View Full Version : Methylphenidate Neurotoxicity


rmon18
09-13-16, 10:22 AM
Methylphenidate exposure induces dopamine neuron loss and activation of microglia in the basal ganglia of mice:


(http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0033693)
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0033693


1 mg/kg for a mouse would be 1 * 0.081 = 0.081 mg/kg for a human and 10 mg/kg for a mouse would be 0.81 mg/kg for a human.



Hi, I've been recently diagnosed with ADHD and have been postponing taking medication for a while (although i know medication is inevitable if i ever want to achieve anything in life). One major reason for this delay are results like this (regarding ritalin, as that will probably be my drug of choice). They make me feel hopeless, helpless, and afraid that I will never get better. It seems to me that i only have two choices: remain unmedicated and completely useless; or take ritalin, improve in the short term, but suffer inevitable brain damage in the long term (particularly dopamine neuron loss). Can someone please offer me advice? I beg you, because I'm honestly depressed.

Lunacie
09-13-16, 11:46 AM
If I understood that source correctly, they only saw a decrease in dopamine neurons on a large (or recreational) use of Ritalin.

Were these mice diagnosed as adhd-equivalent or neurotypical-equivalent before testing began?

Perhaps these results are not consistent with someone who has adhd and takes the therapeutic dose?

Hopefully Namazu will weigh in on this as she understands scientific lingo better than I do.

sarahsweets
09-13-16, 01:10 PM
Recreational doses and theraputic doses are completely different.

namazu
09-13-16, 03:04 PM
Don't have time to read whole article now, but as a point of reference:

The effects on dopamine neurons were seen when they gave mice 10mg/kg, but not at 1mg/kg. (I'm not sure where you're getting the conversion factor of 0.081...what is the basis for it? It is nice to build in some margin for safety, but I'm not sure where the 0.081 comes in.)

A 150lb. person weighs about 68kg, so 10mg/kg would be roughly equivalent to a daily dose of 680mg for that person (making a number of assumptions). As far as I'm aware -- and I have been prescribed higher-than-typical doses of methylphenidate -- that's pretty much unheard-of in a therapeutic context for treatment of ADHD. (I'm not sure what the typical range of doses is for narcolepsy.)

There were also some effects seen at lower doses (1mg/kg), but I'll have to spend more time on the article to interpret what they mean.

I agree that there are a lot of unknowns and potential concerns about long-term use of stimulants. As you noted, there are also known and real harms that come with struggling with ADHD and the associated stresses (which themselves have adverse effects on the brain). There are other options if this is a deal-breaker for you.

C15H25N3O
09-13-16, 04:29 PM
1mg/kg theory is empiric scientific ********!

There are 55kg users not supported with 120mg and more of Ritalin IR.
And there are users with 150kg who are overdosed with 25mg Ritalin IR.

I think I should read it first before writing any more. :-)

yepimonfire
09-13-16, 05:26 PM
Even my monster dose of 120mg a day doesn't approach that.

rmon18
09-13-16, 07:31 PM
Don't have time to read whole article now, but as a point of reference:

The effects on dopamine neurons were seen when they gave mice 10mg/kg, but not at 1mg/kg. (I'm not sure where you're getting the conversion factor of 0.081...what is the basis for it? It is nice to build in some margin for safety, but I'm not sure where the 0.081 comes in.)

A 150lb. person weighs about 68kg, so 10mg/kg would be roughly equivalent to a daily dose of 680mg for that person (making a number of assumptions). As far as I'm aware -- and I have been prescribed higher-than-typical doses of methylphenidate -- that's pretty much unheard-of in a therapeutic context for treatment of ADHD. (I'm not sure what the typical range of doses is for narcolepsy.)

There were also some effects seen at lower doses (1mg/kg), but I'll have to spend more time on the article to interpret what they mean.

I agree that there are a lot of unknowns and potential concerns about long-term use of stimulants. As you noted, there are also known and real harms that come with struggling with ADHD and the associated stresses (which themselves have adverse effects on the brain). There are other options if this is a deal-breaker for you.

Apparently, you cannot directly convert mouse to human doses. For this, you need to calculate HED (Human equivalent dosage).

