Modafinil May Be Addictive

NIDA study casts doubt on safety of “brain booster” drug.

Despite the headlines, most new drugs are not addictive. Very few medications show the distinctive side effects associated with clinical drug addiction: tolerance, withdrawal, and continued use despite adverse consequences. Such drugs are relatively rare—so it was with interest and alarm that addiction specialists confronted a small pilot study, led by Dr. Nora Volkow of the National Institute on Drug Abuse (NIDA), which appeared to demonstrate that the sleep drug modafinil has addictive potential.

Modafinil, sold as Provigil, has found increasing off-prescription use for the treatment of ADHD and other psychiatric disorders. The drug is also being used as a so-called “cognitive enhancement” drug or “brain booster,” particularly among college students and military field personnel. Modafinil had even shown early promise as a drug for the treatment of cocaine addiction.

In the March 18 issue of the Journal of the American Medical Association (JAMA) , the researchers reported on levels of extracellular dopamine in the brains of 10 healthy men on either placebo or modafinil.

According to the researchers, “Modafinil acutely increased dopamine levels and blocked dopamine transporters in the human brain. Because drugs that increase dopamine have the potential for abuse, and considering the increasing use of modafinil for multiple purposes, these results suggest that risk for addiction in vulnerable persons merits heightened awareness.”

Scientists were initially excited about a drug which showed stimulant properties but did not appear to have a direct effect on the dopamine pleasure systems of the brain—a finding that set it apart from drugs like amphetamine and cocaine. However, as reported online by Heidi Ledford of Nature, “Animal studies showed that rodents that lack dopamine receptors are unresponsive to the drug, and in 2006, researchers found that modafinil affects dopamine levels in the brains of rhesus macaques.”

Dr. Volkow stressed that patients taking modafinil for recognized medical conditions such as narcolepsy should continue to do so, while doctors should monitor modafinil patients for signs of dependency.

Still, dopamine is not all there is to addiction. As reported in Nature, Bertha Madras of Harvard Medical School notes that some drugs that boost dopamine have other properties that make them aversive, and therefore not addictive. “The full spectrum of the pharmacology of the drug is what drives the abuse potential,” she said.

[The following added 8.00 pm 3-18-09]: In addition, Corpus Callosum has an excellent in-depth look at why the results of the study should be interpreted conservatively.]

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