NEW YORK (Reuters Health) – Modafinil, a wake-promoting drug initially used to treat narcolepsy, increases extracellular dopamine — an effect that increases the drug’s potential for abuse — results of a pilot study indicate.

“The growing use of modafinil in clinical medicine and as a cognitive enhancing agent and the uncertainties surrounding the mechanisms underlying its pharmacological effects highlight the need to better understand its mechanisms of action,” the research team explains in the Journal of the American Medical Association for March 18.

Led by Dr. Nora D. Volkow at the National Institute on Drug Abuse in Bethesda, Maryland, the investigators measured the effects of modafinil in 10 healthy men. Positron emission tomography was used to compare the effects of modafinil (therapeutic doses of 200 mg or 400 mg dose) versus placebo on extracellular dopamine and on dopamine transporters.

Results showed that modafinil produces elevations in brain dopamine through blockade of dopamine transporters similar in magnitude to those produced by methylphenidate, which is used to treat attention deficit/hyperactivity disorder.

“The dopamine-enhancing effects of modafinil in the nucleus accumbens may help explain reports of its abuse, since this pharmacological effect is considered crucial for drug reinforcement,” Dr. Volkow and colleagues write.

Despite the fact that “modafinil is much less potent as a reinforcer than stimulant drugs, and reports of modafinil abuse are rare and much less frequent than those for stimulant drugs,” the team warns that “risk for addiction in vulnerable persons merits heightened awareness.”

Reference:
JAMA 2009;301:1148-1154.