Your wording is a bit confusing but I think you understand the concept of converting mg/kg dosages for mice and for humans. However, I will just explain it briefly: the average lab mouse weighs roughly 20 grams; 20g = 0.02kg; 1mg * 0.02kg = 0.02mg dosage for said mouse. For humans, we take the calculated animal (20gram) dosage of 0.02mg * Km factor (the surface area to weight ratio) ratio between model animal and human; so the human equivalent dosage for said 1mg/kg animal dosage is: 0.02mg * [(km for animal, 3 for a mouse of weight 20grams)/(km for an adult human, 37 for an adult of weight 60kg)]. One would then get a human equivalent dosage of 0.0812mg/kg -- which then goes to be extrapolated with respective human weight of interest for pertinent dosage. Also, I apologize as I have not been able to read your first post due to Uni responsibilities -- however, I will do so on the weekend and tell you what I think about it. With that said, I don't think you should worry about taking MPH for your ADHD due to fears of possibly developing Parkinsons down the road. If it puts you at ease, throughout my academic career, both undergraduate in Neuroscience, and graduate, I have not read a study about chronic MPH use showing a correlation in an increase chance of developing Parkinsons. However, off the top of my head, I can recall reading about 6-7 studies correlating chronic amphetamine usage with an increase chance of developing Parkinsons; in one study, the risk chance was ~16%, if my memory serves me right.





I found a discussion on this over at the addforums: http://www.addforums...ad.php?t=122014

They think that mice and human dosages are equivalent, i.e. 1 mg/kg for a mouse is the same as 1 mg/kg for a human. I guess they don't know the doses are supposed to be converted. So 1 mg/kg for a mouse would be 1 * 0.081 = 0.081 mg/kg for a human and 10 mg/kg for a mouse would be 0.81 mg/kg for a human.


So for the 10mg/kg, that's equivalent to a 20 kg child having a dose of 24 mg.

namazu
09-13-16, 08:29 PM
Apparently, you cannot directly convert mouse to human doses. For this, you need to calculate HED (Human equivalent dosage).

Thanks.
I think this (http://www.fda.gov/downloads/Drugs/Guidances/UCM078932.pdf) may be the source for that info, or at least a technical reference.

Will re-read later.

There are some comments on the paper at PLoS (a "letter to the editor" and a response by the original authors) that discuss the dosage issue, but interestingly neither mentions any conversion factors. The discussion seems to focus mostly on plasma levels and mode of delivery (oral vs. injected).

C15H25N3O
09-13-16, 08:30 PM
This scientific study is a very interesting read full of details.

Who paid it? I hope not Shire or Lilly. :-)

Let me comment it with some personal experience:

I used to take mostly about 45mg/day in rare cases about 70-80mg.

In the end of my 2 years on Ritalin (not permanently) I experienced my head
twitching while walking which felt like parkinson for seconds.

Also a friend of mine was shocked of my twitching hand crossing a street next
to her which I did not full recognize but what felt like some nervous stress which
should be typical for parkinson.

I am 44 years old and I never had experienced any twitches before.
Since this experiences I know or have a fear to end with parkinson.

My bad experience after 2 years on SSRI (Lexapro) that induced a 13 years lasting
anxious disorder and the Ritalin-experience explain my very careful intake of Vyvanse.

Reflecting 10 months of Vyvanse I know even weak amphetamines are a harder
drug than Ritalin although it is subtle and I dont feel comfortable using it more
than 8 weeks in a row why I worked on reducing it to micro-dosages or finding
the correct patterns of intake when the full dosage is needed.

I self-medicate for 30 years with pure nature without any bad experience.

Planet earth cannot be polluted by nature but by chemical products. Nature can
heal itself if it is not over-polluted. Chemical substances mean progress but kill life
on this planet or make lands infertile in agriculture.

C15H25N3O
09-13-16, 08:38 PM
Recreational doses and theraputic doses are completely different.

Yes.

Recreational dosages are lower than therapeutical dosages which are lower than addictive dosages.

yepimonfire
09-14-16, 04:57 AM
http://www.ncbi.nlm.nih.gov/pubmed/16736241
Methylphenidate exerts no neurotoxic, but neuroprotective effects in vitro.
Ludolph AG1, Schaz U, Storch A, Liebau S, Fegert JM, Boeckers TM.

Abstract
Methylphenidate (MPH) is the most common used drug in child and adolescent psychiatry. Despite of this fact, however, little is known about its exact pharmacological mechanisms. Here we investigated the toxic effects of MPH in vitro in human embryonic kidney (HEK-293) cells stably expressing the human dopamine transporter (HEK-hDAT cells) and in cultured rat embryonic (E14.5) mesencephalic cultures. MPH alone (up to 1 mM) affected neither the growth of HEK-hDAT cells nor the survival of dopaminergic (DA) neurons in primary cultures after treatment up to 72 h. No differences in neuronal arborisation or in the density of synapses were detected. 1-methyl-4-phenylpyridinium (MPP(+)) showed no toxic effect in HEK-293 cells, but had significant toxic effects in HEK-hDAT cells and DA neurons. MPH (1 microM - 1 mM) dose-dependently reduced this cytotoxicity in HEK-hDAT cells and primary mesencephalic DA neurons. The presented results show that application of MPH alone does not have any toxic effect on DA cells in vitro. The neurotoxic effects of MPP(+) could be significantly reduced by co-application of MPH, an effect that is most likely explained by MPH blocking the DAT.

sarahsweets
09-14-16, 05:52 AM
Yes.

