Tuesday, July 22, 2008

How smart are 'smart drugs'?

There's a buzz about modafinil, meant to make you brighter and more energized. But does it work, and at what cost?

Is your memory so perforated that you fear early-onset Alzheimer’s? Your attention so centrifugal that you’ve self-diagnosed attention deficit hyperactivity disorder (ADHD)? Perhaps you don’t have time to sleep, or maybe you would just like to function as a super-you. The sci-fi solution we have all been waiting for is already here, and it’s circulating in student unions and school. These days, the kids are all on “smart drugs”.

A group of pharmaceuticals designed for sufferers of narcolepsy, Alzheimer’s and ADHD, smart drugs are increasingly being used “off label” (unsupervised, as a lifestyle choice) by healthy people, who procure them from online pharmacies, friendly physicians and illicit prescription sales. “This stuff is being passed around all the time,” says one male A-level student with something of a smart-drug habit — “this stuff” largely being Ritalin, usually prescribed for children with ADHD, and Modafinil, which is used to treat narcolepsy. Students are rejoicing and cramming for exams with smart-drug- fuelled all-nighters. One told me that he buys his from a mate who sells on his larger-than-necessary prescription; another offered to put me in touch with her “very kind doctor”.

The government, meanwhile, is sweating. It recently commissioned a report on brain science that concluded more work is needed. What students and the government both know is that in Ritalin improves attention, memory and cognitive flexibility in healthy subjects; Modafinil improves attention, memory, planning and decision- making and leaves you in a state of wakefulness without the wired bit, liability of addiction or “obvious toxic effects”. So what’s not to like?

Imbued with visions of a new, improved me, I visit that conveniently unregulated online pharmacy. Ritalin costs $116 for 10 pills; Modafinil, $20 for 10. No questions asked, no electrocardiograph tests required. I plump for cheapo Modafinil. My sister, a doctor, phones with a warning: “I’ve been discussing your drugs trial with a colleague, and we don’t think it’s safe to experiment with your brain like this.” I fall silent as she explains there are scant statistics on Modafinil’s long-term effects, even fewer on the effects on healthy subjects. Plus, as with all neurological drugs, there can be atypical side effects. And a new report claims three in five medicines bought online are fake, some dangerously so.

A dodgy package arrives in the post. Wrapped in low-grade manila, wonkily stamped “Mumbai — India”, is a loose strip of 10 x 200mg legit-looking Modafinil pills (the website was recommended by a genuine American pharmacy that refused to ship to the UK). There are no instructions, no warnings of harmful contraindications, only this: “Dosage: as directed by the neurologist/ psychiatrist/specialist.” I turn to my old friend the internet to check the dose (one or two pills) and side effects (insomnia, decreased appetite, anxiety, headache and rapid heartbeat). Some, of course, may see these cons as pros.

First thing the next morning, down it goes, and I await the “eureka!” moment. It never comes, but an hour later, I feel undoubtedly alert. Actually, I feel pretty normal (no cleverer, no less hungry), if a little edgy. A persistent, dry headache develops, like I have drunk one too many coffees (after all, caffeine and Modafinil both stimulate the central nervous system), but where my attention usually drifts, today it can’t. Streams of consciousness babble endlessly; I feel spirited and industrious. The steady energy endures with no 4pm fogs, and I fantasise about Thatcher-style productivity. Perhaps this is the key to the mythological 25-hour day?

There are stories of off-label users finally conquering their intellectual Everests (lifelong battles with War and Peace); the American poker player Paul Phillips claimed that when he was prescribed Modafinil, it helped him win more than $3.4m. One A-level student told me: “On Ritalin and Modafinil, no matter what you’re doing, you’re interested. I studied politics, which usually I couldn’t give a toss about. Four hours in, you have the choice to work or not, and you prefer to work. I screwed around all year and then worked really hard for my exams — on drugs. Some say it’s cheating, but it’s not like in sport, where you can be banned for taking steroids.” According to the Department of Health, buying these drugs from illegal organisations is not against the law, as they are legal.

