Is Provigil Addictive?

March 17, 2009 - Provigil promotes wakefulness without getting you hooked. But now it seems that addiction may very well be a Provigil risk.

Provigil (generic name, modafinil) is FDA approved for promoting wakefulness in people with narcolepsy, sleep apnea, and shift work sleep disorder. Because of its relatively benign safety profile, it's often prescribed "off label" for people complaining of fatigue.

Some prominent scientists have suggested that responsible, healthy adults should be allowed to use safer stimulant drugs such as Provigil and even Ritalin to boost intellectual creativity.

But now researchers led by Nora D. Volkow, MD, director of the National Institute on Drug Abuse (NIDA), report evidence that Provigil might be more addictive than thought.

"There is an increasing use of this medication, and people have promoted the off-label use of stimulants and Provigil as cognitive enhancers with the belief that these drugs are safe," Volkow tells WebMD. "But these drugs have side effects, and their use without proper medical oversight could lead to abuse and addiction."

In their pilot study, Volkow's team recruited 10 healthy men who underwent two sets of PET brain scans after taking either Provigil (200 milligrams or 400 milligrams) or an inactive placebo pill.

The brain scans showed that Provigil blocks dopamine transporters, the molecules that remove dopamine from brain synapses. This increases the amount of dopamine in the brain -- the brain's "reward" mechanism.

Addictive drugs such as cocaine and methamphetamine trigger the same mechanism, although they do it much faster and more powerfully than Provigil does.

"The changes we are observing in dopamine concentrations with modafinil are equivalent to those we have reported for [Ritalin] in the human brain," Volkow says. "So not only does [Provigil] increase dopamine in the human brain, but does it by similar mechanisms to Ritalin and cocaine, by directly blocking the dopamine transporter. It is not working by some distinct, different mechanism."

Volkow notes that Provigil has no effect on mice lacking dopamine transporters. This indicates that while the drug may have other effects in the brain, its dopamine-enhancing effect is crucial.

Provigil: How Addictive Is It?

David Weinshenker, PhD, associate professor of human genetics at Emory University, Atlanta, has performed some of the mouse studies Volkow cites.

Weinshenker agrees with Volkow that Provigil shares at least one brain receptor with cocaine, but he downplays the drug's addiction potential.

"What is Provigil's street value? It is zero. There are not addicts walking around buying and selling modafinil," Weinshenker tells WebMD. "Most people who take Provigil don't report euphoria or being high. They don't even report feeling particularly stimulated, like caffeine. In terms of addiction and withdrawal, it just doesn't do that."

Weinshenker notes that because of Provigil's relative safety, its possible benefits are being explored for a wide number of disorders, including ADHD, autism, and depression. He says the drug offers a major benefit over amphetamine-like stimulants in that it promotes wakefulness without the sleep rebound -- a need for extra sleep when the drug wears off.