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Methylphenidate Exposure Induces Dopamine Neuron Loss in Mice

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Re: Methylphenidate Exposure Induces Dopamine Neuron Loss in Mice

#12
post #6

A 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'm pretty sure the side effects would be utterly intolerable even at half of that dose.

I'm absolutely sure. My son takes methylphenidate for traumatic narcolepsy and hyperphagia. At ~60 kg with a 30mg dose, he's got tremors, sweats, chattering teeth, etc.

I can only assume that the researchers have reason to study using these higher doses in mice, but 1mg/kg and 10mg/kg was the first thing that caught my eye. Neurological degeneration seems entirely plausible when you're frying a brain with speed (so to speak).

Re: Methylphenidate Exposure Induces Dopamine Neuron Loss in Mice

#13

Flagged for exaggerated headline, only demonstrated in mice now, which react differently to many stimulants.

Maybe I've missed something but where is the exaggeration in the headline 'Methylphenidate Exposure Induces Dopamine Neuron Loss in Mice '? You mean it doesn't and they're wrong?

Re: Methylphenidate Exposure Induces Dopamine Neuron Loss in Mice

#14
post #6

A 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 grinding. So I was living the same sped up and fucked up life after all. Then I quit all of it which was followed by severe depression, while I never had such problems before that period of abuse. Depression, which afaik has been linked to dopamine functioning. Depression, which even years after the facts still sometimes wants to kick in. I'd almost say something is borken in my brain. Now I read an article saying use of MP might yield damage to dopamine neurons. Hey, sounds familiar. Now don't get me wrong, I'm not saying it's the same, but just using the fact that dosages in this study were way higher than what you normally use on your kids for instance means there's nothing to worry about seems a bit far fetched.

Re: Methylphenidate Exposure Induces Dopamine Neuron Loss in Mice

#15
I think this is the money quote -- noting that these effects are noted on neurotypcial, and not on ADHD brains and therefore may or may not be generalizable:

These results can only be interpreted in the context on normal brain structure and function, and thus would have direct implications for the illicit/neurocognitive use of MPH. Since the underlying anatomy and biochemistry of ADHD has not been definitively characterized, our findings may or may not be generalizable to the vast majority of humans who are properly diagnosed with ADHD and are prescribed methylphenidate. Nevertheless, this work supports studies [51], [57], [58], [59] that demonstrate that drugs shown to increase the levels of dopamine in the synaptic cleft can contribute to degenerative changes in the basal ganglia.

Re: Methylphenidate Exposure Induces Dopamine Neuron Loss in Mice

#16
post #6

A 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…

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) application of the drug. You are correct in noting that this study does not directly translate to humans taking the typical therapeutic dose, but it certainly does raise questions.

Re: Methylphenidate Exposure Induces Dopamine Neuron Loss in Mice

#17
post #13

Flagged for exaggerated headline, only demonstrated in mice now, which react differently to many stimulants.

Maybe I've missed something but where is the exaggeration in the headline 'Methylphenidate Exposure Induces Dopamine Neuron Loss in Mice '? You mean it doesn't and they're wrong?

It could be that HN mods altered the headline by the time you saw it.

Re: Methylphenidate Exposure Induces Dopamine Neuron Loss in Mice

#18
post #6

A 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…

Exactly. Dosage relative to weight matters when drawing conclusions.

Its easy to read articles/papers like the OP link and be alarmed, but the three biggest risk factors with Ritalin (and similar drugs) is that the dose is appropriate for weight, the dosage is scheduled properly and sleep.

If the dosage schedule is above the half life of the medication, and blood level is still high at +12 hours later then neurons will get "burned" and lost.

Don't sleep for the required hours and schedule, neurons get "burned" as well.

This is also why recreational crystal meth [1] is very bad for the brain. Crystal meth overloads the neurons and definitely not equivalent to Rx Ritalin as intelligently prescribed.

[1] http://www.drugabuse.gov/publications/drugfacts/methamphetam...

Re: Methylphenidate Exposure Induces Dopamine Neuron Loss in Mice

#19
post #6

A 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…

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

Re: Methylphenidate Exposure Induces Dopamine Neuron Loss in Mice

#20

Are 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…

I'm also interested in long-term studies on modafinil. Please let me know if you find any.

As for the sleep patterns, I've found sporadic use of melatonin to be quite helpful:

http://www.gwern.net/Melatonin

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