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As a part of the enormous wave of popularity that smart drugs have ridden recently, many people are now wondering about Modafinil long term effects.
The short term benefits of the brain-boosting pharmaceutical, generic for Provigil, are well-established. Modafinil can clearly increase concentration, improve cognition, and help with mental focus.
What happens if the drug is used over long periods of time? Will users have to deal with any long term side effects of Modafinil? Here is a complete run-down of what is known about Modafinil and other similar cognitive enhancers.
Alertness
Mental Acuity
Focus- Stimulates wakefulness in the brain
- Promotes mental acuity & processing
- Enhances focus, motivation & energy
The Development of Modafinil
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 developed by the French chemist and neurophysiologist Michel Jouvet for Lafon Laboratories in 1976. In 2001, Lafon was bought out by Cephalon Inc; to this day Cephalon makes the most well-known name brand version of Modafinil, Provigil.
Modafinil was first discovered due to testing on Adrafinil, a benzhydryl sulfinyl compound that was first developed in 1974 by Lafon. Modafinil and Adrafinil are very similar compounds; their molecular structure only differs by one hydroxyl group that Adrafinil has on its terminal amide that Modafinil lacks.
The reason for this similarity is that Adrafinil is in fact the prodrug of Modafinil. In the body, Adrafinil is metabolized in the liver into its component parts: the inactive modafinilic acid, and the active Modafinil. Modafinil is the primary active compound in Adrafinil that causes it to have effects in the body.
The exact mechanism of action of Modafinil is still unknown at this time. However in various research studies, it has been seen that Modafinil has an effect on the transport and signalling of many different neurotransmitters including Dopamine, Serotonin, Epinephrine, Norepinephrine, Histamine, and Hypocretin (Orexin).
Adrafinil and Modafinil act as analeptic, eugeroic compounds in the brain, promoting wakefulness and alertness. It has been suggested that the main mechanism of action of Modafinil may be through stimulating the central nervous system by boosting the release of CNS Histamine and Orexin. These two compounds, act in the brain to fire up the activity of several important systems that regulate wakefulness, arousal, and appetite.
Modafinil and Sleep Disorders
Testing first done with Modafinil on animals found that it increased locomotor activity and alertness, and at high doses could cause hyperactivity. Due to these stimulant-like effects, that first trials with Modafinil in humans were for the sleep disorder narcolepsy.
Narcolepsy is a sleep disorder that affects the maintenance of wakefulness during the day. Regardless if the person had an appropriate amount of high-quality sleep the night before, they experience excessive daytime sleepiness and can even fall asleep randomly multiple times per day.
Multiple double-blind placebo-controlled clinical trials using Modafinil for narcolepsy have shown that compared to a placebo, Modafinil is significantly better at improving scores on various measures of sleepiness and wakefulness, including the Epworth Sleepiness Scale, the Multiple Sleep Latency Test, and the Maintenance of Wakefulness Test.
Modafinil was approved by the Food and Drug Administration (FDA) in the United States as a prescription treatment for narcolepsy in 1998. Since that time, its official approved uses have expanded to include two other sleep disorders that involve excessive sleepiness: shift work sleep disorder and obstructive sleep apnea/hypopnea syndrome.
Shift-work sleep disorder is a circadian rhythm disorder. While people naturally sleep at night and are awake during the day, sometimes jobs with work shifts that are late at night or overnight necessitate people switching this schedule and being awake at night and sleeping during the day. In some people this change does not agree with their biological clock, causing excessive sleepiness while awake, and possibly insomnia when trying to sleep.
Various research studies have found that compared to a placebo, Modafinil is significantly better at reducing excessive sleepiness in people with shift work sleep disorder.
In one study, patients took either a placebo or a dose of Modafinil 30-60 minutes before a nighttime work shift started. It was seen that compared to scores seen with placebo, Modafinil significantly improved scores on the Functional Outcomes of Sleep Questionnaire that evaluated measures such as patient vigilance, general productivity, and activity level.
Modafinil has also been approved as an adjunct treatment for improving the excessive sleepiness sometimes experienced with obstructive sleep apnea/hypopnea syndrome.
