Is Provigil Addictive?
Addiction Risk Seen in Wakefulness Drug Provigil
By Daniel J. DeNoon
WebMD Health News
Reviewed by Louise
Chang, MD
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.
Weinshenker and Vogel both note that because it blocks the brain receptors
needed by cocaine and methamphetamine, researchers are exploring whether
Provigil might help wean addicts from these life-threatening addictions.
But Volkow maintains that because drugs have very different effects in
different people, Provigil may very well be dangerously addictive to vulnerable
individuals.
"A vulnerable person would be anyone who has a present or past history of
addiction, whether to alcohol, nicotine, or cocaine," Volkow says. "Or, your
family history may indicate your risk, if you have close relatives with a
history of addiction. But if you don't have this history, it does not mean you
are completely safe."
Anecdotal evidence of Provigil addiction can be found on the non-judgmental
Erowid web site, in a section where drug users report their experiences.
"It is now day 5 and I am back up to 1200 mg per day and cannot imagine not
having this stuff," writes one user, who started off with one 200 milligram pill
from her husband's Provigil prescription. "I guess I'm the one person out of a
million that can actually get addicted to this miraculous 'non-addictive' drug."
Along with Xanax and
Ambien, Provigil is classified by the Drug Enforcement
Administration as a Schedule IV drug -- a controlled substance with low
potential for abuse relative to Schedule III drugs such as codeine or
anabolic
steroids.
Provigil maker Cephalon agrees with the NIDA position that Provigil should
not be taken by healthy individuals. But the company says the product's label
accurately describes the drug's abuse potential.
"After 10 years on the market, millions of patients treated, as well as
ongoing monitoring of abuse and diversion by Cephalon, the DEA, the FDA, and
other international regulatory agencies, we believe that the potential risk of
abuse and dependence is accurately reflected in the product labeling," Cephalon
spokeswoman Candace Steele tells WebMD. "We believe that there is a low relative
potential for abuse with modafinil, which is at least consistent with the DEA
scheduling for Provigil."
The Volkow study appears in the March 18 issue of the Journal of the American
Medical Association.
SOURCES:
Volkow, N.D. Journal of the American Medical Association, March 18, 2009; vol
301: pp 1148-1154.
Erowid Experience Vaults: Modafinil, "Addicted Instantly" by Cparobbins.
Mitchell, H.A. Pharmacology Biochemistry and Behavior, December 2008; vol 91: pp
217-222.
FDA approved label for Provigil.
Candace Steele, senior director for product communications, Cephalon.
© 2009 WebMD, LLC. All rights reserved.
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