Adrafinil is a drug that is claimed to make users feel awake and alert. It has become somewhat popular as a “nootropic” (“cognition-enhancing”) drug, in part due 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 what the science has to say about how adrafinil works, what it does, and some of the potential medical uses that have been proposed for it – read on to learn more!
Disclaimer: This post is not a recommendation or endorsement for adrafinil. This drug has not been approved by the FDA for any specific medical uses, 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 goal is solely to inform people about the science behind adrafinil’s mechanisms and potential effects.
What Is Adrafinil?
Adrafinil is a synthetic drug that is often touted to promote long-lasting mental arousal. Adrafinil is a non-amphetamine psychostimulant which reduces drowsiness but does not increase heart rate or anxiety [1].
It is often experimented with as a “nootropic” or supposedly “cognitive-enhancing” drug. However, this use is not medically approved, and the science behind its potential effects on cognition is still in a very early stage, with highly mixed (and often conflicting) results.
As a “prodrug” (an inactive compound that is converted into the active drug inside the body) for the prescription stimulant modafinil, adrafinil becomes active by converting to modafinil in the body. Adrafinil’s effects and mechanisms are therefore most likely identical to those of modafinil, although the relative lack of research on adrafinil specifically means that some significant differences are still a possibility [1].
Adrafinil was originally designed to treat narcolepsy and attention disorders in the elderly. It was sold in France under the name Olmifon, but was discontinued in 2011. Adrafinil was discontinued because it was less potent than modafinil, and required higher doses to achieve a similar effect [1].
Adrafinil is unscheduled in the United States, Canada, and the UK, where it is considered a “dietary supplement” rather than a prescription drug. This means it is neither FDA-approved nor controlled, and does not require a prescription to purchase or possess. In contrast, adrafinil does require a prescription in other countries, such as Australia, Germany, and New Zealand.
However, don’t be misled by the fact that it’s “technically legal” in some places. As a prodrug of modafinil – which is a controlled substance with known potential for abuse – it shares essentially the same risks and potential dangers that come with abuse of modafinil. In other words, “technically legal” does not necessarily mean “safe”, “harmless”, or “effective”!
In fact, if anything, adrafinil’s unusual legal status means that it is much less well-studied than many other medically-approved prescription drugs, and cannot be used under the guidance of a legitimate medical professional – two very good reasons for added caution against casual use or experimentation with this drug.
It’s also worth noting that, due to concerns over the potential for illegal abuse of adrafinil, the World Anti-Doping Agency (WADA) has banned adrafinil for use by professional athletes, who might try to use it to enhance their own performance [2].
Mechanism of Action
Adrafinil is inactive in its initial form. It becomes active by converting to modafinil in the liver (i.e. it is a “prodrug” of modafinil) [1].
Only a small amount of adrafinil converts to modafinil, with the majority becoming entirely inactive. Thus, relatively greater amounts of adrafinil than modafinil are required to achieve similar effects [1].
Adrafinil has a short biological half-life (the time it takes a substance to lose half of its biological activity) of only 1 hour. However, some of it is converted to modafinil, which has a 12-to-15-hour half-life. This means that a user may continue to feel its effects many hours after initial consumption [3].
According to one study (randomized controlled trial) of 10 elderly patients, peak blood levels of adrafinil occurred 1 hour after consumption. Meanwhile, its main effects on the brain and behavior reportedly began to occur roughly 2 hours after initial consumption [4].
In theory, adrafinil produces its effects using the same mechanisms as modafinil. Some of these potential mechanisms include:
- Increasing dopamine [5, 6, 7, 8, 9, 10, 11, 12]
- Increasing serotonin [13, 14, 15, 16]
- Increasing norepinephrine [17, 18, 19]
- Increasing histamine release via orexin [20, 21, 22, 23, 20]
- Increasing glutamate and decreasing GABA [24, 25, 26, 27, 28, 29]
Potential Medical Uses (Unapproved)
A few potential medical uses have been proposed for adrafinil, although this is mostly just because of its similarity to modafinil, which has been much better-studied in comparison.
Because sufficient scientific and medical evidence is lacking, none of the below uses have been officially approved by the FDA, nor are they currently used by doctors. The only evidence available so far is still too limited to allow any firm conclusions about adrafinil’s potential for treating any specific medical conditions.
1) Narcolepsy and Other Fatigue Disorders
Because adrafinil works by being converted to modafinil in the body, in theory adrafinil could be used to treat some of the same conditions that modafinil is approved for, such as narcolepsy, work-shift sleep disorder, and other fatigue-related conditions [30].
