In all likelihood you've heard a radio or television advertisement promoting the treatment of something called "shift work disorder." Though this clinical diagnosis sounds like a ridiculous excuse for a disease, the drugs used to treat the disorder are not ridiculous in any way.
Classified as eugeroics (meaning positive arousal), they are mild CNS stimulants with very few peripheral effects, and a lot of reason to believe that they can aid in boosting the cognition of even healthy and well-rested individuals.
Adrafinil (Olmifon), acts as a prodrug for modafinil, a scheduled prescription medication.
Other than adrafinil having a slightly longer duration of onset (it must metabolize into modafinil), the two drugs have an identical pharmacodynamics profile. Thus, many of the below mentioned statements are inferred from research on modafinil.
Put simply, adrafinil can improve cognition. The foremost obvious effect is improving performance during a state brought about by lack of sleep.
Imagine adrafinil as an "anti-Benadryl" (a common OTC sleep aid).
Adrafinil elevates brain histamine levels (Benadryl, or dypenhydramine, is an antihistamine). Histamine is essential for vigilance and alertness. Below is a list of benefits.
Imagine the first cup of coffee in your life. Now imagine that lasting twelve hours without feeling jittery.
Adrafinil shares some similarities to classic stimulants such as amphetamine or methylphenidate, but uniquely triggers the activation of neurons in a portion of the hypothalamus responsible for regulating wakefulness.
Adrafinil has been clinically proven to improve certain aspects of working memory, such as digit span, digit manipulation, and pattern recognition memory. This means finding Waldo might get easier. And you just might not have to ask your coworker to repeat a phone number.[4, 5]
As with other stimulants, adrafinil can reduce appetite and promote thermogenesis. A 2008 study showed that it caused an average 28% decrease in calorie intake, but unlike stimulants, such as amphetamines, the dose effective for reducing food intake does not significantly increase heart rate.
This could be seen as both a benefit or a detriment, depending on your athletic and health goals.
Modafinil (adrafinil's metabolite) was shown to be an effective treatment for attention deficit hyperactivity disorder.
There are near-proven mood-elevating effects. So effective that it is currently under review for treatment-resistant depression.
When rats were exposed to a powerful neurotoxin (one that induces irreversible Parkinson's disease-like symptoms), the rats pretreated with modafinil showed no significant loss of "tyrosine-hydroxylase-immunoreactive cells," (a marker for dopamine neuron destruction) and it prevented the "decline in motor activity normally produced by MPTP treatment."
For those still not convinced, the United States military has done exhaustive research on adrafinil and similar compounds. They have proven more effective at reducing the debilitating effects of sleep deprivation than the military's former benchmark wake-me-up, dextroamphetamine -- and with fewer side effects.
The common daily dose is 300mg to 600mg, depending on the condition you're treating.
Since the European prescription is dispensed in 300mg increments, it is recommended that most users start with 150mg to 300mg to assess sensitivity. Although adrafinil has fewer side effects than traditional stimulants, it shares similarities, such as an affinity for the dopamine transporter.
So we suggest you assume major caution.
These statements are not approved by the FDA, and you should always consult your doctor before consuming any drug.
Since there's stimulant-like behavior, let's take a look at how it shapes up against common stimulants most people are familiar with:
Adrafinil vs. caffeine
Caffeinated beverages contain the world's most widely consumed psychoactive chemical, and are usually consumed to restore vigilance.
Caffeine acts by blocking the action of the inhibitory neurotransmitter, adenosine. This increases the release of many neurotransmitters, resulting in wakefulness.
Both adrafinil and caffeine increase neurotransmitter release and produce wakefulness.
These are the primary differences:
The half-life of adrafinil is approximately 12 hours, whereas the half-life of caffeine is roughly five hours. This means that unlike caffeine, the average person only has to take a single dose of adrafinil for a full day of wakefulness.
Blood pressure and heart rate
At the dose required for cognitive enhancement, adrafinil has negligible effects on blood pressure and heart rate. Caffeine, on the other hand, increases both heart rate and blood pressure, at even low doses. So adrafinil may be preferable for people who don't want sympathetic effects.
With that said, adrafinil is still shown to reduce calorie intake and stimulate fat burning (lipolysis).
Adrafinil vs. ephedrine and amphetamine
Since ephedrine and amphetamine have similar MOAs (mechanism of action), it's simpler to compare them to adrafinil simultaneously.