Recreational dosages are lower than therapeutical dosages which are lower than addictive dosages.

I disagree. Recreational doses are usually meant to get high, therefore they are higher than a theraputic dose.

rmon18
09-14-16, 07:37 AM
Hey guys,

After holding my little self-pity party, being perfectly miserable and all (ironically, the most dangerous and addictive non-pharmaceutical drug), i came to the joyful and liberating realization that life just isn't fair; there's isn't an expiration date to our suffering nor will our good deeds see us receive some sort of cosmic reward.

The fact of the matter is that, through no fault of our own, we are all faced with the complicated and difficult decision to take medicine (and face the risks); or not take medicine, and face the debilitating and sometimes excruciating symptoms that come with ADHD.

But life is what you make it. And I've chosen to accept my disorder because things could always be worse. In fact whilst I'm typing this, countless people around the world are breathing their last breath. I think that's the biggest challenge we all face: be grateful and self compassionate (not self-esteem, as that abandons us at the time we most need it - when we fail).

Thanks for your responses everyone! Namazu (and anyone else), i can't wait to hear what your thoughts are on the study referenced in the OP (taking into consideration the conversion factors and all)!

Lunacie
09-14-16, 10:35 AM
This scientific study is a very interesting read full of details.

Who paid it? I hope not Shire or Lilly. :-)

Let me comment it with some personal experience:

I used to take mostly about 45mg/day in rare cases about 70-80mg.

In the end of my 2 years on Ritalin (not permanently) I experienced my head
twitching while walking which felt like parkinson for seconds.

Also a friend of mine was shocked of my twitching hand crossing a street next
to her which I did not full recognize but what felt like some nervous stress which
should be typical for parkinson.

I am 44 years old and I never had experienced any twitches before.
Since this experiences I know or have a fear to end with parkinson.

My bad experience after 2 years on SSRI (Lexapro) that induced a 13 years lasting
anxious disorder and the Ritalin-experience explain my very careful intake of Vyvanse.

Reflecting 10 months of Vyvanse I know even weak amphetamines are a harder
drug than Ritalin although it is subtle and I dont feel comfortable using it more
than 8 weeks in a row why I worked on reducing it to micro-dosages or finding
the correct patterns of intake when the full dosage is needed.

I self-medicate for 30 years with pure nature without any bad experience.

Planet earth cannot be polluted by nature but by chemical products. Nature can
heal itself if it is not over-polluted. Chemical substances mean progress but kill life
on this planet or make lands infertile in agriculture.


At one time I was quite anemic and experienced twitching. Not fun.

Is "pure nature" a brand of supplements and vitamins? Some of us have found the supplement Omega 3 fish oil to be helpful.
/

rmon18
09-14-16, 11:50 AM
Another study I find particularly disturbing:

''Long-term stimulant treatment affects brain dopamine transporter level in patients with attention deficit hyperactive disorder:''

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0063023

Does this mean long-term use of ritalin will actually result in long-term worsening of adhd symptoms, and chronic depression?

Lunacie
09-14-16, 12:50 PM
Another study I find particularly disturbing:

''Long-term stimulant treatment affects brain dopamine transporter level in patients with attention deficit hyperactive disorder:''

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0063023

Does this mean long-term use of ritalin will actually result in long-term worsening of adhd symptoms, and chronic depression?

Most of the time with meds, we have to consider the benefit vs the risk.

The long term risks of not being medicated? Problems with relationships, trouble with the law, not finishing school, risk of car crashes, difficulty keeping a job, self medicating with alcohol, tobacco or other drugs.

The long term risks of taking meds? This possibility that over the long term, say 30 years, you'll have an even greater need of the meds.

And is it the meds or is just a result of aging?

I began wearing eyeglasses when I was 10 and needed stronger glasses for several years after than. Then it leveled out and I was fine until my early 40's, which is when everyone experiences difficulty with eyes adjusting between long and close, light and dark.

So if most people experience a decline in vision in our 40's, is it possible that most of us experience a decline in neuronal activity at some point in the aging process? Whether or not we're taking stimulant meds. Hm.

C15H25N3O
09-15-16, 05:38 AM
I disagree. Recreational doses are usually meant to get high, therefore they are higher than a theraputic dose.

Thats theory but practically if someone would steal/buy a box of 5mg DEX with two sheets of 20 pills
containing 200mg at all a recreational user would not intake half a sheet (50mg) or 10 pills.

