Cambridge neuropsychologist Barbara Sahakian on modafinil

For years the mainstream British newspaper The Guardian has been featuring articles about modafinil and smart drugs. Best among them from novelist MJ Hyland, who suffers from multiple sclerosis and wrote a paean to the drug– also a few interviews with Cambridge neuropsychologist Barbara Sahakian. Her book on how modafinil may help those with poor decision making available hereIncluded below are are few relevant and interesting parts from the interviews:

How does the modafinil work?

“We believe modafinil is a drug with multiple actions,” Sahakian says. “This is because it acts on several neurotransmitter systems in the brain. I suspect that because it’s got these multiple actions, you’re getting a number of things improving but not all for the same reason.”

Neurotransmitters are the chemicals which transmit signals between cells in the brain and Dr Peter Morgan from Yale University believes that modafinil affects three in particular. “Modafinil definitely affects the dopamine system and dopamine will make you more alert, and also more interested in things,” he says. “It affects norepinephrine which can again make you more alert and better able to focus, and it also affects histamine which can keep you awake.”

But it is modafinil’s boost to the working memory that interests many, in particular students engaged in last-minute cramming. It is believed to enhance the short-term memory by as much as 10%, through its influence on a neurotransmitter called glutamate.

And while the side effects of modafinil are considered relatively minor – a headache, most frequently, or stomach upset, or relatively rare, serious skin reactions have occurred in a handful of patients – perhaps the biggest issue is that there simply haven’t been any long-term studies into its effects.

Barbara Sahakian is a leading authority on the effects of smart drugs on the brain and she’s continually making just this point. She’s a professor of clinical neuropsychology at Cambridge University and she was one of the first people to realise that the drugs she was studying in her laboratory, drugs to ameliorate the effects of Alzheimer’s and Parkinson’s, or to enhance the cognition of stroke sufferers, were being used for very different reasons.

“I was over in Florida where I was due to speak on my research and I hadn’t been scheduled until late in the day and I turned to my colleague and said, ‘It’s such a shame I’m so jetlagged.’ And he said, ‘Would you like some of my modafinil?’ It was a drug we used in the lab but I’d never thought of it in any other context and I was totally shocked. And then at the break I started asking other colleagues if they took any of these drugs and one said, ‘Yes, I use Adderall.’ And another was using modafinil and somebody else was taking Ritalin. I was quite amazed. At least half the people around the table were using them.”

She wrote about it for Nature magazine. “And they conducted an online survey and out of 1,400 people who responded, one in five was using something. I mean this is people who are [choosing] to fill in a survey on it, but it was still very surprising.”

There are ways that the drug is useful and could be even more useful, she believes. It’s been sho

wn to improve surgeons’ performances. “They’re like shift workers essentially. They work late into the night and they mainly use caffeine and you get serious tremor with that, which is not ideal. It’s been shown to reduce impulsivity in the sleep-deprived, to improve problem-solving ability. If it reduces accidents in the workplace or bus drivers who fall asleep at the wheel, this has to be a good thing.”

What’s more, some of her most recent work has shown that it increases “task motivation. It motivates you to do the things you’ve been putting off. They become more pleasurable. It makes boring things more interesting. It’s the tax return drug.”

But she’s worried about the increasing number of students who come up to her after she gives talks. “Some of them are quite angry – they don’t want to use the drug but they feel they’ll be at a disadvantage.” More than that though is the lack of proper research into the effects over time.

“We just don’t have any long-term studies. That’s why it’s so inadvisable to use them until that’s done and that’s why I’ve been pushing the government to work with the pharmaceutical industry to do that. The other thing with young people is that their brains are still in development. If you have severe ADHD then you need a treatment like Ritalin to be able to function, but if you are a healthy young person… and you are putting these drugs into a developing brain. Well, we just don’t know enough about what this does.”

In the US, surveys have shown the highest levels of usage are at elite universities in the north-east, where academic pressure is at its most acute; where students are most competitive; where intelligence, and all the things that supposedly come from it, jobs, money, success, are perhaps most highly valued, most highly desired.

Sahakian also makes a comparison with cosmetic surgery. “We are already enhancing ourselves in all sorts of ways. I was shocked when those problems with those French breast implants came to light and the number of women who had to have them removed by the NHS. But it just all depends what you’re valuing. And if you go to a good university and expect a high salary, it’s likely you are going to be valuing certain things and if you can enhance these things that’s going to be attractive.”

