It seems, from the time I first heard about it, there’s been an eternal flare-up about Ritalin, and its similar counterparts, including things like Concerta and Tranquillyn. Issues with who should get it, who HAS attention-deficit/hyperactivity disorder (ADHD), whether or not ADHD is is even a real diagnosis. Issues about whether people who DON’T have ADHD should get Ritalin, and whether it’s ethical to use Ritalin (or other stimulant medications used for ADHD) for things like “cognitive enhancement”, whether it amounts to use of something that is no more harmful than using caffeine, or whether it’s something more sinister.
But that’s not what Sci is going to blog about today. Because I get a lot of people asking me whether Ritalin is bad, mentioning they’ve snorted it once or twice or took it once or twice and it did/didn’t work for them, etc, etc. But Sci’s a scientist. She hopes that people might be able to determine for themselves whether Ritalin is good or bad, once they know how it works.
So what is methylphenidate, and what does it do?
Methylphenidate is what we like to call a DAT/NET blocker. This means that it blocks the dopamine (DAT) and norepinephrine (NET) transporters in the brain. Dopamine (DA) and norepinephrine (NE) are both very important neurotransmitters in the central nervous system (CNS). Dopamine is associated with things like movement (people with Parkinson’s disease suffer from loss of their DA neurons, though the whole disease is a lot more complex than that, the loss of DA neurons is thought to be behind some of the motor impairments), and it is also associated with systems of motivation and reward. Dopamine has very few actions outside of the central nervous system, but its actions on the CNS can vastly affect how the rest of the body is doing. Due to the movement actions, there are many DA based drugs (such as Levadopa) that target DA systems for movement disorders, and due to the motivation and reward aspects, there are a lot of drugs out there targeting those as well (like, well, crack).
NE, on the other hand, has a much wider role. NE can act both as a hormone and as a neurotransmitter. As a hormone, NE is well known for it’s role in “fight or flight” changing blood pressure and heart rate and increasing blood flow to skeletal muscle. As a neurotransmitter, it is released all over the brain and is thought to have roles in ADHD, depression, and psychosis. So it’s a pretty big molecule to mess with. Despite this, there are a LOT of drugs targeting the NE system, in particular drugs for depression, ADHD, and hypotension, as well as, well, crack.
So how does a DAT/NET blocker like Ritalin work?
To start, here’s a DA synapse (courtesy of NIDA). In this post, the DA and NE synapses, when Ritalin is present, will have the same thing happen to them (we think), so I will just show the DA synapse, because it’s simpler.
You can see there’s a top neuron (presynaptic) and a bottom neuron (postsynaptic), and there are little orange bits. The orange bits are DA, being released from vesicles (those clear bubbles) into the synapse. Once in the synapse, they bind to the blue things on the other side, which are DA receptors. But you don’t want them to remain around in the synapse for long, the brain needs the stimulus to be a quick pulse. So there are the fuchsia things on the presynaptic neuron (the top neuron). These as transporters. These take the DA in the synapse and flip it back up into the top neuron, to be broken down or re-packaged.
So what happens when you block the transporters?
Here you can see the effect on the synapse when it’s under the influence of cocaine, which is a powerful DAT blocker. Cocaine is in green, and is stopping the transporter from taking up DA. This means that DA will build up in the synapse, hitting the postsynaptic receptors over and over again. These high levels of DA in the synapse, and subsequent stimulation at receptors, are what’s responsible for the high feeling and the stimulating effects of cocaine.
Well, you might say, what does that have to do with Ritalin?
Ritalin works the same way. Really. Sub Ritalin in for cocaine here and you have the same effect on DA and NE as you would with cocaine.
Sounds scary, right? Not quite so much. There are other factors with drugs than their mechanism that determine how they will make you feel. Cocaine has a very short active period, only about 20 minutes total. That’s not a lot of time, but the first rush is REALLY intense. Ritalin has a much longer active period, between 2.5 and 5 hours, depending what kind you use. And the WAY people take it makes a difference, too. If you, say, snort cocaine, it gets through the mucus membranes in the nose and into the bloodstream very quickly, giving you a rush as it hits the brain quickly. Ritalin is taken as a pill, which means it needs to get dissolved in the GI tract, and is often dissolved over a long period of time in long release formulas. This means that it comes on to your CNS very slowly, and won’t slam your transporters and have intense effects. And keep in mind that most people taking Ritalin are taking it in very low doses, doses too low to really feel good when taken orally (snorted is another matter), though high enough to increase concentration and focus.
So that’s Ritalin. Like cocaine, but not. Sci will save the debates for later.
