Modafinil

2-[(diphenylmethyl)sulfinyl]acetamide

Overview

Modafinil belongs to Nootropics.

Key safety note: Modafinil is generally well tolerated.[3][4]
Effects
Subjective effects vary. What a substance feels like depends on dose, individual physiology, mindset, and setting. The points below describe commonly reported effects, not guaranteed, uniform, or desirable outcomes.
  • The core effect is wakefulness and reduced fatigue and sleepiness, with improved alertness and sustained attention: most robustly in sleep-deprived people.
  • Users often report increased focus, motivation and mental stamina. Unlike amphetamine it produces little euphoria or 'rush', which is part of why it is experienced as subtle or 'flat'.
  • In well-rested people the cognitive-enhancement effect is modest and inconsistent, and can come with over-focus, irritability, headache or difficulty sleeping later.
  • Common unwanted effects are headache, dry mouth, reduced appetite, anxiety or jitteriness, and insomnia if taken late in the day.
Dosing & duration
Harm-reduction note: These are commonly cited reference ranges, not a recommendation or a “safe” dose. Potency, purity, body chemistry, tolerance, and drug combinations vary widely. Start low, go slow, wait for full effects before redosing, and never assume an unknown product matches these figures. Missing data is not evidence of safety.

Oral. Prescription doses for approved sleep disorders. Modafinil has roughly linear kinetics across 100–800 mg. Taking it late in the day disrupts night-time sleep. This is reference information, not medical advice: modafinil is a prescription-only, scheduled medicine.

Dose ranges

Narcolepsy / OSA (typical)

100–200 mg once daily (morning)

Shift-work disorder

200 mg ~1 h before the shift

Armodafinil (R-enantiomer) equivalent

≈50–250 mg (≈50 mg ≈ 100 mg modafinil)

Duration

onset

≈0.5–1 h (Tmax ≈2–4 h)

total

≈11–15 h (wakefulness across the day)

Chemical & Physical Properties
FormulaC15H15NO2S
Molar mass273.35 g/mol
StateSolid
Melting point164–166 °C
Boiling pointNot reported
DensityNot reported
Vapor pressureNot reported
pKaNot reported
LogP0.6
SolubilitySlightly soluble, Practically insoluble in water and cyclohexane. Sparingly to slightly soluble in methanol and acetone., 6.22×10⁻¹ g/L
Refractive indexNot reported
Identifiers & Synonyms
CAS68693-11-8
CAS (enantiomer)
PubChem CID4236
InChIKeyYFGHCGITMMYXAQ-UHFFFAOYSA-N
InChIInChI=1S/C15H15NO2S/c16-14(17)11-19(18)15(12-7-3-1-4-8-12)13-9-5-2-6-10-13/h1-10,15H,11H2,(H2,16,17)
SMILESC1=CC=C(C=C1)C(C2=CC=CC=C2)S(=O)CC(=O)N

Synonyms

  • Provigil
  • Modafinil
  • 2-(diphenylmethylsulfinyl)acetamide
  • Modasomil
  • Modalert
  • Armodafinil (R-enantiomer)
  • Nuvigil
Pharmacodynamics & Biochemistry

Modafinil is a wakefulness-promoting agent ('eugeroic') whose pharmacology is distinct from that of classical stimulants. Its best-established molecular action is atypical, low-affinity inhibition of the dopamine transporter (DAT), which raises extracellular dopamine slowly and modestly, without the rapid surge, euphoria or strong reinforcement of amphetamine or cocaine. This DAT interaction appears necessary for its effect: modafinil does not promote wakefulness in dopamine-transporter-knockout mice. Downstream of that dopaminergic action it engages the brain's arousal networks: activating hypothalamic orexin (hypocretin) and histaminergic (tuberomammillary) wake-promoting neurons and raising noradrenergic tone, and at the cortical level tips the balance toward glutamatergic excitation and away from GABAergic inhibition. Its precise molecular mechanism is still not fully resolved despite decades of clinical use. It has little direct affinity for the noradrenaline or serotonin transporters or for classical monoamine receptors at therapeutic doses. Nonetheless the DAT occupancy seen on human PET imaging is enough to raise abuse-potential concerns, which is why modafinil is a scheduled drug. Modafinil is sold as the racemate: an equal mixture of (R)- and (S)-modafinil. The two enantiomers share a similar terminal half-life, but (S)-modafinil is cleared faster in the early phase, so at steady state the longer-lived (R)-enantiomer makes up the large majority of circulating drug and sustains higher late-day levels. (R)-modafinil is the more potent, longer-acting enantiomer and is marketed on its own, enantiopure, as armodafinil (Nuvigil): roughly 50 mg of armodafinil is equivalent to about 100 mg of racemic modafinil. Because armodafinil is simply this single enantiomer of modafinil, it is covered here rather than on a separate page.