Such masses of pills are linked to suicide!

This kinds of stupid idea only have hardcore drug addicted people or a reacreational user who thinks Dex is too weak.

50mg are a lot and no morning dosage.

Ok, thats also theory but should illustrate what I mean.

:-)

yepimonfire
09-15-16, 10:36 AM
Most of the time with meds, we have to consider the benefit vs the risk.

The long term risks of not being medicated? Problems with relationships, trouble with the law, not finishing school, risk of car crashes, difficulty keeping a job, self medicating with alcohol, tobacco or other drugs.

The long term risks of taking meds? This possibility that over the long term, say 30 years, you'll have an even greater need of the meds.

And is it the meds or is just a result of aging?

I began wearing eyeglasses when I was 10 and needed stronger glasses for several years after than. Then it leveled out and I was fine until my early 40's, which is when everyone experiences difficulty with eyes adjusting between long and close, light and dark.

So if most people experience a decline in vision in our 40's, is it possible that most of us experience a decline in neuronal activity at some point in the aging process? Whether or not we're taking stimulant meds. Hm.

Exactly, I ain't proud to admit it, but in my 4 year hiatus from meds, I went backwards in life and ruined my finances.

yepimonfire
09-15-16, 10:44 AM
Thats theory but practically if someone would steal/buy a box of 5mg DEX with two sheets of 20 pills
containing 200mg at all a recreational user would not intake half a sheet (50mg) or 10 pills.

Such masses of pills are linked to suicide!

This kinds of stupid idea only have hardcore drug addicted people or a reacreational user who thinks Dex is too weak.

50mg are a lot and no morning dosage.

Ok, thats also theory but should illustrate what I mean.

:-)

I won't say much because of the rules on this forum, but there are places on the internet with people detailing their experiences that beg to differ. Do you get high from your daily dose? Most of us don't. Even me taking 30mg every 3 hours or even 40mg of ritalin does not cause me any sort of high. A good example is methamphetamine or desoxyn. A total daily dose for someone with adhd would be at the most 25mg. There are people who use an entire gram of meth a day who abuse amphetamines.

C15H25N3O
09-15-16, 12:04 PM
Hmmmm,

if some one would take 1g of Ritalin to get high (what an idiot) he also would snort uranium to melt his brain.

Having a prescription will not change a substance. It will be legal safe but not medical safe.
Our bodies and brains dont ask for prescriptions and not everything that can be prescribed is medical safe.
Mind the medication guidelines in each pack of a med is not in there to protect us but to protect pharma and docs.

Lunacie
09-15-16, 12:25 PM
Hmmmm,

if some one would take 1g of Ritalin to get high (what an idiot) he also would snort uranium to melt his brain.

Having a prescription will not change a substance. It will be legal safe but not medical safe.
Our bodies and brains dont ask for prescriptions and not everything that can be prescribed is medical safe.
Mind the medication guidelines in each pack of a med is not in there to protect us but to protect pharma and docs.

Non-adhd people are just as reliant on the neurochemicals in these meds as adhd people are.

It's just that their bodies produce them naturally and ours don't.

I believe our bodies and brains DO ask for these neurochemicals, and that is part of the diagnostic process.
.

aeon
09-15-16, 01:32 PM
Thats theory but practically if someone would steal/buy a box of 5mg DEX with two sheets of 20 pills
containing 200mg at all a recreational user would not intake half a sheet (50mg) or 10 pills.

Some do, and some take more than that, but per forum rules, I will not discuss this further.

50mg are a lot and no morning dosage.

I take 60mg of Dex in the morning. ;)


Cheers,
Ian

C15H25N3O
09-15-16, 02:17 PM
I did not start a discussion about recreational use of our meds and I am not interested in it.

I think this thread has been about methylphenidates mighty neurotoxity.

We have a lack of neuro-transmitters but no lack of pills and unabated side-effects, I hope.

Lunacie
09-15-16, 02:35 PM
I did not start a discussion about recreational use of our meds and I am not interested in it.

I think this thread has been about methylphenidates mighty neurotoxity.

We have a lack of neuro-transmitters but no lack of pills and unabated side-effects, I hope.

Actually, I read the article and came away with the impression that the only neurotoxicity was a result of large, or what I'd call recreational, doses.

There didn't seem to be any neurotoxicity at theraputic doses.

These meds are not intended for recreational use, which amounts to abuse of the meds. They are to be taken as prescribed only under a doctor's supervision.

sarahsweets
09-15-16, 04:20 PM
Actually, I read the article and came away with the impression that the only neurotoxicity was a result of large, or what I'd call recreational, doses.

There didn't seem to be any neurotoxicity at theraputic doses.

