuropsychopharmacol, 2015; Caldwell et al., Aviat Space Environ Med, 2000
The proof, claim by claim.
These words describe the research, not the molecule's worth. Research strength is how much work stands behind one claim, and it is never a product score.
Modafinil has emerging evidence. Based on 7774+ studies.
- wakefulness during extended sleep lossMeta-analysis
- sustained attention in sleep-deprived adultsRandomised trial
- alertness across night shift hoursRandomised trial
- working memory in rested healthy adultsMeta-analysis
- clearance shifts in co-administered CYP3A4 and CYP2C19 substratesRandomised trial
Questions people ask about Modafinil.
- When should I take it?
- Timing matters less than consistency. Pick a time that works for you and take it daily.
- Can I take it with other supplements?
- Usually fine. The main thing to watch is not doubling up on the same ingredient from different products. If you're on prescription meds, check with your pharmacist first.
- Any side effects to watch for?
- Most people tolerate it well at recommended doses. GI upset is the most common complaint with any supplement. Start with a lower dose and work up. If something feels off, stop and reassess.
Why these belong in the same formula. Each row says what the basis is, from settled biochemistry through to a trial that measured the pair.
Caffeine blocks adenosine A1 and A2A receptors; modafinil raises extracellular dopamine by binding the dopamine transporter with low affinity. The two arrive at wakefulness from separate directions, so effects on alertness, heart rate and jitteriness can stack. Anyone combining them is taking two wake-promoting agents at once rather than one.
Theanine is a glutamate analogue that crosses into the brain and shifts inhibitory tone; modafinil pushes catecholamine signalling upward. The pairing is used to blunt the edgy feel of a stimulant, and that use rests on each compound's separate pharmacology, not on a trial of the two together. No combination study grounds a size for the interaction.
Hyperforin activates the pregnane X receptor and raises CYP3A4 expression in liver and gut. Modafinil is partly cleared by CYP3A4, so co-use is a recognised pharmacokinetic interaction rather than a nutritional pairing. This is textbook enzyme induction and needs no combination trial to be worth flagging.
Melatonin signals biological night through MT1 and MT2 receptors; modafinil promotes wakefulness. Taken close together they pull the same axis in opposite directions, which is a timing consideration rather than a benefit. Nothing here says one cancels the other by a measured amount.
Nothing specific on file for Modafinil. Match the label to the daily amount above, and tell your doctor what you take.
Not medical advice. Show the label to your pharmacist.What Modafinil actually does.
Modafinil binds the dopamine transporter with low affinity and slows dopamine reuptake, raising extracellular dopamine in wake-regulating regions.
Modafinil is cleared mainly by hepatic amide hydrolysis to modafinil acid, with CYP3A4 contributing; it induces CYP3A4 and inhibits CYP2C19, so it changes the clearance of other CYP substrates.
The molecule carries a sulfoxide stereocentre, so it exists as R and S enantiomers with different elimination half-lives; the R form is eliminated more slowly.
Downstream of that dopaminergic step, modafinil increases signalling in histaminergic and orexinergic wake-promoting circuits, which is why its profile differs from classical amphetamine-type releasers.
Where Modafinil comes from.
It is made in a chemical plant from petrochemical-derived building blocks. Nothing about it is extracted from a plant or an animal, and the single-enantiomer version needs an extra separation step.
Chemically synthesised. The molecule is identical to the one a plant or an animal makes, and building it deliberately means a known purity, a fixed dose and no crop contaminants. For several nutrients this is the only route that reaches a usable amount.
Production starts from diphenylmethane chemistry, the source of the two phenyl rings that define the molecule.
A sulfur-linked acetamide side chain is built onto the benzhydryl carbon, giving the thioether precursor.
The thioether sulfur is oxidised to a sulfoxide, which creates the chiral centre and therefore the two enantiomers.
The product is crystallised and recrystallised to remove over-oxidised sulfone and unreacted precursor.
Content is assayed by chromatography and the powder is milled to a consistent particle size for tabletting.
Blended with excipients and compressed; single-enantiomer product requires an added chiral resolution or asymmetric step before this point.
Getting Modafinil from food.
The whole-food sources on file. A supplement closes the gap, it does not replace dinner.
A gram-for-gram figure (how much of each you would eat to match a dose) will appear here once it is sourced and reviewed. This page will not print a number it cannot cite.
The forms it comes in.
The essence, in one line each.
