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Narcolepsy Drug Might Be Addictive
Date:3/17/2009

Finding comes as use of stimulant for enhanced mental function is on the increase

TUESDAY, March 17 (HealthDay News) -- A drug used to treat narcolepsy is increasingly being taken to sharpen mental skills, but researchers now report troubling evidence that it also harbors the potential for abuse.

Modafinil (Provigil) apparently alters the dopamine "reward system" in the brain, the new study shows.

"This drug does seem to show properties that it can be habit-forming," said Dr. Richard A. Friedman, director of the Psychopharmacology Clinic at Weill Cornell Medical College in New York City. "This is the first human study that shows that it does cause the release of dopamine, which is a hallmark of drugs of addiction. This is a little bit of an early warning that this drug may not be free of habit-forming properties."

Friedman also said that he had used the drug for treatment-resistant depression and in people who have circadian rhythm problems who have commonly reported that "they feel really good."

"It's important that these medications be utilized under the proper surveillance of a physician," said Dr. Nora D. Volkow, director of the National Institute on Drug Abuse. "If you're taking modafinil without a medical indication, then the risk-benefit ratio becomes very different."

Volkow is lead author of a paper on the finding in the March 18 issue of the Journal of the American Medical Association.

In addition to being used for sleeping disorders, modafinil is also used to boost cognitive functioning in individuals with schizophrenia and attention-deficit/hyperactivity disorder (ADHD).

This new finding suggests that the drug may work more like stimulants such as methylphenidate (Ritalin) and amphetamine than previously thought. These drugs, used to treat ADHD, increase dopamine levels.

And now people are also buying it without a prescription, on the Internet or from France, Volkow said.

Animal studies had indicated that the drug does not work the same way as other stimulant medications, but lately evidence has emerged suggesting that is not the case.

The authors used PET scans to study the effect of modafinil on the brains of 10 healthy men aged 23 to 46. Participants received either 200 milligrams of the drug (recommended for narcolepsy), 400 milligrams of the drug (effective for ADHD), or a placebo.

"We were interested in seeing if modafinil increased concentrations of dopamine in the brain reward areas, because that's where all the concern around stimulant medication and addictive potential lies," Volkow said.

In fact, the drug did raise dopamine levels in the brain and, particularly, in the nucleus accumbens region, a "pleasure center" of the brain.

"The data are consistent with what we've known about modafinil for 16 years, that it was a very, very weak inhibitor of dopamine uptake," said Jeffry Vaught, chief scientific officer and executive vice president of Cephalon Inc., which makes the medication. "At its launch, we worked with several groups to track the illicit use of modafinil and evaluate any misuse or abuse. The conclusions continually have been that, if there is any, it is very limited. Could this be part of the drug's mechanism? Maybe. Does it explain the mechanism? I don't think so, and I don't think it changes the abuse liability we've tracked now for some 15 years."

More information

Visit the U.S. National Institute on Drug Abuse for more on addiction.



SOURCES: Nora D. Volkow, M.D., director, National Institute on Drug Abuse, Bethesda, Md.; Richard A. Friedman, M.D., director, Psychopharmacology Clinic, and professor, clinical psychiatry, Weill Cornell Medical College, New York City; Jeffry Vaught, Ph.D., chief scientific officer and executive vice president, Cephalon Inc., Frazer, Pa.; March 18, 2009, Journal of the American Medical Association


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