Modafinil

Our evidence-based analysis of Modafinil features unique references to scientific papers and anecdotal reports.

What Is Modafinil?

Modafinil is a powerful stimulant and wakefulness-promoting drug developed for the treatment of narcolepsy and other daytime sleep disorders. Its ability to prevent sleepiness and fatigue is only part of the picture; extensive testing has shown that modafinil offers an impressive list of cognitive benefits ranging from enhanced mood and mental alertness^‍[1] to increased motivation,^‍[2] improved reaction time,^‍[3] and better memory.^‍[4]

Modafinil is a fast-acting, highly bioavailable derivative of the ground-breaking non-amphetamine stimulant adrafinil. It was developed in the 1970s and approved by the US Food And Drug Administration for use as a narcolepsy treatment in the late 1990s.^‍[5]

Modafinil is listed as a Schedule IV controlled substance in the US and is sold as a prescription drug in the US and Canada, where it is typically prescribed under the names Provigil and Alertec. However, its proven cognitive benefits also make it a potent and increasingly popular nootropic or “smart drug,” used off-label by students, business people, shift workers, and others who are interested in increasing wakefulness and enhancing mental performance.

Though the effects of modafinil are similar to those of amphetamines like Adderall, it’s a very different substance. Modafinil is a eugeroic that specifically improves alertness, while Adderall and other amphetamines are psychostimulants that produce a temporary increase in overall psychomotor activity. Because modafinil’s actions are more targeted and selective, it is thought to provide a “smoother,” less jittery energy, have fewer serious side effects, and be better tolerated with a lower potential for abuse or addiction than amphetamines.^‍[6]

Benefits and Effects of Modafinil

Modafinil has been extensively studied and found to have several benefits.

Promotes Wakefulness and Alertness

Modafinil excels at what it was originally designed to do: it promotes wakefulness, increases alertness, and enhances mental function in a sleep-deprived state.

Modafinil has consistently been shown to effectively prevent excess daytime sleepiness without disrupting normal nighttime sleep, which makes it an extremely valuable treatment for people with narcolepsy^‍[7] or related sleep disorders such as obstructive sleep apnea.^‍[8]

It is also useful for people whose jobs require them to be alert and active at night when their circadian clocks are telling them to sleep.

The US military has successfully used modafinil to help helicopter pilots stay alert throughout sustained operations.^‍[9]

A 1997 study determined that modafinil is more effective than methamphetamine at inhibiting the sleep drive, even though modafinil increased motor activity only slightly while methamphetamine produced profound increases in motor activity.^‍[10] The same study also demonstrated that modafinil produced more consolidated periods of wakefulness than methamphetamine.

Interestingly, modafinil has been shown to restore normal levels of learning ability in methamphetamine addicts.^‍[11]

While modafinil addiction is recognized as a possibility, it is widely believed to have significantly lower addiction risk than amphetamines^‍[12] and has even been proposed as a treatment for methamphetamine and cocaine addictions.

Cognitive Effects

Modafinil has been shown to enhance cognition significantly, both in healthy non-fatigued people^‍[13] and in people experiencing sleep deprivation.^‍[14]

Studies indicate that modafinil can improve attention, executive functions, memory, and learning in healthy people, whether sleep-deprived or not.^‍[15]

Some studies suggest that modafinil’s effects may be most marked among low-performing subjects.^‍[16]

Clinical trials confirmed that modafinil improves mood in healthy subjects but may result in anxiety.^‍[17]

Many users report that modafinil also enhances focus, memory, motivation, and verbal fluency.^‍[18]

It has also been shown to improve mental function for people with conditions that impair attention processing, such as ADHD,^‍[19] cognitive decline related to physical or neurological disorders,^{‍[20]‍[21]} or drug dependence.^‍[22]

Enhanced Exercise and Sports Performance

Modafinil has been shown to improve sports and exercise performance, largely by significantly extending the time before feelings of exhaustion are experienced and reducing the perception of fatigue.^‍[23]

Modafinil was added to the World Anti-Doping Agency’s list of prohibited substances in 2004.^‍[24]

Neuroprotectant

Research suggests that modafinil may promote brain health.

