- Modafinil is a non-amphetamine CNS stimulant used to treat medical conditions like narcolepsy, sleep work shift disorder (SWSD), and obstructive sleep apnea.
- Modafinil produces euphoric and psychoactive effects accompanied with alterations in thinking, mood, feelings and perception in case of an abuse. That makes modafinil stimulant-like (reinforcing properties) and thus physicians should follow modafinil users, with history of stimulant and/or drug abuse, closely.
FDA-Approved Modafinil Treatment Options: Narcolepsy, Obstructive Sleep Apnea, and Sleep Work Shift Disorder
Modafinil (brand name Provigil) is a medication applied in the management of somnolence . Modafinil is used off-label in the treatment of attention deficit hyperactivity disorder (with ADHD symptoms) .
According to the Journal of Environmental Health and Toxicology, Modafinil is also considered in the management of conditions like fatigue, Alzheimer’s disease, depression, schizophrenia, and jetlag . Modafinil is also used to treat obstructive sleep apnea or sleep apnea . The Journal of Environmental Health and Toxicology describes modafinil as an “exclusive psychostimulant” .
According to a research paper published in the Journal of Drug Abuse Treatment, modafinil has shown a clear stimulant or stimulant-like effect in animals . This is also supported by a study published in the Journal of Pharmacology and experimental Therapeutics . Interestingly, such significant nervous system stimulant effect was not found in human studies .
Modafinil As a Stimulant
In a scientific study published in the Brain and Cognition journal in 2021, modafinil was classified as a stimulant  alongside other substances like caffeine and methylphenidate.
Both modafinil and caffeine are nervous system stimulants (CNS). Findings by Wong and See also confirm that modafinil should be classified as a stimulant . To be exact, it was called a “wakefulness-promoting stimulant”, able to improve wakefulness . In the Textbook of Addiction Treatment, modafinil is described as a stimulant drug approved by the FDA .
Mild Stimulant Effects
In a paper published in the PLoS One Journal, modafinil is described as a mild psychostimulant . This reinforces the earlier point that, while taking modafinil does help to keep patients awake, it is not a typical stimulant. It does not appear to have the highly stimulating effect of other CNS stimulants .
In a research paper published in the Journal of Drug Assessment, the stimulant classification of the medication was discussed . Since modafinil can treat excessive sleepiness caused by underlying medical conditions then frequent prescription is justified .
The study concluded that modafinil is a stimulant alongside with others CNS agents like methylphenidate and amphetamines (like Adderall – Schedule II controlled substance prescription stimulant).
Modafinil is used in the management of daytime somnolence, treating narcolepsy, excessive daytime sleepiness, cataplexy, and nocturnal sleep disruption was noted .
Sleep disturbances and sleep disorders are positively influenced by modafinil. These were projected as beneficial for increasing awareness, cognitive performance, improving perception and thinking, and keeping one awake . Modafinil is a useful drug for shift work disorder, shift work sleep disorder and those having trouble sleeping.
Modafinil Adverse Effects
Modafinil is not without adverse effects. For example, taking this medication at therapeutic doses may interfere with hormonal birth control (one of the drug interactions) .
Other Side effects
The most common side effects include headache and nausea . Other side effects of modafinil may include chest pain (with or without trouble breathing), irregular heartbeat, and high blood pressure [23, 25, 28].
To reduce side effects, modafinil dose reduction is recommended by physicians immediately in elderly patients, those with renal function issues and for severe hepatic impairment .
Stevens Johnson syndrome has been reported, as well as skin rashes and suicidal ideation, as effects of modafinil [24, 26]. Avoidance may be allergy related .
Low Abuse potential
However, the above study noted a contrast. Unlike other stimulants, modafinil showed a low potential for abuse (one of the major side effects). Modafinil causes little or no euphoria or pleasurable feelings . Thus modafinil is a stimulant with low probability of abuse. An important point for the Drug Enforcement Agency (FDA).
This position on modafinil is also supported by Current Sleep Medicine Reports (2022) . The research noted that, unlike traditional stimulants and sodium Oxybate, there is less concern about abuse and misuse with taking modafinil. The paper then positions it, pitolisant, and solriamfetol as agents with low abuse and misuse potential (limiting side effects) .
Modafinil as a Controlled Substance
Because of its low abuse potential, modafinil is a schedule IV controlled substance, classified by the FDA in the United States of America. A schedule IV drug has a low potential for abuse. Modafinil is currently classified under schedule IV drugs .
In The Treatment of Narcolepsy
Thanks to modafinil’s less harmful side effect profile compared to other CNS drugs, modafinil is consider as the first-line medication in narcolepsy treatment. This is according to the Journal of Paediatric Sleep Medicine, Springer . This position on its side effects is promulgated by several other papers [13,14,15,18].
