Modafinil is an FDA-regulated drug that is available by prescription for the treatment of daytime sleepiness and fatigue. It reliably promotes wakefulness and alertness and has been used (illicitly, off-label use) as a nootropic (cognitive enhancer) in highly competitive environments such as workplaces and universities.

What cognitive enhancements does modafinil provide that it attracts popular illicit use? What are the mechanisms and how does it compare to other stimulants such amphetamines or caffeine? Does modafinil have risks?

Keep reading to find the answers to these questions.

Summary

Modafinil is a reliable wakefulness-promoting substance used for the treatment of sleepiness (narcolepsy) and fatigue. In the US, it is an FDA-regulated substance and can be only obtainable under prescription. However, it has been widely used off-label as a cognitive enhancer.

Modafinil is capable of improving a wide range of cognitive functions, such as wakefulness, ADHD, memory, athletic performance, and reaction time.

Modafinil is banned in most sports events as a doping agent, while popular among competitive workplaces and universities.

Its mechanisms of action are complex acting on serotonin, norepinephrine, dopamine, histamine, orexin, glutamate, and GABA receptors.

Modafinil produces fewer side effects, abuse potential, and euphoria than amphetamines while showing similar levels of cognitive stimulation.

Modafinil usually provides a mood and wakefulness boost, from individual reports published online, and might even reduce brain fog.

However, its usage on the developing brain (during youth or adolescence) might have an impact on brain plasticity and other unclear long-term consequences.

What Is Modafinil?

Modafinil is an FDA-approved stimulant used for chronic fatigue, excessive daytime sleepiness (narcolepsy), obstructive cessation of breathing (apnea) during sleep, and shift work disorders [R].

This drug produces reliable and safe stimulatory effects, and it has significantly less abuse potential than other stimulants such as amphetamines [R, R].

Modafinil is classified by the FDA as only available under prescription [R].

Modafinil is also used by astronauts to combat fatigue, improve focus, and help adjust circadian rhythm in an artificial lighting environment [R].

Many reliable survey studies have found that modafinil is often illicitly used and popular within competitive work or study environments. Some studies showed that up to 1 in 5 students had used a stimulant to improve their focus and attention [R, R, R, R].

modafinil effects

 

Modafinil Health Benefits

1) Modafinil Reduces Fatigue

Modafinil improved attention in well-rested individuals, while maintaining wakefulness, memory, and executive functions in sleep-deprived individuals compared to placebo, as shown by a meta-analysis of human studies [R].

However, repeated doses of modafinil were unable to prevent deterioration of cognitive performance over a longer period of sleep deprivation [R].

In a trial with 41 participants under conditions of 64-hour sleep deprivation, 300 mg modafinil significantly improved cognitive capabilities compared to placebo, while amphetamine (20 mg) and modafinil scored similarly in mood, fatigue level, and cognitive tests [R].

Also, this study showed that even after 64 hours of sleep deprivation, participants under the influence of modafinil reported almost the same fatigue and mood levels as the participants had when they were well rested [R].

fatigue

2) Modafinil Helps With Addictions

Three studies (RCT of 83, 30, 65 participants) showed that 200-400 mg modafinil significantly reduced alcohol and cocaine addictions [R, R, R].

Also, modafinil (200 mg) reduced gambling desire in 20 pathological gamblers as shown by another (DB-RCT) study [R].

3) Modafinil Improves ADHD Symptoms

In a study (DB-RCT) of 248 adolescents, 170-425 mg modafinil significantly improved ADHD symptoms at school and home compared to placebo, as evaluated by clinicians, teachers, and parents [R].

A recent meta-analysis of 5 studies (DB-RCT) of 927 participants (adolescents) showed that modafinil significantly improved symptoms of ADHD as compared to placebo [R].

4) Modafinil Improves Processing Speed And Accuracy

In a study (DB-RCT) of 16 healthy volunteers, 200 mg modafinil significantly reduced the number of errors in several difficult performance tasks (such as visuospatial maintenance tasks) [R].