These meds are not intended for recreational use, which amounts to abuse of the meds. They are to be taken as prescribed only under a doctor's supervision.

Thanks for saying this. I also gleaned that the neurotoxicity was because of recreational, high doses, not what would be considered theraputic.

Lunacie
09-15-16, 06:25 PM
Do I understand this correctly?

The present study investigated the pathological effects of acute and chronic MPH in the basal ganglia using two different doses that span the therapeutic window of MPH use for ADHD and narcolepsy in humans (1 mg/kg and 10 mg/kg

Does that mean the mice were given 1 mg ritalin per 1 kg of weight?
Or 10 mg of ritalin per 10 kg of weight?

Since mice weigh less than .10 kg, it seems they were given very high doses.

Am I misunderstanding the numbers?

namazu
09-15-16, 06:39 PM
Do I understand this correctly?
The present study investigated the pathological effects of acute and chronic MPH in the basal ganglia using two different doses that span the therapeutic window of MPH use for ADHD and narcolepsy in humans (1 mg/kg and 10 mg/kg


Does that mean the mice were given 1 mg ritalin per 1 kg of weight?
Or 10 mg of ritalin per 10 kg of weight?

Since mice weigh less than .10 kg, it seems they were given very high doses.

Am I misunderstanding the numbers?
They tested two different doses, one lower and one higher:
Some mice were given 1 mg/kg, and some mice were given 10 mg/kg.

For a mouse weighing 0.1kg, to use the number you mentioned as an example:
1mg/kg would be a dose of 0.1mg
10mg/kg would be a dose of 1mg.

From what I could gather, there were no more than 10 mice in each group (and for some of the imaging, possibly as few as 3 mice per group were studied).

Lunacie
09-15-16, 06:42 PM
They tested two different doses, one lower and one higher:
Some mice were given 1 mg/kg, and some mice were given 10 mg/kg.

For a mouse weighing 0.1kg, to use the number you mentioned as an example:
1mg/kg would be a dose of 0.1mg
10mg/kg would be a dose of 1mg.

From what I could gather, there were no more than 10 mice in each group (and for some of the imaging, possibly as few as 3 mice per group were studied).

Then it does sound like they gave the mice a larger dose per weight than most of us are prescribed, no?

And that's a pretty small study. Has it been replicated? Hm.

namazu
09-15-16, 06:50 PM
Then it does sound like they gave the mice a larger dose per weight than most of us are prescribed, no?

And that's a pretty small study. Has it been replicated? Hm.
Not at the low end, no.

Ignoring any possible mouse-to-human conversion factors:

A 150lb. person weighs about 68kg.
1mg/kg for that person would be 68mg of methylphenidate.
10mg/kg for that person would be 680mg of methylphenidate.

1mg/kg (per day), or 68mg for a 150lb. person, is within the range of commonly-prescribed doses for treatment of ADHD.

(I have to go back to see how they administered this -- all at once, or over the course of the day.)

I agree that it's a small study and the findings would need to be replicated to see if they were repeatable and consistent across studies.

C15H25N3O
09-15-16, 06:59 PM
Maybe it is not about the doses the mice got but about finding the potential
neurotoxic effect releasing MPTP. About a year later I learn I should have
immediately called my doc after experiencing the twitches. I didnt.

Take care.

namazu
09-15-16, 07:15 PM
Maybe it is not about the doses the mice got but about finding the potential neurotoxic effect releasing MPTP.
The MPTP (a substance linked to destruction of dopaminergic neurons) was something the researchers administered to the mice.
Supposedly, the strain of mouse they used was normally resistant to the effects of MPTP.

When the researchers administered MPTP to the mice after the mice had been exposed to methylphenidate, they observed some changes (as though the mice had become less resistant to the neurotoxin).




As to your earlier question about study funding:
Funding: The authors thank the American Lebanese Syrian Associated Charities (ALSAC) for financial support. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Per Wikipedia, ALSAC "is the fundraising and awareness organization for St. Jude Children's Research Hospital" in Memphis, Tennessee, USA, where the researchers work. I think it's called that because the people who established the hospital (including Danny Thomas, an American singer/actor) were of Lebanese/Syrian descent.

rmon18
09-16-16, 12:26 AM
Thanks for saying this. I also gleaned that the neurotoxicity was because of recreational, high doses, not what would be considered theraputic.
Again, you have to calculate human equivalent doses from rat doses. Apparatanly, at least according to some chap on reddit, ''It would come out to roughly .8mg/kg for a 60kg human.. or 48mg total. Still a little high, but not quite as egregious.'' Obviously referring to the chronic adminstration of 10mg/kg MPH.

The results are very concerning IMO, and would suggest then when treating ADHD, one should take the lowest dose possible (that is still effective in respect of addressing the ADHD symptoms of course).

