Modafinil has potential for causing severe allergic reactions, psychiatric effects,[3] hypersensitivity, adverse interactions with prescription drugs, and misuse or abuse.

[17] While modafinil is used as a cognitive enhancer, or "smart drug", among healthy individuals seeking improved focus and productivity,[18][19] its use outside medical supervision raises concerns regarding potential misuse or abuse.

When prescribed for MS-related fatigue management, modafinil works by promoting wakefulness and increasing alertness without causing drowsiness or disrupting nighttime sleep.

[65][66][49] Whereas modafinil and armodafinil are approved for narcolepsy, they have been repurposed as adjunctive treatments to alleviate symptoms of acute depressive phase in people with bipolar disorder.

[78] The use of modafinil in military contexts without sleep deprivation is not recommended due to inconclusive evidence on its cognitive enhancement benefits and potential risks of adverse effects.

[101] The FDA does not endorse modafinil for children's medical conditions due to an increased risk of rare but serious dermatological toxicity, manifested as Stevens–Johnson syndrome which is a type of severe skin reaction.

[8][13] Modafinil is also contraindicated in certain cardiac conditions, including uncontrolled moderate to severe hypertension, arrhythmia, cor pulmonale,[110][111] and in cases with signs of CNS stimulant-induced mitral valve prolapse or left ventricular hypertrophy.

[71] While modafinil is generally found to be safe and significant adverse effects are rare, including in pediatric narcolepsy cases (sleep disorders in children), there is evidence that long-term usage can lead to tolerance in some individuals.

Still, modafinil therapy as a eugeroic agent to treat narcolepsy does not typically lead to drug tolerance, i.e., the effectiveness does not usually decrease on prolonged use, although individual responses may vary.

[123] In comparison to classical stimulants, modafinil exhibits a low propensity for abuse, as it lacks significantly expressed pleasurable or euphoric effects.

[124] Despite the initial belief that modafinil carried no abuse potential, emerging evidence suggests that it works at the same neurobiological mechanisms as other addictive stimulants.

[125] The US Drug Enforcement Administration has classified modafinil as a Schedule IV controlled substance;[2][8] the medicine is recognized for having valid medical uses with low addiction potential.

Psychiatric symptoms may include psychosis, mania, hallucinations, and suicidal ideation, which can occur even in individuals without a history of mental illness and may persist after discontinuation of the drug.

Acute one-time total overdoses up to 4500 mg have not been life-threatening but resulted in symptoms like agitation, insomnia, tremor, palpitations, and gastrointestinal disturbances.

[133][134][135] The main way to deal with modafinil overdose is supportive care, which includes sedating the patient and stabilizing their blood pressure, and muscle activity in case of manifestations such as agitation or tremor.

[20][153] However, studies have shown that elevated concentrations of norepinephrine and serotonin can occur as an indirect effect following modafinil administration due to increased extracellular dopamine activity.

[153][20] Unlike traditional psychostimulant drugs,[23] such as cocaine or amphetamine, modafinil shows low potential for causing euphoria due to differences in how it interacts with dopamine transporters at a cellular level.

The use of modafinil for non-medical purposes, such as with the aim to improve cognitive performance or to stay awake for long periods of time, is strictly prohibited and can result in legal consequences.

[203][204] Cephalon licensed Alfresa Corporation to produce, and Mitsubishi Tanabe Pharma to sell modafinil products under the trade name Modiodal in Japan.

[213] Individuals may legally bring modafinil into the US from a foreign country for personal use, limited to 50 dosage units, with a prescription and proper declaration at the border.

[216] Modafinil is sold under a variety of brand names worldwide, including Alertec, Alertex, Altasomil, Aspendos, Bravamax, Forcilin, Intensit, Karim, Mentix, Modafinilo, Modalert, Modanil, Modasomil, Modvigil, Modiodal, Modiwake, Movigil, Provigil, Resotyl, Stavigile, Vigia, Vigicer, Vigil, Vigimax, Waklert, and Zalux.

[217] Originally developed in the 1970s by French neuroscientist Michel Jouvet and Lafon Laboratories, modafinil has been prescribed in France since 1994,[168][36] and was approved for medical use in the United States in 1998.

[8][36] Concerns have been raised about the growing use of modafinil as a "smart drug" or cognitive enhancer among healthy individuals who use it with the aim to improve concentration and memory.

Still, modafinil sold under the brand name Provigil accounted for over 40% of Cephalon's global turnover for several years, according to the information published in 2020.

[227] The regulation of modafinil as a doping agent has been controversial in the sporting world, with high-profile cases attracting press coverage since several prominent American athletes tested positive for the substance.

[162] Several athletes, such as sprinter Kelli White in 2003,[229] cyclist David Clinger[230] and basketball player Diana Taurasi[231] in 2010, and rower Timothy Grant in 2015,[232] were accused of using modafinil as a performance-enhancing doping agent.

[234] The BALCO scandal brought to light an unsubstantiated (but widely published) account of Major League Baseball's all-time leading home-run hitter Barry Bonds' supplemental chemical regimen that included modafinil in addition to anabolic steroids and human growth hormone.

[93] The research on the use of modafinil for treating individuals with Autism Spectrum Disorder (ASD) who also exhibit ADHD symptoms is currently in its early stages with no results delivered.

[269] Modafinil is being researched as a potential remedy for excessive daytime sleepiness in myotonic dystrophy (DM), an inherited condition characterized by progressive muscle loss, weakness, and myotonia.

[271] Brain injuries can impair consciousness through neuroanatomic lesions involving the bilateral cerebral hemispheres, rostral brainstem, diencephalon, or basal forebrain.