A paper published in the Journal of Military Medicine noted that, while modafinil is said to have no abuse risk, there is a need for caution. This is because, regarding exact mechanism of action, it has been noted to work on the same neural pathways as other addictive stimulants. This paper warns about a lack of what it termed “thorough” research into the potential risk of overconfidence . This concern is echoed by other scientific papers .
For example, according to a paper published in the Journal for Critical Care Medicine, as a stimulant, it may have a bigger side effect profile than previously thought .
1. Lyons, T. J., & French, J. (1991). Modafinil: the unique properties of a new stimulant. Aviation, space, and environmental medicine, 62(5), 432–435.
2. Biederman, J., et al (2005). https://doi.org/10.1542/peds.2005-0617
3. Kim D. (2012). https://doi.org/10.5620/eht.2012.27.e2012007
4. Dackis, C. A., Kampman, et al (2012). https://doi.org/10.1016/j.jsat.2011.12.014
5. Zolkowska, D., Jain, R., et al (2009). https://doi.org/10.1124/jpet.108.146142
6. Schmitt, K. C., et al (2011). https://doi.org/10.1371/journal.pone.0025790
7. Adam, L. C., et al (2021). https://doi.org/10.1016/j.bandc.2021.105802
8. Ooi T, Wong SH, See B. https://doi.org/10.3357/AMHP.5298.2019
9. Seyed MohammadReza Hashemian & Tayebeh Farhadi (2020) A review on modafinil: the characteristics, …, Journal of Drug Assessment, 9:1, 82-86, DOI: 10.1080/21556660.2020.1745209
10. Ngo, Q., Plante, D.T. Curr Sleep Medicine Rep (2022). https://doi.org/10.1007/s40675-022-00227-4
11.Bioulac, S., Franco, P. (2021). https://doi.org/10.1007/978-3-030-65574-7_22
12. Martine Van Puyvelde, et al, A State-of-the-Art Review on the Use of Modafinil …, Military Medicine, Volume 187, Issue 11-12, November-December 2022, Pages 1286–1298, https://doi.org/10.1093/milmed/usab398
13. Bioulac, S., & Franco, P. (2021). Stimulants 22. Pediatric Sleep Medicine: Mechanisms and Comprehensive Guide to Clinical Evaluation and Management, 291.
14. Ooi, T., Wong, S. H., & See, B. (2019). Modafinil as a stimulant for military aviators. Aerospace medicine and human performance, 90(5), 480-483.
15. DeVito, E. E., et al (2022). Modafinil does not reduce cocaine use…. Drug and Alcohol Dependence Reports, 2, 100032.
16. Chudow, Melissa1; Adams, Beatrice2. 977: EVALUATION OF THE SAFETY AND EFFICACY …. Critical Care Medicine: January 2020 – Volume 48 – Issue 1 – p 468. doi: 10.1097/01.ccm.0000633444.89554.8d
17. D’Souza, P. D., & Mascarenhas, J. J. (2019). A case report on modafinil dependence. Galore Int J Health Sci Res, 4(3), 8-11.
18. Johnson, B. (2022). Modafinil for ADHD: Is it an effective treatment?.
19.Dambreville, et al (2021). Attention Deficit/Hyperactivity Disorder & Substance Abuse in Adults & Children. Textbook of Addiction Treatment, 1357-1371.
20. Carr, Z. J., et al (2018). A double blind randomized placebo controlled pilot study …. Medicine, 97(39).
21.Tardner, P. (2022). How to Get a Modafinil Prescription.
22.Tardner, P. (2022). Can you take Modafinil every day?
23. Sousa, A., & Dinis-Oliveira, R. J. (2020). Pharmacokinetic and pharmacodynamic of the cognitive enhancer modafinil: …. Substance abuse, 41(2), 155-173.
24. Greenblatt, K., & Adams, N. (2022). Modafinil. In StatPearls [Internet]. StatPearls Publishing.
25. Mutlu, D., Kültürsay, B., & Karagöz, A. (2022). Modafinil-induced ventricular arrhythmia: A case report. Turk Kardiyoloji Dernegi Arsivi, 50(1), 79.
26. Prince, V., et al (2018). Stevens–Johnson syndrome induced by modafinil. Clinical and Experimental Dermatology, 43(2), 191-192.
27. Sheikhina, N., et al (2021). Evaluation of the effectiveness of methylphenidate and modafinil…. American Journal of Neurodegenerative Disease, 10(5), 69.
28. Winkler, A., & Hermann, C. (2019). Placebo-and nocebo-effects in cognitive neuroenhancement…. Frontiers in psychiatry, 10, 498.
29. Hama, T., et al (2021). Modafinil decreased thalamic activation…. Journal of Nippon Medical School, JNMS-2021_88.