It has antioxidant properties that can reduce the presence of damaging free radicals in the brain tissue, making it an effective neuroprotectant.^‍[25]

Treatment of Other Conditions

Research indicates that modafinil is comparable to amphetamine in the treatment of ADHD.^‍[26] Though it is now sometimes used as an alternative to conventional stimulants for the treatment of adult ADHD, it is currently not approved as a treatment for childhood ADHD.

Studies also suggest that modafinil is an effective treatment for both the fatigue and memory impairment related to multiple sclerosis.^‍[27]

Ongoing clinical trials are testing modafinil as a treatment for a broad range of conditions, including depression, schizophrenia, seasonal affective disorder, and nicotine addiction.

How It Works

Modafinil’s effects are similar in some ways to those of conventional stimulants, but its unique mechanisms of action set it apart.

Unlike amphetamine and other central nervous stimulants that induce wakefulness by general widespread neuronal activation, modafinil activates neurons selectively, focusing primarily on the hypothalamus and amygdala.

While it is known that modafinil modulates the brain’s histamine, norepinephrine, serotonin, dopamine, and orexin systems, the exact mechanisms of its action have not been identified in terms of locating a single site of action or major receptor binding.^‍[28]

However, modafinil’s effect on various neurotransmitters is at the heart of its potential as a eugeroic and as a nootropic.

• Orexin/Hypocretin: Much of modafinil’s wakefulness-promoting action is attributable to its action on the brain’s orexin/hypocretin system, which is located in the hypothalamus and is responsible for regulating wakefulness, arousal, and appetite.^‍[29] The most common form of narcolepsy is caused by a lack of orexin, which modafinil is believed to address by acting directly on orexin neurons. Stimulating these neurons also increases the production of histamines and other important neurotransmitters that are related to wakefulness and alertness.
• Histamine: Though we usually hear about histamine in relation to allergies and local immune responses, it also plays an important role in the regulation of the sleep/wake cycle. Modafinil’s action in the hypothalamus is believed to elevate histamine levels, contributing significantly to wakefulness and alertness.^‍[30]
• Dopamine: An important neurotransmitter associated with the stimuli/reward response, dopamine can improve mood and increase motivation and focus. Unlike amphetamines and other stimulants which directly stimulate dopamine release and increase dopamine levels in a very rapid and highly amplified manner, modafinil works indirectly by blocking the dopamine transporter or DAT, a protein that pumps dopamine out of the synapses back into intracellular fluid to be stored for future release. By blocking the DAT, modafinil effectively elevates the amount of dopamine available for immediate use in the brain.^‍[31] This gradual and somewhat indirect action on the dopamine system is an important feature of how modafinil works because it reduces the “rush” type of euphoria that is associated with addiction.
• Norepinephrine: Modafinil increases the availability of norepinephrine, a stimulant neurotransmitter that promotes wakefulness and increases alertness. The exact means by which modafinil accomplishes this increase is unclear. However, studies suggest that it blocks the norepinephrine transporter or NET in much the same way that it blocks the dopamine transporter, thus increasing the amount of immediately available norepinephrine.^‍[32]
• Glutamate and GABA: Modafinil has been shown to both elevate levels of glutamate, the brain’s principal excitatory neurotransmitter, and decrease levels of the primary inhibitory neurotransmitter, GABA.^‍[33] Glutamate plays a crucial role in cognitive function, and increased availability is believed to play an important role in modafinil’s nootropic effects.^‍[34] GABA produces a calming and relaxing effect that is necessary for sleep, and decreased levels are thought to play a role in Modafinil’s eugeroic effect.
• Serotonin: Modafinil is known to increase levels of serotonin, a neurotransmitter important for regulating mood by stimulating the serotonergic system in the cortex, hypothalamus, and amygdala. While modafinil appears to enhance serotonin release, research indicates that it doesn’t cause serotonin release or reuptake.^‍[35]

Dosage

Modafinil is a regulated drug that is approved for use only as a treatment for specific disorders, so there is no official recommendation for dosage when it is used off-label as a nootropic. Many users report optimal results with dosages between 50–200 mg daily.^‍[36]

In the treatment of narcolepsy or sleep apnea, modafinil is most commonly prescribed in a single daily dose of 200 mg, to be taken immediately upon waking. For Shift Work Disorder, the recommended dosage is typically 200 mg, taken one hour before the commencement of the shift. ^‍[37] For adult ADHD, daily doses ranging from 200–400 mg have been prescribed. Doses up to 400 mg/day have been well-tolerated, though there is no consistent evidence that doses greater than 200 mg/day provide additional clinical benefit. ^‍[38]

