ADHD Medication Explained: How It Works and Side Effects

I knew exercise could help. I knew I wanted to get support. I knew I needed to do my taxes. What surprised me about ADHD medication was feeling able to start.

But clearer focus came with other questions. Why did I crash in the evening? Why did another medication make me calmer but also sleepy? And how could I tell whether treatment was helping when some changes took weeks to notice?

For our second Science Corner conversation, I brought those questions to Akif, a biochemist, an old friend, and someone who also has ADHD. In Part 1, we talked about diagnosis and what happens in the brain. This time, I came with my pillbox.

At the time of recording, I was still working with my doctor in Japan to find the right treatment. We talked about how the different medications work, but also about the things that are harder to explain in an appointment: feeling switched on, feeling too sleepy, struggling to switch off, and noticing changes only when you look back.

Translated from German and edited for clarity, length and flow. Sections have been reordered and brief factual clarifications are labelled as editor’s notes. Medication experiences and availability describe the time of recording. This conversation offers lived experience and scientific context, not individual prescribing advice.

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Now back to the interview…

Boris: Let me explain where I am. I’m working with my doctor to get my medication right. I’ve been on this journey since the autumn, so a few months now. I’ve tried several of the common options, both stimulants and non-stimulants. There have definitely been some aha moments. But it still feels as though I’m halfway there.

One reason is that I responded quite well to stimulants. Medikinet was one of them. But here in Japan, the methylphenidate option available to me was Concerta. At the time, there was a shortage, and I couldn’t start it as a new patient. So my doctor suggested trying non-stimulants first. I tried Strattera and Intuniv, which I’m now taking together.

Akif: And how does that combination feel?

Boris: With stimulants, it felt a bit like putting on glasses. Even physically, I felt as though my eyes had been going in every direction and suddenly I could look straight ahead. Almost like wearing blinkers. It was incredibly calming because I felt: I’ve got this. I can concentrate. That gave me a sense of security.

But I also felt the side effects. There was a crash in the evening. It didn’t just feel as though I was going back to zero. Sometimes it swung a little in the other direction. I also had problems sleeping. I could still feel very active at night, and I often woke up during the night. Strattera is different. It doesn’t have that same on-off feeling. You increase the dose gradually, and the effect develops over weeks. I’m at 80 milligrams now.

It feels more like a low, constant warmth. As though the heating is always on a little. There isn’t that light-switch moment. It has calmed me down, but sometimes in a more sedating way. I find it difficult to describe. Am I tired? Drained? Sleepy? Those feelings become a bit of a soup for me. With Intuniv, “sleepy” is probably closest.

Akif: That one can feel more subtle. You might notice an improvement but find it much harder to describe exactly what has changed.

Boris: We added Intuniv because it felt as though something was still missing with Strattera. But I’m hoping I’ll be able to try Concerta. The stimulant experience felt closer to what I was looking for. I’m also trying to keep a journal because some of these things are difficult to explain. Is this the medication? Is it something else? My partner notices things too, sometimes before I can describe them myself. That’s where I am. I want to know whether what I’m experiencing is typical and what else might help.

I managed without medication for most of my life. But now I’m at a point where I want to understand what it could change for me.

Akif: We can broadly distinguish between stimulants and non-stimulants. But before getting into those, there’s a question many people ask: Why medication at all? There are other approaches. Psychoeducation means learning about ADHD and understanding your own patterns. There are psychological therapies, including cognitive behavioural therapy.

Boris: I’m doing that at the moment too.

Akif: Right. Those things can happen alongside medication. There’s exercise, looking at your diet, individual therapy and group support. My point is that medication has a particularly strong evidence base for reducing the core symptoms of ADHD. When you look at how much it can help, you understand why it plays such an important role in treatment.

Boris: Of course the biochemist would say that. You have to represent your industry.

Akif: The reason I emphasise it is the response people can have. A large proportion benefit, and finding the right medication can make a substantial difference.

Boris: What would come second in that comparison?

