Things I like to Blog About: Ritalin

Sep 14 2009 Published by under Physiology/Pharmacology

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?
dopamine synapse NIDA.gif
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?
dopamine synapse NIDA2.gif
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.

26 responses so far

  • it's a cerebration says:

    It sounds like you are suggesting that cocaine taken in the same form as Ritalin — as low-dose, slow release pills — would produce the same effects as the ADHD medication does. But, clearly, the FDA has seen fit to outlaw cocaine and place its seal of approval on doctor-prescribed Ritalin. Not that I think the FDA is infallible or anything, but did they really make the mistake of controlling one substance and permitting another that are essentially equivalents? Benzoylmethylecgonine and methylphenidate are clearly not the same chemical compounds, but if they act in synonymous ways on the brain, shouldn’t they be treated equally under the law?
    And what about the all-touted maxim that patients who have not been prescribed Ritalin should not take it but those who have been shouldn’t miss a dose? Is there really such a neurological difference between those with ADHD and those who haven’t been diagnosed with it, or is it just a matter of how much rapport you establish with your psychiatrist? (I am not trying to patronize; I legitimately want to know!)
    Similarly, are their patients for whom controlled doses of cocaine would yield medical benefits equal to or exceeding those of Ritalin? Or are there manifold side effects that discourage the use of cocaine as an ADHD/ concentration medication in spite of its similarities to Ritalin?
    Personally, I’m skeptical of many of the diagnoses of ADHD that I see and of the politician-worthy campaigns that I hear that deny the efficacy of Ritalin for patients who have not been diagnosed with ADHD. It seems to me that for a disorder whose diagnosis is so imprecise and objective, it’s a convenient coincidence that most takers of Ritalin who have been diagnosed with ADHD (regardless of whether or not the diagnosis is accurate) show marked improvement in concentration…

  • it's a cerebration says:

    *are THERE patients

  • Scicurious says:

    cerebration: these are great questions!! In fact, they're so great, and are going to require SO much space, that I'm going to give them their own post. Which I still need to write. Hold on to your hats. 🙂

  • Michael P. says:

    It is ironic that you wrote this post today, since I just realized that my son may have forgotten to take his Concerta this morning. Thanks for the informative post. I often question whether giving our son medication is the best solution and was never really quite sure what exactly was going on in his brain while medicated. In the end we think that it is the best option along with the usual behavior modification exercises, etc. If we thought that he would be able to function in a traditional school setting without medification, we would jump at the option. Maybe there is some school out there that would allow a very intelligent boy who can't sit still, pay attention to what doesn't interest him, etc., to have a meaningful school experience, but in the meantime this is where he is.

  • Does dextroamphetamine work the same way?

  • Jon H says:

    " Maybe there is some school out there that would allow a very intelligent boy who can't sit still, pay attention to what doesn't interest him, etc., to have a meaningful school experience, but in the meantime this is where he is."
    Even if there was, life isn't so accomodating overall. And there are many worthwhile goals which are simply not amenable to making more "fun" or "exciting", but require lots of frankly boring repetition in order to develop skill.
    If an ADHD child wants, of their own accord, to be a pianist, the hours of practice may be a stumbling block. Patient instructors will help, but they won't always be present. Video-game style instruction might help get the child interested at first, but will become boring and sooner or later the kid's going to be confronted with the daily drudgery of practicing.

  • Michael P. says:

    Jon H,
    What people who have never come into close contact which a child with ADHD is that they CAN concentrate for long periods at a time, it is just that they are extremely selective when they can do that. That most children who often don't enjoy school can stay somewhat focussed despite this, isn't possible with others. My son loves to read and learn about new things, the hours that he spends on Wikipedia reading about different things or working on a merit badge for Boy Scouts is inspiring, but the traditional classroom will probably always be difficult for him.

  • Michael P. says:

    Sorry for the horrendous English. The first sentence should be "What people who have never come into close contact with a child that has ADHD don't know is that..."

