Modafinil is a powerful stimulant and wakefulness-promoting drug that was developed for the treatment of narcolepsy and other daytime sleep disorders. But 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 to increased motivation, improved reaction time, reduced fatigue, and better memory.
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, is thought to provide a “smoother,” less jittery energy, have fewer serious side effects, and be better tolerated and have a lower potential for abuse or addiction than Adderall.
Benefits and Effects
First and foremost, modafinil excels at what it was originally designed to do: it increases wakefulness and alertness, and enhances mental function in a sleep-deprived state.
A derivative of the ground-breaking non-amphetamine stimulant adrafinil, modafinil is both faster-acting and more bioavailable than adrafinil and has been marketed as a separate drug since the late 1970s. After extensive testing, modafinil was approved by the US Food And Drug Administration for use as a narcolepsy treatment in the late 1990s.
As a eugeroic or wakefulness-promoting agent, modafinil has been shown to effectively prevent excess daytime sleepiness without disrupting normal nighttime sleep. This makes it an extremely valuable treatment for people with narcolepsy or related sleep disorders such as obstructive sleep apnea. 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.
It’s important to understand that while modafinil enhances wakefulness, it’s not a long-term substitute for sleep. Though modafinil can be used to stay awake through regular sleep periods for a short period of time without incurring an immediate burdensome sleep debt, adequate sleep is absolutely essential for good health and cognitive function. Many off-label users who take modafinil as a nootropic report that they get the best cognitive boost and most significant nootropic effects from modafinil when they are not sleep-deprived.
Promoting wakefulness is only one of modafinil’s effects. It’s particularly good at enhancing cognition, both in healthy, non-fatigued people and in people experiencing
sleep deprivation. It is also proven to improve mental function for people with conditions that impair attention processing, such as cognitive decline, ADHD, or drug dependence.
Interesting new research suggests that modafinil can actually 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.
Treatment of Other Conditions
Research indicates that modafinil is comparable to amphetamine in the treatment of ADHD.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. 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, methylphenidate, 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 precise mechanisms of its action have not been identified in terms of locating a single site of action or major receptor binding.
However, it is clear that modafinil’s effect on various important neurotransmitters is at the heart of its potency, both 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. 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 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.
- 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 more gradually by blocking the receptors that remove dopamine from the synapses, which effectively elevates the amount of dopamine available for immediate use in the brain. 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 is believed to increase the availability of norepinephrine, a stimulant neurotransmitter that promotes wakefulness and increases alertness. The exact means by which modafinil increases the availability of this stimulant neurotransmitter is unclear, though it may be related to modafinil’s action on the orexin system and dopamine receptors.
- Glutamate: Modafinil elevates levels of glutamate, the brain’s principal excitatory neurotransmitter, by stimulating the extracellular release of glutamate in the hypothalamus. Glutamate plays a crucial role in cognitive function, and this increased availability plays an important role in modafinil’s nootropic effects, from increased memory to improved focus and even brain plasticity.
Though not everything about modafinil’s mechanisms of action is completely understood, more than 40 years of extensive research have provided invaluable insights on its effects.
- Effects in Comparison to Amphetamines: A 1997 study determined that modafinil is more effective than methamphetamine at inhibiting the sleep drive, despite the fact that modafinil increased motor activity only slightly while methamphetamine produced profound increases in motor activity. 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. While modafinil addiction is recognized as a possibility, it is widely believed to have significantly lower addiction risk than amphetamines and has even been proposed as a treatment for methamphetamine and cocaine addictions.
- Effects on 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. It was added to the World Anti-Doping Agency’s list of prohibited substances in 2004.
- Effects on Cognitive Abilities: Decades of research support the idea that modafinil results in measurable improvement in a wide array of cognitive abilities, ranging from working memory and fluid intelligence to both spatial and episodic memory, pattern recognition, executive function, and performance on tasks that require higher-level thinking. Some studies suggest that modafinil’s effects may be most marked among low-performing subjects. Clinical trials confirmed that modafinil improves mood in healthy subjects but may result in anxiety.
