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How Does Modafinil Work- The Science Behind Its Cognition And Wakefulness Enhancement

How Does Modafinil Work- The Science Behind Its Cognition And Wakefulness Enhancement

Last updated on 13 May, 2024

Modafinil mainly works by affecting several neurotransmitters in the brain, such as orexin, glutamate, dopamine, serotonin, and norepinephrine, among others, that promote wakefulness and improve cognitive functions.

Scientists and researchers have been meticulously trying to uncover the Modafinil Mechanism of Action. Most of their findings are covered in medical and science journals, resulting in users being aware of how they really work.

Developed by Michel Jouvet and Lafon laboratories' Modafinil is a well-tolerated eugeroic, and it was the 302nd most frequently prescribed drug in the United States, with over 1,000,000 prescriptions written.

In this context, we will explore how Modafinil works to understand the science that contributes to its cognitive and wakefulness-promoting properties.

Modafinil: An Overview

Modafinil smart drug is also known as a wakefulness-promoting agent or eugeroic. Doctors prescribe Modafinil to treat excessive daytime sleepiness associated with narcolepsy, shift work sleep disorder, and obstructive sleep apnea. Apart from its FDA-approved benefits, it has various off-label benefits as well.

It was developed in the 1970s and approved for medical use in the United States in 1998 [1]. People often also purchase Modafinil 200mg tablets for their off-label uses, including cancer and multiple sclerosis-related fatigue, treatment for cocaine addiction, attention deficit disorder, and improvement in cognitive function.

How Does Modafinil Work?

Modafinil is a drug with multiple actions, and this is because it works on various neurotransmitters in the brain - Sahakian [3]. Modafinil's method of action involves changing the amounts of natural substances known as neurotransmitters in the areas of the brain that are responsible for controlling the sleep-wake cycle [2].

What Does Modafinil Do To The Brain-?

Modafinil Do To The Brain


The wakefulness-promoting effects of Modafinil are notably different from those of other psychostimulants, such as amphetamine.

  • Modafinil is a weak dopamine reuptake inhibitor through its competitive binding to the cell membrane dopamine transporter (DAT). Its binding affinity is less than that of bupropion (an antidepressant). This interaction with the dopamine transporter and the subsequent increase in dopaminergic tone are responsible for wakefulness-promoting effects.

  • It has no effect on dopamine receptors, directly or indirectly.

  • Modafinil also binds similarly to the norepinephrine transporter (NET) and has additional effects on other CNS systems like GABA, histamine, and glutamate [4].

Modafinil And Other Neurotransmitters

  • The smart drug raises serotonin and norepinephrine levels, which help regulate mood and mental arousal, or alertness, in the brain.

  • The Modafinil neurotransmitter pathway in the brain includes glutamate and orexin. These pathways regulate a person's cognitive function, attention, and wakefulness.

The Half-Life Of Modafinil

The half-life of medicine typically refers to the period of time required by a drug to reduce to half.

The Modafinil elimination half-life ranges from 10 hours to 12 hours for most patients but can last up to 15 hours for some individuals.

Also, the question arises,How long does Modafinil last?

Modafinil requires 4-5 half-lives to be completely removed from the system. Therefore, it requires 60–75 hours to be completely removed from the system. 

Factors Affecting Modafinil Half-life

Certain factors, such as age, and poor kidney and liver function, can slow down the Modafinil metabolism and increase the duration of its effects.

How Is Modafinil Metabolized In The Body?




Modafinil undergoes hepatic metabolization via multiple pathways and is assisted by the CYP3A4 enzyme, and its inactive metabolite is excreted in the urine. Urinary excretion of the drug (unchanged) ranges from 0 to 18.7%, depending on various factors.

Renal excretion of unchanged Modafinil accounts for around 10% or less of an oral dose. Two major metabolites of this drug are Modafinil sulfone and Modafinil acid. Both of these metabolites are inactive and do not contribute to the eugeroic or wakefulness-promoting effects of Modafinil.

Peak levels, also known as the Cmax of the stimulant, occur between 2 and 3 hours after its administration. Food can slow down the absorption of Modafinil.

In vitro measurements indicate that 60% of the drug is bound to plasma proteins at clinical concentrations of the drug. When the concentration of Modafinil changes, this percentage can change but at very low levels.

How To Make Modafinil Work Better?

To make Modafinil work better or to enhance its potency, one can follow the points mentioned below.

