10 Dec

How does Modafinil work?

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Now there’s a question that needs answering, and it’s one that people have been asking for several years now. There’s a bit of a myth that nothing is known about how modafinil affects the human brain, and that it’s mostly a mystery. In fact, there are quite a few studies out there that have examined small groups of patients with fMRI technology while using modafinil, so we DO have information and CAN answer this question to an extent.

Neurotransmitters at play

To set the table for this, we should go back in time just a bit. Modafinil was supposed to be a non-dopamine alternative to the classic amphetamine family of wakefulness drugs. Amphetamines increase the amount of dopamine in the brain. Dopamine is basically the brain’s way of saying “Hey, I like what you did there! Do that again!” Dopamine causes euphoria and reinforces our good actions. It pumps us up when we do something right. Think of the thrill of nailing a play in sports, perfect marks in school, absolutely killing a job interview, you’ll find the same dopamine rush at the end.

Part of the problem is that dopamine active drugs tend to be addictive, and modafinil was presented as the anti-dopamine alternative. Yet some studies have called that into question.

A 2009 JAMA study actually revealed that modafinil increases dopamine in the brain, much like the aforementioned amphetamines. It appears to do this by blocking dopamine transporters. Dopamine, like every other neurotransmitter, is stored in the brain until it is needed, then it is transported out to trigger a certain response, like the ones we just mentioned. If you block the transmission, however, then as your brain continues to produce dopamine as usual you end up with a surplus. That surplus then affects all cells, instead of just specific ones that are targeted by a dopamine release.

The 2009 study tested this by measuring dopamine levels, as well as administering a form of iodinated cocaine which can be detected in an fMRI. It showed that after taking modafinil it was at least twice as difficult for the 11c-cocaine to bind to the usual sites. This is important, because cocaine operates by releasing heaps of dopamine, and it was more difficult for it to work precisely because something was already in cocaine’s parking space: modafinil.

Norepinephrine is another neurotransmitter implicit in modafinil’s mechanism of action. Norepinephrine is in part responsible for a mental state of alertness and attention, and so it seems to be a good explanation of modafinil’s effects. Studies have shown that norepinephrine is slightly increased by modafinil. So modafinil’s mechanism of action can be largely explained by an increase in dopamine and norepinephrine in the human brain, although that’s not the only factor that matters.

Bloody mess

Modafinil increases blood flow in the brain, though not to every place. Both of your pre-frontal cortexes light up like Christmas trees on modafinil. Why does that matter? Your pre-frontal cortex is effectively the part of your brain that handles the most complex thinking and decision making. It’s the part that is most active when you judge whether or not to do something, like when you weigh the pros and cons of an action. It’s also the part of your brain that cares most about reaching goals and planning for the future.

So increased blood flow here means increased activity and that means better brain performance. Sounds like it’s starting to make sense.

Still, it’s not all entirely sunshine and roses. Modafinil actually decreased blood flow to several parts of the left side of your brain. The left side tends to be the analytical and logical side of the brain, with areas that handle maths quite well. The right side is usually the more creative side, handling abstract thought and imagination. So what does that mean for a modafinil user? You might have increased brainpower when you’re deciding how to handle a task and what to take care of next, but if you were planning on knocking out some maths assignments you might find it harder than you had hoped.

So, how modafinil works isn’t really such a mystery at all. It’s building up dopamine in your brain and that explains many of its active effects. The perceived increase in cognitive function can be blamed squarely on increased blood flow to the pre-frontal cortexes and their role in higher thought. The brain is a fascinating place and it just gets more interesting with modafinil. Hopefully more studies will come out revealing more of its functions.