From The Carlat Addiction Treatment Report, September 2014, Stimulant Abuse

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Most of us prescribe cognitive enhancers every day. Examples include stimulants for attention-deficit/hyperactivity disorder (ADHD) and various dementia medications. Modafanil (Provigil), which is prescribed for sleep apnea and shift work sleep disorder, probably fits the bill, too.

But today’s conversation about “smart drugs” is fundamentally different and refers to the use of medications by people without psychiatric disorders who seek a boost or cognitive edge.

The use of drugs for both performance and physical enhancement is already occurring in other areas. Some professional athletes engage in doping and use performance enhancing drugs, most of which are banned by sports organizations. And some areas of medicine—most notably dermatology and plastic surgery—have moved well beyond treating illness into aesthetics and physical enhancement.

From that standpoint, cognitive enhancement—which some have described as cosmetic neurology or “Botox for the brain”—is a seemingly logical extension.

Who’s Using Them?

We have the most data on the use of cognitive enhancers by college students. The largest investigation surveyed a representative sample of undergraduates at 119 colleges and universities—some 11,000 students in total (McCabe SE et al, Addiction 2005;100(1):96–106). About 7% admitted to non-medical stimulant use in their lifetime. Those rates of use were roughly 4% and 2% for the past year and past month, respectively.

Stimulant users is this study were more likely to be Caucasian, male, members of fraternities and sororities, and have lower grade point averages. Use was higher at colleges in the northeastern United States and institutions with more competitive admission standards. These students were also more likely to use alcohol, cigarettes, marijuana, illicit stimulants such as cocaine and Ecstasy, and engage in other risky behaviors.

Use of cognitive enhancers in non-student populations is less well-studied. An online survey conducted by Nature magazine found that about 20% of readers who responded—1,400 people from 60 countries—had used medications for non-medical purposes to augment cognitive performance (Maher B, Nature 2008;452(7188):674–675). Their stated reasons were to improve focus, concentration, or memory. Interestingly, use did not differ greatly with age. Methylphenidate (Ritalin and others) was the most popular medication (62% of users), followed by modafanil (44%), and beta-blockers (15%), with some overlap.

Can They Help?

Do cognitive enhancers, in fact, improve cognitive performance in healthy adults without psychiatric disorders? The available evidence is mixed. In the most comprehensive review published to date, researchers from the University of Pennsylvania found 45 relevant studies, most of which compared methylphenidate or amphetamines to placebo under highly controlled conditions (Smith ME & Farah MJ, Psychol Bull 2011;137(5):717–741). Here were their main findings:

• Long-term memory. According to 22 studies, stimulants generally improve “declarative learning,” known more colloquially as rote memorization. Examples include memorizing the names of presidents or all of the steps in the Krebs cycle. Overall, stimulants improved memorization, leading the authors to conclude that these medications “enhance learning in ways that may be useful in the real world.”
• Short-term memory. Working memory, which roughly corresponds to short-term memory, includes tasks such as remembering a string of digits—for example, a telephone number—long enough to use it. There were 23 studies that tested various forms of working memory. In some cases stimulants appeared to improve this type of memory; in others, they were equivalent to placebo. In no cases, however, did stimulants negatively impact performance. This led the authors to this rather tepid conclusion: “Stimulants probably do enhance working memory, at least for some individuals in some task contexts, although the effects are not so large or reliable as to be observable in all or even most working memory studies.”
• Cognitive control/impulsivity. Cognitive control, which is basically the opposite of impulsivity, is the ability to recognize when “the most natural, automatic, or available action is not necessarily the correct one.” Examples include resisting the urge to hit the brakes when your car starts skidding on ice or perhaps ignoring that e-mail alert that pops up on your computer screen. Here the authors found 13 articles “with slightly more null results than overall positive findings” and one study actually demonstrating impaired performance.
• Other executive functions. Five studies measured the effect of stimulants on a mixed bag of executive functions. Examples include fluency tests—“Name all the words you can think of that start with the letter F”—and performing certain tasks according to defined rules. They found no consistent benefits or impairment.

Can They Hurt?

Every pill that we pop involves a trade-off between benefits and harm. The psychiatric side effects of stimulants are many and include anxiety, insomnia, agitation, and mania. Other problems include anorexia, cardiac arrhythmias, high blood pressure, tics, and seizures—and, of course, addiction.

Micromedex, the drug resource, states that mixed amphetamine and dextroamphetamine (Adderall) causes anorexia in 33% of adults, followed closely by insomnia (27%) and anxiety (13%). For methylphenidate, the stated incidence of tics is 7%.

Should We Prescribe Cognitive Enhancers?

As you can see from the research, the risk-benefit ratio for cognitive enhancers is not yet clear. Nonetheless there is some evidence that doctors are receptive to using such medications themselves. In a survey of physicians in North America, over 75% reported drinking caffeinated beverages, with “mental alertness” being one of their primary reasons (Banjo OC et al, PLoS One 2010;5(12):e14322). Twenty-three percent of these physicians stated that they would personally take a cognitive enhancer if it was approved for such use, had demonstrated effectiveness, and had no significant side effects. Only 29% gave a definite “no” to the use of cognitive enhancers, with the remaining 48% responding “maybe.”

The American Academy of Neurology, while taking no official position, leaves the door open for individual prescribers. Its Ethics, Law and Humanities Committee acknowledged “strong arguments” for and against the use of cognitive enhancers and provided a 14-point framework for responding to patient requests (Larriviere D et al, Neurology 2009;73(17):1406–1412). It noted that prescribing medications for cognitive enhancement is neither legally nor ethically obligatory, neither legally nor ethically prohibited, and is legally and ethically permissible. In other words, you could, if so moved, prescribe cognitive enhancers on an off-label basis. (See “Recommendations on Prescribing Cognitive Enhancers” on this page.)

Ethical Issues

Cognitive enhancers raise a number of novel ethical questions starting with fairness. Significant health disparities already exist in the United States. Will cognitive enhancers, much like plastic surgery or cosmetic dentistry, only be accessible to those with the personal resources to afford them? If so, does this place the have-nots at further social disadvantage (Hyman SE, Neuron 2011;69(4):595–598)?

Or, what if cognitive enhancers substantially improved workplace productivity? (This isn’t too far-fetched: the military has been using stimulants for decades.) Could employers force their employees to take cognitive enhancers or face termination? Where do you draw the line between reasonable expectations—such as wearing a uniform to work—and coercion?

Finally, is using cognitive enhancers cheating? And, who exactly, is being cheated, particularly if there are positive outcomes for society?

CATR’s Take: Cognitive enhancers appear to improve long-term memory and might have a positive impact on working memory, depending on the person and situation. These benefits, which may be difficult to estimate for individual patients, need to be weighed against very real harm and the absence of a clear consensus concerning prescribing. Physicians inclined to prescribe these drugs will want to carefully consider available guidance from the American Academy of Neurology.

Dr. Bobrin is a psychiatrist who has been treating adults with addiction for the past 10 years. He is board certified in addiction medicine.