  • By increasing the dosage- The standard Modafinil dosage recommended is 200 mg. But if you are taking a lower dose, then it may be a reason for not experiencing the desired results. People already taking 200 mg of Modafinil should make any change in their dose after consulting a doctor.

  • Try split the dosage Another effective way to make Modafinil last longer is by splitting the standard 200 mg dosage in half. You can do the first half (100 mg) in the morning and the second half (100 mg) in the afternoon. This increases the absorption rate of Modafinil, thus making it last longer.

  • Taking Coffee: Mixing Modafinil with coffee is a great idea. Both are brain stimulants that help enhance the effectiveness of Modafinil.

Modafinil And Cognitive Function

Some recent behavioural studies have shown that Modafinil can enhance cognitive functions in domains like memory, executive functions, and attention, increasing alertness and response accuracy [5].

Dr. Ruairidh Battleday and Dr. Anna-Katharine Brem from the University of Oxford reviewed all research papers from January 1990 to December 2014 on cognitive enhancement with Modafinil (Modalert). They found 24 studies addressing the various benefits of taking eugeroic for learning, planning, and decision-making, as well as for memory, flexibility, and creativity [6].

In a 2017 study, researchers monitored 60 participants, either on a single dose of Modafinil 200 mg or a placebo, for changes in their cognitive function. Drawing conclusions from both neurocognitive tests and the participants, the researchers found that the modafinil group performed significantly better on episodic memory and working memory tests [7].

Unlike some nootropics, there is some good evidence to back up the effects of the smart drug Modafinil.

  • Modafinil has been shown to improve mood and increase resistance to fatigue [8].

  • In a review, it was found that Modafinil improves motivation, vigilance, and reaction time in healthy adults [9].

  • Modafinil is effective at reducing poor decisions or impulsive actions, according to another study by the University of Cambridge [8].

Modafinil Mechanism Of Action: Our Final Thoughts

This blog sheds light on how the potent and popular Nootropic Modafinil works.

The following are some key points from this blog:

  • Modafinil is known as a smart drug because of its ability to improve cognitive functioning.

  • It works by affecting neurotransmitters (Chemical messengers) such as dopamine, serotonin, orexin, and others.

  • The half-life of this drug is 10–12 hours for most people.

  • The onset of action of Modafinil is 30 minutes.

  • The effects of Modafinil 200 mg last for about 12 hours.

However, it is crucial to use the Nootropic after consulting a healthcare professional. If you are intrigued by the medical benefits of Modafinil and wish to give it a try, you can choose.


Modafinil blocks dopamine transporters which in turn increases dopamine levels in the brain.

Modafinil is a Central Nervous System stimulant.

Yes, Modafinil increases dopamine levels in the brain.

The duration of action of Modafinil is 30–60 minutes.

The half-life of Modafinil is 10-12 hours for most people, but in some individuals, it can last for 15 hours.

Modafinil is metabolized in the liver.

At clinically relevant doses, Modafinil increases Dopamine in the human brain,this is done by blocking dopamine transporters.

Do not skip Modafinil intentionally, and if you unintentionally miss a dose, skip the missed dose and return to your regular dosing schedule.

There have been no reports of clinical injury to the liver due to Modafinil intake.

Modafinil reaches its peak concentration in about 2-3 hours after its administration.

The duration of action of Modafinil is 12-15 hours.


  1. Modafinil, Wikipedia

  2. Modafinil, Medlineplus

  3. Is Modafinil safe in the long term, the guardian

  4. Modafinil: a review of neurochemical actions and effects on cognition, NCBI

  5. Modafinil-Induced Changes in Functional Connectivity in the Cortex and Cerebellum of Healthy Elderly Subjects, frontiersin
  6. Study shows ‘Smart Drug’ Modafinil Does Enhance Cognition, neuroscience

  7. Does Modafinil Really Increase Brain Function? Labroots

  8. Modafinil: The Rise of Smart Drugs, daveasprey
  9. The neurobiology of modafinil as an enhancer of cognitive performance and a potential treatment for substance use disorders, NCBI


Disclaimer: We do not provide any medical advice.

The contents of HealthMatter are for informational purpose only and is taken by a thorough evaluation of research papers and Journals. We do not provide professional medical advice, treatment, or diagnosis. We advise all readers to consult a physician before consuming any medication mentioned on the website.