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Medically Clear: The Neuroenhancing Drug that Could

Ballard, Dustin MD

doi: 10.1097/01.EEM.0000473744.84607.6a
Medically Clear

Dr. Ballardis an emergency physician at San Rafael Kaiser and the medical director for Marin County Emergency Medical Services in San Rafael, CA.

“A tablet a day, and I was limitless.”

Bradley Cooper as Eddie Morra in the movie “Limitless” (2011)





Imagine unlocking the hidden potential of your brain with a petite pill. One dose replaces fuzziness with clarity, you know what needs to be done and how to do it, details stick, and obscure patterns are revealed in shocking simplicity. Sounds pretty awesome, right? It sure was for Eddie Morra through much of the film “Limitless.” But could neuroenhancement therapy work in real life in our lifetime? I'm skeptical that anyone can create a pill that might, for example, somehow turn my penchant for butchering foreign languages into fluency. The science of brain-enhancing drugs has never seemed more promising. And, really, the concept is not that new. Many of us have been using and relying on caffeine to boost our brainpower for decades.

But is there something safe and effective beyond caffeine? Maybe, maybe not. Let's look at some new evidence.

Recently, European Neuropsychopharmacology published a systematic review of evidence regarding the cognitive benefits of the neuroenhancing drug modafinil. ( Modafinil (Provigil) is a relatively new drug that achieved popularity among Air Force pilots who needed help staying awake while flying extended missions. Its intended medical use was to treat narcolepsy and sleep-disorders, and extreme sleepiness, but some research has suggested that modafinil may act on neurotransmitters not only to help people stay awake, but to help them to stay focused and think more clearly. I suspect I am not alone in reporting experimentation with this drug to combat the mental fuzziness caused by shift work. Certainly, I recall several 4 a.m. patients with ingrown toenails or dental abscesses who were far more interesting while dosed on modafinil than they would have been otherwise. But that is anecdotal; what does the evidence say?

Ruairidh Battleday and Anna-Katharine Brem, MSc, PhD, from the department of experimental psychology at Oxford University, parsed through the medical literature to find studies of the cognitive impact of modafinil on non-sleep-deprived adults. Starting with 267 studies, they whittled the pile down (by tossing out animal studies and those not using placebo) to 24 quality studies that incorporated validated cognitive tests. Next, they organized the findings by cognitive domains: attention, learning and memory, creativity, and executive function. (No, executive function is not the latest Donald Trumpism.)

Mr. Battleday and Dr. Brem found that modafinil offered some cognitive benefit in 20 of the 24 studies. Many cases showed that the benefit was quite modest (minor improvement in reaction time on the Stroop Color and Word Test with higher doses of modafinil,) but evidence of a more significant and sustained cognitive improvement was seen in a few cases. One study that examined a complex multiday task (involving 10 days of cognitive training) reported better early learning in the modafinil group, interestingly, with greater improvements in those with higher IQs than those with lower IQs.

Importantly, to the variable extent that the 24 studies assessed and reported side effects of modafinil, which can include allergic reactions, irritability, sleep disturbances (duh!), and headache, little evidence of such effects or of any negative cognitive consequences of modafinil use were seen.

Where does this leave us? Modafinil is certainly no limitless-type wonder drug, but it does seem to have some enhancing properties, and the review study seems to support the rather significant under-the-counter use of modafinil that's been going on for a while now, especially among students (somewhat like the non-medical use of Adderall). But should we condone this type of usage? A British Medical Journal editorial about the Battleday and Brem study addresses this, but no simple answer is found. Guy Goodwin, FMedSci, the president of the European College of Neuropsychopharmacology, wrote an editorial saying the nonmedical use of mind-altering drugs has been popular but leads to a range of harms.

Modafinil's harms may seem elusive at this time; it does not have the same sort of effects on sympathetic tone (blood pressure, heart rate, etc.) as other stimulants in the amphetamine class and does not appear to be particularly habit-forming. Remember, however, that (unlike caffeine) this is a young drug and we certainly have more to learn about it. Some preliminary research suggests, for example, that long-term use of modafinil might result in potentially severe sleep disorders. Anyone considering under-the-counter use should be careful about ordering modafinil, or any medication for that matter, over the Internet. Purity and safety issues are rampant.

Too many questions remain. What are the long-term ramifications? What are the possible effects on young developing brains? I'd say (and I bet many would agree with me) that it's still too early to declare smart drugs like modafinil the dawn of a new cognitive renaissance. But that could very well help some docs (and their patients) as an occasional antidote for hump night in a string of nocturnals. For those till looking for something limitless, there's a television version every Tuesday night.

You can learn more about this topic by listening to the Medically Clear podcast on iTunes or on Dr. Ballard's website,

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