Experts are highlighting the benefits and potential dangers of cognitive-enhancing or “smart drugs,” intended to treat psychological disorders but increasingly used by healthy people to gain an edge in performance.
These include methylphenidate (sold as Ritalin and approved by the U.S. Food and Drug Administration for treating attention-deficit hyperactivity disorder) and modafinil (sold as Provigil, used to treat narcolepsy and shift work disorder). Both have distinct mechanisms, effects, and legal status, and trials examining short- or long-term use of these substances have shown improvements in cognition in various patient groups.
Writing in The Lancet Psychiatry, Professor Barbara Sahakian and Dr. Sharon Morein-Zamir of Cambridge University, U.K., stated, “A range of pharmaceutical substances, from psychotropic drugs to nicotine and caffeine, have been regarded by health-care providers, patients, researchers, and the general public to change, improve, and enhance mental processes.”
But the authors warn that governments, the global pharmaceutical industry, and national medical organizations must work together to clarify the harms and benefits of these drugs.
“We simply do not know enough about how many healthy people are using cognitive-enhancing drugs, in what ways and why,” they write. “Medical complications and potential for misuse are key concerns that could go unaddressed when pharmacological cognitive enhancers are taken without oversight from health-care professionals. The complexity of the brain and human behavior cannot be understated.”
Many of these drugs affect several neurotransmitters simultaneously, and can have opposing actions on the same neurotransmitters. Furthermore, the optimum dose for some brain systems may cause an overdose in other systems. “Hence, pharmacological cognitive enhancers can have a range of effects in the same individual, enhancing specific aspects of cognition while simultaneously impairing others,” the authors write.
A major issue in assessing these drugs is the benefits on cognition. Effects vary by drug, but are generally seen to be moderate or small in research studies.
For example, Dr. Dimitris Repantis of the Charite-Universitatsmedizin in Berlin, Germany, and colleagues found that Ritalin improves memory but there is no consistent evidence for other enhancing effects. Provigil, on the other hand, improves attention, and maintains wakefulness and memory in sleep-deprived individuals.
Writing in the journal Trends in Cognitive Sciences, Dr. Masud Husain of University College London, U.K., states, “There is no universal, standard battery of tests that has been agreed on, so comparisons across studies are not easy. It is not possible to compare effect sizes for different drugs if the tests used differ in the level of difficulty or method of measurement (e.g. reaction time vs error rate).”
Very few studies have examined the effects of repeated doses or long-term effects, which might be far more revealing and representative of the overall costs and benefits of taking cognitive enhancers on a regular basis.
It appears these drugs are being used to gain an advantage at school, university, or work, and for maintaining attention and performance when sleep-deprived or jet-lagged. Between five percent and 35 percent of students in the U.S. are thought to use them. But this could be just the tip of the iceberg, say the authors.
“Present cognitive-enhancing drugs have wide ranging effects and side effects and are not predictable,” the experts write. “We also know next to nothing about their long-terms effects in healthy people. Use among healthy adolescents and young adults raises a concerning safety issue of the effects of these drugs on the developing brain.”
They urge funders and policy-makers to “consider how best to promote rigorous scientific research in this domain that is socially and ethically responsible,” as “increased knowledge of the effectiveness and harms of pharmacological cognitive enhancers in healthy adults is clearly in the best interest of health-care professionals and the public.”
The use of these drugs may grow substantially and “reliable evidence is crucial for a balanced view on the risks and benefits of these drugs and to set out clear regulatory guidelines for their use.”
In terms of their legal status, pharmacological cognitive enhancers are often treated as a single class. But the experts point out that “a case-by-case discussion of regulation is needed.”
They believe that, because knowledge and opinions vary greatly among physicians, “national medical organizations should provide clear information and guidelines about benefits, risks, safety, and potential coercion to all health-care providers, and ensure that providers are aware of their availability.”
Finally, “accessibility via the Internet, as shown in other instances such as legal high purchasing (used for recreational purposes), is a growing yet poorly understood issue.”
The experts conclude that immediate action is needed to establish the long-term risks and benefits of these drugs, and to continue to develop novel, more effective drugs for patients with impairments associated with brain injury or neuropsychiatric disorders.
Sahakian, B. J. and Morein-Zamir, S. Pharmacological cognitive enhancement: treatment of neuropsychiatric disorders and lifestyle use by healthy people. Lancet Psychiatry, 1 April 2015. The Lancet
Husain, M. and Mehta, M. A. Cognitive enhancement by drugs in health and disease. Trends in Cognitive Sciences, January 2011 doi: 10.1016/j.tics.2010.11.002. NCBI
Repantis, D. et al. Modafinil and methylphenidate for neuroenhancement in healthy individuals: A systematic review. Pharmacolgical Research, September 2010 doi: 10.1016/j.phrs.2010.04.002. NCBI