Interestingly, in another study (DB-RCT) of 39 male volunteers playing over 3000 chess games, modafinil reduced the average time per move and improved win-loss ratio [R].

Modafinil enhances the efficiency and cognitive information processing of a region of the brain responsible for higher cognitive function (prefrontal cortex) [R].

5) Modafinil Enhances Memory

Multiple studies (60, 17, and 64 participants) have shown that modafinil improved working memory, even in healthy humans. Modafinil, at 100, 200, and 250 mg, showed significantly better results in memory tasks such as delayed verbal recall, digit span, and visual pattern recognition [R, R, R].

6) Modafinil Increases Task Enjoyment, Motivation, And Confidence

In a placebo-controlled study of 64 participants, 200 mg modafinil significantly increased task enjoyment, well-being, and attention compared to placebo [R].

Another study on 41 healthy people under 64-hour sleep deprivation conditions noted that modafinil produced overconfidence and overestimation of one’s cognitive abilities [R].

7) Modafinil Improves Athletic Performance And Reaction Time

Modafinil improved reaction time in both healthy and cognitively impaired individuals [R, R].

A study (DB-RCT) of 60 adult male volunteers showed that high-dose (200 mg) modafinil offers the most significant improvement in reaction time compared to low-dose (100 mg). Modafinil also improved performance on cognitively demanding tasks [R].

https://www.ncbi.nlm.nih.gov/pubmed/12417966

Reaction time and cognitive functioning are key elements in athletic performance. Doping with modafinil offers an advantage in almost every sport, and such cases have been reported in sprinting [R, R].

Hence, modafinil has been prohibited as a stimulant by the WADA (World Anti-Doping Agency) since 2004.

8) Modafinil Reduces Cognitive Symptoms Of Multiple Sclerosis

Symptoms of multiple sclerosis (MS), such as fatigue and cognitive impairment, have been reduced by modafinil across 4 studies of 122 participants (only two were DB-RCT) [R, R, R, R].

9) Modafinil May Protect Neurons And Improve Their Communication

In a cell-based study (cortical astrocytes), modafinil improved the communication between these cells (gap junctional communication), which may play a role in modafinil’s stimulatory effects [R].

A similar cell-based study noted modafinil improved communication (electrical coupling) between neurons (cortical) [R].

In multiple cell studies, modafinil prevented the damage or death of neurons due to overactivation of receptors by glutamate (excitatory neurotransmitter) and degeneration of dopamine-releasing neurons [R, R, R].

Modafinil’s protection of dopamine-releasing neurons (seen in animal studies) has shown promise in treating Parkinson’s disease [R].

10) Modafinil May Decrease Anger and Anxiety

Human studies have shown that modafinil reduces reactivity to threatening stimuli in the amygdala, a brain region involved in anxiety [R].

Although not statistically significant, there were trends for reduced anxiety, as well as decreased anger-hostility on modafinil [R].

Another study on 30 adolescents showed modafinil increased aggression, stress, and anxiety at 100 mg, but not in 200 mg group paradoxically. In fact, the 200 mg group showed a reduction in anxiety [R].

11) Modafinil Enhances Emotional Processing

Multiple studies (40 and 54 participants) shown modafinil significantly improves emotional processing, such as recognition of facial expressions, as compared to placebo [R, R, R].

Modafinil Mechanisms Of Action

1) Modafinil Increases Serotonin

Modafinil mildly increases serotonin in certain regions of the brain (frontal cortex, amygdala, and dorsal raphe) [R, R].

Modafinil has also shown synergistic actions with SSRIs (selective serotonin reuptake inhibitors) amplifying the amount of serotonin [R, R, R].

Despite promising animal and cell studies, a human trial (DB-RCT) that co-administered modafinil and SSRIs for major depressive disorder (MDD) with fatigue and sleepiness failed to show their synergistic actions for the treatment of depression [R].

