Adrafinil

A prodrug that is metabolized in the liver to modafinil. Adrafinil provides the same wakefulness and cognitive effects as modafinil but is available without a prescription in most countries. The tradeoff is that it takes longer to kick in (45-60 minutes vs 20-30 for modafinil) and puts additional load on the liver due to first-pass metabolism.

Dosage

Standard: 300-600 mg once in the morning. 600 mg adrafinil roughly equals 200 mg modafinil. Do not use daily for extended periods due to liver metabolism. Cycle 2-3 times per week maximum.

Dosages shown are for research reference only. Always consult a qualified healthcare provider.

Half-Life

1 hour (adrafinil itself), but modafinil metabolite: 12-15 hours

Administration

Oral (capsules, powder). Takes 45-60 minutes for effects (liver conversion time).

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Mechanism of Action

Adrafinil is a prodrug—it is pharmacologically inactive until metabolized by hepatic cytochrome P450 enzymes (primarily CYP3A4) and possibly esterases into modafinil (the active metabolite) and modafinilic acid (inactive byproduct). The conversion involves oxidation of the sulfinyl group. Once converted, adrafinil acts identically to modafinil: inhibition of the dopamine transporter (DAT), activation of orexin/hypocretin neurons in the lateral hypothalamus, increased histamine release from tuberomammillary nuclei, and elevation of norepinephrine and serotonin in cortical regions. The hepatic first-pass conversion step explains the delayed onset (45-60 minutes vs 20-30 for modafinil) and the concern about liver enzyme elevation and oxidative stress with chronic daily use.

Regulatory Status

Unregulated in most countries — available without prescription as a supplement or research compound. Not a controlled substance in the US (unlike modafinil). Discontinued as a prescription drug in France (Olmifon) in 2011.

Risks & Safety

Common

Headache, nausea, anxiety, insomnia, stomach discomfort.

Serious

Liver enzyme elevation with chronic daily use — periodic liver function tests recommended. Same SJS risk as modafinil (extremely rare).

Rare

Skin irritation, orofacial dyskinesia.

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Research Papers

10
Adrafinil-induced orofacial dyskinesia.

Published: August 9, 2004

AI Summary

We describe the first case of orofacial abnormal movements induced by adrafinil, a vigilance promoting agent of the same pharmacological class as modafinil. They were secondly dramatically improved by tetrabenazine, a presynaptic dopaminergic depleting drug which was introduced after the 4-month adrafinil-free period.

Identification of adrafinil and its main metabolite modafinil in human hair. Self-administration study and interpretation of an authentic case.

Published: January 28, 2020

AI Summary

These results demonstrate the dual identification of both compounds after a single consumption, even after administration of a low dose. According to these results, the analysis of the hair strand from the authentic case does not match with a consumption of adrafinil, in accordance with abuse of modafinil alone.

Adrafinil disrupts performance on a delayed nonmatching-to-position task in aged beagle dogs.

Published: August 18, 2003

AI Summary

Treatment with 20 mg/kg of adrafinil produced a significant impairment in working memory as indicated by an increase in the number of errors over the 8-day test period. The disturbance of memory functions from adrafinil could be a result of increased noradrenergic transmission in the prefrontal cortex.

Adrafinil: effects on behavior and cognition in aged canines.

Published: July 23, 2000

AI Summary

Adrafinil causes increased locomotion without producing stereotypical activity in canines tested in an open field. 3. These results indicate that adrafinil is novel behavioral stimulant with cognitive enhancing potential.

[Noradrenaline and cerebral aging].

Published: April 30, 1991

AI Summary

The anatomical, histological, biochemical and physiological properties of the central noradrenergic system: extreme capacity for ramification and arborization; slow conduction, non-myelinized axons with extrasynaptic varicosities producing and releasing NE; frequency of co-transmission phenomena, and; neuromodulation with fiber effect responsibl...

[Spironolactone-induced pemphigoid].

Published: December 31, 1996

AI Summary

Sporadic observations would suggest that certain drugs play a role in the development of pemphigoid. A recent case-control study on long-term drug use associated with pemphigoid was unable to confirm the suspected role of these drugs, but did demonstrate a significant association between the develop

Behavioral activating effects of adrafinil in aged canines.

Published: June 5, 2000

AI Summary

The increased locomotion was generally unaccompanied by stereotypical behavior in the test session. There was some variability; a subpopulation of animals showed either no effect, or decreased locomotion.

Doping control analysis for adrafinil and its major metabolites in human urine.

Published: June 28, 2009

AI Summary

The study illustrated that the ESI capillary temperature played a key role in the formation of the protonated molecule. The limits of detection (LODs) of the developed method for the three compounds were lower than the minimum required performance limit (MRPL) of the World Anti-Doping Agency (WADA).

LC-ESI-MS determination and pharmacokinetics of adrafinil in rats.

Published: September 14, 2008

AI Summary

Adrafinil in rat serum was stable over three freeze-thaw cycles at ambient temperature for 6 h. The method had a lower limit of quantitation of 16.5 ng/ml, which offered high sensitivity for the determination of adrafinil in serum.

The role of eugeroics in the treatment of affective disorders.

Published: February 28, 2020

AI Summary

Indications for the use of modafinil include the treatment of narcolepsy, shift-work sleep disorders and excessive daytime sleepiness associated with obstructive sleep apnea. Modafinil has proven to be effective in the treatment of residual symptoms of unipolar and bipolar depression such as fatigue, excessive sleepiness and some cognitive impai...

Frequently Asked Questions

What is Adrafinil used for?

A prodrug that is metabolized in the liver to modafinil. Adrafinil provides the same wakefulness and cognitive effects as modafinil but is available without a prescription in most countries. The tradeoff is that it takes longer to kick in (45-60 minutes vs 20-30 for modafinil) and puts additional load on the liver due to first-pass metabolism.

What are the side effects of Adrafinil?

Common: Headache, nausea, anxiety, insomnia, stomach discomfort. Serious: Liver enzyme elevation with chronic daily use — periodic liver function tests recommended. Same SJS risk as modafinil (extremely rare). Rare: Skin irritation, orofacial dyskinesia.

How is Adrafinil administered?

Adrafinil is administered via oral (capsules, powder). takes 45-60 minutes for effects (liver conversion time)..

What is the half-life of Adrafinil?

The half-life of Adrafinil is 1 hour (adrafinil itself), but modafinil metabolite: 12-15 hours.

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