Armodafinil - An Overview
Armodafinil (sold under the brand name NuVigil) is a wakefulness-promoting drug prescribed to treat narcolepsy, sleep apnea, and shift work disorder.13Mona Darwish, Mary Kirby, Edward T Hellriegel, Philmore Robertson Jr. Armodafinil and Modafinil Have Substantially Different Pharmacokinetic Profiles Despite Having the Same Terminal Half-Lives: Analysis of Data From Three Randomized, Single-Dose, Pharmacokinetic Studies, Clin Drug Investig. 2009
However, it is often used off-label for its nootropic effects on:
- Cognitive enhancement
Armodafinil is chemically similar to its more famous -afinil cousins, modafinil and adrafinil.
In many respects, they have many of the same effects on the brain when taken as supplements.
But there are some differences.
Brand name Modafinil is composed of both the right-handed and left-handed modafinil isomers.
The right-handed isomer is quicker acting and more powerful, while the left-handed isomer is slower-release and long-lasting.
Armodafinil gets its name because it is ONLY the right-handed isomer of modafinil.
This means that it metabolizes slightly differently and may give it more of a kick.
Some nootropics users claim that armodafinil can feel stronger and interfere with sleep more than modafinil.
What Does Armodafinil Do?
Armodafinil For Sleep Apnea and Sleep Improvement
Armodafinil’s developers originally intended it as a wakefulness-promoting agent used to treat excessive sleepiness caused by sleep apnea, narcolepsy, or shift work sleep disorder.
A meta-analysis of five randomized control armodafinil trials (a total of 1009 subjects) showed improvements in both daytime sleepiness and wakefulness. Modafinil showed similar results in the same meta-analysis.2Yi-Chun Kuan, Dean Wu, Kuang-Wei Huang, Nai-Fang Chi, Chaur-Jong Hu, Chen-Chih Chung, Ka-Wai Tam, Yao-Hsien Huang. Effects of Modafinil and Armodafinil in Patients With Obstructive Sleep Apnea: A Meta-analysis of Randomized Controlled Trials, Clin Ther. 2016
Armodafinil For Attention/Wakefulness
According to a 2-week, randomized controlled study of 254 permanent or rotating night shift workers with shift work disorder (SWD), armodafinil can significantly improve cognitive function in sleep-deprived individuals.
In patients with chronic SWD, armodafinil significantly improved wakefulness during scheduled night work, and raising mean nighttime sleep latency above the level considered to indicate severe sleepiness during the daytime.3Charles A. Czeisler, PhD, MD, James K. Walsh, PhD, Keith A. Wesnes, PhD, Sanjay Arora, PhD,† and Thomas Roth, PhD. Armodafinil for Treatment of Excessive Sleepiness Associated With Shift Work Disorder: A Randomized Controlled Study, Mayo Clin Proc. 2009
Physicians originally prescribed armodafinil as a narcolepsy drug, but it has started to gain popularity as an off-label treatment for ADHD.
It is especially popular for people looking for an alternative to medications like Adderall.
It’s effects on attention, cognition, and mood are somewhat similar to amphetamines, but with a much, much lower risk profile.
There is some evidence that armodafinil may have extra benefits for people suffering from attention disorders as opposed to those without.4Shane E Lindsay, Gary A Gudelsky, Pamela C Heaton. Use of Modafinil for the Treatment of Attention Deficit/Hyperactivity Disorder,Ann Pharmacother. 2006
Although the above study looked at modafinil, armodafinil should have similar effects.
Armodafinil For Memory
Armodafinil significantly improved long-term memory in patients with obstructive sleep apnea.
This is most likely due to its anti-fatigue effects allowing better overall cognitive function.5M Hirshkowitz, J E Black, K Wesnes, G Niebler, S Arora, T Roth. Adjunct Armodafinil Improves Wakefulness and Memory in Obstructive Sleep Apnea/Hypopnea Syndrome
, Respir Med. 2007
There have not been any large scale studies on armodafinil and healthy subjects in terms of memory.
Still, there are some anecdotal reports from the nootropics community indicating that this may be the case.
Armodafinil For Fatigue
One military study showed that soldiers who were subjected to 64 hours of continuous mental work performed better when given modafinil, which is very similar to armodafinil.
According to researchers, “subjective estimates of mood, fatigue, and sleepiness, as well as objective measures of reaction time, logical reasoning and short-term memory clearly showed better performance” after administering the drug.