And in Britain, informal surveys, such as one carried out by student website the Tab, have suggested the highest levels of usage are in the more academic universities – Oxford came top of its poll – and students of subjects with the highest workloads tended to show the highest usage. Rivlin, the editor of the Tab, was studying at Cambridge in 2010 when he first heard about modafinil and started using it. “It was my third year and it suddenly appeared and people were like, ‘It’s amazing. It allows you to concentrate.’ And, you know, there’s a lot of pressure to perform and it was very useful for mechanical academic work when you’re just trying to do a lot of notes or something.

And Sahakian points to the increasing lifestyle use of cognitive enhancing drugs, or smart drugs, by healthy people. Published figures suggest a large discrepancy between the number of diagnosed narcoleptics and the amount of anti-narcoleptic drugs sold (Cephalon, makers of Provigil, made $1.2bn in worldwide sales in 2012), and the ever increasing amounts of ADHD medications being prescribed (Dexamphetamine is the second most privately prescribed drug in Britain).

http://www.theguardian.com/society/2015/feb/15/students-smart-drugs-higher-grades-adderall-modafinil

Modafinil has emerged as the crown prince of smart drugs, that seductive group of pharmaceutical friends that promise enhanced memory, motivation, and an unrelenting ability to focus, all for hours at a time.

In the absence of long-term data, the media, particularly the student media, has tended to be relaxed about potential side-effects. The Oxford Tab, for example, simply shrugs: Who cares?

The novelist MJ Hyland, who suffers from multiple sclerosis, wrote a paean to the drug in the Guardian recently – understandably, for her, any potential side-effects are worth the risk given the benefits she’s experienced.

Professor Barbara Sahakian, at the University of Cambridge, has been researching modafinil as a possible clinical treatment for the cognitive problems of patients with psychosis. She’s fascinated by healthy people taking these drugs and has co-authored a recent book on the subject.

“Some people just want the competitive edge – they want to do better at exams so they can get into a better university or get a better degree. And there’s another group of people who want to function the best they can all the time. But people have also told me that they’ve used these drugs to help them do tasks that they’ve found not very interesting, or things they’ve been putting off.”

But it is modafinil’s boost to the working memory that interests many, in particular students engaged in last-minute cramming. It is believed to enhance the short-term memory by as much as 10%, through its influence on a neurotransmitter called glutamate.

Effects can vary greatly in accordance with the dose taken. One recent study by Dr Nora Volkow and colleagues based on PET scans suggested that doses of 400mg had effects in brain areas known to be involved in substance abuse and dependence.

Sahakian’s research also suggests that prolific use over a prolonged period of time could have a potentially damaging effect on sleep architecture.

“Some professionals tend to use it on specific occasions – when they’re jetlagged or when they’ve had a particularly bad night’s sleep,” she says. “They don’t use it every day and they don’t use it in multiple doses. Whereas, if you talk to students, they’ve often taken a dose and then, when they feel it’s wearing off, they’ve taken another dose.

“And of course that does affect their sleep pattern, because when they should be going to bed, they’ve still got the drug in their system, still exerting its wake-promoting effects. This is of course counter-productive, as we consolidate our memories during sleep.”

I spoke to students who used modafinil during exam periods. They revealed that after several weeks, they had the sensation of permanently being trapped in a twilight zone, neither asleep nor awake.

Morgan researches treatments for cocaine addicts with severe sleep disorders and he has a possible explanation. “If somebody takes modafinil long-term, they may develop some of the same deficits in slow-wave sleep as cocaine users,” he says. “Slow-wave sleep is the deep sleep that we tend to get early in the night. But by taking a stimulant that forces the body to be awake more than it wants to be, you’re disrupting its ability to regulate how much sleep it gets and the kind of sleep it gets, so it never feels properly refreshed.”

He believes that long-term use could damage the memory. “Look at nicotine,” he says. “Nicotine is an amazing cognitive enhancer, purely from a lab perspective! But for people who use nicotine chronically, we know their baseline cognitive function goes down and the nicotine is maybe bringing them back up to normal. So now nicotine is no longer a cognitive enhancer, it’s a cognitive normaliser. Because of the chronic use, the brain has adapted and without it, you’re performing at a lower level. There’s no reason to think that modafinil would be any different.”

But whatever the risks, the likelihood is that the demand for smart drugs will continue to grow. “Psychiatrists at an American Psychiatric Association Meeting in the US approached me to comment that they are frequently put under pressure to give a diagnosis of ADHD to a child even though the psychiatrist feels the symptoms are not sufficiently severe to do so,” Professor Sahakian tells me.

“The psychiatrists believe the parents do this for the cognitive enhancing effects of Ritalin for their child. In my lectures, I try to point out that our brains are still in development up until late adolescence to young adulthood, so if you’re a healthy normal child, what are the effects of manipulating the neurotransmitters while your brain’s still developing?