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Misc can memantine reverse methylphenidate tolerance?

J

jasonx11

Bluelighter
Joined
Jan 25, 2016
Messages
81
I want to reverse tolerance to 27 mg xr concerta. So I think increasing by 5 to week 4 when I'm at 20 mg. While taking a month break off of concerta , will it reverse my tolerance?


Since I got a tolerance to concerts , I break it in half so I get the ir formula which hits much harder . Sometimes I would take 1 pill (2 halves) and another half after it starts building up in my system. Do you think my tolerance will be reversed back to 27 mg xr? Then should I maintain the 20 mg of memantine and take with concerts to prevent and future tolerance after it got reversed ? Sorry for rambling , thanks in advance.
 
The only info I could find on mematine and tolerance was a study done with morphine. Apparently when mematine was co-administered with morphine it slowed tolerance build up.

Maybe this could work on methylphenidate but that's not even the issue, as far as I can tell from the study it only worked when administered WITH the morphine. If you already have a tolerance and you want to take a break to lower it then I'm sure taking memantine wouldn't hurt but don't expect it to work miracles. Your best bet is to take a longer tolerance break, that is the only sure fire way to reduce your tolerance plus it's better for your body in the long run.
 
Thanks ! , how long of a tolerance break? And should I take memantine on the break? How about when I get back on concerta again? Your input would be extremely helpful , thanks in advance.
 
Btw I already took a 3 month tolerance break without memantine . But when I got back on concerta , I didn't feel any effects from it. So try with memantine?
 
I guess if you have access to a large supply of memantine it couldn't hurt to take it during your tolerance break. That's great that you can go 3 months without using concerta! Maybe try to go 4 months this time or just 3 months with memantine and if at the end of the three months your tolerance is back to zero you'll know the memantine worked.

From the study I read it seems memantine was effective when used with the morphine so if you want to keep tolerance down it sounds like you'll have to take memantine with your concerta dose.
 
Thanks again ! , the three months of not taking concerta was hellacious not to mention. Because my doctor wanted to see how I will do without concerta for 3 months, but the withdrawal was a ticket to death sentence . Which I succumbed to 'lol'. So what you mean is , if I take memantine with concerta , my tolerance would be reduced (so more euphoria/motivation etc). But if I want to completely reset my tolerance , then I am going to have to take a tolerance break with memantine? Let me know thanks .
 
What do you think about starting The memantine from 5 mg and increasing every week til I get to 20 by week 4? , completely irrelevant , but I am interested in researching to develop more powerful tolerance reversers than memantine. To support anyone else going through the same problem as I am . So helpful people like you is who I appreciate who give hope to people who take medication for their needs . We just need positive minded candidates for biopharmacy , to solve issues regarding medication once and for all. I appreciate the inspiration you have provided me with this far .
 
Tolerance is a very big problem that many great minds have pondered, ultimately what Mematine is antagonizing (NMDA) is responsible for what's called long term potentiation, which basically means sensitization (the exact opposite of tolerance), so I personally think that Mematine won't have much to offer, you could sure try it though. The opiates might be an outlier because things like DXM/Mematine potentiate opiates.
 
So if it can sensitize seretonin/dopamine receptors , doesn't that equate to reduced tolerance? Is my approach to reducing/removing tolerance (protocol above with break) the most efficient for tolerance?
 
NMDA antagonists themselves cause release of most neurotransmitters like dopamine and serotonin so in that respect I wouldn't be surprised if that alone causes downregulation of receptors (tolerance).

What I mean is that when NMDA is working normally it helps sensitize receptors and increase your brains sensitivity, so I think you should leave your NMDA alone and just take a genuine break, a month is a pretty good break.
 
I have taken a 3 month break and after the break. I noticed tolerance fully develop to 27 mg xr concerta, which I found very odd. Also according to some reports , I thought memantine is a d2 agonist so it should help. "The NMDAr antagonist effect of Memantine prevents the receptors from becoming reliant on the D2 agonism, in the same way it helps mitigate tolerance to Dopamernigic drugs"- newcarpenters. https://m.reddit.com/r/Nootropics/comments/36vzbu/memantine_d2_affinity_dopamine_agonist_withdrawal/ plus concerta is a 5ht1a antagonist, where as memantine is a 5ht1a agonist. So should that help? Thanks in advance .
 
http://www.ncbi.nlm.nih.gov/m/pubmed/2671566/ Here is a study concerning NMDA antagonists and dopamine showing that NMDA antagonists block sensitization to amphetamine. So according to this study you would not want to take NMDA antagonists.

