Adrafinil

2-[(Diphenylmethyl) sulfinyl]acetamide, a.k.a. Modafinil, is a synthetic wakefulness agent (eugeroic) typically prescribed by physicians to help treat individuals diagnosed with a number of sleep-related conditions, including narcolepsy and "shift work sleep disorder."^[1] When legally prescribed in the United States, it's typically sold as the drug Provigil®, but also Alertec and Modavigil.

Modafinil is the primary metabolite of another stimulant-like drug called Adrafinil, which was first developed by Louis Lafon Laboratories in the 1970s to similarly treat sleep disorders.

At the time, Adrafinil was deemed a superior alternative to amphetamines because it didn't produce any of the adverse side effects attributed to amphetamine use (i.e. anxiety) and wasn't addictive.^[2] However, researchers felt adrafinil took too long to work following ingestion, since the body has to metabolize it to get to its active component, Modafinil. In response, Lafon developed the metabolite into as standalone ingredient as a separate drug, and called it Modafinil.

Over the past 40+ years since its debut, the "-finil" family has jumped into the spotlight for a different reason altogether -- enhanced cognitive function. Modafinil's rise to stardom can be attributed to the high level Silicon Valley techno-nerds, Wall Street traders, and business moguls who have praised the nootropic for its ability to significantly enhance brain function, focus, and productivity.^[3]

It's also worth mentioning that Modafinil has been used extensively by the military as a means to keep troops alert during prolonged deployments when sleep deprivation is a foregone conclusion.

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How Does Modafinil Work?

Modafinil works differently from conventional stimulants like caffeine or another wakefulness agents like methylphenidate (a.k.a. Ritalin). To really grasp how it works in the body, you need to have an understanding of some basic neurology:

Online & Offline

Consider two "modes" inside of your brain. "Online" refers to the more "active" neurological functions you do on a daily basis such as verbal learning, executive function (skills to get things done), processing speed, working memory, etc. "Offline" processes involve more "passive" actions of the brain, including memory consolidation.^[4]

The reason that Modafinil is so incredibly effective, is that it affects both the online and offline processes,^[4] which is incredibly rare among notable nootropics on the market. Basically, think of it as the ultimate combination of the stimulative effects of Ritalin with the laser-focused brain-boosting effects of piracetam, and the memory-storing effects of bacopa monnieri.

So, back to the question of how it works…

How Modafinil Works, cont'd…

Modafinil inhibits the body's noradrenaline and dopamine uptake transporters. Due to this inhibition, levels of powerful catecholamines including noradrenaline (norepinephrine), adrenaline (epinephrine), and dopamine increase.^[5]

Increasing levels of these three catecholamines in turn raises extracellular levels of histamine, glutamate, serotonin, and orexin, which enhances energy, focus, motivation, etc. Another action that Modafinil exerts is that it dramatically reduces the body's main "downer" neurotransmitter, GABA (Gamma Amino Butyric Acid, which is often taken for sleep support).^[18,24] The takeaway is greater amounts of excitatory neurotransmitters in circulation along with lower levels of inhibitory neurotransmitters yielding incredibly long lasting alertness, cognitive function, motivation, and focus.

As for modafinil's "wakefulness-enhancing" abilities, researchers point to its effect on the orexin-hypocretin axis as well as its impact on the concentrations of dopaminergic and adrenergic transmissions.^[5,24] But, other researchers attribute modafinil's ability to improve all aspects of cognitive function due to its actions on the neurochemical levels of the amygdala, caudate, hippocampus, hypothalamus, thalamus, and midbrain.^[6]

Suffice it to say that Modafinil's effects are far and wide on the different regions of the brain, and that in large part is why it's such an effective smart drug.

We've explained a few ways that modafinil impacts the brain, but now let's put those effects into a list of concrete effects you can experience when using the mighty nootropic:

• Heightened Cognitive Function

  Modafinil Benefits: Cognitive performance during acute administration of modafinil (200 mg) versus placebo in the control and metham-phetamine (MA)-dependent participants.^[8]

  When up for hours on end, either because of work, toddlers, stress, etc., cognitive function is severely impacted. Case in point, emergency room doctors are one of the professions most prone to sleep deprivation due to the demands of their profession, and with that their cognitive function (and ability to operate) could be severely inhibited.