  • inverse_agonist says:

    Cerebration:
    Medical danger is not a consideration in the regulation of any substances that someone might choose to take for fun. The fact that marijuana or LSD are in Schedule I doesn't really mean that either drug is more dangerous than cocaine or amphetamine, which are in Schedule II.
    Issues of pharmacokinetics and intrinsic efficacy are important considerations with drugs, though. Drugs with shorter half-lives, like cocaine, are more unpleasant to withdraw from. The antidepressant paroxetine (Paxil) has a reputation for having a worse discontinuation syndrome than fluoxetine (Prozac), largely because fluoxetine has a longer half life (and active metabolites). Bupropion (Wellbutrin) blocks DAT and NET, just like cocaine, but the experience of taking bupropion every day is nothing like the experience of taking cocaine every day.
    Low-ish doses of stimulants can help pretty much everyone with concentration, since dopamine and norepinephrine are important regulators of attention, working memory, and impulsivity. Caffeine (unrelated mechanism) is routinely used to help people work, but we don't think of it like we do Ritalin because you don't need a doctor's note for it. Whether or not caffeine is treating an underlying deficit in vigilance is a matter of semantics.
    Cognitive abilities like attention and working memory are normally distributed in the population. Those at the lower-normal end of the range will have problems in life to the extent that life requires attention and working memory. A drug that enhances these cognitive abilities will help those people in life. Someone voluntarily using amphetamine to finish their schoolwork is in violation of federal law, but someone doing the same thing at the direction of a doctor is following sound medical advice. Military pilots using amphetamine are "prolonging their operational readiness" or some such military jargon.
    If some children have difficulty behaving appropriately in school and others do not, there are biological differences among the children. Stimulants can help some of those children. The only way to provide those children with amphetamine without being charged with child abuse is to describe their behavior as a medical problem, because only doctors can dispense controlled substances.
    The boom in ADHD diagnosis and stimulant prescriptions is a result of a collective unwillingness to address how we regulate drugs and how we run schools.

  • AK says:

    Did you know that Sherlock Holmes shot cocaine to stimulate his brain? Of course, he was a fictional character, but I wonder about Sir Arthur Canon Doyle (who wrote the original Sherlock Holmes stories):  what he knew about and whether he used cocaine.
    (Just to start you off...)

  • Edmund says:

    Cerebration,
    At least one answer to your questions has to do with cocaine's very short duration compared to methylphenidate, even if cocaine is ingested. The shorter duration helps to accelerate both the creation of compulsive re-dosing behavior, and tolerance.

  • DuWayne says:

