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Provigil is the brand name for the drug, Modafinil.
It is a drug that promotes wakefulness, and is approved by the United States Food and Drug Administration (FDA) as a safe alternative to typical stimulants.
It is also helpful with the treatment of many sleep related disorders. These include narcolepsy, shift work sleep disorder, and daytime fatigue that is associated with sleep apnea.
Provigil is sometimes prescribed for off-label purposes in the treatment of ADHD, certain mood disorders, and as a cognitive enhancer or smart drug.
Even though there has been extensive research into the interaction of Modafinil with numerous neurotransmitter systems, the precise mechanisms of action of the drug remain partially unclear.
That being said, we do have a good understanding of how Provigil works in general.
Alertness
Mental Acuity
Focus- Stimulates wakefulness in the brain
- Promotes mental acuity & processing
- Enhances focus, motivation & energy
Modafinil History
Related Topics
- What is Modafinil? (Provigil)
- How Does Provigil Work?
- Effects and Benefits
- User Reviews
- Typical Experiences
- Recommended Dosages
- How to Take
- Provigil Uses
- Use for ADHD
- Effects on Weight Loss
- Negative Side Effects
- Abuse Warnings & Dangers
- Comparison to Adrafinil
- Comparison to Armodafinil
- Comparison to Adderall
- Where to Buy
- Generic Modafinil Brands
- Is Modafinil Legal?
- How to Get Modafinil
- Review of Online Sources
Modafinil was first discovered in 1976 by the French chemist and neurophysiologist professor Michel Jouvet for the French pharmaceutical company Lafon Laboratories. Lafon was later bought out by Cephalon Inc, who to this day produces the most widely-sold name brand version of Modafinil, Provigil.
For the purposes of this article, Modafinil and Provigil are used synonymously, although generic version of Modafinil exist.
The discovery of Modafinil came about from the previous development of another related compound, Adrafinil. Adrafinil is one of a group of benzhydryl sulfinyl compounds that was first developed in 1974.
During testing to try and determine Adrafinil’s mechanism of action in the body, Modafinil was discovered. It was found that after ingestion, Adrafinil is transported to and then broken down in the liver. The primary metabolites of Adrafinil are the inactive modafinilic acid, and the active Modafinil.
Modafinil was found to be the primary active compound of Adrafinil and the source of its effects in the body. Adrafinil and Modafinil have an incredibly similar molecular structure, with the only difference being that Modafinil lacks a hydroxyl group that Adrafinil has on its terminal amide.
Adrafinil was first used and tested for many of the same uses that Modafinil was eventually tested for. Once Modafinil was able to be synthesized on its own without Adrafinil production of Adrafinil decreased. Eventually Modafinil surpassed its predecessor, and is exclusively used in medical contexts now.
How does Provigil Work in the Body?
Adrafinil, and consequently Modafinil, is classified as a eugeroic, or wakefulness-promoting compound. Researchers have found Modafinil to have stimulant-like effects comparable to the amphetamine type stimulants on the market.
It is, however it is not in fact related to traditional stimulants, and has been seen to cause effects in different ways. The exact mechanism of action of Modafinil is still unknown.
Across various research studies it has been seen that Modafinil has effects on a large number of neurotransmitters and their transporters, including Dopamine, Serotonin, Epinephrine (Adrenaline), Norepinephrine (Noradrenaline), Histamine, and Orexins (Hypocretins).
Provigil helps to elevate levels of hypothalamic Histamine. Histamine acts as a modulator of various other neurotransmitters in the brain and has a primary role in promoting wakefulness, learning and memory, anxiety, locomotion, and eating and drinking.
Provigil has the ability to inhibit many of the actions of the Dopamine transporter. This leads to a boost in extracellular, and thus, synaptic concentrations of Dopamine.
Another target of studies has been the locus of the monoamine action of Provigil. This is in hopes of identifying the effects of the drug on Dopamine in both the nucleus accumbens and striatum. Also, the effects of Norepinephrine in the hypothalamus and ventrolateral preoptic nucleus, as well as Serotonin in the frontal cortex and amygdala are an area of interest.
One of the considered mechanisms of action involved Orexin, which is a brain peptide and also known as Hypocretin. Orexin neurons can be found within the hypothalamus, but also projects to several different parts of the brain, including many areas that can regulate wakefulness in the body.
