The world's favorite smart drug is much safer than Adderall and a promising treatment for substance abuse and neurodegenerative disorders—so why can't we use it?
Chances are you've heard of the drug modafinil. You know the one: the "smart drug," sometimes called the Limitless pill, that turns sleep-deprived college students and young professionals into energetic work horses.
It turns out modafinil can do even more: It's a promising treatment for stimulant drug abuse, as well as neurodegenerative disorders like Alzheimer's and Parkinson's. It's also been shown to normalize cognitive function in sleep-deprived populations (which is basically everyone these days) and is the drug of choice for astronauts on the International Space Station and members of the armed forces on long duration missions. And since modafinil is non-addictive, it's only about as risky as drinking a few cups of coffee.
But unlike the UK, Australia, India, Germany, Canada, Mexico, and other countries that have approved modafinil as a non-controlled prescription drug, the United States still classifies modafinil as a Schedule IV controlled substance, putting it alongside drugs like Xanax and Valium. Given America's ongoing amphetamine crisis and generalized sleep deprivation, legalizing a safer alternative like modafinil makes a lot of sense. So why don't we?
Modafinil was developed in the 1970s by a French professor of experimental medicine to treat narcolepsy and other sleep disorders. After decades of clinical trials in France, the US Food and Drug Administration (FDA) okayed modafinil as a treatment for narcolepsy in 1998. In 1999, the Drug Enforcement Administration (DEA) classified modafinil as a Schedule IV substance.
At the time, there wasn't enough research to clearly show modafinil's mechanism of action. Modafinil didn't appear to directly affect specific neurotransmitters, the chemicals released by nerve cells to communicate with other nerve cells. Instead, it seemed to act indirectly on several different neurotransmitters (namely serotonin, dopamine, and GABA) unlike other stimulants such as Adderall, which work more directly on the dopamine system.
The DEA noted in its ruling that the behavioral effects brought on by modafinil were similar to other stimulants, like cocaine, which do directly affect the dopamine system. Dopamine acts as a sort of natural reward system in the brain and is largely associated with addictive drugs, which gave the DEA reasonable concern.
Yet not all dopaminergic drugs are made equal. Some drugs, like MDMA, work by increasing the release of dopamine in the brain. Others, like cocaine, function as dopamine reuptake inhibitors. That means when the dopamine released by one nerve cell is not entirely absorbed by the receiving nerve cell, the leftover dopamine is blocked from reentering the original nerve cell and stays in the gap between the two nerve cells. It's this extracellular dopamine that gets you feeling the way you do when you do a line. Modafinil is also a dopamine reuptake inhibitor, but it's not nearly as effective as taking something like cocaine.
"It doesn't matter how much modafinil you take—you can never shut off the dopamine transporter as well as a little bit of cocaine or amphetamine would," Peter Morgan, an associate professor of psychiatry at Yale University, told me. "That's part of the reason why people don't really feel high when taking modafinil."
For that reason, research has shown that modafinil is actually an effective way of treating cocaine and amphetamine addiction. If you're chronically using strong dopamine blockers like cocaine, your brain essentially adjusts to the presence of this extracellular dopamine as the new normal. If you then suddenly take the cocaine out of the equation, the brain has a much harder time functioning. Modafinil can function as a safe alternative to coke—it's still a dopamine reuptake inhibitor, but its effects are way milder and there's virtually no addictive potential.
Although modafinil has been successfully used to treat cocaine addiction in certain populations, this isn't one of its FDA-approved uses—so insurance companies won't pay for it as a treatment. This means that those who need it most are forced to pay out of pocket for access, which generally isn't an option for someone recovering from a serious coke habit. When I called a pharmacy to inquire about pricing, I was told 30 100mg pills would cost $870.
Some who use modafinil off-label order it illegally from producers in countries like India for far cheaper (about $2 per 200mg pill), but also risk getting a diluted product. Others turn to "approved" prescriptions for drugs like Adderall, which may accomplish the same results but come with far more risk (namely, that Adderall itself can be addictive).
"There is no question in my mind that modafinil is much, much safer to use than any of the amphetamines or amphetamine-like drugs, like Adderall or Methylphenidate [Ritalin]," said Morgan. "It's not clear to me that it's substantially worse than caffeine, but it's definitely much better than the amphetamines."
Part of the issue is that pharmaceutical companies aren't too keen on re-introducing modafinil as an addiction treatment. "There isn't a lot of [corporate] support for pushing modafinil as a treatment for cocaine dependence," Morgan added. "It's hard to get any drug company interested in a treatment for cocaine dependence because no brand wants their brand associated with cocaine dependence."
But plenty of people are using modafinil for other things as well—most popularly, as a cognitive enhancer.
Barbara Sahakian, a neuroscientist at Cambridge, conducted a survey on off-label modafinil use after she realized a number of her perfectly healthy colleagues were using it at work. Her 2007 report in Nature surveyed 1,400 people from 60 countries who had used drugs like modafinil or Ritalin. The majority of them used them to increase concentration rather than for medical reasons, and a full one third of the respondents acquired their drugs over the internet, rather than with a prescription.
"The big issue is that there are no long-term safety studies in healthy people with drugs such as modafinil," Sahakian told me. Even though the drug seems to be wholly beneficial, there just aren't enough people researching it to change the FDA classification.
Like any drug, modafinil is not for everyone. Some people experience stomach pains or headaches, and, ultimately, there is no substitute for natural cognitive enhancers like getting more sleep or exercise.
But for those who need it for addiction treatment, to make up for cognitive deficits induced by overwork, or are unable to adjust their lifestyles to accommodate more sleep and exercise, making modafinil accessible could be a godsend. And as of now, the United States is one of the only countries to regulate modafinil as a controlled substance, approving its use only for a handful of sleeping disorders.
The first step toward legalizing modafinil is promoting it as a safe alternative to the widely available stimulants used today and encouraging more research to be done on long-term use. De-scheduling a drug in the United States is a long and arduous process, but given the benefits of legalizing modafinil, the struggle could be worth it.
Follow Daniel Oberhaus on Twitter.