    Hmmm...So much fun to respond to...
    AK -
    It is my understanding that Doyle was rather enthusiastic about the cocaine. It has been several years and I cannot for the life of me remember the biography that discussed it(I read a few of them back in the day), but it is exceedingly likely he was a regular cocaine user.
    Michael -
    If you click on my name and scroll down a little ways, I have several links to attention deficit forums. If you scroll down quite a ways further, past my blogroll, there are tags for methylphenidate and ADHD that have some posts that might put your mind at some ease.
    There have been a number of studies now, that have found that people with ADD or ADHD who have been medicated for it when they are young, have far less likelihood of symptoms carrying over into adulthood and even more importantly, have far less a likelihood to fall into the substance abuse and addiction that is so exceedingly common in people with attention deficit issues. And speaking from extensive personal experience, trust me, you do not want your child to end up down that road.
    It isn't a lot of fun medicating a child, but when it is needed, it is needed. That said, there are a lot of things that you can do aside from the medication that can help. The forums I link provide a lot of great discussion and I delve into some of them in my own posts. Not only do I have severe ADHD, I am also the parent of at least one child with ADHD - the second is way too young to tell yet.
    it's a celebration -
    Unfortunately, there are only subjective tests that are widely available at this time, for diagnosing attention deficit issues. However, there is a likelihood that we will have more widespread availability of objective testing in the near future. To put it very simply (which as a laymen who is very early in his educational journey towards a neuropsych and linguistics degree, is the only way I can put it), yes there are some significant differences. I have linked a fair amount of attention deficit neuroscience at my blog and look forward to adding this and Sci's response to your questions to that list.
    I won't even try to dive into the science, because someone far more qualified than myself is going to do that. I can however, provide some of my own personal experience - I have lived my whole life with severe ADHD and have only been medicated for it, for less than a year. The difference has been profound to say the least. I would not be capable of functioning in school if I wasn't taking ritalin.
    To whit, I have spent most of my life as the sort of guy who regularly has to make three or four trips to the corner store, before I actually manage to get what I originally went to buy - in spite of the corner store being a two or three minute walk. As a very good handyman and remodeler, I have left pry bars, utility knives, tape measures, short levels, all sorts of small tools, inside of walls - in roof cavities - under showers or baths. I spent a great deal of time searching for tools - often enough, the tool in my fucking hand. I could go on, but if you have an interest, I have blogged about it rather extensively. I also have spent years starting and not finishing projects, reading several books at the same time - often enough putting some of them down for months at a time, or permanently.
    Now that I am on meds - I actually have short term memory. I am capable of sitting through the most intensely boring lectures and actually taking notes, instead of a nap. I can more or less function like a typical human being for the first time in my life. Some of that can be attributed to the Wellbutrin too - which helps not only with the ADHD, but the bipolar and unipolar depression as well, but even before I started taking anything else, the ritalin was making a major difference. And it is even more noticeable when I drop my dosage to almost nothing - which I do when I am off school for more than the weekend.
    I would also note that ritalin can be effective aid in concentration for those who do not have attention deficit issues. There is little question in my mind that attention deficit is diagnosed way too often and that there are a lot of kids on ritalin who probably don't need it. I doubt it is nearly as bad as you would think it is, but it certainly happens and happens a lot.
    And in case you were wondering, yes, that pisses me off - a lot. The overabundance of diagnosis makes it very easy for people like you, who are skeptical of the frequency, become skeptical of the neurological reality of attention deficit disorders. This in turn translates to convincing some people (I was one of them way back when) who have attention deficit issues that there is nothing wrong - except that we are lazy, procrastinate too much, are way too impulsive and if we would just buckle down it would be fine. Only it won't be fine, because the bottom line is that we aren't lazy and have a strong pathology driving our procrastination and impulse control. And it ultimately does a disservice to the kids who are getting shit diagnoses.

  • DuWayne says:

    Celebration -
    Click on my name for a crosspost from Corpus Collosum that includes several great links.
    I heart Nora Volkow...

  • Scicurious says:

    DuWayne: Excellent points, as usual. 🙂 But I did want to add one thing to the idea that medicated kids with ADHD do better. They most certainly DO, with improved grades and socialization, and are much less likely to abuse drugs as adults (though some of the follow up studies on that aren't so encouraging). But there are two issues at hand: (1) do these kids end up abusing drugs less because they are medicated, or because they are doing better in school and are capable of better support networks? and (2) unfortunately, the big fish who did all this human research on kids with ADHD and treatment, Biederman, was just found to have MASSIVELY violated IRB protocols in giving kids high doses of antipsychotics that weren't called for. That doesn't necessarily mean that his earlier research was BAD, but it certainly gives people a certain jaundiced eye. It probably means people are going to have to redo the studies, unfortunately, to verify them independently.
    As far as symptoms carrying over into adulthood, I think there's about a 25% chance of that...though I'm not sure of the real number and would have to look it up, Sci is very tired right now. And again, there are more questions. If there is no carryover if the kids are medicated, is that because the drugs have reversed neurological deficits? Or is it because the enhanced concentration gave them the ability to learn and benefit from behavioral therapy? And if there IS carryover, what is making the difference? How many of these kids would have "caught up" neurologically (some studies suggest that ADHD may be a developmental delay in some kids, though probably not in all cases) even without drugs?

  • KatyB says:

    From the material I have read, which is quite a bit, a child does not lose ADHD in adulthood. The medication and learning how to compensate and take care of oneself can bring great relief, but the symptoms don't disappear.
    The maxim that is touted is not at all familiar to me. It does remind me of what is said about individuals who are bipolar. That they should not take anti-depressants or stimulants because these drugs could trigger a manic episode. But, I have seen written that if someone who is dx'd bipolar has already been taking an antidepressant to no ill effect, then it could be okay to continue. There is disagreement among practitioners about these things.
    Also, it is never said that one cannot miss a dose of stimulant medication. Some children can seem like a nightmare in a classroom without them, because of their behavior. But it is not dangerous to not take a dose. In fact, some college kids take their meds only when they have a paper due, or for certain activities. Michael Phelps is ADHD. He took meds when he was young. He decided to quit, but his life has been very, very structured, much around something he is passionate about.
    As an adult who only found help from stimulant medication late in life (BTW none of the many stimulants helped until I used Vyvanse), I can attest to what the earlier poster said about feeling crummy about oneself. Being the "underachiever". Alternately despising myself for being so lazy, and being defensively proud that I wasn't a conformist.
    Late in life I learned how to stick with the boring stuff. But it takes a HUGE, HUGE effort. Even with Vyvanse on many days. Some stuff literally puts me to sleep. And it is not for lack of sleep at night!

