Modafinil

Other names Provigil, CRL-40476

Several systematic reviews have concluded that Modafinil enhances cognitive performance in healthy humans. This wakefulness-promoting drug is one of the most widely used cognitive enhancers and is described by many of the people who use it as a productivity- and motivation-booster. But is it safe? Read on to find out what the science says about the risks and benefits of Modafinil.

This nootropic has no healthy human placebo-controlled studies that meet our inclusion criteria. Negative side effects can occur if used carelessly, so make sure you’re aware of the risks of Modafinil.

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Benefits

Read about the effects of Modafinil in relation to the amount of evidence we've found

Modafinil for cognitive enhancement

The authors of one systematic review concluded that Modafinil improved reaction time, logical reasoning, and problem-solving in healthy young (12-25 years) people. [1]

In another systematic review, it was found that the strongest beneficial effect from Modafinil on cognitive functioning was a moderate/large positive effect on visuospatial memory accuracy. [2]

Yet another systematic review, which analyzed data from 3 studies, found that Modafinil was an effective cognitive enhancer for healthy people. [3]

Some placebo-controlled studies find no beneficial cognitive effects from Modafinil in healthy humans. [4] This could be due to the psychological tests used (meaning the test measures something Modafinil doesn't improve) or due to individual variance in response to Modafinil (some people may not get cognitive benefits at all from it).

Another meta-analysis and systematic review found Modafinil effective for improving attention for healthy non-sleep-deprived individuals. It was also concluded in this study that Modafinil helped preserve several aspects of normal cognitive functioning in sleep deprivation circumstances. [5]

The authors of yet another systematic review concluded the following:

”We found that whilst most studies employing basic testing paradigms show that modafinil intake enhances executive function, only half show improvements in attention and learning and memory, and a few even report impairments in divergent creative thinking. In contrast, when more complex assessments are used, modafinil appears to consistently engender enhancement of attention, executive functions, and learning.” [6]

Except for the possible negative side effect on divergent creativity (which will be discussed further in the risks section), all of these meta-analyses and systematic reviews on the effects of Modafinil in healthy humans have concluded one of two things. Either that there’s a need for more research or that Modafinil effectively enhances many different aspects of cognitive performance (including memory, attention, and reaction time) for many of the people that used it in the placebo-controlled studies from which data was analyzed.

Based on data from thousands of healthy human participants, Modafinil effectively enhances several aspects of cognitive performance in healthy humans, including attention, memory, and problem solving.

Specific cognitive benefits of Modafinil for healthy humans include:

Improves working memory (especially in people with low baseline performance) [8]
Improves long term visual pattern recognition memory [9]
Improves spatial working memory, planning and decision making [10]
Enhances visuospatial attention accuracy [12] and visuospatial memory accuracy [14]
Improves reaction time performance [15][16]
Improves logical reasoning [17]
Improves problem solving performance [19]
Improves convergent creativity [20]

Other benefits, more related to mood, but still of relevance to cognitive performance, include:

Increases motivation [22]
Increases task enjoyment [23]
Reduces fatigue [25]
Increases vigilance [26]
Improved cognitive control (concept related strongly to discipline) [27]

These benefits are all backed by evidence from at least one placebo-controlled study, and several of them (specifically reaction time, memory, and attention benefits) are backed by many studies that examined the effects of the drug in hundreds of healthy humans.

Most of these studies have examined the acute effects of Modafinil, but some have found benefits also after prolonged daily use.

If you are a healthy person looking to improve your cognitive performance, Modafinil taken in appropriate doses is likely going to help you do that. But is it safe? Let's find out.

Risks

The legality and side effects of Modafinil

You should always consider the risks of a nootropic before you use it.

