Modafinil Side Effects | Short-Term, Long-Term, Interactions, and More

Are you curious about Modafinil side effects?

Modafinil is one of the most popular “smart drugs” in the world today. Millions of people are taking Modafinil to improve their energy, focus, and concentration.

But whether you’re a narcolepsy patient in search of something to fight off daytime sleepiness, or a student looking for a significant boost in cognition, smart drug users are heavily concerned about the side effects of Modafinil.

You may have questions like:

• Is Modafinil safe to take?
• How often can I take Modafinil?
• What’s the best Modafinil dose to minimize side effects?
• Are there any Modafinil interactions with other drugs, supplements, or foods that you should know about?

Our team has reviewed all of the latest scientific studies to answer these questions. We also have extensive first-hand experience using Modafinil, so we know what to expect when taking this smart drug.

This guide will inform all beginner-level and veteran smart drug users of the potential ills associated with taking Modafinil.

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What is Modafinil?

Before we talk about Modafinil side effects, we need to discuss the basics of Modafinil, including its origins and why so many people are using the nootropic.

Modafinil was originally developed in the 1970s in France as a wakefulness-promoting agent. It wasn’t until 1998 where the FDA approved Modafinil to treat excessive daytime sleepiness for the following ailments [1]:

• Narcolepsy
• Obstructive sleep apnea
• Shift work sleep disorder

However, this prescription drug did not remain as a narcolepsy treatment for very long. Healthy individuals eventually started using it off-label for cognitive enhancement purposes [2]:

“Indeed, the cognitive-enhancement literature had been marked by positive effects on different cognitive functions across studies, with limited replication of findings for effects in specific cognitive domains, raising concerns about the reliability of cognitive enhancement effects in healthy, non-sleep-deprived samples”

Despite some conflicting research and opinions within the scientific community, real-world experience proves that Modafinil has many “off-label” benefits, including:

• 10-12+ hours of focus
• Improved overall cognition
• Enhance memory retention
• Increased productivity
• Ability to pull all-nighters

If you talk to 99% of Modafinil users, they will state unequivocally that Modafinil works for getting a massive amount of work done in an limited amount of time.

However, just like the NZT-48 pill from the movie Limitless, there are side effects of Modafinil you have to be wary of.

And irresponsible use of Modafinil can definitely bring them about.

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Modafinil Side Effects | Short-Term

Is Modafinil safe to use? Researchers at Harvard University and Oxford University think so [3]:

“Modafinil is the world’s first safe “smart drug”, researchers at Harvard and Oxford universities have said, after performing a comprehensive review of the drug.

They concluded that the drug, which is prescribed for narcolepsy but is increasingly taken without prescription by healthy people, can improve decision- making, problem-solving and possibly even make people think more creatively.”

Nevertheless, there are some common side effects of Modafinil you need to know about.

The majority of Modafinil side effects tend to be quite mild in nature, and will usually disappear 24-48 after your last dose of Modafinil.

These side effects have been reported in the medical literature and confirmed by hundreds of test subjects we have been in close contact with…

• Sleeplessness

One of the main benefits of Modafinil is the ability to produce enhanced concentration (i.e. heightened focus) for several hours at a time.

Due to Modafinil’s half-life of 12-15 hours, this practically means you will not be able to sleep for at least 10-15 hours after taking the smart drug.

Here is how Modafinil’s wakefulness-promoting properties work [4]:

“The drug possesses wakefulness-promoting properties which are mediated through the interaction of orexinergic system with the activated sympathetic nervous system. [Modafinil] exerts a synergistic effect on the orexin system, controls energy expenditure and strengthens the ability of the individual to exercise”

And just to showcase how powerful these properties are, some studies have found that narcolepsy patients can sustain wakefulness throughout the day on a 600 mg dose of Modafinil [5]:

“…a 600-mg split-dose regimen of modafinil significantly improved wakefulness in patients with narcolepsy-associated residual late-day sleepiness and was well tolerated…The improvement in executive function demonstrated with modafinil may contribute to improvements in functional status and quality of life in patients with narcolepsy”

If patients who suffer from excessive chronic fatigue and daytime sleepiness experience improvements in wakefulness, imagine the effects on a healthy individual who does not suffer from any kind of sleep deprivation!

As such, we recommend taking this smart drug first thing in the morning, and no later than 11 AM. This will allow you to fall asleep at a semi-reasonable hour after working all day on Modafinil.

