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

Modafinil is a prescription drug that’s used for the treatment of narcolepsy, shift work sleep disorder, and idiopathic hypersomnia. However, it’s gained popularity as nootropic among those who find themselves waking up in the middle of their night without an alarm clock or wanting to stay awake all day – often due to professional obligations like school or work. While these side effects are typically only temporary (lasting anywhere from 8-24 hours), they’re still something you should be aware of before using this nootropic medication. Furthermore, there may be some interactions with other medications which could have longer lasting effects on your health if taken at the same time as modafinil

Modafinil is a medication that is used to treat narcolepsy, sleep apnea, and shift work disorder. It can also be used as a study aid. The “modafinil teeth” are one of the side effects of modafinil.

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

What are the Modafinil adverse effects that you should be aware of?

There’s no denying that millions of individuals across the globe are beginning to use Modafinil at an alarming pace.

Whether you’re a Narcolepsy sufferer searching for a way to combat daily drowsiness or a student looking for a considerable increase in cognition, the side effects of Modafinil are a major issue for smart drug users.

Is it safe to use Modafinil? Is there anything you should know regarding Modafinil interactions with other medicines, supplements, or foods?

This article will enlighten both new and experienced smart drug users on the risks associated with Modafinil usage.

 

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What exactly is Modafinil?

To better comprehend Modafinil side effects, we must first review some background information on the nootropic’s origins and why individuals use it.

Modafinil was first developed as a wakefulness-promoting drug in France in the 1970s. Modafinil was not licensed by the FDA until 1998 to treat excessive daytime drowsiness for the following conditions [1]:

  • Narcolepsy
  • Obstructive sleep apnea (OSA) is a kind of sleep apn
  • Sleep disturbances caused by shift work

This prescription medicine, however, did not last long as a narcolepsy therapy. Healthy people soon began taking it off-label for cognitive improvement [2]:

“In fact, the cognitive-enhancement literature had been marked by positive effects on various 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,” says the author.

Despite some contradicting data and perspectives among the scientific community, anecdotal evidence suggests that Modafinil is quite effective for giving benefits such as:

  • 10-12 hours of intense concentration
  • Overall cognitive improvement
  • Improve your memory retention
  • Productivity has increased.
  • Ability to stay up all night

If you ask 99 percent of Modafinil users, they will tell you that the drug helps them get a ridiculous amount of work done in an absurd length of time.

However, much like the NZT-48 medication from the movie Limitless, Modafinil has adverse effects to be aware of.

And the misuse of Modafinil may certainly contribute to them.

 

Short-Term Modafinil Side Effects

Is it safe to use Modafinil? Harvard University and Oxford University researchers believe so [3]:

“Modafinil is the world’s first safe “smart medicine,” according to Harvard and Oxford academics who conducted a thorough assessment of the drug.

They came to the conclusion that the medicine, which is recommended for narcolepsy but is increasingly being used by healthy individuals without a prescription, might enhance decision-making, problem-solving, and potentially even help people think more creatively.”

However, there are certain Modafinil adverse effects that you should be aware of.

The majority of Modafinil adverse effects are minor and will go away within 24-48 hours following your final dosage.

These negative effects have been documented in medical journals and validated by hundreds of test volunteers with whom we have worked with…

  • Sleeplessness

Enhanced attention (i.e. heightened focus) over many hours is one of Modafinil’s most notable effects.

Because Modafinil has a half-life of 12-15 hours, you won’t be able to sleep for at least 10-15 hours after taking the smart medication.

Modafinil’s wakefulness-promoting effects act as follows [4]:

“The medication has wakefulness-promoting qualities that are mediated through the orexinergic system’s interaction with the activated sympathetic nervous system.” [Modafinil] has a synergistic impact on the orexin system, which regulates energy consumption and improves an individual’s capacity to exercise.”