Researchers also noted that it also performed better than amphetamines, and with fewer side effects.6R Pigeau, P Naitoh, A Buguet, C McCann, J Baranski, M Taylor, M Thompson, I MacK I. Modafinil, D-Amphetamine and Placebo During 64 Hours of Sustained Mental Work. I. Effects on Mood, Fatigue, Cognitive Performance and Body Temperature
, J Sleep Res. 1995
Modafinil Vs. Armodafinil
In comparison with modafinil, armodafinil maintains higher plasma concentrations later in the day in healthy subjects.7Mona Darwish, Mary Kirby, Edward T Hellriegel, Philmore Robertson Jr. Armodafinil and Modafinil Have Substantially Different Pharmacokinetic Profiles Despite Having the Same Terminal Half-Lives: Analysis of Data From Three Randomized, Single-Dose, Pharmacokinetic Studies, Clin Drug Investig. 2009
Data in healthy subjects who underwent acute sleep deprivation suggest that a single dose of armodafinil 200 mg may increase the ability to sustain wakefulness and attention later in the dosing interval compared with the same dose of modafinil.8David F Dinges, Sanjay Arora, Mona Darwish, Gwendolyn E Niebler. Pharmacodynamic Effects on Alertness of Single Doses of Armodafinil in Healthy Subjects During a Nocturnal Period of Acute Sleep Loss, Curr Med Res Opin. 2006
Armodafinil improved alertness at all doses studied. Relative to modafinil, the same dose of armodafinil showed a comparable peak plasma concentration, but with higher concentrations 6-14 hours after the dose.
In short, armodafinil stays in your system longer than modafinil, with fewer fluctuations.
How Armodafinil Works In The Brain
Armodafinil is a single right-handed isomer of modafinil. Its exact mechanism of action is unknown.
Armodafinil belongs to a class of drugs known as eugeroics (“wakefulness promoting”), which are stimulants that provide long-lasting central nervous system arousal.
Armodafinil does not bind to or inhibit many of the receptors or enzymes potentially relevant for sleep/wake regulation, making it’s specific mechanism a bit of a mystery.
However, researchers do have some ideas about how it might affect the relevant systems.
Armodafinil is not a direct dopamine receptor agonist. However, it does bind to the dopamine transporter and inhibits dopamine reuptake, indirectly modulating the dopamine system.
In vitro, it terminates the action of dopamine by its high-affinity reuptake into presynaptic terminals.
This action on dopamine could be responsible for some of its effects on mood, attention, and motivation.9Loland CJ, et al. target=”_blank”>R-modafinil (armodafinil): a unique dopamine uptake inhibitor and potential medication for psychostimulant abuse, Biol Psychiatry. 2012
Norepinephrine is a byproduct of dopamine, so armodafinil increases levels of this neurotransmitter as well.
Norepinephrine is heavily involved with wakefulness and arousal, so increasing the levels of this chemical in the brain can increase general alertness.
Adrafinil seems to work by blocking the reuptake of norepinephrine from the synapse, rather than triggering a release of the chemical.10Madras BK, et al.Modafinil occupies dopamine and norepinephrine transporters in vivo and modulates the transporters and trace amine activity in vitro, J Pharmacol Exp Ther. 2006
Armodafinil also works on the orexin/hypocretin system is located in the hypothalamus.
This region is responsible for regulating wakefulness, alertness, and hunger. Deficiency in this system can cause narcolepsy.
Researchers believe armodafinil directly stimulate these neurons, which is why it has been useful in treating narcolepsy.
Histamine is a critical component of the sleep/wake cycle as well. Armodafinil increases histamine, likely through the same action as it has on the orexin and hypocretin system.
This may promote wakefulness and stimulation.11Tomoko Ishizuka , Tomotaka Murotani, Atsushi Yamatodani. Action of Modafinil Through Histaminergic and Orexinergic Neurons, Vitam Horm. 2012
Glutamate is your brain’s primary excitatory chemical and is one of the most critical factors in regulating cognition and energy levels.
Armodafinil can raise levels of glutamate in the brain, which can increase overall mental activity.
At the same time, it seems to lower GABA levels, the main inhibitory transmitter.12Maddalena Mereu, Antonello Bonci, Amy Hauck Newman, and Gianluigi Tanda1. The neurobiology of modafinil as an enhancer of cognitive performance and a potential treatment for substance use disorders, Psychopharmacology (Berl).2013
Armodafinil Potential Side Effects
Armodafinil is more powerful than most other substances that are branded as nootropics. As such, you should use more caution when taking it.
The most common side-effects of armodafinil are:
The main complaint in the nootropics community is that it can cause sleeplessness if you take it too close to bedtime.
If seriously misused, armodafinil could even result in a trip to the hospital, although these reactions are extremely rare.
We strive to bring you the most up to date, research-based information about Armodafinil and other nootropics.
Something we missed? Do you use Armodafinil? Share your thoughts and experiences in the comments below.
About the author:
Erik Levi is a co-founder of HolisticNootropics.com and a certified holistic nutritional therapy practitioner.
As an NTP Erik takes a nutrition first approach to health. He has worked with many different people to help them use nutrition to optimize their quality of life.
Erik believes that mental health is a physiological process and cognitive enhancement is not something that can be achieved by just taking some pills with good Amazon reviews.
Instead, true cognitive enhancement comes with the right balance of nutrients, movement, and gratitude. Erik continues to stay up to date with the most current nootropic and holistic health research and promises to deliver the best solutions possible.
You can check out his personal health blog/podcast/YouTube Channel all under the name Holistic A-Hole.