Cognition-enhancing modafinil shows addictive properties

Students may think they are getting smarter from the cognitive boost possible with prescription drug modafinil(Drug information on modafinil). They need to learn, however, that claims about its lack of serious side effects are wrong.

A National Institutes of Health study published this week in the Journal of the American Medical Association (2009;301[11]:1148-1154) used PET to demonstrate that modafinil can be habit-forming, especially for individuals who are susceptible to addiction.

Modafinil, a wake-promoting drug prescribed to treat narcolepsy, may actually enhance cognition, as indicated in previous clinical trials. It is used for off-label treatment of cognitive dysfunction in some psychiatric disorders, such as schizophrenia, and in attention-deficit/hyperactivity disorder. The Physicians' Desk Reference cautions that it can produce psychoactive and euphoric effects typical of central nervous system stimulant drugs.

Modafinil has long been considered an atypical stimulant drug, however, said study coauthor Joanne Fowler, Ph.D., a senior chemist at Brookhaven National Laboratory, in an interview. By reputation, it supposedly works mainly through nondopominergic mechanisms.

PET research conducted by Fowler and Dr. Nora D. Volkow, director of the National Institute on Alcohol Abuse and Alcoholism, indicates that modafinil's mechanism of action is actually similar to known addictive compounds, including methylphenidate(Drug information on methylphenidate) and amphetamine.

In the pilot study, 10 healthy men, aged 23 to 46, received a placebo or one of two dosages of modafinil recommended for narcolepsy or attention-deficit/hyperactivity disorder. C-11 raclopride PET was performed before and two hours after administration of the agents to measure extracellular dopamine(Drug information on dopamine) in the nucleus accumbens, a brain region critical for stimulating the pleasurable emotional effects of addictive drugs.

C-11 cocaine, a tracer that binds to the dopamine transporter, was injected after drug administration. The resulting dramatic decline in cocaine binding after modafinil administration compared with the placebo showed researchers that modafinil had bound to the same receptor sites on the dopamine transporter that attract cocaine molecules.

"Now we know it increases dopamine just like the other addictive agents," Fowler said. "It has the potential for abuse."

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