What Do We Know About Adrafinil? Potential Programs and Side-Effects

Adrafinil is a medication that’s promised to make users feel awake and alert. It’s become somewhat popular as a “nootropic” (“cognition-enhancing”) drug, in part owing to its supposedly low rate of side-effects and lack of legal regulations. But how much do we really know about the effectiveness and safety of this drug? In this post, we’ll discuss exactly what the science has to say about how adrafinil functions, what it does, and a few of the potential medical applications which have been suggested for it — continue reading to discover more!

Disclaimer: This post is not a recommendation or endorsement for adrafinil. This medication hasn’t been approved by the FDA for any particular medical applications, and relatively little is known for sure about its effects or safety in humans. We have written this post for informational purposes only, and our aim is solely to inform people about the science behind adrafinil’s mechanics and potential effects.

What’s Adrafinil?

Adrafinil is a synthetic medication that’s often touted to promote long-lasting psychological stimulation. Adrafinil is a non-amphetamine psychostimulant which reduces drowsiness but doesn’t raise heart speed or anxiety.

It’s frequently experimented with as a “nootropic” or allegedly “cognitive-enhancing” drug. But this usage is not scientifically accepted, and the science behind its potential effects on cognition remains in a really early stage, with exceptionally mixed (and often conflicting) results.

As a “prodrug” (an inactive chemical that’s converted to the active drug inside the body) for its prescription stimulant modafinil, adrafinil gets active by switching to modafinil in the body. Adrafinil’s effects and mechanisms are most likely equal to those of modafinil, although the relative absence of a study on adrafinil especially means that some substantial differences continue to be a possibility.

Adrafinil was originally made to treat narcolepsy and attention disorders in the elderly. It had been marketed in France under the name Olmifon but has been stopped in 2011. Adrafinil was stopped because it was less potent than modafinil, and demanded higher doses to achieve a similar effect.

Adrafinil is unscheduled in the United States, Canada, and the UK, in which it is regarded as a “dietary supplement” rather than a prescription medication. This implies it’s neither sterile nor controlled and doesn’t require a prescription to purchase or have. By comparison, adrafinil does take a prescription from other countries, such as Australia, Germany, and New Zealand.

However, don’t be fooled by the very fact that it is “technically legal” in some places. As a prodrug of modafinil — that is a controlled substance with known potential for abuse — it shares basically the very same risks and possible risks that have misuse of modafinil. In other words, “technically legal” does not necessarily mean “secure”, “benign”, or “effective”!

In fact, if anything else, adrafinil’s unusual legal status means it is much less well-studied than several other medically-approved prescription medications, and cannot be used under the advice of a valid medical professional — two very good reasons for added caution against casual use or experimentation with this particular drug.

It’s also worth noting that, due to concerns over the prospect of illegal misuse of adrafinil, the World Anti-Doping Agency (WADA) has prohibited adrafinil to be used by professional athletes, who may try to utilize it to enhance their own operation.

Mechanism of Action

Adrafinil is dormant in its first form. It will become active by switching to modafinil in the liver (i.e. it’s a “prodrug” of modafinil).

Only a little bit of adrafinil converts to modafinil, together with the majority getting entirely inactive. Therefore, relatively greater quantities of adrafinil compared to modafinil have been needed to achieve similar effects.

Adrafinil includes a brief biological half-life (the time it takes for a substance to eliminate half of its biological action ) of just 1 hour. However, some of it’s converted to modafinil, which has a 12-to-15-hour half-life. This means that a person can continue to feel its effects many hours after the first consumption.

According to a study (randomized controlled trial) of 10 older patients, peak blood levels of adrafinil occurred 1 hour after ingestion. Meanwhile, its most important effects on the brain and behavior reportedly began to occur roughly two hours after initial consumption.

In concept, adrafinil produces its effects with the very same mechanisms as modafinil. Some of the potential mechanisms include:

• Increasing Dopamine
• Increasing serotonin
• Increasing norepinephrine
• Increasing histamine release through orexin
• Increasing glutamate and decreasing GABA

Potential Medical Uses (Unapproved)

A couple of possible medical uses are proposed for adrafinil, although this is mostly only due to its similarity to modafinil, which has been much better-studied in comparison.

Because sufficient scientific and medical proof is lacking, not one of the below uses has been formally approved by the FDA, nor are they used by physicians. The sole evidence available so far is still too limited to allow any firm conclusions about adrafinil’s possibility of treating any specific health problems.