To demonstrate how potent these qualities are, several studies have indicated that narcolepsy sufferers need up to 600 mg of Modafinil per day to stay awake throughout the day [5]:

“…a 600-mg split-dose regimen of modafinil enhanced alertness and was well tolerated in individuals with narcolepsy-associated residual late-day drowsiness… The increase in executive function shown with modafinil may help people with narcolepsy improve their functional status and quality of life.”

If patients who suffer from extreme chronic tiredness and daytime drowsiness enjoy improvements in alertness, consider the consequences on a healthy person who does not suffer from any form of sleep loss.

As a result, we suggest taking Modafinil no later than 11 a.m., preferably first thing in the morning. After working all day on Modafinil, this will help you to fall asleep at a semi-reasonable hour.

  • Anxiety/Nervousness

One of the Modafinil adverse effects that tends to be inconsistent among smart drug users is this.

While some Modafinil users report no change in anxiety, others report feeling anxious or apprehensive for up to 7-9 hours after taking the smart medication.

Although the degree of beginning anxiety is normally tolerable, a few people experience increased levels of anxiety, which may wipe out the benefits of Modafinil.

Our own observations seem to be supported by scientific evidence [6]:

“Modafinil seems to be linked to increased anxiety in both animals and people, although the data is conflicting and dose-dependent.”

“…Another research of mood and cognitive performance in healthy young people revealed that a single 100 mg dosage of modafinil was related with more subjective and physical anxiety symptoms than placebo, while a larger dose (200 mg) had no such effects.”

Modafinil-induced anxiety was found in research including both clinical populations (those suffering from the conditions Modafinil is intended to treat) and healthy people, according to the scientific review stated above.

The most straightforward reason for this adverse effect is that some users are unable to cope with the increased cognition without being overstimulated.

This is one of the Modafinil side effects that should not cause you any big worry, but it should be kept in mind.

Nootropic users with a history of anxiety or uneasiness, in particular, should exercise caution and restrict their usage of Modafinil.

  • Diarrhea

This seems to be the most “black and white” of all the Modafinil side effects: You may not experience it at all, or it may become a common occurrence if you take Modafinil often.

Typically, Modafinil users will not have stomach discomfort on the day they take the drug, but will wake up the following morning with diarrhea.

Even while diarrhea is a frequent side effect reported in most clinical trials, it is usually minor in intensity and only rarely merits stopping Modafinil usage [7].

We don’t know why this Modafinil side effect occurs, however some experts believe it’s due to intestinal tissue irritation caused by Modafinil’s delayed breakdown in the digestive tract [8]:

“This causes a variety of gastrointestinal problems.” Modafinil also activates the body’s fight or flight response system by raising norepinephrine levels in the brain. To maintain life, the body must redirect energy to more vital systems such as the neurological and muscular systems, and the digestive system must be inhibited as a consequence.”

In conclusion, diarrhea isn’t a serious problem, but it’s something to be aware of before using Modafinil.

  • Sinus Pressure/Headache

When it comes to Modafinil side effects, headaches and sinus pressure are the most typically mentioned by study participants.

There are a variety of reasons why a smart drug user could have a Modafinil headache, but here’s one oversimplified explanation…

Modafinil boosts the synthesis of two neurotransmitters called glutamate and orexin, which are both linked to enhanced alertness.

However, excessively high levels of these neurotransmitters have been linked to the start of migraines [9, 10].

Dehydration and not eating enough food during the day are two more causes of Modafinil-induced headaches.

Because Modafinil offers such intense attention on the work at hand, it’s all too easy to forget to drink water or eat properly.

Both circumstances will usually result in a little headache, and even long-term Modafinil users are susceptible to this adverse effect.

We have two simple suggestions to assist you deal with this problem:

  • Consume your meals at the same intervals as you would throughout a regular working day.
  • On days when you’re taking Modafinil, drink at least a gallon of water.

The majority of our test volunteers do not experience headaches when taking Modafinil while following this strategy.