Activating these neurons will help to increase the Dopamine and Norepinephrine levels in those areas, and increases Histamine levels in the histaminergic tuberomammillary neurons. Studies involving rats have shown that Provigil increases the Histamine release levels in the brain, which can be a possible mechanism of action in humans as well.
Orexin receptors 1 and 2 are the two orexin receptors in the body. Animals that have defective Orexin systems give off signs and symptoms that are similar to that of narcolepsy, and treatment of which Provigil is approved for by the FDA.
Provigil appears to activate these Orexin neurons in the animal models, and they are expected to promote and increase wakefulness.
Provigil and Narcolepsy
As has been discussed, Modafinil has many different mechanisms that cause it to be a wakefulness promoting agent. Because of these observed effects in animal studies, the first human trials involved using Modafinil as a treatment for narcolepsy.
Narcolepsy is a sleep disorder in which people cannot properly maintain a wakeful state, and in severe cases often fall asleep randomly multiple times per day. It is thought that one of the primary causes of narcolepsy is a decreased number of Orexin producing neurons in the brain. This deficit of Orexin can cause poor regulation of wakefulness.
Even in narcoleptics who do not fall asleep much during the day, excessive sleepiness is a common symptom many experience. This excessive daytime sleepiness occurs regardless of high quality sleep the previous night.
Multiple double-blind placebo-controlled clinical trials have been conducted that have definitively shown that Provigil significantly improves wakefulness and decreases sleepiness levels in narcoleptics compared to a placebo. Scores on the Maintenance of Wakefulness test and the Epworth Sleepiness Scale have been seen to significantly improve when patients are given Modafinil in many different studies.
Modafinil has been proven to be such a successful treatment for narcolepsy that other new drugs have been tested against it to prove their efficacy. Studies have been conducted comparing Modafinil to sodium oxybate and pitolisant. In the studies, the active medications were seen to significantly improve sleepiness scores compared to a placebo, and to perform similarly to Modafinil, showing they could also be efficacious new treatments for narcolepsy.
Provigil has been approved as a prescription treatment for narcolepsy. It was approved for this purpose in France in 1994, and by the FDA in the USA in 1998. Since that time it has been officially approved to treat other sleep disorders that involve excessive sleepiness.
- Increases energy, wakefulness and motivation
- Boosts mental performance and focus
- Supports memory and cognition
Provigil and Other Sleep Disorders
Circadian rhythm is the nearly 24 daily sleep/wake cycle that is dictated by our bodies biological clock. Humans are naturally diurnal and typically are awake during the day and sleep at night. Some people by necessity need to alter their normal sleep/wake schedule for their jobs.
Shift-work sleep disorder (SWSD) is a circadian rhythm disorder that can occur in some people that either on a continuous or intermittent basis work late night, overnight, or extended shifts. Because they are awake during non-standard hours (i.e. awake at night) they can feel excessive sleepiness when awake, and also some sleep disturbances like insomnia when trying to sleep during non-standard hours (i.e. sleep during the day).
Multiple studies have been done using Modafinil to curb the excessive sleepiness experience by SWSD sufferers. One study compared the effects of a dose of Provigil or a placebo taken one hour before a night work shift. Compared to the placebo, Provigil significantly improved scores on the patient administered Karolinska Sleepiness scale, and on the Psychomotor Vigilance scale. Patients who received Modafinil had significantly fewer and shorter attention lapses compared to placebo patients.
In another study, patients were randomly assigned to receive a placebo or Modafinil 30-60 minutes before a nighttime work shift; patient functioning and quality of life were assessed using the Functional Outcomes of Sleep Questionnaire at the start of the trial as a baseline, and at 4 and 12 weeks.
It was found that compared to the patients who received placebo, patients who received Modafinil showed significant improvement of scores on the Functional Outcomes of Sleep questionnaire in the productivity, activity, and vigilance categories.
Obstructive sleep apnea/hypopnea syndrome (OSAHS) is a medical condition that affects breathing during the night. Multiple times throughout the night, and even each hour, the airway is either partially or completely obstructed by the tongue, soft palate, and /or the uvula, due to the muscles of the mouth relaxing involuntarily. Partial obstruction leads to shallow breathing (hypopnea), and complete obstruction leads to the temporary stopping of breathing breathing (apnea).
Due to experiencing many of these breathing episodes per night and having lower blood oxygen levels while sleeping, most people with this syndrome have very poor quality of sleep, and subsequently experience excessive daytime sleepiness.