However, because adrafinil is less well-studied – and because modafinil is already the officially-established treatment for such conditions, adrafinil is not widely used by doctors for these conditions. Additionally, adrafinil is generally less potent than modafinil, which means that doctors would have to use larger doses to get the same effects as they would by using smaller – and therefore generally safer – amounts of modafinil [1].
Therefore, adrafinil will probably not become medically approved (e.g. by the FDA) for these uses any time soon.
2) Depression
One early study (from 1999) first suggested the potential of adrafinil to treat depression. According to this one placebo-controlled clinical trial in 70 elderly patients with depression, 2 months of treatment 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 [31].
However, this study has some major limitations to note. For one, the cases of depression treated were not “full” depression, but just a milder sub-form of depression sometimes seen in older adults. Second, adrafinil’s effect on depression severity scores was most likely primarily due to improvements in some of the “psychomotor” symptoms of depression (such as slowed movements and decreased energy), rather than any genuine effect on mood symptoms per se. Lastly, although the study’s authors concluded that adrafinil may have some (limited) potential in treating depression that they proposed should be followed up on by further studies, not much follow-up work seems to have been done in the time since this initial study was published over 20 years ago [31].
In just the few follow-up studies that have been done, a few (including 1 double-blind randomized controlled trial in 471 adults) have reported that adrafinil may partially reduce symptoms of depression [1].
Adrafinil was also reported to reduce symptoms of depression similar to an antidepressant (clomipramine) in a study of 70 depressed patients. The group receiving clomipramine reported frequent side effects, but adrafinil was comparatively well-tolerated [1].
Nonetheless, without a lot more clinical evidence to back up these preliminary findings, it’s quite unlikely that adrafinil will become widely-used in treating depression any time soon – especially since there are many other effective treatments for depression currently available.
Other Potential Uses & Effects
Because adrafinil becomes active by converting to modafinil, both drugs have similar effects on the brain and body (at least in theory).
The following studies highlight some of the research conducted on adrafinil. However, these findings are all still very preliminary and have not strongly established a scientific case for using adrafinil for these uses.
Additionally, adrafinil’s lack of FDA approval – as well as a general lack of data regarding its safety in human users – means that caution is advised against experimenting with adrafinil in order to get any of these effects.
As always, we at SelfDecode are not endorsing or encouraging the casual use of adrafinil; the information below is strictly to inform people of what science currently says about some of its potential mechanisms and effects.
1) May Affect Mental and Physical Function
According to one study, adrafinil reportedly increased participants’ ability to perform daily activities in a randomized controlled trial of 548 older adults with attention and memory problems [1].
Adrafinil has also been reported to improve slowness of thought and movement (psychomotor impairment) compared to an antidepressant (clomipramine) in a study of 70 depressed older adults [1].
However, some early evidence from animal studies has reported that adrafinil increases movement and overall exploratory behavior in mice, rats, monkeys, and dogs [32, 33, 34, 35]. While inconclusive, these findings may suggest that some of the supposed “improvements” reported in the human studies may just be due to a general “stimulating” effect of adrafinil, as opposed to any specific or targeted effect on cognition and behavior per se.
In light of the relatively small amount of evidence, as well as the fact that only one of these preliminary studies was done in healthy humans, it is definitely still way too early to know whether adrafinil would consistently have any similar effects in non-depressed human users, and a lot more research would be needed to find this out for sure.
2) May Affect Awareness and Focus
According to a small handful of studies (including 2 double-blind randomized controlled trials and 1 randomized controlled trial), adrafinil was reported to increase attention, concentration, and vigilance in 744 older adults [1].
In one other study (randomized controlled trial) of 10 elderly adults, adrafinil reportedly decreased brain activity (“brain waves”) associated with sleep (slow-wave delta and theta wavelengths) and increased brain activity associated with “engagement in the present” (alpha wavelengths) [36, 37].
Nonetheless, many more clinical trials in humans would be needed to fully confirm this effect.
3) May Affect Some Cognitive Functions
Some preliminary studies in older animals (dogs) reported some potential effects of adrafinil on cognitive functions such as learning and memory [38, 39, 40].
However, not much research work has been done in humans to confirm these early findings.
According to just two studies in 951 older adults (including 1 double-blind randomized controlled trial and 1 randomized controlled trial), adrafinil was reported to reduce forgetfulness, while improving information recall [1].