Akif: Cognitive behavioural therapy is an important one. But when we’re talking specifically about reducing core symptoms, medication can have a much more immediate effect. We also shouldn’t assume that everything outside medication is effortless or has no downsides. Therapy can bring difficult things to the surface. People may feel uncomfortable or stigmatised. The relationship with a therapist doesn’t always work well. And building an exercise routine or making other changes takes time and energy. Those are precisely the resources that can be difficult to access when you have ADHD.

Boris: What do you mean by side effects of therapy? Opening things up without necessarily helping someone feel better?

Akif: That can be one example. Or treatment not helping in the way someone hoped, or the process itself being difficult.

Boris: Well, as the German saying goes, “Sport ist Mord.” Exercise is murder. But seriously, I hadn’t really thought about therapy, exercise or changing your diet in terms of side effects. I still think it makes sense for each person to try different approaches.

Boris: I already knew that exercise would help. I knew that eating better would help. I knew that therapy could help. What medication helped me do was actually start doing those things.

Boris: The first time I tried ADHD medication was also the day I started putting the steps in place to get treatment properly arranged here in Japan. That was surprising. I had been thinking about it, intending to do it, and not doing it. Then suddenly I could take the first step. The same thing happened with exercise. Once I could get moving, the other things became easier too.

Akif: That connects directly to the problems we’re trying to treat: getting started, organising yourself and following through. You didn’t suddenly discover that seeking help was a good idea. You were able to act on something you already wanted to do.

Boris: It’s strange to discover that a medication can make you want to do your taxes. Not just know that you should. Actually want to sit down and deal with them, and all the other things you’ve been putting off. I didn’t really know that feeling was possible.

Akif: And that’s why it matters to recognise the neurobiological part of ADHD. I have ADHD too, and I know that language doesn’t always feel good. But there are symptoms we can treat. For some people, medication makes a major difference. Adding therapy can help with the patterns and difficulties that have built up around those symptoms.

Boris: When I talk about medication, people in my family often ask about the side effects. Which is a fair question. But there’s another question I think belongs alongside it: What are the effects of leaving ADHD untreated? People may start finding their own ways to regulate how they feel. Coffee, sugar, endless scrolling, alcohol. For some, other drugs. Those things aren’t all the same, obviously. But there can be a shared desire underneath them: trying to feel normal, or trying to make your brain cooperate.

I think that belongs in the conversation about risks too.

Akif: Definitely. ADHD can affect health and safety as well as concentration. Stress, risky behaviour, driving, alcohol use and other difficulties can accumulate.

Akif: So when we weigh up treatment, we need to think about the whole picture. Medication has a strong evidence base and has been used for many years. That’s why I push back against treating it as an inherently unreasonable or extreme option. And to be clear, I’m not speaking on behalf of a company producing these ADHD medications. That isn’t the area I work in.

Boris: And nobody is paying us for this conversation.

Akif: It helps to briefly return to the two neurotransmitters we discussed last time: dopamine and noradrenaline. A useful simplified way to think about ADHD is that the regulation and timing of these signals are not working as they should. That connects to difficulties with attention, organisation, impulsivity, restlessness, forgetfulness and patience. It can also mean difficulty starting a task, difficulty stopping one, talking more than you intended, or struggling to regulate emotions. Dopamine is involved in motivation, drive and reward. Noradrenaline is involved in attention, alertness and filtering information.

Boris: Where does irritability fit into that?

Akif: That falls under emotional regulation too. Getting irritated quickly can be one expression of difficulty regulating emotions. There’s also an interesting question about what we learn over time. Are we simply quick to get angry, or do we sometimes learn to use that state to get ourselves moving? Anger creates arousal. If getting started is difficult, that activation can become part of how you get things done.

I wouldn’t present that as a complete explanation. It may be a mixture of things, and it isn’t necessarily conscious. But irritability is something many of us struggle with.

Boris: And anxiety? That can be part of the picture too.

