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September 19, 2019

Medical use

Modafinil is a stimulant, meaning that it stimulates and accelerates body functions. It was developed at the end of the 1980s for the treatment of narcolepsy, which causes a sudden daytime state of sleep. Approximately 0.02–0.03 percent of the population suffer from narcolepsy. In Finland, modafinil is available as a prescription drug and its indication is adult narcolepsy. The recommended initial dose is 200 mg/24 hrs. A single dose should be not more than 400 mg [1].

In addition to narcolepsy, modafinil is also used in the treatment of other conditions causing daytime drowsiness. Furthermore, it is used sporadically in the treatment of memory and attention deficit disorders, Alzheimer’s disease, and depression [2].

Use as a doping substance

Modafinil is on the World Anti-Doping Agency (WADA) list of banned substances and it is classified as a stimulant [3]. Its effect on performance has been researched only little, but based on its effects it is believed to improve endurance and explosiveness. It is known that due to its appetite-suppressing effect modafinil is used in conjunction with bodybuilding to reduce adipose tissue.

Modafinil is also used to improve cognitive performance capacity (i.e. the so-called brain doping). Studies on healthy subjects who do not suffer from sleep deprivation modafinil have found that modafinil has a positive effect, for instance, on attention, learning and memory [4]. Unsurprisingly, students and shift workers have been found to use modafinil and other similar substances [5]. Modafinil as a potential performance capacity enhancer has also been studied by the United States Armed Forces [6].

Properties and mechanism of action

The modafinil mechanism of action differs from that of stimulants like amphetamine and ephedrine. Furthermore, modafinil is not created in the body from amphetamine or ephedrine derivatives.

Modafinil affects several different parts of the brain [7]. Presumably, the most important vitality-enhancing effect of modafinil targets the hypothalamus at the base of the diencephalon, where it activates the neural pathways, which use orexins (i.e. hypocretins) as their neurotransmitters and which are important in the regulation of the states of sleeping and waking. It also activates the sympathetic alpha-1-receptors of the central nervous system, increases the activity of accelerating glutamine and histamine neurotransmitters, and strengthens the effects of serotonin in the cerebral cortex. Moreover, it reduces the activity of the nerve cells, which use the inhibitory gamma-aminobutyric acid as their neurotransmitter. The precise mechanism by which modafinil furthers wakefulness is not known, however [1].

Contrary to amphetamine, modafinil does not excite the dopamine system of the central nervous system.

Adverse effects

Modafinil can induce pleasure and addiction, but clearly less than amphetamine. In therapeutic doses, it is well tolerated, but it may present some side effects, including insomnia, diminished appetite, abdominal pain, nausea, headaches, blurred vision, nervousness, anxiety, aggression, increased blood pressure and cardiac symptoms [1, 2, 4, 7, 8].

Some known trade names (9/2019): Alertec, Modafinil Orion, Provigil, Modiodal.

Timo Seppälä
Medical Director
Finnish Center for Integrity in Sports FINCIS (previously the Finnish Antidoping Agency FINADA

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[1] Duodecim lääketietokanta. 2019. Modafiniili. Terveysportti

[2] Kumar. Approved and investigational uses of modafinil: an evidence-based review. Drugs. 2008; 68(13):1803-39.

[3] World Anti-Doping Agency. The World Anti-Doping Code, International Standard. Prohibited List, January 2019

[4] Battleday RM, Brem AK. Modafinil for cognitive neuroenhancement in healthy non-sleep-deprived subjects: A systematic review. Eur Neuropsychopharmacol. 2015;25(11):1865–81

[5] Wilms W, Woźniak-Karczewska M, Corvini PF, Chrzanowski Ł. Nootropic drugs. Methylphenidate, modafinil and piracetam – Population use trends, occurrence in the environment, ecotoxicity and removal methods – A review. Chemosphere. 2019; 233:771–785

[6] Kelley A, Webb C, Athy J, Ley S, Gaydos S. Cognition Enhancement by Modafinil: A meta-analysis. Aviation, Space, and Environmental Medicine. 2012;83(7):685–690

[7] Minzenberg, Carter. Modafinil: a review of neurochemical actions and effects on cognition. Neuropsychopharmacology. 20087; 33(7):1477-502

[8] Spiller, Borys, Griffith, Klein-Schwartz, Aleguas, Sollee, Anderson, Sawyer. Toxicity from modafinil ingestion. Clinical Toxicology (Philadelphia) 2009; 47(2):153-6