Negative side effects of Modafinil

General negative side effects

Modafinil did not lead to tolerance or dependence (in a study in which people received the drug daily for 3 years, and in another study in which some received the drug for up to 9.5 years) [28][29]
It did not lead to any negative side effects in 32 patients who used it daily for up to 10 years, except for possibly (1 out of 32 patients experienced each of the following, but causality cannot be established) loss of appetite, headache and nausea, and anxiety/agitation [30]
It may lead to headache and nausea for some (10-34% of people) [31], and other rare side effects can occur, including nervousness, anxiety, decreased appetite, dyskinesia, dizziness, and problems falling asleep

There is a need for more data on the safety of using Modafinil daily for several decades.

Effects on creative thinking

Convergent creativity is essentially the cognitive process of taking many ideas and connecting them in a relevant manner in order to arrive at a single solution to a problem. Divergent creativity on the other hand is the cognitive process of taking one idea and generating many related ideas in order to provide many potential solutions to a problem.

The authors of a systematic review reported that they had found studies showing impairments in divergent creative thinking subsequently to use of Modafinil. [4] The only mention of a negative effect on divergent creativity is in the abstract of the study, with all other mentions reporting no effects on divergent creativity. Several studies from which data was analyzed in this review found beneficial effects from Modafinil on measures of convergent creativity. We looked into the studies referenced in this systematic review and found that one small study reported negative effects from Modafinil on measures of divergent creativity. [33]

Modafinil may improve convergent creativity, and likely has no effect or a small negative effect on divergent creativity.

Cognitive enhancement tip: If you feel like you're lacking divergent creativity, a walk can help you.

Effects on emotional processing

A large dose (600mg) of Modafinil was found to increase fearfulness, suggesting potential negative side effects on emotional processing. [35] There’s a need for more research, especially on the effects of normal (100-200mg) doses of Modafinil on emotional processing, before it can be known if this is something likely to occur frequently for users of the smart drug, and if so, how large the negative effect is.

Modafinil (600mg) did not increase pupil dilation, subjective good drug effects, drug liking, happiness, trust, well-being, and alterations in consciousness, when compared with MDMA in one study in healthy humans. [36] These findings, together with evidence from several other studies, suggests that Modafinil is unlikely to result in effects associated with a psychoactive ”high”.

Single 600mg doses resulted in relatively impaired classification of emotions, tending to rate them as more angry, in one study. [37]

It should be noted that even though these studies are generally of high quality and relevance to healthy humans looking to enhance cognitive performance with Modafinil, very large doses (3x higher than normal) were used, which obviously increases the risks for negative side effects. Using way too much of anything is likely to result in negative side effects, so these findings do not reflect the side effects to expect if you use it in normal doses (see FAQ’s below for definition of what a normal dose is). This is not to say normal doses don’t have any of these negative side effects, only that more data is needed before it can be known what Modafinil's effects on emotional processing in such doses are.

A single dose of 300mg Modafinil given to sleep-deprived but otherwise healthy individuals led to over-estimation of cognitive abilities. [15] Modafinil shares some mechanisms of action (see FAQ’s below to read about these) with Cocaine (but is generally not as potent and risky), which could be the reason for these over-confidence effects. This effect is also likely highly dose-dependent, meaning lower doses might not result in over-confidence. Modafinil (≈300mg) did not result in over-confidence in healthy people who weren’t sleep deprived in another study. [22]

Modafinil is safe for most people if used in appropriate doses (300mg or less).

Headaches are quite common, occurring in up to 34% of users. Nausea, sleep problems, dizziness, and nervousness are relatively common side effects that occur in less than 10% of people. Higher doses may lead to negative emotional side effects such as increased fearfulness.

Side effects

Interactions

Supplements and drugs can interact with Modafinil to increase or decrease the positive or negative effects you experience. If you are already using any supplements or drugs, speak with your trusted medical professional before you experiment with Modafinil. To learn more about the potential interactions between Modafinil and other substances, use interaction-checker.

Legality

Is your country not included? Learn how to find out if Modafinil is legal in your country.

Legality Disclaimer

FAQ

Frequently asked questions about Modafinil

How much and often should you dose Modafinil?