Akif: Yes. Some of it may develop through what you experience while living with ADHD. Repeated difficulties, misunderstandings and negative reactions from other people can contribute to anxiety, including social anxiety.

Boris: So something that develops alongside the symptoms as you get older?

Akif: Exactly. The symptoms and what happens around them can have consequences of their own.

Editor’s note: This is a simplified account of ADHD, not a complete explanation of its biology. Anxiety can also be a separate co-occurring condition.

Akif: Let’s return to stimulants and non-stimulants. The word “stimulant” can sound surprising when you’re talking about a treatment that helps someone feel calmer. But the effect we’re interested in is better regulation of attention and behaviour. Methylphenidate is one of the main stimulant medications. You’ll recognise names such as Ritalin, Medikinet and Concerta. There are generic versions too. It increases the availability of dopamine and noradrenaline by inhibiting their reuptake.

Boris: What does reuptake mean in practice?

Akif: These neurotransmitters are released to transmit a signal. Transporters then take them back up so that the signal doesn’t continue indefinitely. Methylphenidate blocks those transporters. In simple terms, more of the neurotransmitter remains available to act. That’s the main idea: reducing reuptake.

Boris: Friends in the US have access to other medications, such as Adderall. Does that actually produce dopamine, rather than just stopping it from being taken back up?

Akif: Not quite, but you’re pointing to the difference. Amphetamine medications also affect dopamine and noradrenaline signalling. They can increase release as well as affect reuptake. One part of that involves transporters moving neurotransmitters in the other direction. So you have more being released, rather than only preventing what is already there from being taken back up. Adderall is an amphetamine medication. Elvanse contains lisdexamfetamine, which the body converts into an active amphetamine.

People sometimes describe amphetamines as feeling stronger, and some people respond better to them or tolerate them better. But the experience isn’t the same for everyone.

Boris: Comparing Elvanse with Medikinet, I sometimes felt that Elvanse was a little too much for me. I was building my sauna and finished it in a few days. I got intensely focused on it and really wanted to get it done. Then I’d notice I was still concentrating and working late into the night. I couldn’t come down. With Medikinet, I could feel it wear off after a few hours.

Akif: Part of that difference can be the formulation: how the medication is released. Some products release the active ingredient quickly. Others release it over a longer period. So even with the same active ingredient, the experience can be different. With a shorter-acting formulation, you may notice it starting and wearing off more clearly. That can connect to the crash you described earlier. A rebound is when symptoms temporarily feel worse as the medication wears off. It can feel like dipping below your usual baseline before settling again.

Boris: Is that a generic-versus-brand issue, or does it happen with branded medication too?

Akif: It can happen with either. The important distinction here is the release formulation, rather than simply whether it’s generic or branded.

Boris: Are there different versions of Medikinet?

Akif: Yes. The product and its release profile matter, so you need to know which version you’re taking.

Boris: Could you solve it by opening a tablet or capsule and taking half first?

Akif: Splitting the amount doesn’t automatically solve the timing problem. If the issue is how the medication wears off, the release profile matters too. The aim is to get an appropriate dose working over the period you need it, rather than just divide it arbitrarily.

Editor’s note: Whether a medicine can be opened or divided depends on the exact product. Concerta XL must be swallowed whole. Changes to dose or timing should be planned with the prescriber. [1]

Akif: Going back to what you described with Elvanse: staying active for a long time, finding it hard to sleep, and not feeling the same sharp drop. Lisdexamfetamine is a prodrug. That means it has to be converted in the body into the active drug. That’s part of why its time course differs from an immediate-release medication. The duration can be helpful, but it can also become a problem if it keeps you active later than you want.

Boris: Just to clarify, I’ve tried Elvanse, not Adderall.

Akif: Right. And that’s why taking it early in the day matters when sleep is an issue.

Editor’s note: Lisdexamfetamine is converted into active dexamfetamine primarily by red blood cells. Elvanse is taken in the morning; afternoon doses can interfere with sleep. [2]

Boris: Something that helped me was the curve people use to explain this: too little isn’t helpful, but too much isn’t helpful either. There’s a point in between. Can you explain that better than I can?

