A pilot study on 10 healthy men found that at normal doses, the Cephalon Inc (CEPH.O) drug known generically as modafinil increases levels of the reward chemical dopamine in the same part of the brain that becomes active with other drugs of abuse.

“It has the signature that it could potentially be addictive,” said Dr. Nora Volkow, director of the National Institute on Drug Abuse, whose study appears in the Journal of the American Medical Association.

“Studies have shown consistently that all of the drugs of abuse … have a common effect of increasing dopamine in this area, in the nucleus accumbens,” Volkow said in a telephone interview.

“That is believed to be crucial for their reinforcing effect and ultimately their underlying potential for producing addiction.”

Cephalon said in a statement the findings are consistent with what is already known about the drug, noting that it is classified as a schedule IV medication by the Drug Enforcement Administration, meaning it has some potential for abuse and dependence.

While officially approved only for excess sleepiness associated with narcolepsy, sleep apnea, and shift work disorder, Provigil is also used for weight loss, attention deficit hyperactivity disorder, fatigue and depression. Last year, it had sales of more than $852 million.

But its increasing use on college campuses to improve cognitive performance led Volkow to look more closely at the drug’s potential for addiction and abuse.

“The main problems that we see are not the people who are properly prescribed the medication, but individuals who may be misusing and abusing the medication,” Volkow said.

BRAIN-BOOSTER

In December, Volkow said recent surveys on college campuses suggest drugs such as Novartis’ Ritalin (NOVN.VX), or methylphenidate, and Provigil are being used by students, professors and others as a brain-boosting drug.

Volkow said it had not been clear before the study whether Provigil increases dopamine — the same chemical reward system in the human brain as other drugs of abuse.

The researchers used positron emission tomography and a well-known drug of addiction to trace the activity of modafinil in 10 healthy men between the ages of 23 and 46.

Volkow said the preliminary findings show modafinil activates the dopamine reward system in the brain. “That potential had been dismissed for modafinil because it was believed it had no significant dopinergic effects. Our findings question that,” she said.

“The message for individuals who are taking this medication who want cognitive enhancement is that its use could result in very serious cognitive effects, including addiction.”

Volkow said her agency plans to begin monitoring use of modafinil in its regular surveys of potential drugs of abuse.

http://www.reuters.com

“It would be wonderful if one could take a drug and be smarter, faster or have more energy,” said Dr. Nora Volkow, director of the National Institute on Drug Abuse, who led the study with a Brookhaven National Laboratory scientist. “But that is like fairy tales. We currently have nothing that has those benefits without side effects.”

The study, appearing in Wednesday’s Journal of the American Medical Association, may bust the myth that the drug is safe for healthy people, experts said.

Provigil is approved to treat excessive daytime sleepiness caused by narcolepsy. On the market since 1999, it’s the flagship product of Cephalon Inc. of Frazer, Pa., and its sales approached $1 billion last year. The company is developing a spin-off called Nuvigil.

Modafinil’s reputation as a brain enhancer stems from an Air Force study that found it improved the performance of sleep-deprived fighter pilots. College students buy and sell it illegally, as they do Ritalin and Adderall, to stay alert while studying.

Several scientists recently wrote in the journal Nature that healthy people should have the right to boost their brains with pills like Provigil. One author of that commentary, brain scientist Martha Farah of the University of Pennsylvania, said the new study “goes to show that we need a little caution and a little humility when we’re messing around with our brain chemistry.”

“But even now, after all the years that it has been on the market, we are still learning things about it that are relevant to its safety,” Farah said.

The men in the study were 23 to 46 years old. They received either a dummy pill or modafinil. Effects were measured by PET scans, which showed that the drug increased dopamine, the brain’s “feel-good” neurotransmitters.

Modafinil once was thought to be safer than conventional stimulants because it was believed that it did not engage the brain’s dopamine system, which is linked with addiction. Studies in mice and monkeys suggested otherwise.

The new study is the first human evidence that a typical dose of modafinil affects dopamine in the brain as much as a dose of Ritalin, a controlled substance with clear potential for dependence.

Volkow said modafinil acts slowly when swallowed and is difficult to inject, making it less likely to be abused. Its high price, about $10 per pill compared to Ritalin at $2 per pill, also makes it less attractive to people seeking a high. That may change when generics become available in 2012, Volkow said.

Jeffry Vaught, chief science officer for Cephalon, said the company has seen no evidence the drug is highly abused.

“If abuse is a problem with modafinil, it’s minimal at best,” Vaught said. “We’re not seeing it used at rave scenes.”

Prescribing information for the drug warns of severe rashes and other side effects such as headache, nausea and anxiety. Cephalon doesn’t support the drug’s use as a cognitive enhancer.

“There’s no substitute for sleep,” Vaught said.

http://www.google.com/hostednews

Well, now the folks at Nature are at it again, this time with an opinion piece supporting the idea of brain boosters.

“we should welcome new methods of improving our brain function,” the authors wrote, saying that using drugs to do so is no more immoral than it is to eat right or get a good night’s sleep.

The Nature commentary calls for more research into these alternative uses and offers some tips for managing the risks.

It makes sense to take a reasonable approach to the idea, one of the authors said, because as baby boomers age, they’re going to want to keep their brains agile. “Almost everybody is going to want to use it,” Martha Farah told the AP.

“I would be the first in line if safe and effective drugs were developed that trumped caffeine,” another told the news service, reminding us that coffee became the brain-booster of choice during the Enlightenment, when thinkers such as Rousseau and Voltaire would slam down upwards of 20 espressos a day to get their writing done.

Could Ritalin, Adderall and other ADHD drugs–plus anti-narcoleptics such as Provigil–be the next wave of socially acceptable stimulators? We’ll have to wait and see. But given the world of deadlines and distractions we navigate daily, there’s likely to be plenty of demand if and when the time comes.

- read the AP story

Related Articles:
Pros use pills to boost brainpower
Provigil study sparks debate
Provigil–Top 10 Warnings and Recalls

http://www.fiercepharma.com

Well, they might want to turn their more-productive brains toward analyzing the potential risks.

A new study shows that Provigil isn’t the benign little puppy it seemed to be.

Word was, Provigil was less likely to be addictive than other stimulants because it doesn’t boost dopamine levels.

But researchers used PET scanning to find that, lo and behold, Provigil actually does raise dopamine levels.

Not as much as amphetamines do, but as much as the ADHD stimulant Ritalin (methylphenidate) does.

Study author Nora Volkow, who’s director of the National Institute on Drug Abuse, said she hopes this small study inspires others to dig deeper into the potential risks of using Provigil off-label.

A risk-free drug to make people better, smarter, faster–”that is like fairy tales,” she told the Associated Press. “We currently have nothing that has those benefits without side effects.”

For its part, Cephalon said people shouldn’t pop Provigil willy-nilly: Jeffry Vaught, chief scientific officer, called Provigil “a very serious medication for serious medical disease.

This is for pathological sleep disruption, narcolepsy, not for people who’ve stayed awake for 24 hours.”

- read the USA Today story
- check out the article from the Associated Press

http://www.fiercepharma.com

The agency warned doctors of sensitivity reactions–including rare but potentially deadly Stevens-Johnson syndrome–and of psychiatric side effects like hallucination and suicidal thoughts.

Provigil is also approved for use against drowsiness in shift worker–and it’s been used off-label by truckers, med students and other types who want to stay awake all night, or even two to three days at a time.

One of its selling points? Few side effects.

- read the new warning from the FDA
- see this story from the Houston Chronicle
- read about off-label use in Wired

http://www.fiercepharma.com