For cognitive enhancement, 200mg is the most science-backed dose. [4]

We suggest that if you are going to use Modafinil, start with 200mg or less and only increase the dose if you don't experience any negative side effects and do experience more benefits.

In one study, 100mg Modafinil had negative effects on mood, while placebo or 200mg Modafinil didn't, in healthy humans. [59]

What time of day should you take Modafinil?

Modafinil may be the worst substance in the world to take before sleep. It is literally used by millions of people to prevent sleep.

If you are going to take Modafinil, take it in the morning as early as possible after wake-up to minimize negative effects on sleep.

What substances may stack well with Modafinil?

There's no high-quality research on the effects of combining Modafinil with other substances, such as nootropic drugs or supplements. The safety and efficacy of the below-listed combinations are supported only by anecdotal reports. People tend to report better effects from Modafinil when they also use:

Choline sources, such as Alpha-GPC, Choline Bitartrate, or CDP- Choline
L-Theanine
Magnesium
Bacopa Monnieri

Before combining any drugs or supplements, talk with your trusted medical professional about the risks involved.

What other "afinils" do people use as cognitive enhancers?

Other "afinils" that some people use for their possible cognitive benefits include:

Adrafinil
Fladrafinil
Flmodafinil
Hydrafinil
Armodafinil

If Modafinil is so science-backed, why do you never recommend it via your recommendation engine?

There are indeed a lot of placebo-controlled studies in healthy humans finding benefits of Modafinil on cognitive functions and mood. However, none of these studies have presented data in a format that allows for a calculation of the effect size measure that is used in our recommendation engine.

This entails that while there is a lot of evidence suggesting it is effective for example for enhancement of focus and memory, the size of these effects cannot be compared with the effect sizes for other nootropics that improve focus and memory. In the future, we may investigate the possibility of merging different effect size statistics in our recommendation engine in order for us to be able to compare other data formats than Cohen's D. But this is something that would take a lot of time and man-power, and we're currently investing all our efforts into the self-experimentation feature that enables you to find out if a nootropic helps you feel or perform better.

How does Modafinil work?

The mechanisms of action of Modafinil have not yet been fully discovered by researchers.

Scientists have found that Modafinil can exert the following neurobiological effects:

"Modafinil has shown the ability to increase HA, NE, 5-HT, and DA levels in the brain" [72]
- HA = Histamine
- NE = Norepinephrine
- 5-HT = Serotonin
- DA = Dopamine
Increased hippocampal glutamate levels [73]
"... GABA levels were reduced by modafinil in most brain regions studied: the cortex, medial preoptic area of the hypothalamus, posterior hypothalamus, nucleus accumbens, pallidum, and striatum ..." [74]

Researchers have also found that the neurochemical effects of Modafinil are highly dependent on the states of other neurochemicals in the brain. For example, its effects on cortical GABA levels are entirely reversed when serotonin neurons were killed. [75]

All of these findings are from cell and animal studies.

Is Modafinil neuroprotective?

It is likely that the neuroprotective effects of Modafinil depend on what the factor that is damaging neurons in the brain is. For example, lack of oxygen or dangerously high glutamate levels in the brain can lead to increased neuronal death. Modafinil is likely going to protect your neurons from some forms of neurochemical toxicity but not from everything you might expose your brain to.

For example, Modafinil has been found to protect the dopaminergic system (in monkeys) from chemical insults [77], and prevent glutamate-induced excitotoxicity (in cortical neurons). [78]

It is important to note that none of these studies were conducted in humans, so it is not certain that these effects occur in the human nervous system.

How fast does Modafinil reach peak concentrations in the blood and how long is its half-life?

Modafinil has the following pharmacokinetic profile, meaning this is how it moves in the body upon ingestion:

"After single or multiple oral doses, modafinil is readily absorbed, reaching maximum plasma concentrations at 2-4 hours after administration and pharmacokinetic steady state within 2-4 days. Its pharmacokinetics are dose-independent between 200 and 600 mg/day. The elimination half-life is approximately 12-15 hours ..." [79]