Akif: If the dose is too low, you may not get enough benefit to improve the symptoms you’re trying to treat. If it’s too high, you can become overstimulated. You might feel restless, sweaty, wired or overwhelmed. In that state, it can become difficult to focus again. There’s too much going on. So the aim isn’t simply to increase the dose until you feel as much as possible. You’re looking for the amount that helps you function.

Boris: I was thinking of having too many ideas, taking too much on, filling your plate because suddenly you feel you can do everything.

Akif: I mean something more like being physically and mentally overactivated. The kind of state where it’s clearly too much. That’s what we want to avoid.

Boris: So the feeling of being able to do more isn’t automatically the same thing as having found the right dose.

Boris: I take Strattera in the morning and Intuniv in the evening. If I still feel I need more activation and want to add Medikinet, what happens? Would the other medications continue, or would you leave them out that day? It sounds like a lot at once.

Akif: Combining medications can change the effects and side effects, including the possibility of feeling too activated. That needs to be discussed with the clinician managing the treatment. The difference between the medication types matters here. Stimulants can have noticeable effects on the day you take them. Atomoxetine, the active ingredient in Strattera, is assessed over a longer period. It primarily inhibits the reuptake of noradrenaline. The way its clinical benefits develop is different from the immediate experience you may have with a stimulant.

You can’t judge it in the same way after a single dose. It may take several weeks to get a useful sense of how it’s working. That’s why casually stopping and starting it to compare individual days doesn’t give you the same kind of comparison.

Boris: And Intuniv works differently again?

Akif: Yes. Its active ingredient is guanfacine. It isn’t working by blocking those same reuptake transporters. A simplified way to describe it is that it affects how signals are processed, rather than simply increasing how much neurotransmitter is available. That’s why different mechanisms can sometimes be considered together. The idea is to see whether you can improve the benefit without creating too many side effects. But you have to assess the actual combination and the person taking it.

Boris: It’s difficult to compare. With one medication, you really feel something on that day. With another, you’re looking for a change after weeks.

Akif: You need time to work out whether there’s a benefit and whether it’s worth the side effects you’re experiencing.

Editor’s note: Combining or changing medicines requires individual medical assessment. Guanfacine should not be stopped abruptly because blood pressure and heart rate can rise. [3]

Boris: That’s the question, isn’t it? Which side effects are you willing to live with? With Medikinet, I felt more switched on. With the non-stimulants, I felt calmer, but not always in a good way.

Akif: All of these medications can have side effects. You’re looking at the balance between the benefit and how the treatment feels in everyday life. Some people find that certain side effects settle with time. That doesn’t mean you should ignore something that is making life difficult, but your experience at the beginning may not be the same as your experience later. There can be gastrointestinal effects, changes in appetite and other physical effects.

Boris: With stimulants, I noticed much less of an urge to snack. That craving for food was noticeably different for me. I also think the non-stimulants have affected my libido. I can’t describe it very precisely, but something feels different.

Akif: Reduced libido and sexual difficulties can occur with atomoxetine. Guanfacine can also make people feel tired or sedated, which connects to what you described. So the overall experience of a combination matters, not just what each medication does on paper.

Boris: If Intuniv is making me too tired, does that mean the Strattera should go up or down? I’m taking 80 milligrams at the moment, after increasing it. What comes next?

Akif: That’s difficult to answer from the conversation alone. Effects and side effects can overlap. Did the tiredness start with atomoxetine, or did it appear when guanfacine was added?

Boris: When guanfacine was added.

Akif: That makes guanfacine a possible contributor. But increasing atomoxetine doesn’t automatically mean the tiredness will disappear. It could change, stay the same or get worse. You need to look at the pattern rather than assume one medication will cancel out the effects of another.

Boris: What about the question of addiction? I think concerns about misuse are part of why access is so restrictive in Japan.