Biological targets

  • DAT

Binding & functional measurements

TargetMeasurementSpecies
DATpKi 5.4Rat
Pharmacokinetics
BioavailabilityHigh (oral)
Tmax≈2–4 h
Half-life≈12–15 h
VdNot reported
Protein binding≈60%
MetabolismHepatic hydrolysis and CYP3A4. Modest CYP3A4 induction and CYP2C19 inhibition
ExcretionRenal (mainly as metabolites)
Toxicology & Safety
Harm-reduction note: Toxicity and risk depend on dose, route, purity, combinations, setting, and individual health factors. Missing harms should never be interpreted as evidence of safety.

2513 mg/kg (rat, oral)

Modafinil is generally well tolerated. Headache is the most common side effect, with nausea, anxiety, insomnia, dizziness and reduced appetite also frequent, plus modest increases in heart rate and blood pressure. Its serious risk is rare but important: severe cutaneous and hypersensitivity reactions (Stevens–Johnson syndrome, toxic epidermal necrolysis, DRESS and multi-organ hypersensitivity), which led the EMA (2011) to restrict its EU licence to narcolepsy only. It is contraindicated in pregnancy after data linked in-utero exposure to congenital malformations (cardiac defects, hypospadias, torticollis). Dependence potential is low but real and it is a controlled medicine. People with a history of substance misuse or serious cardiac disease/arrhythmia should avoid it. It is a prescription drug, not a benign 'smart drug'.[3][4]

Legal Status
Legal note: Legal status can change over time and may vary by country, region, formulation, analogue status, prescription context, and enforcement practice. Always confirm with current official sources before relying on this section.
Interactions & Contraindications

Drug interactions

Drugs cleared by induced liver enzymes (warfarin, oral contraceptives, many antiepileptics, corticosteroids) Reduces the efficacy of hormonal contraceptives (CYP3A4 induction) for up to a month after stopping, so use an additional non-hormonal method.[3]
Drugs cleared by shared CYP enzymes (e.g. CYP2C9, CYP3A4) Inhibits CYP2C19, raising levels of e.g. diazepam, phenytoin and propranolol, and may alter warfarin and ciclosporin exposure (monitor INR/levels).[3]
MAOIs Hypertensive reactions have been reported with sympathomimetic wake-promoting agents.[4]

Contraindications

Pregnancy or breastfeeding in-utero exposure linked to congenital malformations (cardiac defects, hypospadias, torticollis).[3]
Pre-existing heart-valve disease left ventricular hypertrophy or mitral valve prolapse with prior stimulant use.[3]
Cardiovascular disease, hypertension or arrhythmia serious arrhythmia or significant cardiovascular disease.[3]
Known hypersensitivity to the drug risk of serious rash (SJS, TEN, DRESS).[4]
Usage & Context
  • Prescribed for excessive daytime sleepiness in narcolepsy, and as an adjunct in obstructive sleep apnoea and shift-work sleep disorder (the EU licence is restricted to narcolepsy only).
  • Widely used off-label as a cognitive enhancer / 'smart drug' by students, shift workers and professionals, and studied by militaries for sustained operations, though its benefit in well-rested people is modest and inconsistent.
  • The single (R)-enantiomer is marketed separately as armodafinil (Nuvigil), and the prodrug adrafinil is metabolised to modafinil in the body.
Sources & Evidence

Further Information