It is time to find out what is going on in my head, so I call the Modafinil expert, Trevor Robbins, professor of cognitive neuroscience at Cambridge University and one of the academics behind the government’s recent brain-science report. He is unambiguously excited. “It works like a mental manager, optimising the performance of several different faculties,” he says. “It’s great on tasks requiring reflection and planning, plus it inhibits impulsiveness — and blurting out the wrong thing.” Does he see it as cheating? “Coffee is a cognition enhancer,” he argues. “People don’t think of them as the same, but they’re both chemicals. It’s like taking a vitamin pill.” Except that Modafinil is much more sophisticated and active. But where was super-me?

“Modafinil operates on an inverted U-shaped curve,” Robbins says. “If you’re already functioning at the top of it, you can only go down.” Depressing. He adds that some may not be genetically optimal for enhancement. Has Robbins tried Modafinil? “Never. I perform optimally already.”

Disturbingly, nobody knows exactly how Modafinil works, although it’s generally considered safe (provided, of course, you’re not taking the fakes). Made by Cephalon, it’s been licensed for narcolepsy (as Provigil) for 10 years in the UK. In America, where the licensing regulations are more lenient, plenty of academics have it on repeat prescription. Cephalon refuses to answer my questions about off-label use, saying it has no direct involvement with tests on healthy volunteers, nor any plans for over-the-counter sales.

It was after dark that Modafinil’s potential for 48-hour wakefulness appeared — annoyingly. (I was only after the “smart” bit.) Wide-eyed at 2am, I reached for a sleeping pill. And another. Predisposed to poor sleep, I ended up taking three times the normal dose, yet getting barely two hours’ kip.

Many claim to sleep fine and that there is no sleep debt after all-nighters, provided you get eight hours’ kip the following night. I’m not convinced. The next day, I’m still alert, but I need an extra jolt of caffeine. By 6pm, I’m broken. I see that upper- downer cycle winking at me: Exhausted? Take this little pill. Can’t sleep? Try this.

And I did, a few days later, this time on a hangover. With the stuffing already knocked out of me, I wondered whether Modafinil could be the ultimate hangover cure. But no — I had the same sleep issues (none, all night) and a whole new hangover to deal with. The day after, I felt heavy, woolly and strung out, with a stubborn, brittle headache — not dissimilar to the aftermath of a drugs bender. Unsurprisingly.

According to the US military, sequential dosing has diminishing returns: Modafinil can work for 48 hours, but then people need sleep. After all, people eventually die from sleep deprivation. As far as I can work out, it doesn’t do to mess with your circadian cycle: power pills are no substitute for real sleep. But in these time-obsessed days, off-label use is predicted to rise, and more cognition-enhancing drugs are in development. I haven’t touched my stash since, but if I were a truckie or on the eve of exams, I could be tempted. But you would be foolish to treat smart drugs like the new coffee.


New hope for Alzheimer’s patients?

A drug injected into the spine has produced rapid improvements in verbal fluency in a trial of 12 patients with Alzheimer’s disease. Etanercept (Enbrel), an antiTNF drug developed to treat rheumatoid arthritis, transformed the behaviour of some patients in a matter of minutes, the researchers say.

The results, published in BMC Neurology, are the latest in a series of bold claims made by Edward Tobinick, from a private medical group in Los Angeles, and Hyman Gross, of the University of Southern California. Their theory is that TNF is used in the brain to regulate the transmission of nerve impulses. They say that in Alzheimer’s high levels of TNF interfere with this process, so suppressing TNF with Enbrel should cause a reduction in Alzheimer’s symptoms.

BMC Neurology is accessible on the internet and includes a video showing the rapid improvements in language skills. Dr Tobinick said: “There are limitations to the data presented; the clinical trial was open label and not controlled. These caveats notwithstanding, the scientific rationale for the further investigation of antiTNF treatment of Alzheimer’s disease is compelling.”

Alzheimer’s experts have been sceptical of Dr Tobinick’s research. They say that Enbrel, even when injected into the spine, might not reach the brain in sufficient quantities to have any effect. Dr Tobinick has called for a full-scale trial of his methods.


1 comment:

Anonymous said...

Both myself and one of my good friends tried a run of Modafanil for several weeks, trying all manner of different dosing regimens and neither one of us felt *anything* at all.

As near as we can tell, it doesn't do anything except lighten your wallet (I tried it out because I work a lot of freelance and it sounded like a miracle drug to help meet crushing deadlines).