2) Modafinil Increases Norepinephrine

Modafinil occupies the norepinephrine transporter (NET), which leads to an increase of norepinephrine in the brain (hypothalamus and prefrontal cortex) [R, R, R].

However, even when the receptors for norepinephrine were blocked, modafinil’s stimulatory properties were not reduced, as modafinil was still able to promote wakefulness [R].

3) Modafinil Increases Dopamine

Modafinil, although at a low potency, blocks the dopamine transporter (DAT), which increases dopamine. Although this is the same mechanism of cocaine, modafinil’s activities on the transporter are unique and significantly more soothing [R, R].

Interestingly, modafinil’s “atypical” properties at inhibiting DAT might be responsible for its low abuse potential. In fact, due to these properties, modafinil is being researched as a drug for dopamine-acting substance (such as cocaine) withdrawal [R, R, R, R].

In animal studies, modafinil partially activated the dopamine D2 receptor and promoted wakefulness by significantly increasing dopamine in the brain (nucleus accumbens) [R, R].

Modafinil’s actions on the dopamine receptor might be responsible for its effects on motivation, confidence, and task enjoyment [R, R].

4) Modafinil Increases Histamine Release Through Orexin

Modafinil increases histamine release by acting on orexin-releasing neurons, as reported by multiple animal studies [R, R, R, R, R].

Orexin is a neurotransmitter that increases arousal and wakefulness. Modafinil’s effect on orexin might contribute to its stimulatory effects [R].

Histamine is also involved in the mechanisms of the wake-sleep cycle. Modafinil’s effects on histamine levels might contribute to its wakefulness-promotion properties [R, R].

5) Modafinil Increases Glutamate And Decreases GABA

Modafinil increases glutamate (excitatory) and decreases GABA (inhibitory) in different regions of the brain [R, R, R, R, R, R]. Some of these studies showed conflicting results and region-specific effects; therefore, the exact mechanism is not yet conclusive.

Modafinil Compared To Other Common Stimulants

1) Modafinil vs. Amphetamines

As referenced above, in a 60-participant study, modafinil and d-amphetamine produced similar results in improving cognitive function, fatigue, and mood during a 64-hour sleep deprivation [R].

Another study by the same author noted that modafinil produced overconfidence and overestimation of one’s own cognitive abilities. While modafinil disrupted one’s self-monitoring cognitive performance, participants given amphetamine performed accurate self-monitoring throughout the study [R].

However, amphetamines are capable of increasing anxiety levels, while modafinil is not, as shown by both animal and human studies [R, R].

While modafinil has much lower abuse potential, amphetamines, on the other hand, increase dopamine levels across the brain to a greater extent. For this reason, addiction to prescription amphetamines is common [R, R, R].

2) Modafinil vs. Caffeine

Modafinil was compared to caffeine, d-amphetamine, and placebo in a 16-volunteer study, which noted that modafinil, similar to caffeine, did not produce euphoria and less self-well-being compared to d-amphetamine. Amphetamine also increased anxiety and blood pressure levels more than caffeine and modafinil [R].

Caffeine was also unable to sustain alertness awareness during sleep-deprivation studies. In a 48-subject study using a placebo, caffeine, modafinil, and d-amphetamine, modafinil scored better than caffeine in improving fatigue [R].

3) Modafinil vs. Methylphenidate

Methylphenidate, most popularly sold as Ritalin, is similar to modafinil regarding its cognitive enhancing properties [R].

Although therapeutic doses of methylphenidate no not produce addiction, higher doses could cause euphoria and dependence if often used [R, R].

Modafinil Risks

Modafinil Drug Interactions

It has been shown that modafinil inhibits CYP2C19 and, to a lesser extent, CYP3A4 enzymes, which metabolize many drugs [R].

One study suggested that modafinil may affect the metabolism of drugs by CYP2C19 [R].

