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Comment by fasteo | Hacker News Reader

You cannot directly convert mouse to human doses. For this, you need to calculate HED[1] (Human Equivalent Dosage). Using your numbers:

HED (mg/kg) = Animal Dose (mg/kg) x [Animal Km / Human Km]

We use 3 for mice and 25 for human (child)

HED = 10 x ( 3 / 25) = 1,2 mg/kg

In a 20kg kid we have a dose of 24 mg, which is only slightly higher than a normal dose.

[1] http://www.fasebj.org/content/22/3/659.full.pdf

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That's a fair comment. One can't assume that an equal dose per kg will translate reliabily from an animal to a human.

My only reply is that the BSA method of dose conversation has issues of it's own (referred to in your paper) with regards to drug metabolism.

Also, the focus of the paper is on dose translations from animal to human studies. One would obviously want to be conservative in that regard.

You are right. Drug metabolism is key here; that´s why I am not too worried about the results of this study.

I have a child (24kg) with - properly diagnosed - severe ADHD on 20mg daily and the benefits clearly outweigh the potential risks; as with everything in life, nothing has zero risk.

That's the difficulty with animal studies. There are general rules that can be used to guide interpretation of results, but every drug is unique and there are a lot of exceptions to any rule.

And that's ignoring individual variation in response.

It shouldn't surprise anyone that so many drugs in development fail.

Adult here who has taken Methylphenidate for 28 years. I would strongly suggest that weekends and holidays are also days off the medication.

Out of curiosity why do you recommend this?

Because Ritalin exists to medicate children into submission so they can sit at a desk for 8 hours a day like good little workers, and it's less important to comply with this constraint on weekends and holidays, when the parents, not the school system, have to deal with the child's desire to not sit at a desk for 8 hours a day like a good little worker.

As someone who's taken (and continues to take) various stimulants to manage ADD:

Because you build up a tolerance over time, which requires larger doses, and because untreated ADD/ADHD is also linked to increased creativity and some degree of impulsiveness (which can be a good thing, vs. indecisiveness).

If I were doing more creative work, I would probably go without during creative phases and with while producing (for example, as a journalist, go without to come up with ideas for stories, then back on to burn through the associated research, production, refining, etc.).

At higher doses, I'm able to fixate on one task to the exclusion of all else (e.g. distractions, music, hunger, illness); at moderate doses, I tend to flit between interesting topics until I find something I can easily focus on (or perhaps until the medication kicks in at full strength).

Methylphenidate was inducing psychosis in me: delusions and hallucinations, which gradually got worse over time. This is a known side effect of amphetamine and similar drugs (like methylphenidate) when taken for long periods of time. When I started going off it on weekends, the psychosis stopped, and I was able to take it for several more years before I finally stopped taking it altogether. I took it ages 6 to 12 or so.

Withdrawing every weekend was uncomfortable, but better than psychosis.

As every one else said, but I will add a couple of notes.

ADD is part of who I am its just not very compatible with current work environments. I don't like to feel drugged all the time and I know that i'm ok with out being medicated.

I have developed sufficient coping skills as an adult to enable me to choose when I need to be medicated and when I don't.

I just wanted to thank you for still answering on this thread. Your sharing of your experiences is very much welcome, I've only been on Ritalin for over a month and already feel exactly as you describe it. Still, I'm asking myself if you couldn't also harm your wiring by having this on/off thing going on (I'm currently on 30mg Ritalin LA which presumably is a rather high dosage). I've always been more interested into computers so this brain thing is kind of new to me - a blacker kind of box than it already is so to say :)

I would have been kicked out of school with out ritalin so there wasn't much option when I started taking it at 9. You have to judge for yourself as an adult if the costs out weight the risks.

Thanks for the hint. Our neuro suggested to halve the dose during weekends and holidays to avoid potential withdrawal symptoms

Thank you for posting this. I do not personally work with animals, but I knew there must be a way to convert doses between mice and humans given how often my colleagues test drugs on rats and mice.

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