In this medical condition, while sleeping, the upper airway becomes blocked by the tongue, soft palate, and/or uvula, due to the supporting muscles involuntarily relaxing. This leads to either partially blockage, causing poor breathing (hypopnea), or completely blockage, causing the temporary stopping of breathing (apnea).
These breathing episodes can happen multiple times per hour per night, leading to very poor quality sleep, and subsequent excessive daytime sleepiness. The most common treatment for this syndrome is wearing a nasal continuous positive airway pressure (nCPAP) machine while sleeping, which helps keep the airway open.
Even with treatment, some people still experience residual daytime sleepiness, and in these cases, Modafinil has been seen to help. In studies, Modafinil has been seen to improve excessive daytime sleepiness as measured by the Epworth Sleepiness Scale significantly over placebo.
Modafinil for ADHD
Any use of Modafinil that is not one of the above approved uses is considered “off-label.” One of the most commonly prescribed off-label uses of Modafinil is for attention-deficit disorder (ADD) or attention-deficit hyperactivity disorder (ADHD).
Modafinil as a treatment for ADHD has been tested many times in all different age groups, from children to adults. Many different studies have shown that Modafinil is significantly better at improving symptoms of ADHD than a placebo.
One study in children found that a compared to placebo, Modafinil significantly improved scores on the Teacher and Parent ADHD Rating Scale-IV. Another very similar study found improved scores with Modafinil on the ADHD Rating Scale-IV School and Home Versions as well as the Clinical Global Impressions-Improvement scale conducted by the researchers.
One randomized double-blind placebo-controlled crossover study in adults with ADHD found that compared to results in the placebo group, significant improvements were found in the Modafinil group on tests of visual memory and short-term memory, as well as a spatial planning task and stop-signal motor inhibition test. In several tests, improved accuracy was accompanied by a decrease in response time, indicating an inhibition of impulsive prepotent reponding.
Modafinil has even been tested for efficacy against a conventional amphetamine-based ADHD medication, dextroamphetamine (Dexedrine). Researchers found that both active medications significantly improved scores on the DSM-IV ADHD Behavior Checklist for adults compared to a placebo, and that Modafinil had similar efficacy of treatment as dextroamphetamine.
Due to all of the positive study results that have come out over the years, there are some doctors who will prescribe Modafinil off-label to their patients with ADD or ADHD, most commonly in situations where traditional stimulants have not worked or caused serious side effects. Off-label prescriptions are entirely legal, and are up to individual physician’s discretion if they want to write them or not.
Nootropic Usage and Experience
Just as in the world of fashion or music, we often see “fad” prescription drugs sweeping through popular culture during any given era. In the past few years, no smart drug has received more attention than Modafinil.
Using Modafinil as a nootropic drug is the most popular off-label use by far. Profiled in dozens of news stories, magazine and online blogs like Bulletproof Exec, Modafinil has permeated pop culture. Multiple user reviews detail that people use the drug to improve concentration, focus, productivity, learning, and memory.
The alertness-promoting, stimulant-like action of Modafinil is the source of all of its mental benefits, including heightened alertness, the ability to focus upon tasks without distraction for hours on end, and a sense of very sharp, easy to articulate thoughts.
The drug has become very popular among students and professional people who have trouble concentrating for long periods of time, even though we still don’t have comprehensive scientific proof of cognitive benefits.
Some limited research has been done testing Modafinil for cognitive effects, and generally it has shown positive results. One study found that Modafinil showed improvement in scores on tests of motivation, reaction time, fatigue levels, and vigilance compared to placebo group scores. Another study found that compared to placebo, Modafinil showed significant improvement of scores on tests of digit span and visual pattern recognition memory, a spatial planning task, and a test of stop-signal reaction time.
Will this smart drug remain popular in years to come? That could depend in large part on what the Modafinil long term effects end up being.
- Increases energy, wakefulness and motivation
- Boosts mental performance and focus
- Supports memory and cognition
Modafinil Long Term Effects and Risks
The exact nature of Modafinil long term effects is not known. Furthermore, most of what we know about the drug pertains to its official use as a treatment for narcolepsy. One pediatric study of Modafinil used for narcolepsy found that no significant negative effects were seen over a very long-term period of use in patients (up to 10 years).