In one study (double-blind randomized controlled study) of 48 elderly adults with attention and processing speed problems, adrafinil was reported to reduce reaction time on a psychological test [36].
Overall, it’s still too early to say what cognitive effects adrafinil would have in a healthy human adult — not only because the bulk of the existing research was done in animals, but also because even most of the human studies have been done only in older populations. A lot more research would still be needed to confirm any “nootropic” (“cognition-enhancing”) effects in typical human users.
Potential Advantages of Adrafinil Over Other Stimulants
Many stimulants – such as amphetamines – are known to produce frequent side effects such as appetite loss, sleep problems, and mood disturbances. They can also be highly addictive [41, 42].
Some early evidence suggests that adrafinil (and/or modafinil) may have some advantages over more common stimulant medications – although overall the evidence is not nearly strong enough to form any firm conclusions, since relatively much less research has been done on these compounds compared to “traditional” stimulants (which have been very extensively studied).
1) May Produce Relatively Fewer Side Effects
In general, side-effects such as appetite loss, sleep problems, and mood disturbances don’t seem to be reported all that commonly in many of the human and animal studies that have been done on this drug [1, 43, 44].
However, it’s difficult to form any solid conclusions from this, because it’s also the case that adrafinil has been studied much less than other, more common medications – so this could just be due to the relatively smaller amount of research that has been done on adrafinil.
2) May Have Somewhat Lower Addiction Potential
No studies have been done directly on adrafinil in the context of addition. However, one study on modafinil (the active byproduct of adrafinil) reported that modafinil could be taken for up to 3 years without causing serious tolerance or dependence – at least, according to just one study in 42 participants with excessive sleepiness and narcolepsy [45].
Although somewhat promising, the very small sample size, together with the fact that this is only one study, means that the long-term safety of modafinil and adrafinil should be considered pretty much entirely unknown. A lot more long-term clinical studies would be needed to establish the safety of these drugs on an official medical level.
Side-Effects
Most studies report adrafinil to be relatively well-tolerated. A small number of participants have noted increased stress and aggression, nausea, irregular heartbeat, mouth dryness, stomach pain, and skin irritation [1, 46].
One participant developed abnormal facial movements after taking 900 mg/day of adrafinil for 10 months. This symptom did not improve after 4 months off adrafinil but subsided after taking a dopamine-lowering medication [47].
Because adrafinil converts to modafinil in the liver, there is concern that it can elevate liver enzymes or cause liver damage. Human research does not support this claim, although this may simply be because there have been relatively few clinical studies of adrafinil [1].
Drug Interactions
Adrafinil reportedly increased blood pressure in one case study of a 63-year-old woman on blood pressure medications (aliskiren and piretanide) [48].
No other drug interactions have been reported in the literature – but again, this is most likely because it’s relatively under-studied, especially compared to most other drugs.
Modafinil, the active byproduct of adrafinil, has been reported to increase cytochrome P450 liver enzyme activity (CYP1A2, CYP2B6, and CYP3A4/5) in cell-based studies. It has also been reported to lower CYP2C19 activity [49].
Although the potential significance of these findings is unknown so far, these mechanisms may be part of the reason that people with liver conditions are highly discouraged from using modafinil (as they are at significantly increased risk of adverse side-effects and other complications from modafinil) [50].
Forms and Dosage
Note: The information in this section describes the information that is currently available regarding some of the former medical applications of adrafinil: it is not a guide to recreational or other non-medical use.
It is generally believed that only a small amount of adrafinil converts to modafinil, with the majority becoming inactive. Thus, adrafinil typically requires much higher doses than modafinil to achieve similar effects.
Adrafinil often comes in the form of powder or tablets. The standard recommended dose is 600 to 1,200 mg. This was the suggested dose for the prescription drug Olmifon (300 mg adrafinil per tablet) to treat narcolepsy when it was available [51, 1].
However, information about effective doses for other conditions and effects is not widely available – again largely due to a lack of relevant clinical research.
Limitations and Caveats
Research on adrafinil is limited; most have instead focused on modafinil. This is because unlike adrafinil, modafinil does actually have some FDA-approved medical uses, and is therefore comparatively better-studied. Modafinil is also generally more potent and requires a lower dose to cause an effect, which makes it somewhat safer.
Most of the human studies on adrafinil were conducted in elderly patients in France in the late 1980s and early 1990s. These results were published in French scientific journals, and are not available online.
They are summarized in a 1999 review article, which is cited in this post wherever references to those studies are made [1].