• Anxiety/Nervousness

This is one of the side effects of Modafinil that appears to be inconsistent amongst smart drug users.

While some Modafinil users report no differences in their anxiety, other users report feeling anxious or nervous for 7-9 hours after taking their dose.

The severity of onset anxiety is usually manageable, but a few individuals report magnified levels of nervousness that may cancel out the increase in cognition provided by Modafinil.

The scientific literature seems to agree with our personal observations [6]:

“Modafinil appears to be associated with greater anxiety in both animal and humans, but the evidence is mixed and might be dose-dependent.”

“…Another study of mood and cognitive function in healthy young adults found that a single 100 mg dose of modafinil was associated with greater subjective and physical symptoms of anxiety than placebo, but a higher dose (200 mg) did not show these effects”

In the scientific review mentioned above, Modafinil-induced anxiety was present in studies involving clinical populations (i.e. those suffering from the ailments Modafinil is prescribed to treat) and healthy adults.

The simplest explanation for this side effect is that some users simply cannot handle the boost in cognition without feeling overstimulated.

You should not have any major concerns over this side effect, but it should nevertheless be on your radar.

In particular, nootropic users with a history of anxiety and nervousness may want to be cautious when using Modafinil and limit their use of the drug.

• Diarrhea

Out of all the Modafinil side effects, this one appears to be more “black and white”: you either don’t suffer from it at all, or it becomes a regular occurrence with frequent use of Modafinil.

What usually happens is that Modafinil users won’t feel any stomach upset on the day of taking Modafinil, but then wake up the next morning and experience diarrhea.

But even though diarrhea is a commonly listed side effect in most clinical studies, it tends to be mild in severity and very rarely warrants discontinuing the use of Modafinil [7].

“This results in a range of gastrointestinal issues. Furthermore, by increasing norepinephrine levels in the brain, Modafinil triggers the body’s fight or flight response system. In this state, the body needs to divert energy to more important systems such as the nervous and muscular systems to ensure survival and the digestive system needs to be suppressed as a result.”

In short: Diarrhea is really not a major issue, but something to be on the lookout for before using Modafinil.

• Headache/Sinus Pressure

When it comes to Modafinil side effects, headaches and sinus pressure tend to be the most commonly reported amongst research subjects.

There are many reasons for why a smart drug user may experience a Modafinil headache, but here is an overly simplified explanation…

Modafinil increases production of two neurotransmitters known as glutamate and orexin, both of which are associated with increased wakefulness.

However, both neurotransmitters are commonly associated with the onset of migraines when present in extremely large quantities [9, 10].

Other reasons for Modafinil-induced headaches include dehydration and failing to eat enough food throughout the day.

Since Modafinil provides laser-like focus on the task at hand, it can be extremely easy to forget about the need to drink water or get adequate nutrition.

Both conditions will normally lead to a small headache, and it is fairly common for even veteran users of Modafinil to experience this side effect.

We have two easy recommendations to help counteract this common problem:

• Eat your meals at the same time you normally would during a typical working day
• Drink at least a gallon of water on the days you take Modafinil.

Following this protocol, the majority of our test subjects do not have any issues with headaches while using Modafinil.

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Modafinil Side Effects | Long-Term

The longest period of time Modafinil usage has ever been studied in clinical settings is 9.5 years, where signs of dependency or tolerance to Modafinil was never observed [11]

“When modafinil effect on [excessive daytime sleepiness] was evaluated according to a scale varying from 0 (no effect) to 3 (excellent effect), 64 1% of the subjects, scored good or excellent. The mean duration of treatment was 22.05 months f 24.9, ranging from 1 to 1 14 months. Dependency signs were never observed.”

This same observation was noted in narcolepsy and stroke patients who were treated for as long as 2-3 years without developing any Modafinil side effects [12]:

“In most cases (92%), modafinil produced no side effects, even when administered during 2 or 3 years. With this drug we have never observed tolerance or dependence phenomena, nor night sleep disturbance. Conversely, narcoleptic patients frequently reported an improvement of dysomnia: their nocturnal sleep became more stable and refreshing.”

However, this does not mean that long-term side effects of Modafinil are impossible. Even though they only occur in 1% or less of all Modafinil users, they are still worth watching out for.

Many people express concerns about consistent long-term Modafinil use (+20 years), as the long-term Modafinil side effects are currently unknown.

Does cognition increase in the short-term, only to gradually decrease over several years with repeated Modafinil use? Are any other aspects of a user’s health improved or worsened?