Long term side effects and benefits for use as a cognitive enhancer are largely anecdotal. We do know of a number of short term side effects, which are detailed in the section below. Whether or not any of these symptoms persist into chronic conditions is mostly unclear, due to insufficient research.
From user reports on online forums, the following are some of the potential reported negative long term effects of Modafinil:
Chronic headaches
Headaches are the number one reported mild side effect of Modafinil use, with estimates of over half of users experiencing headaches at some point. For most part, these headaches are often transient and fairly mild.
However in some people, the headaches never seem to go away or get any better. While they often can be remedied with over-the-counter painkillers, this may not be an adequate long term solution for everyone.
Sleep Deficit
As previously discussed, Modafinil is a wakefulness and alertness promoting agent. While this is often good for reducing sleepiness, and improving productivity and concentration, it can lead to a sleep deprivation or a sleep deficit. People on Modafinil report not feeling as if they need to sleep, even when they should. In these people, the desire for sleep is diminished, leading them to not sleep as much as they should.
This can lead some people to not get adequate sleep each night, leading to a sleep debt, which is the cumulative effect of not getting enough sleep over the long term. This can have various physical and mental effects, including amino acid imbalances, mood disorders, and increased stomach and mouth acidity, which can lead to dental issues.
Neurotransmitter Imbalances
While the exact mechanism of action of Modafinil is still unknown, it is known to interact with various neurotransmitters and their transports and receptors in the brain and central nervous system.
Long term use of any psychoactive compound has the potential to change or disrupt the normal homeostatic levels and functioning of neurotransmitters. Modafinil acts as a reuptake inhibitor on Dopamine and Norepinephrine, and extended use could lead to depleted stores or a deficiency of these compounds.
Modafinil is known to increase levels of Orexin and Histamine, which could also lead to a depletion or eventual downregulation of endogenous production. Alternatively, if a user becomes tolerant to a lower amount and continually increases their dosage, Histamine levels could rise, which may lead to an allergic reaction and allergy-like symptoms.
Depression
Some people who have been taking Modafinil for a very long time have reported developing depression. This is thought to be due to the effects Modafinil has on various neurotransmitters, specifically the dopaminergic and noradrenergic transmission systems, however this has not been studied or proven yet.
Dependence or Tolerance
Two sides of the same coin, some people find that after they take Modafinil for an extended period of time they become dependent on its effects, while other people have reported that they developed a tolerance and the drug does not work for them anymore.
Some users have reported that after using Modafinil for a long time that they need its effects for normal daily functioning. They say that they feel unable to perform well at school or work and cannot maintain adequate levels of cognitive functioning. This dependence often passes after a while off of the drug, but it can be difficult adjusting for many people.
Anecdotally, tolerance is an effect that develops in some people that use Modafinil everyday for years at a time. Their bodies become use to the amount of drug they take each day, and the benefits become less and less.
Some people will then increase their dosage to try and recapture the benefits they experienced before, although this can lead to a greater risk of side effects. Cycling off of Modafinil has been suggested in user reports as a way to avoid tolerance when using Modafinil long term.
Long Term Modafinil Benefits
What about long term Modafinil benefits? Do any of the cognitive boosts like increased concentration or sharper mental acuity last after individuals stop taking the medication? While we don’t yet have all of the facts (the drug has been taken as a recreational cognitive enhancer for just over a decade), the preliminary evidence seems to point to no.
Once Modafinil therapy has ceased, cognitive conditions gradually return to what they were before treatment. Users have reported that when they are not taking Modafinil that they “revert back” to their normal cognitive functioning. For some people, this can seem as if their brain is moving in slow-motion for a while as they readjust to not having Modafinil in their system.
Others report that they may not seem as motivated or able to concentrate for as long as on the drug, but overall they readjust well. For people who reported that Modafinil only gave them mild stimulating effects similar to a few cups of coffee, the loss of these effects is hardly noticeable, and they get by just fine without doses of Modafinil.
Modafinil Side Effects
Separate from the chronic long-term effects discussed above, there are some more immediate, acute side effects associated with Modafinil use. Modafinil is generally well tolerated, however every person’s physiology is different, and some users have reported mild side effects. At times these effects occur just when first taking the drug as your body adjusts, and pass after a few weeks.
