Adrafinil is a wakefulness-promoting drug that appears to have impressive nootropic properties. Used responsibly, it may be an effective tool for supporting lengthy mentally demanding tasks.
What Is Adrafinil?
Adrafinil is a stimulant that can increase energy, prevent fatigue, and enhance wakefulness, without causing anxiety or other side effects that are typically associated with stimulants.
It may also improve mood, focus, and learning ability, and may even help keep your brain healthy.
Adrafinil is a prodrug, a biologically inactive compound that is converted to an active drug inside the body. When Adrafinil is metabolized, it is converted to modafinil, a stimulant that increases wakefulness without increasing anxiety and hyperactivity that is typical of amphetamine stimulants.
Because modafinil is the active form of adrafinil, the pharmacological actions and effects of the two compounds are almost identical. However, only a portion of adrafinil is converted to modafinil. Therefore, a larger dose of adrafinil, compared to modafinil, is required to create the same effect.
Adrafinil was discovered by Lafon Laboratories in 1974, and two years later they isolated modafinil. Modafinil was selected for further clinical development (brand names Alertec, Modavigil, and Provigil) but both forms of the compound reached the market. Adrafinil was sold throughout Europe as the prescription drug Olmifon from 1986 until it was discontinued in 2011.
It remains unregulated in the US, Canada, and the UK and can be legally purchased in those countries.
It is widely used off-label to fight fatigue and enhance energy, and many users consider it an effective cognitive enhancer.
The World Anti-Doping Association classifies adrafinil as a prohibited in-competition stimulant.
Adrafinil has a low incidence of side effects and appears to have a low potential for dependence, tolerance, or addiction.
Research on adrafinil is relatively limited, with most human studies focusing instead on its active form, modafinil.
Benefits and Effects of Adrafinil
Wakefulness Without Stimulant Side Effects
Adrafinil’s eugeroic or wakefulness-promoting properties are the most thoroughly studied and documented of its effects.
Extensive animal testing indicates that adrafinil increases both wakefulness and locomotion, and is particularly effective during periods when the research subjects would ordinarily be asleep.
Testing also confirms that while adrafinil’s wakefulness-promoting properties are on a par with amphetamine, it doesn’t trigger the anxiety, hyperactivity, elevated heart rate, and other negative side effects associated with amphetamines.
Research on adrafinil’s wakefulness effects on human subjects is limited. However, the animal study findings are confirmed by tests in which human subjects were given modafinil, adrafinil’s active form. Modafinil has been proven effective against excessive daytime sleepiness in humans with sleep disorders.
A US Army test indicated that modafinil significantly diminished the effects of sleep deprivation among healthy subjects as well. Aviators who took modafinil during a period of 40 hours without sleep demonstrated the ability to perform highly demanding tasks, reduced slow-wave EEG activity, and lessened self-reported problems with mood and alertness compared to placebo.
In addition to promoting wakefulness and increasing energy, adrafinil may improve the speed of learning and enhance overall cognition.
A study on aged canines showed that treatment with adrafinil produced substantial improvement in learning, as indicated by a decrease in errors and an increase in successful task completion.
The few studies on adrafinil’s effect on human cognition suggest that adrafinil has significant nootropic potential.
A double-blind placebo-controlled study of 100 patients aged 65 and over, all of whom had vigilance problems severe enough to disrupt daily life, showed that those who took adrafinil felt happier and less sleepy than those on placebo and also had improved concentration, attention, and power of recall.
In a similar test on 548 patients with attention and concentration problems, those who took adrafinil showed significant improvement in daily activities, attention, orientation, and memory.
Clinical trials and research reviews of modafinil, adrafinil’s active form, further confirm its potential for cognitive enhancement.
Adrafinil is widely believed to have potential as an antidepressant.
Animal studies suggest that adrafinil may contribute to a significant improvement in aging and neurodegenerative disorders that involve depression.
Human studies on this aspect of adrafinil are limited, but a two-month study involving 70 depressed patients showed that adrafinil treated depressive symptoms as effectively as clomipramine, a known antidepressant, with fewer adverse psychological side effects.
In a 28-day study of 81 non-institutionalized patients, those who took adrafinil demonstrated significantly lowered depression and reduced apathy.