 

 

Long-Term Modafinil Side Effects

The longest term of Modafinil use in clinical settings has been 9.5 years, and no evidence of reliance or tolerance to Modafinil have ever been detected [11].

“When the impact of modafinil on [excessive daytime drowsiness] was rated on a scale of 0 (no effect) to 3 (great effect), 64 percent of the patients gave it a good or excellent rating. The average treatment time was 22.05 months, with a range of 1 to 14 months. “There were no evidence of dependency.”

This was also seen in narcolepsy and stroke patients who were given Modafinil for up to 2-3 years without experiencing any negative effects [12]:

“Modafinil had no negative effects in the vast majority of instances (92 percent), even when given for two or three years. We have never seen tolerance or dependency with this medicine, nor have we ever had night sleep disturbances. Narcoleptic patients, on the other hand, commonly stated that their dysomnia had improved: their nighttime sleep had become more steady and pleasant.”

This does not rule out the possibility of long-term Modafinil adverse effects. They only affect around 1% or fewer of all Modafinil users, but they’re worth keeping an eye out for.

Many individuals are concerned about using Modafinil for an extended period of time (+20 years), since long-term Modafinil negative effects are still unclear.

Is Modafinil usage associated with a gain in cognition in the near term, followed by a steady reduction in cognition over many years? Is there any other area of a user’s health that has improved or deteriorated?

Only a well-designed empirical research spanning decades and tens of thousands of seasoned Modafinil users might provide an answer to this topic.

(To put it another way, tobacco smoking was not thought to be a POSSIBLE cause of lung cancer until the late 1800s, and the relationship was not confirmed clearly until the 1950s [13]).

We’re not implying that long-term usage of Modafinil is hazardous in any manner, shape, or form. We just lack sufficient data to draw any definitive conclusions.

At the same time, there are certain long-term Modafinil adverse effects that we already know about and should be aware of.

  • Hallucinations

Because modafinil is not a psychoactive drug, you should not experience a “high” when taking it. As a result, you should never suffer from hallucinations.

With the exception of those with a history of mental diseases like bipolar disorder or Kleine-Levin syndrome, we only found one case involving a patient who had never had psychosis before.

The patient in issue was a stressed-out 17-year-old girl who began taking Modafinil at 100 mg per day and steadily increased her dosage to 200 mg per day. She attempted suicide with 12 grams of Modafinil due to intense stress and was admitted to the hospital with auditory and visual hallucinations [14].

Aside from this severe case study, none of our test volunteers who have taken Modafinil for many years have reported experiencing hallucinations.

  • Chest Pain and/or Irregular Heartbeat

Patients with cardiovascular issues should take modafinil with caution or avoid it completely since it might raise heart rate and blood pressure [15].

One patient who had an unusually rapid heartbeat and chest discomfort after using Modafinil did so while simultaneously consuming 3-7 grams of glutamate in the form of excessive soy sauce and fast food [16].

An irregular heartbeat is one of the most concerning Modafinil adverse effects.

Long-term Modafinil users have not complained of chest discomfort or an erratic heartbeat.

However, if you use Modafinil and have irregular heartbeats or slight chest discomfort, you should seek medical help right away and stop using the drug.

  • Sores

Another dangerous but uncommon adverse effect of Modafinil is the development of sores (white areas around your mouth and lips).

While none of our study participants have ever experienced it, this negative effect has been reported in some Modafinil users [17].

If you get sores on the inside of your mouth or lips after taking Modafinil, visit a doctor immediately and discontinue usage.

We can’t go into detail about why these sores appear since we’re not medical specialists.

  • Bleeding or Bruising

Both of these events are considered major Modafinil adverse effects, although none of our study participants have ever mentioned them.

We discovered that taking Modafinil combined hormonal contraceptives might explain irregular Modafinil-induced bleeding [18].

Bruising is another exceedingly unusual side effect that has no explanation other than the fact that it occurs in a small percentage of Modafinil users [19].

If you have any unusual bleeding or bruising after taking Modafinil, get medical help at the local emergency hospital right away.