The most commonly reported mild side effects from research studies and user reviews of Modafinil include:
- Headaches
- Nausea
- Nervousness/Anxiety
- Back pain
- Rhinitis
- Dry mouth/skin
- Indigestion
- Heartburn
- Vomiting
- Diarrhea
Sometimes side effects are related to dosage. A dosage that is considered average for most people can be too strong for others and bring on negative effects. Reducing the dosage may help with this.
After side effects are managed, you can try slowly increasing your dosage back to recommended levels. If you find that your side effects return, and the lower dosage did not provide the benefits you want, then it is possible that Modafinil just is not the right drug for your personal body chemistry.
While quite rare, there is the possibility of developing serious dermatological conditions when taking Modafinil, including Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN), or drug reaction with eosinophilia and systemic symptoms (DRESS). While not confirmed, there is strong evidence showing that certain people may have a genetic predisposition to developing these conditions when they take certain medications, including Modafinil.
These conditions are quite serious, and can be life-threatening. It is recommended that if you develop symptoms (fever; flu-like symptoms; a spreading, blistering rash) that you stop taking Modafinil and seek immediate medical attention by calling your doctor or going to an emergency room.
Where to Get Modafinil
The US government has classified Modafinil as a Schedule IV controlled substance. It cannot be legally purchased or consumed without a prescription.
Ordering Modafinil online may seem like an attractive option at first. With prices as low as 80 percent less than U.S. pharmacy prices (a Modafinil 200 mg tablet can be purchased as low as $2 per pill when bought in bulk from an overseas website, vs $50 for that same pill in the U.S.), many people try to stock up with large bulk orders.
However, consumers face some serious risks when shopping at these sites. With no FDA oversight over issues like purity, dosage accuracy, and Modafinil long term effects, you have no way of knowing if pills are safe and authentic.
Furthermore, U.S. border officials are on the lookout for shipments of controlled substances like Modafinil, and will quickly confiscate packages upon discovered. With no refunds, recourse, or customer service, consumers will be left with lost funds and no medication.
A far safer and more effective option is to utilize U.S. vendors. If no Modafinil prescription is available, you can simply shop for comparable nootropic compounds which have similar benefits.
Safe and Legal Modafinil Alternatives
Many people will never get to experience the positive Modafinil long term effects and benefits due to the huge risks involved in buying Modafinil online. Luckily, it is still possible to easily access Modafinil in the form of its pre-cursor, Adrafinil.
Adrafinil is converted by the liver directly into Modafinil, allowing the user to feel the same mental effects associated with Modafinil (Provigil).
Adrafinil is still legal and does not require a prescription to buy. Reputable U.S. nootropic supplement websites carry Adrafinil, making it quite easy to buy.
The only additional long term side effects that Adrafinil seems to exhibit is added strain on the liver (similar to OTC drugs like Tylenol). This is the result of extra liver enzymes required to convert Adrafinil into Modafinil.
The long term results of this side effect are not known, so for now it is advised to only take Adrafinil on an occasional basis. Consumed responsibly, Adrafinil is safe and can deliver the full Modafinil experience to users.
Another Modafinil alternative that some people take is one of the Racetams group of nootropics. This family of compounds are based on the original nootropic compound, Piracetam, which was first developed in the 1960s.
Piracetam has been seen in research to have effects on Acetylcholine in the brain and central nervous system. An increase in cholinergic activity is tied to improved overall cognition and memory formation and recall. Piracetam has also been seen to increase glucose and oxygen uptake into the brain, which is linked to increased mental fluidity and alertness. Cell membrane permeability has also been seen to increase with Piracetam.
Since the development of Piracetam, more potent derivatives have been developed including Oxiracetam, Aniracetam, Pramiracetam, and Phenylpiracetam. Some of these have been seen to have additional effects beyond improving memory and cognition. In studies, Aniracetam has been seen to have anxiolytic effects.
If you are unable to obtain a legal prescription for Modafinil, you do not have to turn to gray market online pharmacies to obtain nootropic effects. Both Adrafinil and the Racetams are unscheduled, unregulated compounds that are available without a prescription in many countries around the world, including the United States.
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Article last updated on: April 10th, 2018 by Nootriment