Adrafinil’s active form has been shown to act as a potent neuroprotectant, helping keep brain cells healthy and intact and even slowing the degenerative process associated with Parkinson’s disease.
It has also been shown to counteract neuroinflammatory processes caused by methamphetamine use.
Preliminary studies suggest its neuroprotective capability could play a role in the treatment of multiple sclerosis.
How It Works
The exact mechanisms of adrafinil are not entirely understood. However, researchers hypothesize that in its metabolized form it acts primarily in two specific areas of the brain, the hypothalamus and amygdala. This sets it apart from amphetamines and other psychostimulants that induce wakefulness by general widespread neuronal activation. This selective neuronal activation may explain adrafinil’s ability to promote wakefulness without the side effects usually associated with stimulants.
One of the ways in which metabolized adrafinil promotes wakefulness is by stimulating the brain’s orexin system. This system is responsible for regulating wakefulness, arousal, and appetite. The lack of orexin in the brain is the cause of the most common form of narcolepsy, and modafinil (adrafinil’s active metabolite) is believed to address this by acting directly on orexin neurons. This stimulation, in turn, increases the production of histamines, which also play an important role in the regulation of the sleep-wake cycle.
Metabolized adrafinil is also known to act on the adrenergic system, the part of the nervous system that releases adrenaline. It is believed to replicate the energy and alertness of an adrenaline release by acting as an adrenergic receptor agonist, boosting levels of adrenergic neurotransmitters in the brain.
Adrafinil indirectly modulates dopamine levels, the neurotransmitter associated with the brain’s reward and pleasure responses. Instead of directly stimulating dopamine release to create the rapid and highly amplified rise in dopamine levels typical of CNS stimulants, adrafinil’s active metabolite is a dopamine reuptake inhibitor, gradually blocking the dopamine transporters from removing dopamine from the synapses.
This gradual and somewhat indirect action on the dopamine system is an important feature of how modafinil works because it reduces the “rush” type of euphoria that is associated with addiction.
Adrafinil is also believed to positively modulate levels of two important excitatory neurotransmitters, glutamate and norepinephrine. Increased availability of these neurotransmitters may result in enhanced neuronal communication, which may improve memory, focus, and enhance general cognitive function.
Concentrations of adrafinil in the blood appear to peak at about one hour after ingestion, but because the conversion to its active form takes some time, neurological effects are generally not noted until after concentration peaks. There is no available data on adrafinil’s half-life in humans, but animal studies suggest a half-life of approximately five hours.
Dosage recommendations vary, but a range of 300–1200 mg per day of adrafinil for medical purposes has been demonstrated to be safe and effective.
Most clinical studies had the subjects split the dose in two, with one dose being taken upon waking and then another at noon.
Due to its powerful effects, it’s recommended to begin with the lowest effective dose (100–150 mg may be considered a low dose) and gradually increasing as needed.
Effects can typically be felt within an hour, and the duration of a single dose can be 3–4 hours.
Adrafinil should be ingested on an empty stomach.
Adrafinil works efficiently on its own, but it also stacks very well with other nootropics, such as piracetam, phenylpiracetam, and Noopept.
Adrafinil is generally well-tolerated when taken in moderate doses. However, some potential side effects have been documented, and they range from mild to serious.
Common side effects of adrafinil are headaches, dizziness, nausea, irritibility, aggression, and insomnia.
The most serious side effects are related to liver function. There is also the potential for elevated blood pressure and heart problems, particularly at higher doses.
Consult a medical professional before taking adrafinil if you have a history of liver or cardiovascular problems.
Due of its potent wakefulness-inducing properties, it should be taken in the morning to avoid interfering with sleep.
Taking adrafinil on a long-term basis is inadvisable, as it could potentially affect liver function. Using adrafinil in a cycle (for instance, two weeks on, one week off) is preferable.
If you experience any side effects when taking adrafinil, you should stop taking it and seek medical advice.
Adrafinil is a powerful nootropic that can fight fatigue, increase energy, improve mood, and may provide a significant cognitive boost. Its unique combination of mental and physical benefits may make it a valuable supplement for someone looking for more energy, stamina, and mental sharpness.