  • Stevens-Johnson Syndrome is a condition that affects people (i.e. skin rashes)

Stevens-Johnson Syndrome (SJS) is a side effect of Modafinil that is not only caused by Modafinil, but may also be caused by other pharmacological medicines.

Here’s a quick rundown of why it has to be taken seriously [20]:

“…a chemical reaction that occurs in the skin and mucous membrane cells… When the immune system is exposed to anything, it goes berserk and starts generating signaling molecules that induce cell death.

A red or purple rash appears, followed by blisters that break and peel… Large swathes of skin may be peeled away as the spots develop together, leaving the person exposed to infection.”

We decided it was appropriate to put SJS here since it is stated as a side effect in the official Modafinil product monograph [21].

It, too, demands rapid treatment, much like the other major Modafinil adverse effects detailed so far.

  • Deprivation of sleep

This is a Modafinil adverse effect that only occurs when the smart medication is misused.

The term “abuse” in this case refers to taking very high doses of Modafinil, taking it every day, and, most significantly, utilizing it as a sleep replacement.

When you don’t give your body the rest it needs (7-8 hours of unbroken sleep each night), your brain’s capacity to operate correctly suffers. Sleep-deprived people are more likely to have the following symptoms [22]:

  • Paying attention and concentrating on one thing at a time is difficult.
  • Reaction time is slower.
  • Inability to remember and create new memories
  • Feelings of exhaustion and weariness
  • Making poor decisions

Not to add that depriving oneself of sleep on a regular basis is detrimental to your immune system [23]:

“…sleep deprivation causes stress reactions and decreases immune function.” Sleep deprivation causes germs to move from the stomach to the bloodstream. Animals that were subjected to sleep deprivation tests developed a large bacterial infection in their blood.”

The only time Modafinil should be taken to “replace” sleep is if you need to pull an all-nighter to meet a tight deadline.

Because modafinil’s wakefulness-promoting effects are so strong, it must be used on a schedule to prevent interfering with a regular sleeping cycle.

 

The Effects of Modafinil on the Liver

This section does not apply to you if you do not have any current liver issues.

There is currently no evidence that modafinil has caused liver harm directly [24]:

“…despite widespread usage, there have been no reports of modafinil or armodafinil-related clinically evident liver damage.”

It’s unclear how modafinil and armodafinil induce liver damage. Modafinil undergoes significant liver metabolization but has minimal drug-drug interactions.”

The liver eliminates 90% of Modafinil, while the kidneys remove the remaining 10%. It typically leaves your body via urine.

Modafinil dose should be reduced by 50% for those with liver disease, according to the official product monograph. It turns out that such people can’t get Modafinil out of their systems adequately [25]:

“Three patients had cirrhosis in stages B or B+, while six patients had cirrhosis in stages C or C+” (per the Child-Pugh score criteria). Eight of the nine individuals were clinically icteric and had ascites. When compared to normal individuals, the oral clearance of modafinil was reduced by nearly 60%, and the steady state concentration was doubled.”

(In case you didn’t know, cirrhosis is a condition in which the liver is damaged and scar tissue replaces good liver tissue.)

 

Interactions with Modafinil?

Modafinil may interact with other drugs, resulting in unpleasant side effects.

This is because Modafinil both stimulates (increases activity) and inhibits (decreases activity) numerous metabolic enzymes in the liver that are involved in the processing of certain medications [26]:

“The mean activity of microsomal CYP1A2, CYP2B6, and CYP3A4/5 from modafinil-treated hepatocytes were greater (up to 2-fold) than those generated by reference inducers of these enzymes, but they were lower 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.”

You’ll need to check up the enzymes involved in the metabolism of any other medicines you’re taking and talk to your doctor about taking Modafinil with them. A detailed database of these medicines is available at DrugBank [27].