The most common treatment for OSAHS is wearing either a mouth guard that keeps the tongue in place, or a continuous positive airway pressure (CPAP) machine while sleeping. For most people this helps to manage the condition, however excessive sleepiness is still sometimes felt by people receiving treatment, and in these cases, Modafinil has been used as an adjunct treatment to reduce this symptom.
One study compared Modafinil to a placebo in the efficacy of treating residual daytime sleepiness in patients with OSAHS who has been continuously using CPAP for at least two months prior to the start of the trial. It was found that compared to placebo, Modafinli significantly improved daytime sleepiness. There was a significant change from baseline scores on the Epworth Sleepiness Scale as well as in multiple sleep latency times.
Modafinil has been classified as a Schedule IV prescription medication with the on-label uses of treating narcolepsy and shift-work sleep disorder, and as an adjunct treatment for obstructive sleep apnea/hypopnea syndrome. Any other uses of Modafinil are considered off-label.
Off-Label Uses of Modafinil
While only officially approved for the previously discussed sleep disorders, it is estimated that as many as 90% of all Modafinil prescriptions written are in fact for off-label uses.
One off-label use that Modafinil is sometimes prescribed for is disease-related fatigue. Fatigue is a symptom of many different diseases including multiple sclerosis, depression, fibromyalgia, and Parkinson’s disease. Some research has been done using Modafinil for improving fatigue, specifically in people with depression and multiple sclerosis.
It has been found that compared to a placebo, Modafinil significantly improves disease-related fatigue. However, more research is still needed on many other specific diseases to determine if there are any condition related contraindications.
In contrast, Modafinil has been extensively studied for its ability to improve the symptoms of attention-deficit disorder (ADD) and attention-deficit hyperactivity disorder (ADHD).
Multiple double-blind placebo-controlled studies done on children, adolescents, and adults, have all shown that compared to a placebo, Modafinil significantly increases scores on a variety of ADHD tests including the Teacher and Parent ADHD Rating Scale-IV, ADHD Rating Scale-IV School and Home Questionnaires, Conners Rating Scales, and the Diagnostic and Statistical Manual of Mental Disorders IV ADHD Behavior Checklist.
A meta-analysis of studies done using Modafinil for ADHD was published in 2017. The compiled research showed that Modafinil was seen to have superior short-term efficacy compared to placebo in the reduction of ADHD symptoms, while also showing a safety and tolerability profile similar to placebo.
Modafinil has been shown to have an effect on ADHD symptoms, not only compared to a placebo, but also when tested against a conventional ADHD treatment. One randomized, double-blind, placebo-controlled, three-phase crossover study tested Provigil against a placebo, as well as dextroamphetamine (Dexedrine).
There were three treatments: placebo, Provigil, dextroamphetamine. Patients were given one treatment for two weeks, then switched to another treatment for two weeks, and then given the final treatment for two weeks.
It was found that compared to the results seen with placebo, the two active medications significantly improved scores on the DSM IV ADHD Behavior Checklist for Adults, and trend significance was seen on the Controlled Oral Word Association Test. The researchers suggested that due to the similarity in improvement seen between dextroamphetamine and Modafinil, that Modafinil should be considered a viable alternative treatment for ADHD patients.
Provigil as a Cognitive Enhancer
One of the most popular off-label uses of Provigil is as a nootropic smart drug. Many different people from high powered executives to college students to computer programmers have reported using Modafinil as a cognitive enhancer.
User reviews say that Modafinil increases concentration, focus, productivity, memory, learning ability, and alertness. Many people say that they use Modafinil to help them stay alert and focused on work tasks or studying for hours at a time. Enhanced concentration and productivity, along with improved memory make this a popular nootropic choice of university students looking for a competitive edge while studying and taking tests.
There has been some scientific research done that backs up some of the claims that recreational Provigil users have reported. One literature review of a selection of studies done testing the cognitive effects of Modafinil reported that there was a trend seen across the studies of Modafinil having positive effects on memory, specifically working and episodic memory.
Another review found that Modafinil was seen to mainly affect cognition by improving executive function (decision-making, problem-solving, mental control, self-regulation) especially when planning for and executing complex or difficult tasks.
