Neuro Athletes,

Many years ago when I was in med school, I was given this drug to help me fight fatigue and stay awake. I was taking a drug that the movie Limitless is based on; Bradley Cooper plays the lead. In real life, the drug's called ‘Nuvigil’ or ‘Modafinil’. Sadly, I wasn’t as bulletproof as what I thought I would be but it did keep me awake and I was able to study for longer hours. I learnt alot about this bill that has been dubbed the “magic drug” that increases dopamine flow within the brain and, by proxy, fights excessive daytime sleepiness.

During my quest to understand the pharmacology behind this limitless drug, i interviewed Dr Jonathan Wisor, PhD is studies this drug in his lab at Washingtoon State University - you can find the episode here.

Let’s learn a bit more about this limitless drug…

Primer

The drug modafinil was developed to treat narcolepsy (excessive sleeping), but it is widely used off-licence as a ‘smart drug’ to promote cognitive enhancement, where qualities such as alertness and concentration are desired to assist someone with, for example, exam preparation.  Past studies on sleep-deprived individuals have shown a strong positive effect of modafinil on these functions, but there has been less attention and scientific consensus on the drug’s overall effectiveness as a cognitive enhancer in people that are not sleep-deprived – presumably the majority of people taking it. Now, a new systematic review, published online in the peer-reviewed journal European Neuropsychopharmacology shows that modafinil does indeed confer significant cognitive benefits in this group, at least on a particular subset of tasks.

Pharmacology

Modafinil is a stimulant of the central nervous system, which means that it works to get your body ready for action. It reaches peak concentration in your blood about 2 to 4 hours after you take your last dose, and it has a half-life of about 12 to 15 hours.

Here's what we know so far:

• Modafinil is a dopamine reuptake inhibitor, which means it increases the concentration of dopamine in the synapses between nerve cells. One of the effects of this increased dopamine is a boost in mood.

• Modafinil also blocks the reuptake of norepinephrine, a neurotransmitter that is involved in preparing the body for action. Modafinil increases the concentration of norepinephrine, likely part of how it contributes to wakefulness and focus.

• Modafinil also acts on a number of other neurochemicals including histamine, serotonin, orexin, gamma-aminobutyric acid (GABA), and glutamate —each of these plays a role in alertness and wakefulness.

Together, by indirectly upregulating neurotransmitters that play a role in wakefulness, Modafinil is able to exert a significant effect on a number of cognitive factors.

Who has openly taken Modafinil?

How Modafinil enhances your brain and mood

1. A study published by the University of Cambridge found Modafinil to be effective at reducing “impulse response”, i.e., bad decisions

An open-label, randomized, pilot trial examined both the general and differential efficacy of 4 weeks of methylphenidate (MPH) and modafinil (MOD) in 24 brain tumor patients. Participants completed cognitive tests and self-report measures of fatigue, sleep disturbance, mood and quality of life at baseline and after 4 weeks.Following stimulant treatment, there was evidence of a beneficial effect on test performance in speed of processing and executive function requiring divided attention. Patients with the greatest deficit in executive function at baseline appeared to derive the greatest benefit following stimulant therapy. Inconsistent, differential effects were found on a measure of attention in favor of MPH and on a measure of processing speed in favor of MOD. There was also evidence of a general beneficial effect on patient-reported measures of fatigue, mood, and quality of life, with no statistically significant differences between treatment arms in these measures over time (LINK).

1. Improves the motor coordination in doctors

Sleep-deprived and fatigued doctors pose a safety risk to themselves and their patients. Yet, because of the around-the-clock nature of medical practice, doctors frequently care for patients after periods of extended wakefulness or during circadian troughs. Studies suggest that a group of substances may be capable of safely and effectively reversing the effects of fatigue.A parallel, double-blind, randomized, and placebo-controlled study was performed to investigate the effect of pharmacological enhancement on performance doctors.

The results?

Modafinil improved performance on tests of higher cognitive function; participants in the modafinil group worked more efficiently when solving working memory (F1,38 = 5.24, P = 0.028) and planning (F1,38 = 4.34, P = 0.04) problems, were less-impulsive decision makers (F1,37 = 6.76, P = 0.01), and were more able to flexibly redirect their attention (F1,38 = 4.64, P = 0.038). In contrast, no improvement was seen in tests of clinical psychomotor performance (LINK).

Bottom Line

If you suffer from a sleep disorder or another condition in which you experience fatigue or difficulty concentrating – you may be interested in speaking to your doctor about receiving a prescription for modafinil. If so, be sure to talk with your doctor about any safety concerns, including side effects and drug interactions.

Although there is some information about modafinil risks, the evidence on long-term health risks is still limited, meaning side effects from long-term chronic use may still be unknown.

Because of its unclear safety profile, it’s recommended to only use modafinil when necessary.