Potential interactions of modafinil with ethinylestradiol, diazepam, phenytoin, cyclosporin, and triazolam were reported [R, R].

Modafinil Allergic Reactions And Side Effects

Although rare, the FDA published some cases of modafinil-induced Stevens-Johnson syndrome (SJS), a skin allergy reaction that is potentially life-threatening if not treated [R].

A review study on long-term effects of modafinil reported that all adverse effects were mild to moderate, being the most common headaches, nervousness, insomnia, and nausea [R].

The same review also noted that, at therapeutic doses, modafinil did not elevate the average blood pressure or heart rate compared to placebo in populations at risk for heart disease [R].

The most common severe side effects of modafinil are tachycardia, agitation, dizziness, and anxiety [R].

A case of overdose (unsuccessful suicide attempt) with 5 grams modafinil was reported. Even at a high dosage, modafinil showed no signs of toxicity to vitals, liver, and kidney function [R].

Symptoms of the overdose included insomnia, severe headache, impaired movement (dyskinesia), and a mild heart complication (long QT interval), all of which subsided the next day [R].

Although addiction and withdrawal are rare, a case report has been published [R].

Modafinil Tolerance And Dependence

Modafinil’s low abuse potential has been one of the reasons why it is a popularly used nootropic [R].

As discussed in the dopamine section, modafinil’s interaction with the dopamine transporter is atypical (unlike cocaine) and is thought to be the reason why it does not produce as much euphoric and abuse potential [R].

Although addiction and withdrawal are rare, cases have been reported. Dependence resulted after daily use for an extended period at high dosage. Withdrawal symptoms included fatigue, anxiety, and inability to feel pleasure (anhedonia) [R].

Modafinil Adolescent Usage And Long-Term Consequences

A 16-week human study of sleepy (narcoleptic) patients taking 300 mg modafinil did not notice significant side effects [R].

Although modafinil seems to be relatively safe, usage during adolescence might cause permanent consequences [R, R].

Modafinil has shown to stimulate dopamine, glutamate, and norepinephrine. Frequent activation of these pathways during adolescence could cause permanent changes in the frontal cortical networks [R].

A review study looking at potential damage from nootropics and stimulants (including modafinil), noted that frequent activation and alterations of dopamine and glutamate receptors could impair brain plasticity in the long term [R, R].

The same study also suggested that the adolescent brain is sensitive to the effects of stimulants such as methylphenidate and modafinil; therefore, even low doses might result in excessive levels of dopamine and norepinephrine. This could result in impaired executive functions and altered circadian rhythm. However, long-term consequences are still unclear [R].

Modafinil Individual Experiences

Modafinil has been hailed to reduce brain fog, and for one user, “felt like me for the first time in years”.

Many users said that modafinil reliably produced cognitive enhancing effects.

Going over the therapeutic dosage is not recommended. One report of a user taking 4,000 mg of modafinil, experienced a severe headache along with dizziness, or what he described as “Worst Experience of My Life!”

Other severe side effects of modafinil are already reported in scientific publications, such as racing heart (tachycardia). One user was taken to the ER and was given IV beta blockers after IV adenosine failed.

Some Redditors also reported tolerance after daily use.

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8 COMMENTS

  • Ricia Banther

    Comment; mostly OT to a fellow poster and not specifically about Modif.

    Wow and more Wow, was going to congrat you on CBT but not sure you are using it? The badly crashing socialized Med (NHS) here in the UK pushed CBT down everyones throat for everything the last few years. Few wks ago a mental Health nurse told me the game is up and results have not panned out and it has had low success. However human reluctance to change esp when in strife…takes a huge amount of what the Buddhist call ‘Suffering’ for patterns to be sincerely addressed. IMO the longer it takes us to get ill the longer it takes us to recover and patience is not a factor of this era. I am getting huge success from Eckhart Tolles Utube suggestions on relationships with ourselves. Perhaps stress=illness/dysfunction is the path to some human paradigm shift?? Complex Abe folks get complex issues needing new solutions? Look at our noble leader Joe

