Does this come as a surprise to anyone?
Methylphenidate Exposure Induces Dopamine Neuron Loss in Mice
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Re: Methylphenidate Exposure Induces Dopamine Neuron Loss in Mice
#32A quick read of the abstract indicates that loss of neurons only occurred in mice at the higher dose (10 mg/kg). Typical doses of Ritalin in kids (6+ years old) is 5-10 mg per day in two doses.[1] 6 year old weigh about 20 kg (50th percentile) so each dose is ~0.25 mg/kg (5/20). Even if you double the dose, it's 0.50 mg/kg, below the 1 mg/kg where the study saw no neuron loss. To get to 10 mg/kg, kids would have to t…
I was on about 60mg/day (across three doses) when I was 8 or 9. Not sure how typical that kind of dosing is.
Very high. How much time were you on that dosage ? Any bad side effect ?
Re: Methylphenidate Exposure Induces Dopamine Neuron Loss in Mice
#33Earlier quoted context omitted.
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.
Re: Methylphenidate Exposure Induces Dopamine Neuron Loss in Mice
#34Earlier quoted context omitted.
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.
Adult here who has taken Methylphenidate for 28 years. I would strongly suggest that weekends and holidays are also days off the medication.
Re: Methylphenidate Exposure Induces Dopamine Neuron Loss in Mice
#35Earlier quoted context omitted.
I was on about 60mg/day (across three doses) when I was 8 or 9. Not sure how typical that kind of dosing is.
Very high. How much time were you on that dosage ? Any bad side effect ?
I was on high doses like that for at least a couple years, but I don't remember what the exact doses I was on when. It's hard to say what was a side effect of the Ritalin and what wasn't, but I suspect the following:
* Stunted height - I'm several inches shorter than my father, grandfathers and uncles (all in the 6'2" to 6'4" range).
* Very short temper and aggressive tendencies (went away entirely in my teens when I was on significantly lower doses)
I also remember having serious withdrawal symptoms if I missed doses.
Re: Methylphenidate Exposure Induces Dopamine Neuron Loss in Mice
#36Earlier quoted context omitted.
There may be pharmacokinetic reasons for using these higher doses in mice. The rate at which drugs absorb through the blood brain barrier, are metabolized by the liver, and are eliminated by the kidneys are all factors one must consider. Not to mention the does response for MPD in mice may in fact be different. The goal of this study was not to simulate therapeutic dosing of MPD, but of chronic (short term, high dose…
I agree. I would love to see what plasma concentrations were achieved in the mice at each dose and compare that to what is typically seen in humans.
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Re: Methylphenidate Exposure Induces Dopamine Neuron Loss in Mice
#37A quick read of the abstract indicates that loss of neurons only occurred in mice at the higher dose (10 mg/kg). Typical doses of Ritalin in kids (6+ years old) is 5-10 mg per day in two doses.[1] 6 year old weigh about 20 kg (50th percentile) so each dose is ~0.25 mg/kg (5/20). Even if you double the dose, it's 0.50 mg/kg, below the 1 mg/kg where the study saw no neuron loss. To get to 10 mg/kg, kids would have to t…
well, just an anecdote: back in 'the days' I used amphetamines (or whatever was supposed to be in the speed I bought from my dealer) for a couple of months, then quit it because it's disastrous for your body and switched to Ritalin for another couple of months because the amphetamine addiction was hard to cope with. And because Ritalin has very, very similar effects, including the side-effects like tremors and teeth…
small sample size
Re: Methylphenidate Exposure Induces Dopamine Neuron Loss in Mice
#38Are there any similar types of research being done for Modafinil? I've recently been prescribed a "therapeutic" dose of Ritalin (I reacted severely to the lowest regular dose of Concerta) but have not started taking it. I'm wondering if this is as bad as it sounds as my technical reading comprehension skills are not that astute. I was using modafinil before with some success. The only problem was that my sleep patter…
Concerta is a prolonged release version of Ritalin: https://en.wikipedia.org/wiki/Methylphenidate
Re: Methylphenidate Exposure Induces Dopamine Neuron Loss in Mice
#39This is anecdotal, but rodents I know never have a hard time focusing or providing requisite attention. I think that ADHD is over-diagnosed in this population. OCD, on the other hand, is prevalent, but actually beneficial for the rodent lifestyle IMHO.
Perhaps if you had finished with "sedentary lifestyle" or "consumption lifestyle" you wouldn't have been modded down so far? What do I know, I'm just another un-diagnosed aberrant.
Re: Methylphenidate Exposure Induces Dopamine Neuron Loss in Mice
#40A quick read of the abstract indicates that loss of neurons only occurred in mice at the higher dose (10 mg/kg). Typical doses of Ritalin in kids (6+ years old) is 5-10 mg per day in two doses.[1] 6 year old weigh about 20 kg (50th percentile) so each dose is ~0.25 mg/kg (5/20). Even if you double the dose, it's 0.50 mg/kg, below the 1 mg/kg where the study saw no neuron loss. To get to 10 mg/kg, kids would have to t…
if you want to read about 0.25 mg kg^-1, see: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2988577/