Akif: We need to distinguish misuse from taking a prescribed medication as treatment. Different medications and formulations also have different characteristics. In practice, we often encounter another problem with ADHD: people forget to take the medication that helps them. You ask, “Did you take it?” And they say, “I don’t know. I forgot again.” Or they leave home without it, or remember too late in the day. Following the treatment plan can itself be difficult.

Boris: That moment of “Did I take it, or didn’t I?” is horrible. You wonder whether to take another one, but you don’t know whether that would mean taking it twice. It feels like a fifty-fifty guess.

Akif: You don’t want to accidentally double up. It’s something you need a clear plan for.

Editor’s note: Forgetting doses does not mean a medicine has no misuse or dependence risk. If you are unsure whether you took a dose, follow the instructions for that medicine and ask a pharmacist or prescriber. [1–3]

Boris: There is one thing that made the improvement more concrete for me. At my doctor’s practice in Tokyo, I get an online questionnaire before an appointment. I don’t know whether that’s common in Germany too. It asks how I’m doing emotionally. Things like whether I feel guilty, and questions about suicidal thoughts. A whole range of mental-health questions. Recently, I asked whether I could see how my results had changed over the last four months.

It turned out to be the Beck Depression Inventory. I hadn’t really understood that this was what the questionnaire was measuring. Depression wasn’t something I’d particularly been thinking about in my own case. But the score had clearly gone down during the period I’d been taking medication. That gave me something I could actually see: there was a trend. It’s one indicator alongside how I feel and what my partner notices. Those things don’t always line up perfectly.

But even while answering the questions, I’d begun noticing that something had changed over time.

Akif: In a positive direction?

Boris: Yes. I just hadn’t realised I was filling out a depression questionnaire.

Boris: Have you ever done that particular test?

Akif: Not knowingly. I’ve had assessments of depressive symptoms, but I don’t remember taking that test by name. Depressive mood hasn’t been a major issue for me personally. I tend to be quite an upbeat person. But mood is something to keep an eye on during treatment too. If someone becomes persistently sad or feels worse on a medication, that matters when reviewing the treatment.

Boris: So you’re looking at changes in mood as well as concentration.

Akif: Yes. And the wider clinical picture matters when choosing a medication or considering a change.

Editor’s note: Questionnaire scores can help show a change in symptoms, but do not establish what caused it.

I was still figuring out what worked for me. The questionnaire gave me something useful to bring into that conversation: a change I could see over time, alongside what I felt and what my partner noticed. Writing things down helped me describe those changes to my doctor.

Read Part 1 at https://neurospicyfounder.com/p/adhd-explained-by-a-biochemist-part-1

Boris: We’re talking quite casually, but the reason I’m asking is that you understand the chemistry and science, while I’m still trying to work out what helps me. I haven’t reached the point where I can say, “This is the right treatment for me.” And then there’s availability. How can a medication suddenly be in such short supply? I’ve seen people talking about shortages in the US, and I was running into the Concerta problem here in Japan.

Akif: I don’t know the specific cause of the shortage you’re describing. Medicines depend on chemical supply chains and access to ingredients. I initially wondered whether disruption around the Strait of Hormuz might play a role, because parts of the chemical industry depend on petroleum-based inputs.

Boris: The shortage was already happening before that.

Akif: Then that wouldn’t explain its beginning. There could be other supply issues. There can also be differences between countries in purchasing arrangements and supply contracts. But we would need to look at the specific situation before saying what caused this shortage.

Medication, psychological treatment and practical support can address different needs. This interview is not a ranking of their value, and individual experiences should not be read as predictions for someone else. Feeling calmer on a stimulant is not a diagnostic test for ADHD.

The product information below supports the editor’s notes. These are UK documents; authorisations, availability and prescribing practices can differ between countries.

[1] Concerta XL prescribing information

https://www.medicines.org.uk/emc/product/6872/smpc

[2] Elvanse prescribing information

https://www.medicines.org.uk/emc/product/14101/smpc

[3] Intuniv prescribing information

https://www.medicines.org.uk/emc/product/7510/smpc

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Boris