C15H25N3O
09-16-16, 05:01 PM
The results are very concerning IMO, and would suggest then when treating ADHD, one should take the lowest dose possible (that is still effective in respect of addressing the ADHD symptoms of course).

You are absolutely right. If you feel something you dont like tell the doc and question your meds.

If I was not dependent on money I could treat myself without any meds but it is about functioning in a system which is not perfect.

rmon18
09-19-16, 05:26 AM
These results seem very concerning as well. What do you guys think? Bloody hell, this is depressing.

http://www.ncbi.nlm.nih.gov/pubmed/24884696 (http://www.ncbi.nlm.nih.gov/pubmed/24884696)

Lunacie
09-19-16, 01:48 PM
These results seem very concerning as well. What do you guys think? Bloody hell, this is depressing.

http://www.ncbi.nlm.nih.gov/pubmed/24884696 (http://www.ncbi.nlm.nih.gov/pubmed/24884696)

Question ... are you PLANNING to abuse stimulant meds recreationally?

Recreational use of drugs is usually considered to be higher than theraputic dosages.

CONCLUSION:
Together, these changes indicate methylphenidate-induced neurotoxicity, altered synaptic and neuronal plasticity, energy metabolism and ubiquitin-dependent protein degradation in the brains of methylphenidate-treated SHRs, which showed methylphenidate CPP and self-administration. In addition, these findings may also reflect cognitive impairment associated with chronic methylphenidate use as demonstrated in preclinical studies. Future studies are warranted to determine the clinical significance of the present findings with regard to long-term recreational methylphenidate use or abuse in individuals with ADHD.

namazu
09-19-16, 02:00 PM
...when treating ADHD, one should take the lowest dose possible (that is still effective in respect of addressing the ADHD symptoms of course).
That's always been the case. More is not always better.

C15H25N3O
09-19-16, 09:52 PM
Let me throw in a thought.

The study is done with mice and there is still a different to human being.

There could be different results depending on the level of DAT which is

the key for success in treating ADHD with methylphenidat or amphetamin.

This study was gold if they gave the mice something to induce all subtypes

of ADHD to recheck MPTP in relation to other neuro-chemics. But so, .....

.... I really dont know, a nice warning for prescription guides to keep big

pharma out of responsibility and make us self-responsible.


In my opinion "parkinsonism" released by MPTP is the worst case MPH can

hurt someone and calling it a side-effect is bad cynism.


I will have to tell my doc as I never mentioned the twitches and I think it is

for me the safest way to treat my ADHD with alternative methods.

I recommended them to someone who is obviously hurt

by his prescribed med.


I begin hating the phrase "scientific approved" and translate it personally

to "profit approved". It is not about healing but about business with health!


Meds can help but also can make damage. Each med! If they were safe there

was no medication guide needed!


Take care!

Lunacie
09-19-16, 10:31 PM
Everything is risky if done to excess, or abused. Even water.

Read the warnings that come with a bottle of tylenol.

C15H25N3O
09-20-16, 12:11 AM
Warning! Everything can happen and you can die. lol

rmon18
09-20-16, 08:37 AM
Question ... are you PLANNING to abuse stimulant meds recreationally?

Recreational use of drugs is usually considered to be higher than theraputic dosages.
The thing is, the mice weren't treated with a recreational dose. They were treated with methylphenidate 5 mg/kg. The human equivalent dosage would be calculated as follows:

HED = 5 x (6/37) = 0.81081.

So that's equivalent to a person who is 80 kg taking approximately (rounding up) a dose of 65ml. That's a high dose, but no where near as egregious.

rmon18
09-20-16, 08:51 AM
This is addition to the first study which showed a 20% reduction in dopaminergic neurons in the Substantia nigra from therapeutic MPH doses. Will this not lead to a increased risk of Parkinsons disease, potentially down the road?

rmon18
09-20-16, 09:06 AM
With regard to the first study, there was even dopamine neuron loss in the mice taking 1mg/kg. More so even then control + MPTP.

C15H25N3O
09-20-16, 03:48 PM
Will this not lead to a increased risk of Parkinsons disease, potentially down the road?

statistical? :giggle:

meadd823
09-20-16, 05:03 PM
Another study I find particularly disturbing:

''Long-term stimulant treatment affects brain dopamine transporter level in patients with attention deficit hyperactive disorder:''

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0063023

Does this mean long-term use of ritalin will actually result in long-term worsening of adhd symptoms, and chronic depression?