The only way to answer this question would be through a well-designed empirical study spanning a few decades and tens of thousands of veteran Modafinil users.

(Let’s put it this way: Tobacco use was not believed to be a POSSIBLE cause of lung cancer until the end of the 19th century, and the link was not definitively established until the 1950s [13])

We’re not suggesting that Modafinil is dangerous in any way, shape, or form when used long-term. We simply don’t have enough solid data to make any definitive conclusions.

At the same time, there are some long-term side effects of Modafinil we already know about and are worth watching out for.

• Hallucinations

Modafinil is not a psychoactive drug, and therefore you should not feel “high” when you are using the smart drug. Therefore, you should never experience instances of hallucination.

Putting aside individuals who have a history of mental illnesses such as bipolar disorder and Kleine-Levin syndrome, there was only one instance we retrieved involving a patient without any prior history of psychosis.

The patient in question was a stressed-out 17-year-old girl who initially took 100 mg of Modafinil a day, gradually increasing her dose to 200 mg per day. Due to extreme stress, she attempted to commit suicide with 12 grams of Modafinil and arrived at the hospital with auditory and visual hallucinations [14].

Outside of this extreme case study, we have never heard any issues with hallucinations from our test subjects who have used Modafinil for several years.

• Irregular Heartbeat and/or Chest Pain

Modafinil is used with caution or avoided altogether in patients with cardiovascular problems, as it can increase heart rate and blood pressure [15].

There are reports of one patient who experienced an abnormally fast heartbeat and chest pain immediately after using Modafinil. He took a 400 mg dose at one time, while also taking 3-7 grams of glutamate in the form of excessive soy sauce and fast food [16].

When it comes to serious Modafinil side effects, an irregular heartbeat is one of the most undesirable ones.

We have not heard any reports of chest pain or irregular heartbeat from long-term users of Modafinil.

However, if you take Modafinil and notice uneven heartbeats or minor chest pain, it’s recommended that you get immediate medical attention and stop using Modafinil altogether.

• Sores

The formation of sores (i.e. white patches around your mouth and lips) is another serious, yet rare side effect of Modafinil.

While none of our research subjects have ever experienced it, there are a few reports of this side effect manifesting in some Modafinil users [17].

You MUST see a doctor if you find sores on the inside of your mouth or lips after taking Modafinil and halt all further use.
As we are not medical professionals, we cannot divulge further into why these sores come about.

• Bruising or Bleeding

Both outcomes are considered to be serious Modafinil side effects, yet none of our research subjects have ever reported it.
One possible explanation for irregular Modafinil-induced bleeding we found involved using it alongside hormonal contraceptives [18].

Bruising is also an extremely unlikely outcome with no explanation, other than it is possible in a tiny subset of Modafinil users [19].

If you start noticing any unusual bleeding or bruising after using Modafinil, seek immediate medical assistance at the nearest emergency hospital.

• Stevens-Johnson Syndrome (i.e. skin rashes)

Stevens-Johnson Syndrome (SJS) is one of the side effects of Modafinil that’s not attributable to Modafinil alone, as it can manifest through the use of other pharmaceutical drugs.

Here is a brief description of why it should be taken seriously [20]:

“…a chemical reaction that takes place in the cells of the skin and mucous membranes…exposure to some agent causes the immune system to go haywire and begin releasing signaling chemicals that trigger cell death.

A red or purple rash springs up that forms blisters that burst and then peel…As the spots grow together, large swaths of skin can be stripped away, leaving the sufferer vulnerable to infection”

As SJS is mentioned as a side effect on the official product monograph of Modafinil, we felt it was necessary to include it here [21].

And just like the other serious Modafinil side effects mentioned thus far, it also requires immediate treatment.

• Sleep Deprivation

This is a side effect of Modafinil that only comes about when the smart drug is abused.

The word “abuse” in this context refers to taking very high doses of Modafinil, taking Modafinil every single day, but most importantly using Modafinil as a substitute for sleep.

When you fail to provide your body with the rest it needs (7-8 hours of uninterrupted sleep each night), you are ruining your brain’s ability to function properly. The following are common in sleep-deprived individuals [22]:

• Difficulty with paying attention and focusing on one thing at a time
• Slower reaction time
• Inability to recall old memories and form new ones
• Feelings of fatigue and tiredness
• Poor decision making

Not to mention that continuously depriving yourself of sleep is extremely bad for your immune system [23]:

“…prolonged sleeplessness induces stress responses and impairs immune functions. Sleep-deprivation translocates microbes from the gut to blood streams. Animals observed in sleep-deprivation experiments eventually became victims of a massive bacterial infection in the blood.”