  However, when sleep-deprived doctors were given modafinil, their cognitive function was significantly improved over baseline measurements.^[7]

  That's not all though, modafinil has also been shown to be incredibly effective for improving the cognitive function of methamphetamine addicts, which decreased cognitive function is a hallmark sign of the condition.^[8]

• Improved Memory

  Another brain characteristic that's severely affected by sleep deprivation (and age) is working memory. Research has shown that modafinil given to sleep-deprived, as well as completely healthy, individuals at a dosage of 100 - 200mg significantly improved working memory, "task enjoyment", planning, and processing accuracy on cognitive assessments.^[9,10]

  In other words, not only does modafinil improve your test taking abilities, it also makes you enjoy those brain power-draining activities too!

• Faster Reaction Time

  The hits just keep on coming with this monster nootropic as consuming modafinil prior to cognitive testing also increases your reaction time and vigilance.^[11,12]

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Other Modafinil Benefits

We've hit the main points of why individuals would want to experiment with Modafinil for enhanced brain function, but over the years, researchers have identified a number of other benefits attributed to its consumption.

• Increased Wakefulness

  This one shouldn't surprise any of you, given the fact that the primary reason Modafinil was developed was to combat narcolepsy and other associated sleep disorders by increasing wakefulness and neurological "arousal".^[12]

  Modafinil upregulates Synapsin I expression and decreases the number of errors made by sleep-deprived individuals. For those of you unfamiliar with Synapsin, it's a family of proteins primarily responsible for the control of neurotransmitter release at synapses.^[14]

• Strong Appetite Suppression

  Effects of Modafinil on Cognition and Other Information-Processing Measures.^[24]

  Have trouble staying on track with your diet? Modafinil may be able to help you out there too!

  One of the "side effects" exhibited by individuals consuming the nootropic has been significantly decreased appetite.^[15] This is why all users should have pre-cooked meals and a dietary gameplan ready to go so that they don't deprive their bodies of necessary nutrients over the course of their Modafinil run.

• Useful for ADHD

  Studies conducted on children diagnosed with ADHD (Attention Deficit Hyperactive Disorder) have documented increased attention span and decreased symptoms of ADHD (excitability, aggression, hyperactivity-impulsivity), as recorded by two of the most prominent ADHD testing protocols, ADHD-RS-IV and CG-I.^[16]

• Non-Habit Forming

  Modafinil has a half-life of 13-15 hours^[26,27]

  Prescription drug addiction is one of the fastest growing epidemics sweeping across the country. However, modafinil is safe to use and has been shown to be non-addictive.^[16]

  This one isn't a benefit per-se, but shows an absence of a serious side effect one may have expected with such a drug, which makes it a benefit.

  If you're unsure of this, see the following cited publications:

  Adult affective disorder patients, whether unipolar or bipolar, can use modafinil to relieve symptoms of depression, including fatigue and sleepiness, without risking a switch in their mood or developing tolerance or abuse of this medication.^[19]

  Modafinil is well tolerated, with no evidence of tolerance developing during 40 weeks of treatment.^[20]

  Modafinil demonstrated an excellent safety profile for up to 40 weeks of open-label treatment and efficacy was maintained, suggesting that tolerance will not develop with long-term use.^[21]

  Unlike the amphetamines, for example, modafinil is reported to have minimal peripheral side effects at therapeutic doses. It also appears to have a low abuse potential, does not interfere with normal sleep, and does not seem to produce tolerance.^[22]

  Modafinil, used for at least 3 years in some patients, produces, in most cases, no peripheric sides effects, does not disturb night sleep and is never responsible of tolerance of drug dependence.^[23]

  Researchers suspect that the reason modafinil is not habit-forming, such as opiates, is that it is unable to stimulate certain pathways in the brain associated with addiction.^[24]

• Mood improvement

  Users often report a better mood with the drug, and this has been backed up in trials that have methods of determining such experiences -- at least in the short term. In a quick three-day study, subjects aged 30-44 were given either 400mg (a very high dose) or placebo. The study was double-blinded, randomized, and crossover. Ultimately, upon looking at the data, researchers concluded that there were mood-elevating effects.^[31]

  Modafinil has been banned by WADA (World Anti-Doping Agency) for well over a decade. But if you're not drug-tested, it could boost VO2Max^[30]...

  Again, this one should be taken with a grain of salt, since it was a short term study with a high dosage, and new stimulants often put people in a good mood. The question is if such benefits can be sustained.

• Athletic Performance Enhancement (Banned in Sport)

  If you're a drug-tested athlete, don't bother with this one. Modafinil has long been on WADA's banned substances list, as it was banned in 2004 just 10 days prior to the start of the 2004 Summer Olympics.

  The primary reason it's banned is because it can extend exercise time-to-exhaustion, for instance in athletes operating at 85% of VO_2max.^[30] The improvement was roughly 15% over placebo for the same individual.