  • katyB says:

    Also, Sigmund Freud was also a frequent cocaine user. I have some vague recollection he burned a hole in his nose. I obviously don't have the precise details on this.
    I think cocaine use was popular among intellectuals (?) around the turn of the 20th Century.

  • Beth says:

    I don't have ADHD but MS. I had to take Ritalin once because of insurance regulations (being that Provigil is much more expensive and Ritalin might be able to give me enough energy to do more than lie around). I tried the smallest dose available. I was surprised that it didn't make me nervous or give me much energy, but it did bring out all kinds of symptoms I've had with MS, particularly those involving nerve pain and involuntary contraction of muscles. Why might that be? Is it related to lowered seizure threshold (and how might that happen)? I have paroxysms with EEG findings identical or similar to myoclonus, but both they and the pain are controlled reasonably well. If methylphenidate is through the blood (and I don't see why not), and the blood-brain barrier was weak, it seems to make sense that more would get in. My best guess is that's what was happening and the drug was stimulating, too, the nerves that made all those bad symptoms, increasing them beyond what my other medication could handle. Is that something like what might have been going on? What would Ritalin do in brains that have other trouble?
    I'm just trying to understand. I won't take it again, I'm sure, but I found what happened almost as interesting as it was painful

  • Scicurious says:

    KatyB: The study most people cite for adult remission is this one: Faraone SV, Biederman J, Mick E. The age-dependent decline of attention deficit hyperactivity disorder: a meta-analysis of follow-up studies. Psychol Med. 2006;36:159–165. Though there are also these:
    Age-dependent decline of attention deficit hyperactivity disorder. Hill JC, Schoener EP. Am J Psychiatry. 1996 Sep;153(9):1143-6.
    Age-dependent decline of symptoms of attention deficit hyperactivity disorder: impact of remission definition and symptom type. Biederman J, Mick E, Faraone SV. Am J Psychiatry. 2000 May;157(5):816-8.
    Advancing age, declining ADHD. Barkley RA. Am J Psychiatry. 1997 Sep;154(9):1323-5
    Of course, there are a LOT of studies that focus on adult ADHD, but it's thought that ADHD adults are a much smaller percent of the population than ADHD children. Most studies cite between 1-26% of cases continuing into adulthood. Of course, this could well be behavioral modifications, but there's also evidence that ADHD may have something to do with developmental delays in some cases (Structural development of the basal ganglia in attention deficit hyperactivity disorder: a diffusion tensor imaging study. Silk TJ, Vance A, Rinehart N, Bradshaw JL, Cunnington R. Psychiatry Res. 2009 Jun 30;172(3):220-5. Epub 2009 Apr 24.), and that these children with developmental delays in cortical development may "catch up" with their peers in adulthood. OTOH, now we just keep treating them anyway, so who really knows.
    Also, I have a post on Freud as a cocaine user: http://scienceblogs.com/neurotopia/2009/01/open_lab_2008.php. He didn't burn a hole in his nose, he only took it orally, snorting it didn't happen until later.
    Beth: I have NO idea as to why that might be the case. Could be related to lower seizure threshold, but I'm afraid I don't know a lot about that. There are reports of it (An expert opinion on methylphenidate treatment for attention deficit hyperactivity disorder in pediatric patients with epilepsy. Baptista-Neto L, Dodds A, Rao S, Whitney J, Torres A, Gonzalez-Heydrich J. Expert Opin Investig Drugs. 2008 Jan;17(1):77-84. Review.), but I'm not sure about the mechanism.