The ONLY time Modafinil should be used to “replace” sleep is when you have an all-nighter to pull so you can meet an extremely tight deadline.

Modafinil’s wakefulness-promoting effects are very pronounced, which is why its use must be scheduled to avoid interference with a normal sleeping schedule.

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How Modafinil Affects the Liver

This section is only relevant for individuals with pre-existing liver problems.

Currently there are no reported cases of short-term or long-term Modafinil use causing injury to the liver [24]:

“…despite widescale use, there have not been reports of clinically apparent liver injury due to modafinil or armodafinil.

…The mechanism by which modafinil and armodafinil might cause liver injury is unknown. Modafinil is extensively metabolized in the liver, but has few drug-drug interactions.”

Approximately 90% of the Modafinil you consume is processed and metabolized by your liver, with the remaining 10% being eliminated by your kidneys. It exits your body primarily through urine.

For individuals with liver impairment, the official product monograph recommends reducing their Modafinil dosage by 50%. It turns out that such individuals cannot properly clear Modafinil from their bodies [25]:

“Three patients had stage B or B+ cirrhosis and 6 patients had stage C or C+ cirrhosis (per the Child-Pugh score criteria). Clinically 8 of 9 patients were icteric and all had ascites. In these patients, the oral clearance of modafinil was decreased by about 60% and the steady state concentration was doubled compared to normal patients”

(FYI: Cirrhosis involves compromised liver function due to damage sustained to the liver, which involves scar tissue replacing healthy liver tissue)

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Modafinil Interactions?

Modafinil has the potential to interact with other medications and cause unwanted side effects.

This is because Modafinil simultaneously induces (i.e. increases activity) and inhibits (i.e. decreases activity) several metabolic enzymes in the liver used to process certain drugs [26]:

“The mean activities of microsomal CYP1A2, CYP2B6, and CYP3A4/5 from modafinil-treated hepatocytes were higher (up to 2-fold) than those in the solvent-treated controls but were less than those produced by reference inducers of these enzymes.

At high concentrations of modafinil (>/=100 microM), the mean activity of CYP2C9 was decreased (up to 60%) relative to that in the solvent controls.”

If you are taking other prescription medications, then it is recommended that you talk to your doctor about possible drug interactions before taking Modafinil. Alternatively, DrugBank contains a comprehensive database of these drugs worth looking into [27].

For instance, Modafinil is well-known to make certain types of birth control less effective and increase the likelihood of pregnancy [28]:

“The effectiveness of steroidal contraceptives may be impaired because of induction of CYP3A4/5 by modafinil. Alternative or concomitant methods of contraception are recommended for patients treated with modafinil”

In plain English, the above quote means that Modafinil leads to faster elimination of steroid-based birth control medications than usual.

Two other interactions worth noting are as follows:

• If you are taking blood pressure pills with Modafinil: Modafinil’s ability to slightly elevate blood pressure can counteract the activity of anti-hypertensive drugs.
• If you are taking Modafinil with caffeine (or any other stimulant): The synergistic “stimulating” effect can prove to be overwhelming for many smart drug users.

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Is Modafinil Safe?

Most Modafinil side effects can be easily avoided if you stick with the following dosing recommendations:

• 100-200 mg per day
• Taken 1-3 times a week in evenly spaced doses (ex. Monday, Wednesday, Friday)
• Dose is administered no later than 10am, but early morning is more ideal
• Taken with food and water

This just so happens to be the standard dosage of Modafinil taken by the majority of smart drug users who have successfully used Modafinil. It is also the standard prescription dose of Modafinil [29].

Assuming the suggestions above are followed, Modafinil is absolutely safe to take for 99.9% of healthy human beings. The Modafinil side effects mentioned in this article will be very unlikely to come about.

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Side Effects of Modafinil | The Verdict

Overall, Modafinil side effects are minor to non-existent for the majority of users.

Even in the cases where side effects do appear, they tend to disappear rather quickly, and the solutions for treating them are very straightforward.

For the vast majority of healthy adults, Modafinil is perfectly safe and the side effects will be mild at best. This true regardless of whether you are well-rested, or sleep deprived.

Plus, there are zero deaths in humans attributed to short-term or long-term Modafinil use.

However, please be mindful of the possible Modafinil interactions with other drugs, along with the list of Modafinil side effects presented in this article.

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