- Pooling 14 studies in healthy, non-sleep-deprived adults, a single dose produced a small overall gain in cognitive performance (standardised mean difference 0.12), with the clearest signal in memory updating (0.28).Meta-analysis. Roberts et al., 2020 (European Neuropsychopharmacology). PMID 32709551 ↗
- In 50 healthy adults kept awake 54 hours, 200 mg and 400 mg doses given after 41.5 hours awake improved performance and alertness above placebo, to about the same degree as 600 mg of caffeine.Randomised trial. Wesensten et al., 2002 (Psychopharmacology). PMID 11862356 ↗
- Among 53 healthy adults randomised to a stimulant or placebo after 44 hours of continuous wakefulness, the 11 given a single 400 mg dose regained reaction speed and had fewer attention lapses on the psychomotor vigilance test than placebo, on par with caffeine and dextroamphetamine, and their reported side effects did not differ from placebo.Randomised trial. Killgore et al., 2008 (Journal of Sleep Research). PMID 18522689 ↗
- In rodents given scopolamine, methylphenidate and modafinil reduced the induced behavioural and memory changes; an animal model, not human evidence.Animal study. Alam et al., 2025 (ACS Pharmacology and Translational Science). PMID 40672679 ↗
- A Cochrane review of interventions for cognitive function in adults after cranial irradiation names modafinil among the agents studied and reports the evidence base as limited; the ingredient is mentioned inside a broader review rather than being its subject.Systematic review. Kirkman et al., 2022 (Cochrane Database of Systematic Reviews). PMID 36427235 ↗
- A review of randomised cognition trials in adults in remission from mood conditions catalogues modafinil among the tested agents and describes cognitive findings across trials as inconsistent; mentions-only, so it grounds context rather than an effect.Systematic review. Miskowiak et al., 2022 (Bipolar Disorders). PMID 35174594 ↗
- An integrative review of pharmacological options for persistent tiredness in adults with a chronic inflammatory bowel condition lists modafinil among the agents examined and reports the supporting evidence as thin; mentions-only.Narrative review. Morais et al., 2026 (Arquivos de Gastroenterologia). PMID 41538673 ↗
- A clinical reference chapter on a rare genetic syndrome names modafinil among options clinicians have used for excessive daytime sleepiness; a reference mention, not a trial.Narrative review. Driscoll et al., 1993 (GeneReviews). PMID 20301505 ↗
- A clinical reference chapter on a rare inherited muscle condition names modafinil among approaches used for daytime sleepiness; a reference mention, not a trial.Narrative review. Kleefeld et al., 1993 (GeneReviews). PMID 20301639 ↗
These are the studies our verdict leans on, chosen from the 2,397 we read for Modafinil. The full linked list is below.
The studies, linked.
12 sources behind our Modafinil verdict: peer-reviewed studies and registered clinical trials. Every one links straight to PubMed, the journal, or ClinicalTrials.gov. Read them yourself.
- Clinical trialA 24-Week, Double-Blind, Placebo-Controlled, Parallel-Group, Fixed-Dosage Study to Evaluate the Efficacy and Safety of Armodafinil (150, 200, and 250 mg/ Day) as Adjunctive Therapy in Adults With SchizophreniaClinicalTrials.gov ↗PHASE2 · 287 participants · Completed
- Clinical trialRandomized Controlled Study to Evaluate the Effects of Modafinil in Cancer Related Fatigue in Patients Undergoing Radiation TherapyClinicalTrials.gov ↗PHASE3 · 217 participants · Completed
- Clinical trialModafinil for the Treatment of Fatigue and Excessive Daytime Sleepiness in Individuals With Traumatic Brain InjuryClinicalTrials.gov ↗PHASE1 · 60 participants · Completed
- Clinical trialAn Active-Comparator Controlled Single Dose Study to Evaluate the Pharmacodynamics/Efficacy of MK-7288 in Sleep Apnea PatientsClinicalTrials.gov ↗PHASE1 · 56 participants · Completed
- Clinical trialA Comparison of the Effects of Modafinil on Olanzapine Associated Eating Behaviors in Normal Human SubjectsClinicalTrials.gov ↗NA · 50 participants · Completed
- Clinical trialInforming Treatment Decisions in the Central Disorders of Hypersomnolence: A Pragmatic Clinical Trial of Modafinil Versus AmphetaminesClinicalTrials.gov ↗PHASE2 · 44 participants · Completed
- Clinical trialComparative Randomized, Single Dose, Two-way Crossover Bioequivalence Study to Determine the Bioequivalence of Modafinil From Bravamax 200 mg Scored Tablets (Chemipharm Pharmaceutical Industries, Egypt) Versus Vigil 200 mg Tablets (Teva GmbH, Germany)ClinicalTrials.gov ↗PHASE1 · 30 participants · Completed
- Clinical trialModafinil in the Treatment of Fatigue in Post-Polio SyndromeClinicalTrials.gov ↗PHASE3 · 30 participants · Terminated
- Clinical trialDopamine Transporter (DAT) in Pharmacological Treatments of Cocaine Dependence. CAIMAN (Cocaine Addiction Imaging Medications and Neurotransmitters) StudyClinicalTrials.gov ↗PHASE3 · 29 participants · Completed
- Clinical trialModafinil for Improving New Learning and Memory in Multiple SclerosisClinicalTrials.gov ↗NA · 20 participants · Completed
- Clinical trialUse of Armodafinil (R-modafinil) for Fatigue in SarcoidosisClinicalTrials.gov ↗PHASE2 · 20 participants · Completed
- Clinical trialA Randomized, Phase II Placebo-controlled Study of the Use of Extended-release Methylphenidate or Modafinil for the Treatment of Excessive Daytime Sleepiness in Children Following Cancer TherapyClinicalTrials.gov ↗PHASE2 · 1 participants · Terminated
Evidence surfaced via Semantic Scholar (Allen Institute for AI) and ClinicalTrials.gov. Ranked by study type and citation weight, not cherry-picked.
Problems people have reported.
Read this carefully. These are 68,551 voluntary, unverified reactions reported to the FDA (openFDA). The number mostly reflects how popular Modafinil is, not how risky it is. A report is not proof Modafinil caused anything. It is a signal of what to watch for, nothing more.
Source: openFDA adverse-event reports. Voluntary reporting, not an incidence rate.
FDA Disclaimer: These statements have not been evaluated by the Food and Drug Administration. This information is for educational purposes only and is not intended to diagnose, treat, cure, or prevent any disease. Consult your healthcare provider before starting any supplement regimen.