    I recognize the gastric issues (experiencing them on and off currently, I attribute to my chemistry intolerant to new formula-inactive ingredient. My guts and sharp back pain behind stomach for yrs seemed closest to wild IGA being blamed, but did not test out and that was just food related. The going sleepy soon after ‘exposure’ I also had to get my head around, rare since I now suffer rather than dare symptom relief. The hot flashes are classic for those trying to learn about what so far is recognized about Histamine issues and I know them well too.

    I am just now pulled together enough to get back to researching. Likely why we meet here?? Previously the most sophisticated and largest group of what I hear called ‘citizen scientist’ is over on multiple forums at phoenixrising , They were the first place I could watch ‘gene speak’ and try to learn some of the ‘language’. It seems a tribe of the those long fallen through the cracks and many seriously well informed focused on solutions, not suffering.

    You might not know about an area somewhat like immunology but much more basic deep metabolism disruption (as far as I can tell) not even a settled term, but a spin off of long recognized extreme intolerance, Mast Cell Activation Disorder (or Syndrome. It was fringe when I tried rounding up data but ck MCAD if you have not already ran across it would be my suggestion for research. NO ans, but sometimes the comfort of just being recognized helps get though the day!

    IMO Sadly things without an obvious profit motive, as in a direct symptom for big pharma to throw research money at to create a drug, is bad health care for the world. Those carrying any new directional torch are vilified by their peers for yrs till gold standards crush under there own mistaken symptom solutions.

    I am experimenting with ‘pulsing’ therapeutic trials (rotating)and alternative delivery systems (inside of lips gums under the tongue)-not working! Breaking up tabs and getting things past my stomach/duodenum as fast as possible and then buffering after by drinking a mug of cooked slippery elm powder. Also either kind of cheap flax seeds soaked overnight in water make a innocuous slim that coats and soothes but doubt it can interrupt signaled cascades your SUFFERRING. Big healer for badly damaged mucus linings and old fashion ulcer cure is straight cabbage Juice. From memory high sulfur beside all the other goodies. I spend lots on food close to its source and still alive. I eat nothing I do not control. But self experiment crashes and getting back to baseline, sends me to listen to ET!

    Sleep is where all DNA repair happens, let us all know what you discover. I Care.
    old and far away

  • pseudonym

    Hi –
    Cons for me are common side effects – nausea during the next two hours after taking a dose (sometimes mild, sometimes just short of vomiting), needing to sit up during that same two hours because of pain in esophagus or upper stomach if I lie down, hot flashes during that two hours. Then I get intensely sleepy, almost like narcolepsy, I can’t stop falling asleep and will sleep about an hour. This symptom goes away if I get at least 3-4 hours sleep (which is almost never). Then I am fine and quite productive the rest of the day. But the experience of the first two hours makes it very hard to contemplate swallowing that next dose.
    Regarding racing mind, sadly I don’t have that issue. I say sadly because there are very successful CBT programs (80+ percent success rate) that can fix that without medications.

  • Ricia Banther

    Hi,
    Pseudonym if you have time, I would very much appreciate your’ cons’ for using ’40mg Strattera’.

    Two months ago I inquire about switching to Strattera from Modif in hopes some of my inflammatory issues are related to TransSulfur metabolism (I think that is what I mean??) but the whole sulfite/sulfur issue I am keen to know more about. Strattera compared to Modif, a chemist explained would be a better option to get away from the often problematic issue so many suffer from, (I do have the modif tech details….)

    Shrink said sure….after three months ‘washout’ and then do a trial run. I declined for now, as 3mo with out calm and quiet at least for a few hours in the morning was a very hard thought.