Long term potentiation is thought to underly some addictive mechanisms concerning dopaminergic drugs, when you activate some pathways like NMDA they get stronger and more sensitive each time you activate them so it's essentially reverse tolerance. If you blocked NMDA you would lose this long term potentiation.

Just wondering, what are you taking the concerta for? Are you looking for a good time or are you trying to study? If you're trying to study there might be better options.

Edit: thought I would just point out that opiates and concerta are very different and the reason why NMDA antagonism helps tolerance with opiates doesn't apply to concerta
 
So you mean taking memantine will further accelerate tolerance by blocking the nmda pathways? Then why does memantine reduce tolerance for some people who have a tolerance to dopaminergic stimulants? So should I take an nmda agonist instead? (I don't see any reports online about nmda agonists) what should my next step be . Because prior to the 3 months of taking the tolerance break , I still responded pretty well to concerta. It was after the three months when I took concerta , I barely noticed a thing. So I resorted to increasing the dosage (modifying xr to Ir) which is basically giving me a very short duration of motivation followed by a horrible crash. But I found something online which gives hope .. "This means that memantine escapes from the ion channel quick enough, to allow normal functioning of the NMDA receptors, allowing passage of calcium and sodium ions critical to the operational circuitry of neuronal firing responsible for glutamine cognition". "Memantine causes massively increased Ca2+ evoked signals by inhibiting one of the main excitatory responses in the human brain. The brain responds compensate for the depleted Ca2+ by building more building more binding sites. This inhibition also stops the spiking or prolonged influx of Ca2+ ions, which gives it neuroprotective effects, as well as blocking tolerance to a degree. It also achieved this by blockading pre-synaptic CA2+ entry which we will return to, as this is its main proposed mechanism for reversing and blocking tolerance" - http://www.khemcorp.com/memantine-research-summary-explained-the-basics/ Pretty interesting information I must say . Also , I take concerta for adhd.
 
Mematine by itself will release dopamine so I suspect some people are not necessarily seeing a reduction of tolerance but rather combined effects of Mematine + whatever. Normally NMDA receptors are excitatory but they have a lot of input to inhibitory interneurons, so when you block NMDA with an antagonist you shut down the downstream inhibitory neurons as well, this results in increased neuronal activation across the board.

Long term potentiation /genetic changes (something called DeltaFosB) probably explains your report of increased tolerance after a break. Long term potentiation basically means that if you keep on stimulating your dopamine every day there are changes that happen in the brain (like dopamine receptor up regulation / sensitization) that make the dopamine stimulation even more powerful, I suspect you lost some long term potentiation when you took your break. When concerta is taken long term it has been shown to improve dopamine flow in the brain.

A lot of long term potentiation is mediated by NMDA so I think it would be wise to avoid it to get the most out of your concerta but you could try memantine, just be aware you might just be getting high off the memantine and it might not actually be a tolerance reduction. Experiments with taking solely memantine would prove wise. NMDA is very important for learning though so if you are studying I would avoid taking it.

Also I wouldn't trust anything you read on these various chemical vendor sites, they are trying to talk up their products.

What I would have you look into is Piracetam, it is a mild stimulant that enhances cognition and focus. It actually boosts NMDA (opposite of Mematine) so it might help potentiate your concerta long term or you might find you don't need your concerta with it. I wouldn't take any racetam regularly though, I would take breaks often. Also get good sleep and take antioxidants like vitamin E regularly! It's a good idea to take anti oxidants with concerta as well.

Just so you know it's pretty hard to always get euphoria from concerta, eventually you build a tolerance at some point. Try to use it for more medicinal purposes haha. But like I said if you need focus you might try experimenting with Racetams like Piracetam/Aniracetam but vary your usage and take breaks.
 
Honestly if you are looking into potentiators to this degree then you need a longer term tolerance break. I've tried different potentiation techniques, mainly on opiates, and they've all turned out to have very minimal effect if any at all. Methylphenidate isn't even good, as a study aid or for recreation, better off just putting it down or awhile.
 
piracetam sounds familiar , are there any reports of people online saying that piracetam helped them reset tolerance? , if piracetam does reset tolerance wouldn't there be numerous reports online of piracetam drastically reducing/removing tolerance online? let me know. What kind of regimen would you recommend to use with piracetam to reverse the tolerance to concerta? sorry for rambling lol
 
methylphenidate always worked for me (took it for 10 months before tolerance break) but like cotcha yankinov said , taking a tolerance break caused the deltafosb to take effect which inhibited long term potentiation.
 
I just started to learn molecular biology ever 2 months ago by reading forums etc , so excuse my limited understanding lol . You guys are yet very helpful :) , I just want this tolerance issue to be over with. No matter what I have to do , I at least want to know that this issue can be resolved.
 
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