Modafinil, for example, is known to reduce the effectiveness of some methods of birth control and increase the probability of pregnancy [28]:

“Modafinil’s activation of CYP3A4/5 may affect the efficacy of steroidal contraceptives.” Patients on modafinil should choose an alternative or concurrent form of contraception.”

In basic English, the preceding quotation suggests that Modafinil causes steroid-based birth control drugs to be eliminated quicker than normal.

The following are two additional noteworthy interactions:

  • If you’re using Modafinil alongside blood pressure medication: The potential of modafinil to modestly raise blood pressure may negate the effects of anti-hypertensive medications.
  • If you’re using Modafinil with coffee (or another stimulant), follow these guidelines: For many smart drug users, the synergistic “stimulating” effect may be overpowering.

 

 

Is Modafinil Addiction Safe?

Modafinil adverse effects may be easily prevented by sticking to the recommended dose:

  • 100-200 mg daily
  • 1-3 times per week, in equally spaced dosages (ex. Monday, Wednesday, Friday)
  • The dose is given no later than 10 a.m., however early morning is preferable.
  • Food and water are required.

This is the usual Modafinil dosage used by the majority of smart drug users who have had success with Modafinil, as well as the standard Modafinil prescription dose [29].

Modafinil is completely safe to consume for 99.9% of healthy people if the recommendations above are followed. The adverse effects of Modafinil listed in this page are very rare to occur.

 

Modafinil Side Effects | The Final Word

The majority of Modafinil users have modest to non-existent adverse effects.

Even when Modafinil side effects do occur, they usually go away fast, and treatment options are uncomplicated.

Is Modafinil, however, safe? Modafinil is absolutely safe for the great majority of healthy individuals, whether they are sleep-deprived or not, and the side effects are minimal at best.

Furthermore, no one fatality has been linked to Modafinil alone.

Please be aware of the potential Modafinil medication interactions as well as the list of Modafinil side effects mentioned in this page.

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References

  1. Performance improvement at the expense of prospective brain plasticity: neuronal consequences of nootropic medications in the developing brain. Urban KR, Gao WJ. doi:10.3389/fnsys.2014.00038. Front Syst Neurosci. 2014;8:38.
  2. MA Kredlow, A Keshishian, S Oppenheimer, and M W Otto. A Systematic Review and Meta-Analysis of Modafinil’s Efficacy as a Cognitive Enhancer 2019;39(5):455-461 in J Clin Psychopharmacol. doi:10.1097/JCP.0000000000001085

  3. Medications for narcolepsy The world’s first safe “smart drug” is modafinil. theguardian.com, retrieved 9 June 2020

  4. Modafinil and the orexin system: interactions and medico-legal concerns, Salerno M, Villano I, Nicolosi D, et al. 2019;24:564-575 in Front Biosci (Landmark Ed).

  5. JR Schwartz, MT Nelson, ER Schwartz, RJ Hughes Modafinil’s effects on alertness and executive function in narcolepsy patients with late-day drowsiness. doi:10.1097/00002826-200403000-00005 Clin Neuropharmacol. 2004;27(2):74-79.

  6. SG Hofmann, JA Smits, A Asnaani, CA Gutner, MW Otto. Anxiety disorders may benefit from cognitive enhancers. doi:10.1016/j.pbb.2010.11.020. Pharmacol Biochem Behav. 2011;99(2):275-284.

  7. J Palliat Med. 2012;15(12):1388-1389. Cheng J, Groninger H. Modafinil #259. doi:10.1089/jpm.2012.9542
  8. A Comprehensive Guide To The Abuse Of Modafinil For The Purposes Of Studying And Enhancing Concentration healthstatus.com (accessed June 7, 2020).
  9. Orexin System: The Key to a Healthy Life. Chieffi S, Carotenuto M, Monda V, et al. 2017;8:357 in Front Physiol. doi:10.3389/fphys.2017.00357
  10. Glutamate and Its Receptors as Migraine Therapeutic Targets, Hoffmann J, Charles A. doi:10.1007/s13311-018-0616-5. Neurotherapeutics. 2018;15(2):361-370.