  So if you're an athlete but not a drug-tested athlete, there are absolutely performance-enhancing effects that may be of interest to you.

In four bolded words: use the lowest effective dose possible. This not only saves money, but avoids any of the potential side effects as well.

One of the great things about modafinil compared to other smart drugs on the market is the vast amounts of research conducted on human subjects. Studies have used a rather expansive range of doses going so high as 400mg in a single dose, while other studies have used as little as 100mg in a single setting and shown great benefit. FYI, Provigil is prescribed in 100mg and 200mg tablets.

If you're interested in test-driving modafinil for yourself, it's highly recommended to start at the lowest dose of 50mg and see how you react to the ingredient on its own. You may be one of the lucky ones to be fine with 50mg, although most will feel better between 100-200mg.

Of course, Provigil is a prescription drug in the US, so follow your doctor's orders / prescription!

Note: Modafinil is incredibly potent and long-lasting, so if you are going to use it, take it EARLY in the morning. Otherwise, you'll be up all night!

Never use Modafinil to replace sleep.

Cycling Modafinil?

Since Modafinil isn't habit-forming, per the studies above, there is often debate regarding the cycling of the drug. Should you take time off of it after you've been on for a while?

The simple answer is to consult with your physician, who's the one who prescribed it in the first place!

But if you're not experiencing any tolerance issues, and can stick to a reasonable 100mg-200mg dose for long periods of time, many argue that there is no need to go off if this is indeed the drug that works for you, and the research cited above seems to back this up.

Day to day cycling?

Another question is whether you should take it every day, or alternate days. This comes down to personal preference and strategies with your doctor. Many take it every day with no problems. Others go every other day, while many do 5 on, 2 off throughout a week.

One conservative strategy we've seen is to take 100mg on Mondays, 50mg Tuesday through Friday, and weekends off. If you don't need to be "mentally online", consider not taking it at all and enjoy a relaxing weekend.

Remember, with a 13-15 hour half-life, when taking it on a Monday, you'll still have a some amount in your system come Tuesday!

As you can see, there are a ton of different strategies, so find the one that safely works for you. Bue once again, use the lowest effective dose possible.

Recommended trick: Start your task first, then take!

As with other similar agents (including amphetamine and methylphenidate / Ritalin), an important trick is to take the Modafinil just after you're starting your desired task. For instance, begin studying, and then take your study stack. Continue studying, and it will "kick in" while you're already on task.

This helps to avoid the problem where you get sidetracked before even beginning, or spend the majority of your time "writing your to-do list" rather than working on your to-do list!

Self-control applies to all facets of nootropic use, ranging from the dosing and cycle timing to the taskwork itself.

Recommended Modafinil Stack

Stacking Modafinil is a difficult discussion, because everyone has different needs. Our primary concern is avoiding side effects - not amplifying the wakeful effects. As such, the biggest concerns aren't supplement stack-based, but hydration and food-based instead! So drink plenty of water first and foremost.

With that said, there are a few conservative recommendations that may help you avoid pitfalls:

• Low-dose caffeine. A small cup of coffee or green tea is fine. You do not need to overdo it with the caffeine since you already get the wakefulness from the Modafinil. 100mg is more than enough.

  L-Theanine comes from tea leaves, and may pair well with Modafinil to offset any potential anxiety.

• Multivitamin and moderate-dose Vitamin D. We always recommend Vitamin D - ~5000IU is safe and smart - and it's no different here. Realize that most multivitamins don't have enough Vitamin D.

• High-DHA fish oil. Same as above, there are very few circumstances where high DHA fish oil is not recommended.

• L-Theanine. A great nootropic in its own right, when combined with caffeine, this is the one that's most recommended to those who become anxious.

• Magnesium. This goes along with supplements we nearly always recommend, since most people are magnesium deficient. The purpose here is to reduce anxiety potential (this is recommended for everyone, not just Moda users).

• Choline supplementation - maybe. This is debated and subject to personal requirement / dietary condition. If headaches happen and they're not hydration-based, consider eating whole eggs a few times a week. However, 250mg of citicoline or Alpha GPC may also help with this.

  The caveat is that too much choline too long and too often can lead to neurotransmitter overuse and set you back.

• Water! Just to emphasize it once again. Your coffee doesn't count. Drink more water.

Additional aggressive nootropics is not better with modafinil

We typically don't recommend any other "hardcore" nootropics (such as amphetamine or even racetams or noopept) in conjunction with Modafinil, although many will argue with the noopept exclusion there.