    If the insomnia is ‘mind running’………. I recommend Eckhart Tolles’, Utube advice. A better ‘flavor’ of ‘mindfulness’ ie bril way to turn OFF the mind. Potassium/electrolites helps me for jitters-various. But tiny amounts of B6-Niacin really really wks if tolerated…something about jolting the Liver (my words/interp!)

    I will assume you know about ‘blue screen’ viewing in the evening, implicated in sleep issues?

    I have very little knowledge about anything but coffee and modif and extreme intolerance’s. If you see this let us know how Strattera compares.

    thanks
    SpocksDaughter

    Moderator??? If my comments are ‘crossing any lines’ please let me know?? I am new

  • pseudonym

    Chronic insomnia for 12 years, at one point was prescribed 100mg modafinil first thing upon waking, this worked well for daytime alertness for several years with no downsides for me. Then for some reason stopped working or gave me the ‘jitters’ even at 50mg. Switched to 40mg Strattera upon waking as off label use for alertness, on it about three months now. It has its pros and cons but so far is more helpful than bothersome. Still trying to hack my insomnia meanwhile…

  • Ricia Banther

    Hi and thanks for good stats in this piece, I only recently got on board and this topic really surprised me! I am Western American, 65 yr old female who convinced UK Dr(Shrink) to prescribe for my newly recognized Aspergers (4+ yrs ago). Consistent 75-100 mg daily since.

    It was like my mind was my own. the world was a calm good place and I was able for what ever! ‘Was’ because, economic pressures forced the manf of the brand (I soon found out I had to insist on being supplied with Myland*) was withdrawn from the market while a cheaper formula was reorganized. Been living in Hell and wild times last 5 months trying now 4 other generics, already with obviously much cheaper/dirtier formulas. Issue; personally likely non active ingredients of various kinds that I personally am wildly intolerant of. Long history of extreme sensitivity ie Asperger dx age 56!

    FYI lots of news in the ‘digital river crowd of citizen scientist’ struggling with personalized med in a a la’ ‘do it your self’. Genome folks esp MTHFR ‘fad?’ but for many of us a at long last serious explanation how intolerance to common things like sulfites, sulfurs histamine, bio-amines…Mast Cell activation issues etc etc are crashing folks who really need to understand their personal limits. Sadly I will be dead before good advice is widely available.

    looking forward to this thread! Lkie I said ‘I am new here’, I am far from the new world civilization but the clever pop up window on my desktop sure helps me notice your skill to help Me be informed.

    Hope this helps. Without staying conscious and self knowledge, sooner or later NO One can push themselves to far! The universe will teach you a lesson, one way or another!
    DOWN with Popular Culture!

    Spocks Daughter
    10 miles from Stonehenge

  • michelle c frankie

    modafanil is toxic too the body…and IM sorry it feels exactly like speed to me..nobody needs to be in that state of mind in my opinion…the best state of mind to be in is restful awareness..not all up in your head and finding things that are boring actually interesting..FInd what really is interesting and that will make u happy. ALso it causes unreal tension and caused my body temp to go so low it was hyperthermia..it killed my right kidney or adrenal too something on lower right side would kill after i take it..and the pain it caused in my neck was rediculous ..totally crunnched.

  • L.

    This stuff is great, but be sure to cycle off once in a while… I got anxiety when using it for about 40 days almost daily & (stomach? pancreas?) ache & skin rash in my face… The negative effects completely wore off after a week or so not taking it… but be careful. Luckily this isn’t really addictive stuff.

  • Brett

    I was legally prescribed modafinil and took it for several years. Not abusively, I took 50 – 100mg 5 or 6 days per week. It gave me tons of energy and drive and focus, but I never really got tired and “crashed” and kept plowing through physical and mental activity. I felt “limitless.” Eventually I developed severe Adrenal Fatigue Syndrome and crashed. I am not blaming it exclusively on the modafinil but I feel strongly that it “enabled” me to live above and beyond my energy means and there were consequences. I would never take a chemical stimulant again, knowing what I know now. I urge caution

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