One double-blind, placebo-controlled, fully within-subjects trial compared the effects of placebo versus Modafinil in a battery of cognitive assessments including serial reaction time, logical reasoning, visual comparison, mental addition, and vigilance. Compared to the placebo group, scores for the Modafinil group were improved for fatigue levels, motivation, reaction time, and vigilance.
In another similar study, healthy volunteers were given either a placebo or Modafinil and then asked to complete a series of memory and attention tests. Compared to placebo, Modafinil significantly improved the scores on a digit span test, a test of visual pattern recognition memory, a spatial planning task, and a stop-signal reaction time test. When asked how they felt on drug, volunteers reported feeling energetic, alert, and attentive.
There was also seen a delayed latency to answer on certain tests, including the spatial planning task, a delayed matching to sample test, and a decision-making task. This slight delay enhanced the ability to inhibit prepotent responses, instead allowing for the natural reactionary response to be overridden by one that was more oriented to the goal at hand.
While this study was conducted in neurotypical volunteers, the researchers concluded that this reduction in impulsive responding could make Modafinil a beneficial treatment for people with ADHD.
Common Provigil Dosages
In America, Provigil is approved by the FDA, but only for the treatment of a few disorders. As mentioned before, these disorders are shift work sleep disorder, narcolepsy, and obstructive sleep apnea.
In some other countries, it has also been approved for those that are hypersomnias (such as idiopathic hypersomnia).
The FDA typically recommends that the prescribed dosage for any of these disorders is one 200 mg dosage each day. There are some circumstances in which 100 to 400 mg each day split over one or two doses is suggested, but that is less common.
For any condition that isn’t shift work sleep disorder, Provigil is typically taken in one dose during the morning hours, or in two separate doses, with one in the morning and another at midday. For those with shift-work sleep disorder, the dosage is taken between 30-60 minutes before the start of a work shift at night.
It is not typically recommended to take Provigil after noon as it is a relatively long lasting drug with a total half-life of 12-15 hours. Taking Provigil later in the day can carry a risk of other sleep disturbances and make it difficult to fall asleep at night.
There are no official dosage recommendations for off-label uses of Provigil. In situations where a prescription has been written for an off-label use such as fatigue or ADHD, then doctors most typically prescribe the standard 200 mg per day, to be taken in the morning.
People who take Modafinil as a nootropic smart drug typically follow dosing regimens similar to other uses, taking 200 mg a day in the morning. Some users have reported that if they have a very long day of studying or work ahead of them then they will take an additional 100 mg around noon or slightly later if they are planning to stay awake late into the night.
Dosages as high as 400 mg per day have been seen to be safe and well tolerated in research studies. However, dosages this large are not typically taken on a regular basis, as there have not been any significant increased benefits above a standard 200 mg dose observed, and the risk of potential side effects can increase with a higher dosage.
Modafinil Side Effects
While it is generally well tolerated, there are some common mild side effects experience with Provigil use. Headaches and nausea are the most commonly reported side effects in research studies and user reviews.
Some other mild side effects that have been reported include:
- Anxiety
- Nervousness
- Back pain
- Dizziness/lightheadedness
- Vomiting
- Diarrhea
- Loss of appetite
- Heartburn
- Indigestion
- Dry mouth
- Dryness of the skin
- Stuffy or runny nose
For some people, side effects are transient and will pass after their bodies adjust to the drug’s effects. Some side effects may be related to the dosage, and a lower dosage may help eliminate or lessen effects.
If your side effects subside, but you do not get the benefits of Modafinil at a lower dosage, then you can try slowly increasing the dosage back to a normal level, checking for side effects as you go. It is advised to speak with your doctor about any side effects you experience, so they can help determine the best dosage for your needs.
There is the possibility of rare, but serious side effects, such as the the skin and mucous membrane disorders Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS). Cases of these conditions in people who have been taking Modafinil have not definitively shown that the drug was the cause, but it is important to be aware of the possibility.
While still considered quite rare, Stevens-Johnson syndrome is considered more likely to develop than the other two even more serious conditions. Symptoms of Stevens-Johnson syndrome include flu-like symptoms such as fever, nausea, headache, body aches, sore throat, and coughing, as well as a red or purple rash that spreads and may blister. If you experience any of these symptoms, then stop use of Modafinil and speak to your doctor immediately or go to an emergency room if necessary.