  11. A. Besset, M. Chetrit, B. Carlander, and M. Billiard. A long-term follow-up research on the use of modafinil in the treatment of narcolepsy. 26(1):60-66 in Neurophysiol Clin. doi:10.1016/0987-7053(96)81535-8

  12. Successful treatment of idiopathic hypersomnia and narcolepsy with modafinil, Bastuji H, Jouvet M. 1988;12(5):695-700 in Prog Neuropsychopharmacol Biol Psychiatry. doi:10.1016/0278-5846(88)90014-0

  13. The history of the cigarette-lung cancer link: evidential traditions, corporate denial, and the global toll, by RN Proctor. Tobacco Control, vol. 21, no. 2, pp. 87-91, doi:10.1136/tobaccocontrol-2011-050338.

  14. Psychiatr Danub. 2019;31(3):369-370. doi:10.24869/psyd.2019.369ahan E, Bölükbau015f. Modafinil Intoxication Induced Persistent Psychosis: Case Report.

  15. Modafinil triggers sympathomedullary activity, according to Taneja I, Diedrich A, Black BK, Byrne DW, Paranjape SY, and Robertson D. 2005;45(4):612-618 in Hypertension. doi:10.1161/01.HYP.0000158267.66763.63

  16. Morgan PT, Malison RT. Modafinil and free glutamate ingestion cause chest tightness and palpitations. 2008;165(4):538. doi:10.1176/appi.ajp.2007.07040717

  17. A startling manifestation of blistering mouth ulcers, Broadbent K. 2016;45(3):118-119 in Aust Fam Physician.

  18. T. Foran. The treatment of irregular bleeding in contraceptive users. 2017;46(10):717-720 in Aust Fam Physician.

  19. Fixed drug eruptions with modafinil, Ghoshal L, Sinha M. doi:10.4103/0253-7613.153437. Indian J Pharmacol. 2015;47(2):224-226.
  20. My Sister’s ‘Rare but Serious Side Effect’ Could Have Killed Her. multiplesclerosisnewstoday.com (June 10, 2020).
  21. Stevens-Johnson syndrome produced by modafinil, Prince V, Philippidou M, Walsh S, Creamer D. doi:10.1111/ced.13282 Clin Exp Dermatol. 2018;43(2):191-192

  22. How Sleep Deprivation Affects Cognitive Performance and Focus sleepfoundation.org (accessed June 9, 2020).

  23. Alhola P, Polo-Kantola P. Deprivation of sleep: Impact on cognitive performance. Neuropsychiatr Dis Treat. 2007;3(5):553-567.
  24. Modafinil. ncbi.nlm.nih.gov (retrieved 6 June 2020).
  25. C-IV PROVIGIL® (modafinil) tablets for oral use. The date is June 7, 2020. accessdata.fda.gov
  26. P. Robertson, H. H. DeCory, A. Madan, and A. Parkinson. Modafinil inhibits and induces human liver cytochrome P450 enzymes in vitro. 2000;28(6):664-671 in Drug Metab Dispos.

  27. Modafinil. drugbank.ca (accessed June 9, 2020).
  28. Davies M, Wilton L, Shakir S. Modafinil safety profile in a primary care context in England across a variety of prescribing indications, including off-label use: findings of a modified prescription-event monitoring study. doi:10.1007/s40264-013-0025-y Drug Saf. 2013;36(4):237-246.

  29. Dosage of Modafinil drugs.com, retrieved on June 8, 2020

 

 

 

Modafinil is a medication that has been used to treat narcolepsy, sleep apnea, and shift work disorder. It is also known for its side effects. The “modafinil reviews” can help you make an informed decision about what to use it for.

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Paul Tardner is the Lead Author at IJEST.org. Paul is a former academic and research scientists. He now dedicates his time to his own research into natural biohacking, with a particular focus on cognitive enhancement.

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