1) Narcolepsy and Additional Fatigue Disorders

Since adrafinil works by being converted to modafinil in the torso, in concept adrafinil may be used to take care of a number of the same ailments that modafinil is approved for, such as narcolepsy, work-shift sleep disorder, and other fatigue-related conditions.

However, since adrafinil is less well-studied — and because modafinil is currently the officially-established treatment for such circumstances, adrafinil isn’t widely utilized by physicians for these conditions. Additionally, adrafinil is generally less potent than modafinil, which means that doctors would need to use larger doses to get the very same consequences as they would using smaller — and consequently generally safer — amounts of modafinil.

Consequently, adrafinil will probably not become medically approved (e.g. by the FDA) for all these uses anytime soon.

2) Depression

1 early study (from 1999) first indicated the possibility of adrafinil to take care of melancholy. In accordance with this one placebo-controlled clinical trial in 70 elderly patients with depression, two months of therapy with adrafinil led a noticeable improvement in depression symptom severity scores on the Hamilton Depression Rating Scale (HAM-D) and other common clinical tests of depression.

But, this research has some significant limitations to note. For starters, the cases of depression treated weren’t”full” melancholy, but just a milder sub-form of depression sometimes seen in elderly adults. Secondly, adrafinil’s impact on depression severity scores was most likely primarily due to improvements in some of those “psychomotor” symptoms of depression (such as slowed movements and diminished energy), rather than some real influence on mood symptoms per se. Last, even though the study’s authors concluded that adrafinil might have some (limited) possibility in treating depression that they proposed should be followed up on by additional research, not much followup work appears to have been completed in the time since this initial research was published more than 20 years ago.

In just the few follow-up studies that were done, some (such as 1 double-blind placebo-controlled trial in 471 adults) have reported that adrafinil can partly decrease symptoms of depression.

Adrafinil was also reported to decrease symptoms of depression similar to an antidepressant (clomipramine) in a study of 70 depressed patients. The team receiving clomipramine reported frequent side effects, however, adrafinil was relatively well-tolerated.

Nonetheless, without a lot more clinical evidence to back up these preliminary findings, it is very unlikely that adrafinil will become widely-used in treating depression any time soon — particularly since there are a number of other effective remedies for depression now available.

Other Possible Uses & Effects

Because adrafinil gets active by converting to modafinil, both drugs have similar effects on the mind and body (at least in theory).

The next studies highlight some of the research conducted on adrafinil. But, those findings are all still quite preliminary and haven’t strongly established a scientific case for utilizing adrafinil for these uses.

Furthermore, adrafinil’s lack of FDA approval — as well as a general lack of information about its safety in human users — means that caution is recommended against experimenting with adrafinil so as to acquire any of these effects.

As always, we do not endorse or encourage the casual use of adrafinil; the information below is strictly to inform people of what science now says about a number of its possible mechanisms and effects.

1) May Affect Mental and Physical Function

According to a study, adrafinil allegedly increased participants’ ability to perform daily tasks in a randomized controlled trial of 548 elderly adults with memory and attention issues.

Adrafinil has also been reported to boost slowness of thought and movement (psychomotor disability ) in comparison to an antidepressant (clomipramine) in a study of 70 depressed older adults.

But some historical evidence from animal studies has demonstrated that adrafinil increases movement and overall exploratory behavior in mice, rats, monkeys, and dogs. While inconclusive, these findings might indicate that some of the assumed “improvements” reported in the human studies might just be due to a general “stimulating” effect of adrafinil, instead of any particular or targeted effect on cognition and behavior per se.

In light of the comparatively small quantity of evidence, in addition to the fact that only one of these preliminary studies was done in healthy humans, it is definitely still far too early to know whether adrafinil would consistently have some unwanted consequences in non-depressed human users, along with much more research could be needed to discover this out for certain.

2) May Affect Awareness and Focus

According to a small number of studies (such as 2 double-blind placebo-controlled trials and 1 randomized controlled trial), adrafinil was reported to increase focus, attention, and vigilance in 744 older adults.

In one other study (randomized controlled trial) of 10 older adults, adrafinil reportedly decreased brain activity (“brain waves”) related to sleep (slow-wave delta and theta wavelengths) and enhanced brain activity associated with”involvement in the present” (alpha wavelengths).

Nonetheless, many more clinical trials in humans are needed to completely confirm that result.

3) Could Affect Some Cognitive Functions

Some preliminary research in older animals (dogs) reported some potential effects of adrafinil on cognitive functions such as learning and memory.

But not much research work was performed on people to confirm these early findings.

In accordance with two research in 951 elderly adults (including 1 double-blind randomized controlled trial and 1 placebo-controlled trial), adrafinil had been reported to reduce forgetfulness, while enhancing data recall.