Amphetamine and ephedrine act as neurotransmitter-releasing agents, elevating many neurotransmitter levels (primarily dopamine and norepinephrine). Adrafanil, as opposed to causing a release, inhibits the re-uptake of these neurotransmitters.
- Adrafinil also elevates histamine in regions of the brain critical for arousal and wakefulness.
- Eurogics, such as adrafinil, also have the unique action of agonizing a newly discovered series of receptors known as orexin or hypocretin receptors.
These receptors were formerly thought to only control food intake, but have recently been discovered to stimulate wakefulness and energy expenditure. As mentioned above,
Adrafinil does not significantly tax the cardiovascular system.
Amphetamine and ephedrine do this to a massive degree.
Most importantly,evidence suggests that adrafinil does not share the same intense tolerance and habituations that amphetamine-based stimulants are known for.
Although adrafinil appears much safer than traditional stimulants, many side effects have been reported.
According to the TEVA brand modafinil pamphlet, common side effects include:
- Back pain
- Stuffy nose
- Upset stomach
- Trouble sleeping
Because adrafinil is metabolized by the liver into modafinil, the side effects are similar. Also important to note, elevated liver enzymes have been reported with prolonged use of adrafinil.
Serious side effects
- Allergic reaction involving the liver or blood cells
- Mouth sores
- Blistering or peeling skin
- Swelling of the face, eyes, lips, tongue, legs, or throat
- Trouble swallowing or breathing
- Shortness of breath[2, 7]
The median lethal dose of adrafinil is not known. The value for rats is approximately 1250mg/kg.
No fatal overdoses have been reported, and suicide attempts (where someone consumed an excess of 5000mg) showed recovery within a few days without apparent long-term effects.
History and legal status
Until September 2011, adrafinil was marketed in Europe as Olmifon. Group Lafon, a French pharmaceutical company, discovered adrafinil in the late 1970s.
Replacement with modafinil
Adrafinil was then replaced by modafinil (the primary metabolite). Modafinil is approved by the FDA and marketed in the United States for narcolepsy, shift work sleep disorder, and excessive daytime sleepiness associated with obstructive sleep apnea.
The FDA has not approved adrafinil. It is currently unscheduled in the United States.[8, 9]
Many include adrafinil into nootropic stacks. It is important to note that these stacks should work outside of the catecholaminergic system (drugs or supplements that elevate dopamine and norepinephrine), as this could cause nasty side effects.
Do not include stimulants with adrafinil because it's stimulating enough alone.
Taking choline precursors, or choline enhancers such as a racetam, may increase the cognition-enhancing nature of adrafinil.
Many people combine dopamine elevators with stacks that potentially promote long-term potentiation (LTP). These stacks claim to promote learning by increasing neuronal growth and adaptation. Common supplements included in this increase cAMP levels via modulation of the PDE enzymes:
- Forskolin: elevates intracellular cAMP
- Artichoke extract: contains PDE4 inhibitors, drugs that block an enzyme responsible for the breakdown of cAMP
Where to buy
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- Czeisler CA, et. al.; New England Journal of Medicine; "Modafinil for excessive sleepiness associated with shift-work sleep disorder;" 2005
- "PROVIGIL(R) (modafinil) - Home". Cephalon, Inc.
- Ishizuka T, et. al.; European Journal of Pharmacology; "Involvement of central histaminergic systems in modafinil-induced but not methylphenidate-induced increases in locomotor activity in rats;" 2008
- Randall DC, et. al.; Journal of Clinical Psychopharmacology; "Does modafinil enhance cognitive performance in young volunteers who are not sleep-deprived?" 2005
- Baranski JV, et. al.; Human Psychopharmacology; "Effects of modafinil on cognitive and meta-cognitive performance;" 2004
- Biederman J, Pliszka SR; The Journal of Pediatrics "Modafinil improves symptoms of attention-deficit/hyperactivity disorder across subtypes in children and adolescents;" 2008
- "Modafinil Information Page" (PDF). Teva Pharmaceuticals. 2012-02-01.
- Smarter Nootropics; "Cephalon Discontinues Olmifon (Adrafinil);" January 2012
- Ballas, CA; Expert Review of Neurotherapeutics; "Modafinil: past, present and future;" 2002
- Jenner P.; Experimental Brain Research; "Antiparkinsonian and neuroprotective effects of modafinil in the mptp-treated common marmoset;" 2000
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