In the treatment of narcolepsy or other sleep disorders, modafinil is most commonly prescribed in daily dosages of 100 mg or 200 mg, to be taken immediately upon waking or at least early enough in the day to permit regular sleep at night.
For Shift Work Disorder, the recommended dosage is typically 200 mg, taken one hour before the commencement of the shift. The average dosage prescribed for the treatment of adult ADHD ranges from 100-200 mg daily, and 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.
When taken as a nootropic, a starting dosage of no more than 50 mg is generally advisable, increasing the amount gradually over a period of time and only as needed to achieve results.
The maximum safe daily dosage is generally recognized as 400 mg, and indeed clinical trials suggest that a 400 mg dose doesn’t provide markedly improved results over a 200 mg dose, though the larger dosage may increase the possibility of adverse effects.
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.
Even when taken at moderate therapeutic doses, psychological dependence is a rare but distinct possibility and has been recorded in isolated case studies, which reported withdrawal symptoms including anxiety, insomnia, lethargy, and the inability to feel pleasure.
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 fluidity of thought, curiosity, and self-perceived creativity. Credit to TramMcD for this stack idea.
Though modafinil is generally considered to be both safe and well-tolerated at moderate dosages, it’s a powerful substance and does have some possible negative side effects, which can range from minor annoyances to major health threats.
The most commonly reported side effects of modafinil are considered minor and non-severe, including anxiety, insomnia, headache, nausea and indigestion, dizziness, diarrhea, dry mouth, and inflammation of the inside of the nose. Many of these side effects may be brief and temporary, though if they persist or worsen over time the user is advised to seek medical advice.
Some less commonly reported side effects that should be noted but are not usually considered serious problems include excessive thirst, involuntary trembling, quaking, or shivering, loss of appetite, vomiting, and backache. As with the most common side effects, these may by brief and temporary but should be reported to a physician if they persist or worsen.
There are a number side effects of modafinil 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 rapid or pounding heartbeat, abnormal heart rhythm, or chest pain; high or low blood pressure; the inability to empty bladder or bowels; chills and/or fever; confusion, depression, loss of memory, or mood changes; dyskinesia, or the impairment of voluntary movement; and problems with eyesight.
There are some side effects of modafinil that are rarely reported but are considered extremely serious. Anyone who experience any of the following while taking modafinil is advised to seek medical advice without delay: asthma, giant hives, suicidal thoughts, abnormal peeling of skin, bloody urine, rash or skin blisters, red or swollen mouth tissue, trouble breathing, visible water retention, or hyperactive behavior.
A medical exam may reveal even more serious side effects, including abnormal liver function, decreased blood platelets or red blood cells, inflammation of heart tissue, or hepatitis, among others.
Where to Buy
In Canada and the US, modafinil is only available by prescription. Some people opt to order modafinil from international pharmacies where they are sold without a prescription. However, ordering from these discreet pharmacies may not only be illegal in your country, but there are additional risks such as 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 actually 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.
Adrafinil can be purchased online from specialized vendors such as AbsorbYourHealth.com, a popular source for cognitive enhancing supplements.
Modafinil is definitely 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, make you smarter, and rewrite the book when it comes to the need for sleep, others caution that the modafinil experience isn’t equally rosy for everyone. Some users report disappointing or even unpleasant outcomes, and others caution that taking it off-label could actually be a very risky business. Which view is correct?
As usual, both sides of the story are important. There’s absolutely no denying the decades of research that have irrefutably proven that modafinil has tremendous cognitive benefits and low addiction potential, but at the same time there’s no way around the fact that it is indeed a very powerful drug that can have some serious side effects, and to which everyone responds differently.
The bottom line? Everyone responds differently to nootropics and indeed to all drugs, but decades of research have shown that modafinil is safe, effective, and well-tolerated. If you’re interested in maximizing your cognitive abilities and minimizing fatigue and sleepiness for limited periods, modafinil is a nootropic worth considering.
Planning to start a new supplementation regimen? See our medical disclaimer.