Study Raises Concerns about Addictiveness of Popular Prescription Medication

By Hugh C. McBride

A small study that was led by the director of the National Institute on Drug Abuse (NIDA) has yielded potentially unsettling results for users of a popular prescription wakefulness drug.

According to a study that was published in the March 18 issue of the Journal of the American Medical Association, a research team under the direction of NIDA Director Dr. Nora Volkow has concluded that the drug modafinil, which is prescribed to counter excessive sleepiness in individuals who are suffering from narcolepsy, obstructive sleep apnea, and shift work sleep disorder, may be addictive.

‘Not Safe at All’

Modafinil, which is marketed by Cephalon Inc. under the brand name Provigil, was approved by the U.S. Food and Drug Administration in December 1998. The drug has been celebrated for its ability to boost wakefulness without leading to the agitation that often accompanies excessive caffeine consumption. It also has joined Attention Deficit Hyperactivity Disorder (ADHD) medications Ritalin and Adderall as an off-label “smart drug” that is believed to promote mental acuity and prolonged focus.

The findings are the latest in a series of revelations related to prescription drug abuse, which is a growing public health concern in the United States.

Until the release of the Volkow report, Provigil was believed to be non-addictive. However, as Dr. Volkow said in a March 17 article by Time writer Jeffrey Kluger, both the assumptions about addiction and the manner in which Provigil has been used have proven to be problematic.

“This drug is not safe to use the way people are using it," says Dr. Volkow told Kluger. “Not safe at all.”

‘A Nap in the Form of a Pill’

The promise of Provigil was expressed in an article titled “Wakefulness Finds a Powerful Ally,” which appeared in the June 29, 2004 edition of The New York Times. In this article, writer Anahad O’Connor described the life-altering effects that could be gained from a drug that at the time was considered to be harmless:

Laurie Coots, a marketing executive who flies to meetings in other countries twice a week, spent years trying to conquer sleepless nights and chronic jet lag. But nothing worked, she says, and every day was a struggle to stay awake.

"It was debilitating," said Ms. Coots, 46, who is from Los Angeles. "I couldn't give an effective presentation because I was always shaky and nervous from being amped up on caffeine and stimulants."

Then she found modafinil, a small white pill that revs up the central nervous system without the jitteriness of caffeine or the addiction and euphoria of amphetamines.

"Without it my life would not be possible," she said.

Since 1998, modafinil … has quietly altered the lives of millions of people. … It has been described as a nap in the form of a pill, making most users feel refreshed and alert but still able to go to bed when they are ready.

O’Connor did note that the news about Provigil wasn’t all good, and that experts such as Dr. Martha J. Farah, director of the Center for Cognitive Neuroscience at the University of Pennsylvania, were concerned that the drug was not as benign as some would like to believe.

“This drug enables us to be that much more workaholic and that much more obsessed with accomplishments and productivity, and I think our society is already extreme along those lines,” Dr. Farah told O’Connor. “The natural checks on that tendency, like needing to go to bed, are being rolled back by modafinil.”

A Pleasure Boost in the Brain

Dr. Farah’s observations have held true over the ensuing half-decade, as Provigil has become more popular as both a fatigue eradicator and a brain booster. For example, surveys indicate that, as is the case with Ritalin and Adderall, Provigil is being misused by high school and college students who take the drugs to help them remain focused during long study sessions.

Though awareness of the risks of Ritalin abuse has increased in recent years, the drug remains popular for recreational and other off-labels uses because it is widely (and mistakenly) believed to be “harmless.” A similar misperception may be behind the popularity of Provigil, though the Volkow study may counter that thought.

According to a March 17 article by WebMD Health News writer Daniel DeNoon, Dr. Volkow’s study used brain-scanning technology to determine the effect of Provigil on a small group of subjects:

• The researchers recruited 10 healthy men who underwent two sets of positron emission tomography [PET] brain scans after taking either Provigil or an inactive placebo pill.

• The brain scans showed that Provigil blocks dopamine transporters, which results in an increased amount of dopamine – a neurotransmitter associated with pleasure – remaining in the brain.

• Addictive drugs such as cocaine and methamphetamine trigger the same mechanism as the one the researchers documented in the Provigil tests, though these popular illicit substances provide a quicker and more intense “high” than Provigil does.

• Dr. Volkow noted that Provigil had no measureable effect on mice that were lacking dopamine transporters, which indicates that the drug’s dopamine-enhancing effect is crucial.

The Time article described the dopamine-addiction connection in the following terms:

“Dopamine transporters perform cleanup work,” says Volkow. “They remove dopamine after it's released and recycle it.” The more dopamine that gets left in the spaces between cells, the longer its rewarding effect on the brain – and the likelier it is to lay down the roots of addiction.

"Cocaine, amphetamines and methamphetamine all block dopamine transporters and leave dopamine in the extracellular areas," says Volkow. "Modafinil does the same."

Is Modafinil Dangerous?

Though the Volkow study indicates that Provigil has the potential for addiction, a consensus among experts remains to be reached concerning the degree to which the general public should be worried about the drug’s effects.

“There are not addicts walking around buying and selling modafinil,” David Weinshenker, PhD, an associate professor of human genetics at Emory University, said in DeNoon’s WebMD article. “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.”

Regardless of the degree to which Provigil is determined to be worthy of our worry, the Volkow study does serve as a reminder that even “safe” prescription pills may have dangerous properties, and that no such substances should be used without the supervision of a qualified healthcare professional. In recent years, prescription drug addiction has emerged as a significant public health concern, affecting individuals from a wide range of age groups and socioeconomic levels.

If you or someone you love is struggling with a dependence upon or addiction to prescription medications, contact your healthcare provider or consult with an addiction specialist to determine the best course of action to treat this problem before any more damage is done.

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Study Raises Concerns about Addictiveness of Popular Prescription Medication