Adrafinil

Authored by Robert Chen • 
July 10, 2016

Adrafinil is a nootropic agent that increases attention in healthy adults. Adrafinil is a prodrug for modafinil, meaning it is metabolized into modafinil and thus carries many of the same physiological and cognitive effects as modafinil. It is similar in structure to modafinil, without the terminal amide hydroxyl group.

Pharmacology of Adrafinil

Adrafinil is a prodrug for modafinil, and is naturally converted to modafinil in the liver.1

arafinil_modafinil_conversion

Adrafinil is a prodrug for modafinil. It is converted to modafinil in the liver.

Adrafinil produces various pharmacological effects. In animals, the most prominent effect is increased behavioral activity. For example, in mice, it has been found that at doses of 60 mg/kg, there is a 100% increase in activity while at doses of up to 90 to 120 mg/kg there is about a 300% increase in activity.1

One study in 10 elderly individuals found that adrafinil administration results in a significant central nervous system effect. Specifically, there is an increase of alpha activity and decrease of delta and theta activity.2Alpha activity is associated with sustained wakefulness in normal adults.3

Adrafinil and Cognition

While there are few studies directly studying the effect of adrafinil on cognition, there is a large body of research involving the effects of modafinil on cognition, particularly with respect to attention.4,5,6,7,8Some studies have observed improvements in creativity9and mood10as well.

Side Effects of Adrafinil

As with modafinil, it is important to note that there are various side effects associated with adrafinil usage and withdrawal.

Sources of Adrafinil

Adrafinil is a synthetic compound. It can be obtained either over the counter or with a prescription. Adrafinil cannot be obtained through natural food sources.

Editorial Opinion

While modafinil has been studied extensively, its prodrug adrafinil lacks a similar robust body of research. It is important to note that adrafinil and modafinil are not classified as a Generally Regarded as Safe (GRAS) compound by the FDA. Individuals choosing to consume adrafinil and modafinil should do so at their own risk, with special regard to the non-trivial withdrawal effects.

  1. Milgram, N. W., Callahan, H., & Siwak, C. (1999). Adrafinil: a novel vigilance promoting agent. CNS Drug Reviews, 5(3), 193-212.

  2. Saletu, B., Grünberger, J., Linzmayer, L., & Stöhr, H. (1986). Pharmaco-EEG, psychometric and plasma level studies with two novel alpha-adrenergic stimulants CRL 40476 and 40028 (adrafinil) in elderlies. New Trends in Experimental & Clinical Psychiatry.

  3. Klimesch, W. (1999). EEG alpha and theta oscillations reflect cognitive and memory performance: a review and analysis. Brain research reviews, 29(2), 169-195.

  4. Rose, S. P. (2002). 'Smart drugs': do they work? Are they ethical? Will they be legal? Nat Rev Neurosci, 3(12), 975-979. doi:10.1038/nrn984

  5. Battleday, R. M., & Brem, A. K. (2015). Modafinil for cognitive neuroenhancement in healthy non-sleep-deprived subjects: A systematic review. Eur Neuropsychopharmacol, 25(11), 1865-1881. doi:10.1016/j.euroneuro.2015.07.028

  6. Turner, D. C., Robbins, T. W., Clark, L., Aron, A. R., Dowson, J., & Sahakian, B. J. (2003). Cognitive enhancing effects of modafinil in healthy volunteers. Psychopharmacology (Berl), 165(3), 260-269. doi:10.1007/s00213-002-1250-8

  7. Randall, D. C., Fleck, N. L., Shneerson, J. M., & File, S. E. (2004). The cognitive-enhancing properties of modafinil are limited in non-sleep-deprived middle-aged volunteers. Pharmacol Biochem Behav, 77(3), 547-555. doi:10.1016/j.pbb.2003.12.016

  8. Randall, D. C., Viswanath, A., Bharania, P., Elsabagh, S. M., Hartley, D. E., Shneerson, J. M., & File, S. E. (2005). Does modafinil enhance cognitive performance in young volunteers who are not sleep-deprived? J Clin Psychopharmacol, 25(2), 175-179.

  9. Mohamed AD, Lewis CR (2014) Modafinil Increases the Latency of Response in the Hayling Sentence Completion Test in Healthy Volunteers: A Randomised Controlled Trial. PLoS ONE 9(11): e110639. doi:10.1371/journal.pone.0110639

  10. Randall, D. C., Shneerson, J. M., Plaha, K. K., & File, S. E. (2003). Modafinil affects mood, but not cognitive function, in healthy young volunteers. Hum Psychopharmacol, 18(3), 163-173. doi:10.1002/hup.456

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