Since there is a risk for the development of hypersensitivity or skin reactions and other neuropsychiatric disorders, it has been recommended by the European Medicines Agency that new prescriptions for patients should only be used for the treatment of sleepiness that is associated with narcolepsy.
There could possibly be serious side effects that could appear within the first twelve weeks of use. For this reason, the guidance does not require patients that are already receiving treatment from Provigil to stop taking the drug.
As described above, Provigil has been tested in all age groups and shown to be an effective treatment option for those that suffer from ADHD. However, in 2006 the FDA deemed Provigil unfit for use by children for the purpose of ADHD.
The reason is was rejected was because there were two cases of serious skin rashes, which may have been related to Stevens-Johnson syndrome or Erythema multiforme among the total of 933 patients that received the drugs.
The doctor who made these diagnoses later recanted and stated that he had misdiagnosed the condition. However, the FDA has not yet reconsidered Provigil for treatment of ADHD.
If you are interested in learning more about how Provigil works, it is recommended to read user reviews and experience logs to hear from others who have used it successfully.
Buying Provigil Without a Prescription
There are some doctors that are willing to write an off-label prescription for Provigil for conditions such as ADHD, especially in cases where traditional medications such as Adderall, Ritalin, and Dexedrine have not been entirely successful, or have caused serious side effects. Theses prescriptions are entirely legal, however many doctors do not want to write them, for fear of increased scrutiny from medical boards.
Additionally, even with a prescription, many insurance companies will not cover off-label uses of drugs. Many people are not able to afford the
Getting a prescription to use Modafinil as a nootropic drug is nearly impossible though, as the use of drugs in healthy people to improve cognition or other bodily functions does not fall under FDA standards.
Many people who want to try Provigil will then turn to the “gray market” to purchase Modafinil without a prescription. There are many online pharmacies based in countries such as China and India where the sale of Modafinil is not as regulated, and it is not classified as a prescription only medication.
There are a number of issue with these online pharmacies though. First of all, there is no guarantee that you will actually receive your shipment. While you may not have any issues buying the product, when it reaches customs in your country, the laws of your place of residence are enforced.
Your package may simply be seized. If your country allows importation of drugs with a prescription, then you will have issues when you cannot produce a prescription. Regardless, you may not receive your purchases.
Additionally, if you do in fact receive your shipment of Modafinil, there is no way to tell if the product you get is in fact Modafinil. Quality control is often lacking from these sorts of vendors, and the product you get may not be Modafinil, or could possibly not be pure.
Non-Prescription Provigil Alternatives
Instead of taking a risk on the safety and efficacy of products from gray market online pharmacies, many people instead turn to alternative nootropics that do not require a prescription.
As discussed before, Adrafinil is the direct prodrug of Modafinil. When consumed, Adrafinil is metabolized in the liver into Modafinil. Because it is not a perfect conversion, you will need to take a higher dosage of Adrafinil than Modafinil to get similar effects.
While less potent, slower-acting, and not as long-lasting as Modafinil, many users report that the effects of Adrafinil are comparable to those of Modafinil. This drug is unscheduled and unregulated and does not require a prescription in the United States and many other countries around the world.
Many people use Adrafinil as a legal non-prescription alternative to Modafinil for nootropic purposes. Because of the conversion process in the liver, there is a risk of an increase of hepatotoxic enzymes if Adrafinil is taken regularly, so many people instead choose to use it on a as needed basis.
The Racetams are a class of compounds that are related to the original nootropic, Piracetam. Piracetam was first developed in the 1960s by a Romanian scientist working for UCB Pharmaceuticals in Belgium. It was the first nootropic ever developed, and prompted the scientist to create the term for this new class of compounds.
Racetams have effects on the cholinergic neurotransmission channels in the brain and central nervous system. These on Acetylcholine are believed to have effects on general cognition as well as memory. Racetams are also thought to increase oxygen and glucose transport in the brain, which may promote mental fluidity and alertness.
The derivatives of Piracetam are more potent than the original compound, and some have specific effects associated with them in addition to the increases to memory and concentration that all Racetams boast. Some of the most popular Racetams include Aniracetam, Oxiracetam, Pramiracetam, and Phenylpiracetam.
If you are unable to get a prescription for Provigil, instead of going through the gray market to buy Modafinil online that could potentially be suspect, consider using a Provigil alternative such as Adrafinil or one of the Racetams.
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Article last updated on: April 12th, 2018 by Nootriment