You may occasionally see phenibut for anti-anxiety purposes, but this adds its own slew of issues that is best avoided (if L-theanine + Magnesium and a lower Modafinil dose doesn't work for you, then Modafinil probably isn't for you).

Sometimes the aforementioned compounds are used on off-days, however.

Yohimbine?! The time researchers gave cats Modafinil and Y

One interesting stack for those who are trying to amplify the effects is to combine it with yohimbine. This alone, however, causes anxiety for many people, and we don't recommend it to the casual user.

This is based upon a cat-based study which reported that:

The effects of both modafinil and amphetamine were enhanced by a pretreatment with yohimbine (1 mg/kg, i.p.), an alpha 2-receptor antagonist.^[25]

Realize that 1mg/kg is an absurd dose of yohimbine that we never recommend (we don't have a cat-to-human equivalent dose conversion). Stacking ~1.5mg yohimbine HCl and Modafinil is reserved for only the most experienced, advanced users. Nearly all people will absolutely want to avoid this.

For the most part, Modafinil has been shown to be safe, non-addictive, and effective for a wide range of individuals, but like everything in life, it does come with a few potential side effects for certain individuals.

A comprehensive review on modafinil listed the following side effects as having occurred in the trials it surveyed:^[17]

In four bolded words: use the lowest effective dose possible.

• Insomnia
• Headache
• Weight loss
• Decreased appetite
• Nervousness
• Nausea
• Vomiting
• Hypertension

Additional side effects can be found in our Modafinil Reviews section below, since they are more anecdotal and not all "officially reported" side effects.

One thing to keep in mind is that Modafinil has a half-life of 13-15 hours^{[26, 27]} -- it lasts a long time. This means your body has most likely only metabolized/eliminated half of it between breakfast and dinner, so you have to keep this in mind when addressing the side effects.

While the prospect of having vastly-improved neurological potential is appealing to just about every one of you reading this, not everyone is keen to take prescription drugs -- they're expensive, require a doctor's order, and the healthcare industry in certain countries have become nothing more of an expensive racket.

So, what alternatives can an aspiring biohacking individual look into?

The answer is to look into Modafinil's "parent" compound -- Adrafinil. It's a prodrug to modafinil, meaning it must undergo conversion in the body before yielding the active metabolite that is modafinil. You can still find this as an over-the-counter (OTC) option if you're wanting to explore the benefits of modafinil without having to actually get a prescription for it.

There are a few other consequences to consider -- since your body and liver have a bit of extra work to do in converting the adrafinil back to Modafinil -- but many have considered this an easy way to experience the effects before moving towards the prescriptions.

Other alternatives: Modafinil vs. ???

If looking at the "competition" to Modafinil, other alternatives (outside of Adrafinil) are typically methylphenidate (Ritalin) and amphetamine salts (Adderall), and perhaps phenylpiracetam in short bursts (such as a week or two, or if only used a few times a week).

The good

Aside from the obvious wakefulness experiences, Modafinil has been rumored to assist with muscular pain support, such as in patients with fibromyalgia.^{[28, 29]}

Many users are simply happier and more content, requiring less external stimulus (such as gratuitous shopping).

The lack of addiction and research showing that Modafinil is non-habit-forming is one of the biggest pro's for users considering taking it.

Compared to competing drugs such as Adderall / amphetamine, Vyvanse, and Ritalin / methylphenidate, many experienced users report that Modafinil is simply "cleaner". In fact, tabloids such as Vice.com have considered it the closest thing to the "Limitless" movie's NZT-48 drug that one can experience.

The bad

Despite what's been published in research, there are some users who complain of anxiety - especially at higher doses. Those with a potential for anxiety may wish to tread carefully, but L-Theanine is a generally-recommended stacking agent.

Headaches are a common experience with Modafinil, ones which reportedly are unphased by standard OTC analgesics like ibuprofen or acetaminophen. This can be attributed to three things that may all be related:

1. Lack of eating due to the appetite suppression
2. Lack of water
3. Possible choline depletion.

These are all easily solved. It's sometimes recommended to take occasional choline supplements alongside Modafinil (see our stack section above), or to eat foods high in choline, such as whole eggs, at least a couple times a week.

Unfortunately, the increased hydration that's required to keep those headaches at bay will increase your urination, but this is worth the trouble for anyone who's experienced these issues.

Heart palpitations have also been reported, but they are also reported to go away with further use.

There are also concerns of sleep deprivation or lessened sleep quality, which must be addressed. Two ways around this are to take lower and/or earlier doses, and to practice cycling between days using any of the strategies above. Remember, Modafinil has a half-life of 13-15 hours!^[26,27]