  • llewelly says:

    Also, I have a post on Freud as a cocaine user: http://scienceblogs.com/neurotopia/2009/01/open_lab_2008.php. He didn't burn a hole in his nose, he only took it orally, snorting it didn't happen until later.

    You have a spurious period at the end of your link. Please make sure a space always follows the link.

  • Dopamine is an important signaling molecule in the enteric nervous system, which regulates gastrointestinal motility.

  • reichiru says:

    Ok, i'm no science expert, but heres a difference between cocaine and ritalin and other drugs used for ADHD.
    Cocaine has a completely different formula from ritalin and the other drugs and they are much more powerful than any of the drugs you have referenced. Ritalin is made in a lab like any other medicine and they are specially made to have certain effects in doses. a prescription of ritalin (if taken correctly) is not the same as a 'hit' of cocaine.
    On the lighter side, your blog post was extremely helpful for a project i'm working on and i needed a diagram of how an amphetamine affects the brain.
    and just to clear things up, i'm a 17 yr old who has had ADHD(diagnosed) since 3rd grade... well, just thought i'd like to add my opinion as everyone is entitled to them.

  • Michael R. says:

    I am wondering why the medical community would not recognize a paradoxical reaction to cocaine as a possible sign of the presence of ADHD, ADD?
    I will try and make my history short. I am a 45 year old male with history of alcoholism, drug abuse, depression, and severe anxiety overlay. I have been admitted to psych units on an emergency basis 5x. I have told medical and psychiatry professionals of the effect cocaine (powder, crack) had of calming me. I found others using cocaine to act differently than me in many ways, and thought my calmness was bizarre, enough so that I mentioned this to doctors on many occasions.
    I self-diagnosed ADHD after learning more about it when my son was diagnosed one year ago. My doctor referred me to a psychologist who performed the battery of tests and confirmed the diagnosis. I must say I was both elated and furious that this diagnosis occurred so late in my life. Many problems could have been averted with medication. Taking Ritalin is comparable to flipping a light switch, but in my case more accurately cutting the light off.
    I am back in school due to a back injury and recently completed a semester of four classes with a 4.0, and that is nothing short of a miracle for me. I am able to concentrate, but the most significant benefit is the calming effect. I believe much of my alcohol abuse was self-medicating my anxiety. I am so relieved to have the diagnosis and medication (80mg daily), yet am bothered by the fact that it could have been caught sooner given the volume of professionals in my life.
    So I am brought back to the paradoxical reaction to cocaine, and why that wouldn’t raise any eyebrows. I did have a significant paradoxical reaction to Risperidone (extreme anxiety and sleeplessness for 36 hours on one dose), but do not know if that is significant. Any thoughts?

  • hello says:

    this still doesn't anwser my question i read the blog but i still don't know what the brain looks like when taking ritaln b/c u don't have a caption on what you're pic is so i can't tell if it is what the cells of the brain looks lie or what

  • Becca says:

    My history with drugs is a short one. I realized that when I snorted cocaine that I became addicted to the high and would chase it all night. I also realized that it affected me in such a way that I would be completely depressed for days afterwards. I too suffer from anxiety and depression and now I am at a place in my life where I can say that I truly do not want to be doing any sort of drug in that manner. I used it for an escape and it was brought on by my deepest disconnection in my life.
    My boyfriend, on the other hand, has adhd, and uses recreationally. He may go weeks without it or he may do it 4 times in one week. I don't want to know it's around, it gives me horrible feelings, brining me back to somewhere I never want to be again.
    My boyfriend says he's done his absolute best work using cocaine and thinks clearer then ever.
    Because I'm soooo against it because it is so bad for my well being, and because of how illegal it is, My relationship is falling apart.
    I have made my demons, his demons. But it is his demon in the fact that he's using a very illegal drug for self-medication?
    I'm not sure my love can stand the test of this weight I feel.
    Thoughts and Comments?
    I really appreciate the support
    Bec

  • Depression says:

    In summary, there are many choices to offer to folks to make informed decisions about what type of treatments they want for various psychiatric conditions. It is my opinion that in current times it is the responsibility of psychiatrists including myself to be able to discuss with our patients not only conventional treatments, but also complementary and alternative treatments, their risks, along with the potential benefits and risks of no treatment at all.

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