Only when not medicated




Conclusion

Upregulation of dopamine transporter availability during long-term treatment with methylphenidate may decrease treatment efficacy and exacerbate symptoms while not under the effects of the medication. Our findings also suggest that the discrepancies in the literature regarding dopamine transporter availability in ADHD participants (some studies reporting increases, other no changes and other decreases) may reflect, in part, differences in treatment histories.


Skimiming past the literally short term study of 12 months compared to decades of using medications this study is not sufficient enough to based a treatment direction upon.



.........

meadd823
09-20-16, 05:20 PM
These results seem very concerning as well. What do you guys think? Bloody hell, this is depressing.

http://www.ncbi.nlm.nih.gov/pubmed/24884696 (http://www.ncbi.nlm.nih.gov/pubmed/24884696)


Honestly I think you should quit reading these stupid studies try the medication and see if it works.

Future studies are warranted to determine the clinical significance of the present findings with regard to long-term recreational methylphenidate use or abuse in individuals with ADHD.


I do not used ritalin because it gave me headaches but I have been on Adderall for over 20 years ten of which I have been a member here.

Recreational used is an insult and I would not value any conclusion drawn by a researcher who failed to research the difference between medical use and recreational use /drug abuse!


.............

meadd823
09-20-16, 05:32 PM
Warning! Everything can happen and you can die. lol

Nothing can happen = we all die some time.

Any thing that has an effect on the body, can have a bad effect. This includes but is NOT limited to prescription medications.


A few other points from previous post. Not sure where you are from but "scientifically proven" is not a term typically used by medical personnel but by advertisers peddling every thing from fat burning pills to skin creams for aging.

What my ADHD doctor as well as the half dozen or so docs I work for during my employment use " EVIDENCE BASED TREATMENT APPROACH" , there is a difference worth noting.

Lunacie
09-20-16, 06:58 PM
Nothing can happen = we all die some time.

Any thing that has an effect on the body, can have a bad effect. This includes but is NOT limited to prescription medications.


A few other points from previous post. Not sure where you are from but "scientifically proven" is not a term typically used by medical personnel but by advertisers peddling every thing from fat burning pills to skin creams for aging.

What my ADHD doctor as well as the half dozen or so docs I work for during my employment use " EVIDENCE BASED TREATMENT APPROACH" , there is a difference worth noting.

:yes: I knew there was something about that "scientifically proven" that was familiar but not in the way it was used.

rmon18
09-21-16, 07:34 AM
Only when not medicated




Conclusion

Upregulation of dopamine transporter availability during long-term treatment with methylphenidate may decrease treatment efficacy and exacerbate symptoms while not under the effects of the medication. Our findings also suggest that the discrepancies in the literature regarding dopamine transporter availability in ADHD participants (some studies reporting increases, other no changes and other decreases) may reflect, in part, differences in treatment histories.


Skimiming past the literally short term study of 12 months compared to decades of using medications this study is not sufficient enough to based a treatment direction upon.



.........
What happens when the treatment becomes less and less effective due to excessive up regulation of dopamine transporters? What are you left with?

rmon18
09-21-16, 07:37 AM
Honestly I think you should quit reading these stupid studies try the medication and see if it works.

Future studies are warranted to determine the clinical significance of the present findings with regard to long-term recreational methylphenidate use or abuse in individuals with ADHD.


I do not used ritalin because it gave me headaches but I have been on Adderall for over 20 years ten of which I have been a member here.

Recreational used is an insult and I would not value any conclusion drawn by a researcher who failed to research the difference between medical use and recreational use /drug abuse!


.............
The doses used AREN'T recreational. You HAVE TO calculate the human equivalent dosage. If you do that, you will realize that the doses used span the therapeutic range.

Lunacie
09-21-16, 09:44 AM
The choice is yours alone. Either continue to scare yourself, or just give the meds a trial run. You can stop them at any time.

yepimonfire
09-23-16, 12:28 PM
I've taken adhd meds for years at a time and then just stopped with no problems other than reverting back to my adhd self.

In a more extreme example that should put your mind at ease, meth users can eventually recover normal dopamine function after a long period of abstinence. Those are much more extreme doses and meth is very neurotoxic so quit worrying.

C15H25N3O
09-24-16, 05:04 AM
Honestly I think you should quit reading these stupid studies try the medication and see if it works.

We do so
but I wish there was a better standard of information available about the substances
before intake. Warnings are everywhere but who tells us how to pass the challenge?
We have to pick up informations and experiences ourself everywhere. Darn!

sarahsweets
09-24-16, 10:45 AM
The doses used AREN'T recreational. You HAVE TO calculate the human equivalent dosage. If you do that, you will realize that the doses used span the therapeutic range.

Did you read the link that Namazu posted?
http://www.fda.gov/downloads/Drugs/Guidances/UCM078932.pdf
It is very informative.
Unless I am a moron, the one you shared is based on a small group at recreational doses and hasnt been replicated.