In 1 study (double-blind randomized controlled research ) of 48 older adults with attention and processing rate issues, adrafinil was reported to reduce response time on a psychological test.

In general, it’s still too early to state what cognitive effects adrafinil would have in a healthy human adult — not just because the bulk of the existing research was done in animals, but also because even most of the human research has been done only in older populations. A lot more study would nevertheless be required to confirm some “nootropic” (“cognition-enhancing”) consequences in ordinary individual users.

Potential Benefits of Adrafinil Over Other Stimulants

Many stimulants — such as amphetamines — have been proven to produce frequent side effects like appetite loss, sleep issues, and mood disturbances. They may also be highly addictive.

Some early evidence suggests that adrafinil (and/or modafinil) might have some advantages over more common stimulant drugs — although overall the evidence is not nearly strong enough to form any firm decisions because relatively much less research has been done on these chemicals compared to”traditional” stimulants (which have been very extensively studied).

1) May Create Allergic ly Fewer Side Effects

In general, side-effects such as appetite loss, sleep problems, and mood disturbances don’t appear to get reported all that common in many of the animal and human studies that have been done with this medication.

But it’s hard to form any solid conclusions from this since it’s also true that adrafinil was studied much less compared to other, more common drugs — so this might just be caused by the relatively smaller amount of research that’s been done on adrafinil.

2) Might Have Somewhat Lower Pot Potential

No studies are done directly on adrafinil from the context also. However, 1 research on modafinil (the energetic product of adrafinil) reported that modafinil may be obtained for up to 3 years without inducing serious tolerance or dependency — at least, according to just one study in 42 participants with excessive sleepiness and narcolepsy.

Although marginally promising, the exact small sample size, along with the fact that this is just one study, means the long-term security of modafinil and adrafinil ought to be considered pretty much completely unknown. A whole lot more long-term clinical studies would be required to ascertain the safety of these drugs within an official medical degree.

Side-Effects

Most studies report adrafinil to be comparatively well-tolerated. A few participants have noted improved stress and aggression, nausea, irregular heartbeat, mouth dryness, stomach pain, and skin irritation.

One participant developed abnormal facial movements after accepting 900 mg/day of adrafinil for 10 months. This symptom didn’t improve after 4 weeks off adrafinil but subsided after having a dopamine-lowering medicine.

Since adrafinil converts to modafinil in the liver, there is concern it may elevate liver enzymes or lead to liver damage. Human research does not support this claim, but this may simply be because there have been relatively few clinical studies of adrafinil.

Drug Interactions

Adrafinil allegedly increased blood pressure within 1 case study of a 63-year-old woman on blood pressure medicines (aliskiren and piretanide).

No other drug interactions are reported in the literature — but again, this is most likely as it’s comparatively understudied, particularly in contrast to most other drugs.

Modafinil, the energetic byproduct of adrafinil, has been reported to increase cytochrome P450 liver enzyme action (CYP1A2, CYP2B6, and CYP3A4/5) in cell-based studies. Additionally, it has been reported to reduce CYP2C19 action.

Even though the possible significance of these findings is unknown so far, these mechanisms might be part of the rationale that people with liver conditions are highly discouraged from utilizing modafinil (since they are at considerably increased risk of adverse side-effects and other complications in modafinil).

Types and Dosage

Notice: The information in this section describes the information that’s currently available regarding some of the former medical applications of adrafinil: it is not a guide to recreational or other anti-inflammatory use.

It’s usually believed that only a little bit of adrafinil converts to modafinil, together with the majority becoming inactive. Therefore, adrafinil generally requires much higher doses compared to modafinil to accomplish similar effects.

Adrafinil often comes in the kind of powder or pills. The standard recommended dose is 600 to 1,200 mg. This was the suggested dose for the prescription medication Olmifon (300 mg adrafinil per pill ) to deal with narcolepsy as it was available.

However, information about successful doses for different conditions and consequences is not widely available — again largely because of lack of relevant clinical research.

Limitations and Caveats

Research on adrafinil is restricted; many have rather concentrated on modafinil. This is because adrafinil, modafinil does really have some FDA-approved medical uses and is consequently comparatively better-studied. Modafinil can also be generally more potent and requires a much lower dose to cause an effect, which makes it marginally safer.

Most of the human research on adrafinil was conducted in older patients in France in the late 1980s and early 1990s. These results were published in French scientific journals, and aren’t available online.

They’re summarized in a 1999 review article, which can be cited in this post where references to those studies are made.