The dosage for the treatment of other conditions, including mood disorder, addiction, and fatigue, and cognitive impairment caused by multiple sclerosis, varies depending on each patient.^‍[39]

Modafinil appears to be safe for prolonged periods at moderate (100–200 mg) daily dosages, and large-scale clinical trials showed no significant indications of the development of tolerance over periods ranging up to several months.^‍[40] However, many off-label users self-report developing tolerance over periods as brief as a few days and recommend intermittent use or cycling.^‍[41]

Modafinil is both fast-acting and long-lasting. It is metabolized in the liver, and peak plasma concentrations occur within 2 – 4 hours, though initial effects may be felt within an hour. It has a long half-life of 15 hours and may potentially interfere with normal sleep patterns if taken late in the day.^‍[42]

Stacking

Modafinil + Phenylpiracetam Stack

This stack has been reported to increase energy and focus, as expected from modafinil, while the addition of phenylpiracetam and ALCAR help increase the fluidity of thought, curiosity, and self-perceived creativity. Credit to TramMcD for this stack idea.

Side Effects

Though modafinil is generally considered both safe and well-tolerated, it’s a powerful substance that may lead to some negative side effects, which can range from minor annoyances to major health threats.

The most commonly reported side effects include headache, dizziness, upper respiratory tract infection, nausea, diarrhea, nervousness, anxiety, agitation, dry mouth, and trouble sleeping. These are considered minor and non-severe but should be reported to a physician if they persist or worsen.

There are a number of side effects that are regularly though not frequently reported, and are considered very serious. Anyone who experiences them is advised to seek medical attention immediately. These include fever, easy bruising or bleeding, hallucinations, depression, chest pain, fast or irregular heartbeat, or mood changes such as confusion, depression, hallucinations, or thoughts of suicide).^‍[43]

Modafinil is known to interact with several drugs, including high blood pressure medications and beta-blockers, blood thinners, warfarin), anti-seizure medications, and some types of antidepressants. It may also decrease the effectiveness of hormonal birth control.^‍[44]

Where to Buy

In many countries, including Canada, the US, the UK, and Australia, modafinil is only available by prescription.

Some people opt to order modafinil from international pharmacies where drugs are sold without a prescription; this may be illegal in your country, and there may be additional risks, including receiving drugs that contain the wrong active ingredient, too much or too little of the active ingredient or contain dangerous ingredients.

However, adrafinil, which is a precursor to modafinil, is a legal alternative that has very similar effects. Like modafinil, adrafinil increases wakefulness and alertness, reduces fatigue, and offers substantial cognitive benefits, including better mood, memory, and motivation.

Click here to learn more about adrafinil.

Adrafinil can be purchased online from specialized vendors such as PureNootropics.net, a popular source for cognitive enhancing supplements.

Closing Thoughts

Modafinil is one of today’s most exciting, widely discussed, and intriguing nootropics, and with good reason: it packs the eugeroic and cognitive “punch” of amphetamines, making it possible to perform both physically and mentally at peak levels for long periods, but without amphetamines’ typical jitteriness, irritability, paranoia, and eventual devastating sleep-debt crash.

It’s generally safe and well-tolerated, and it appears to have a low potential for addiction.

But even a quick read through any of the top nootropic community forums will show that users’ results with modafinil are varied. While some are hailing it as a modern miracle that can change your life, others caution that the modafinil experience isn’t equally rosy for everyone. Some users report disappointing or even unpleasant outcomes, and others caution taking it off-label.

As usual, both sides of the story are important. There’s no denying the decades of research that have irrefutably proven that modafinil has tremendous cognitive benefits and low addiction potential. Still, at the same time, the fact that it is indeed a potent drug that can have some serious side effects, and to which everyone responds differently.

If you’re interested in using modafinil for maximizing your cognitive abilities and minimizing fatigue and sleepiness for limited periods but don’t want to run the risks associated with ordering from international pharmacies, you may want to consider its precursor, adrafinil.

Planning to start a new supplementation regimen? See our medical disclaimer.