Lucky-A
12-16-16, 01:18 AM
In regards to the first study, which I for some reason decided to download and read at 4 in the morning, I would like to share my thoughts.

First, in the paper they base their doses on previous research, stating that dosed below 5mg/kg mirror those used in clinical practices (presumably of adhd) and those of 10mg/kg reflects recreational use, and treatment of narcolepsy (I had no idea narcolepsy was so debilitating)

With that said, it is my not so humble opinion that this paper is not informative enough to trust any of their conclusions.

First where are the descriptives? At the wery least there should be a clear statement of how many subjects were tested in each condition, an preferably some numbers of central tendencies. Smells fishy, like they're trying to hide something (like a lack of evidence maybe? :eyebrow: )

From what I can gather, at most there were 10 subjects (have no idea whether that is the entire group or 10 in each of the conditions. Regardless That's a pretty low number, which would be highly affected by one single extreme case (one out of the ordinary mouse). In the heat maps there are only 3 subjects in each condition 3!

Now at the end they inform that the mice were given their injections only once a day. Which honestly is not comparable to the therapeutic use. However I have no idea if that dose somehow are long acting(like concerta), but I highly doubt that, as surely they would have mentioned that.(i might have missed It if they actually did mention it)

And they mention that their results can only be interpreted in the context of an NT brain and so will have direct implications of illicit/neurocognitive use. And also that they may or may not be generalizable to those of us with Adhd brains. They do not care to share their reasons for how they can defend generalisation from a mouse brain to a human brain at all, NT or otherwise?

I have read my share of quantitative studies, and to be honest, this one seems very secretive. Like they deliberately aren't sharing enough. I feel like there's so much missing for us to get a clear view of the experiment. And also their conclusions are so definitive, and arrogant. I would not trust this for a second. These evidence are vague at best. I honestly hope that this isn't a standard in drug testing. :eek:

sarahsweets
12-16-16, 04:19 AM
In regards to the first study, which I for some reason decided to download and read at 4 in the morning, I would like to share my thoughts.

First, in the paper they base their doses on previous research, stating that dosed below 5mg/kg mirror those used in clinical practices (presumably of adhd) and those of 10mg/kg reflects recreational use, and treatment of narcolepsy (I had no idea narcolepsy was so debilitating)

With that said, it is my not so humble opinion that this paper is not informative enough to trust any of their conclusions.

First where are the descriptives? At the wery least there should be a clear statement of how many subjects were tested in each condition, an preferably some numbers of central tendencies. Smells fishy, like they're trying to hide something (like a lack of evidence maybe? :eyebrow: )

From what I can gather, at most there were 10 subjects (have no idea whether that is the entire group or 10 in each of the conditions. Regardless That's a pretty low number, which would be highly affected by one single extreme case (one out of the ordinary mouse). In the heat maps there are only 3 subjects in each condition 3!

Now at the end they inform that the mice were given their injections only once a day. Which honestly is not comparable to the therapeutic use. However I have no idea if that dose somehow are long acting(like concerta), but I highly doubt that, as surely they would have mentioned that.(i might have missed It if they actually did mention it)

And they mention that their results can only be interpreted in the context of an NT brain and so will have direct implications of illicit/neurocognitive use. And also that they may or may not be generalizable to those of us with Adhd brains. They do not care to share their reasons for how they can defend generalisation from a mouse brain to a human brain at all, NT or otherwise?

I have read my share of quantitative studies, and to be honest, this one seems very secretive. Like they deliberately aren't sharing enough. I feel like there's so much missing for us to get a clear view of the experiment. And also their conclusions are so definitive, and arrogant. I would not trust this for a second. These evidence are vague at best. I honestly hope that this isn't a standard in drug testing. :eek:

Ironically you need a license to catch fish, own a dog or drive, but any as*hole can run a study and make conclusions by cherry picking the things they want to support. I wish stuff like this could have the goal of getting info rather than trying to support a pet theory.

C15H25N3O
12-19-16, 08:29 PM
I believe people called scientists are licensed to do science and not every as*hole can or
should run a study. Science means 90% documentation. Results can be obvious almost
for blinds or a conclusion.

I also believe stimulants do increase a risk of parkinson and dementia or body diseases.

Our DSM-V diagnoses rely on behaviour but not on neuro-chemic-data telling us we have
a lack of MPH or AMP while our behaviour always has intersections with other spectres.

I still read the study as a warning belonging to the calculation of risk-benefit ratio of
prescribing MPH as MPTP could become a problem also in humans brains.

I think it is crazy to believe or to read from the study an ADHD brain has no MPTP risk.
MPH is no neuro-protectant.