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Misc can memantine reverse methylphenidate tolerance?

So staying on just piracetam (to stop delta fosb expression and induce nmda upregulation )with cardio and noopept for a month , then taking concerta *whilst, newly developed brain cells * WITH piracetam isn't going to be much of success? (Of course cycling on and off as usual.
 
DXM is a NMDA antagonist and his action cause AMPA desensitization. Piracetam is AMPA positive allosteric modulator and reverse AMPA desensitization.
DXM don't "touch" directly AMPA but it changes AMPA/NMDA ratio. Piracetam doesn't stimulate NMDA. NMDA uses Ca++ channel, AMPA use Na+ channel. This effect of piracetam is partly responsible for his neuroprotection.

nAchRs are key receptors in the brain that they control everything from the speed of producing virtually all of neurotransmitters to neurogenesis, LTP too.
http://www.nature.com/npp/journal/v32/n1/abs/1301189a.html
http://www.cell.com/trends/pharmaco...ieve/pii/S0165614705001288?showall=true&cc=y=
http://www.annualreviews.org/doi/abs/10.1146/annurev.pharmtox.47.120505.105214


http://www.tandfonline.com/doi/abs/10.1080/10298420290023954
http://www.sciencedirect.com/science/article/pii/000689939190095D
These studies shows that LTP is responsible for BEHAVIORAL sensitization and tolerance development.
Dopamine pathways are responsible for feeling both euphoria and fear. Is need to know where it is well to strengthen LTP.
 
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Piracetam DOES stimulate NMDA, it has been shown to cause upregulation near 20% of NMDAr's with administration of just 2 weeks if I remember correctly.

You are making some pretty strong claims about the role of nicotinic receptors I'm the brain. I'm okay with strong claims as long as there is strong evidence to back it up. And I'm not saying that stimulating an excitatory neurotransmitter receptor doesn't cause LTP.

And once again, I'm not talking about the opoid receptors... And I realize that dopamine and euphoria is a complicated matter, for example, BDNF over expression in the nucleus accumbens has been found in depression
 
"D1 and D5 agonists (eg. Dopamine) cause an increase in ejection ACH and thus cause the stimulation, increase motivation and euphoria. NAChR agonists cause upregultion (increasing the quantity of ligand binding), and desensitization (reduced sensitivity of ligand binding) receptor. MXE reverses the desensitization and at the same time accelerating upregulation receptors. Through this mechanism disociants work antiadiction and refrain build or even lower tolerance for all drugs."
"In general, the negative effects of the stimulant related to their effects on the cholinergic system. First, to big agonizing leads to partially block receptors and thereby created neurotoxicity, further drug use leads to nAChRs desensetization and creates long-term mental deficits among users (attention deficit disorder, anxiety, phobias, psychosis, addiction). Generally, MXE counter both these phenomena."
 
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There is a problem in yours statements. GHB increases strongly ejection of glutamate and certainly does not work procognitive. Of course, this can be explained by the GABA B agonism. The problem is that another agonist of that receptor, Phenibut not working strongly amnesial. To this piracetam also does not seem to be so procognitive and improving perception, though, it is PAM AMPA receptor.
To this cannabinoids strongly inhibit ejection of glutamate and certainly everyone in this forum can confirm that cannabinoids significantly sharpen the senses. To the NMDA receptor is referred to as antyopioidowy. Also they disociants have mixed effects on the senses. At higher doses, yes anestethic they operate, but smaller doses (DXM in particular) rather enhance the perception.
 
That study is saying that both NMDA receptors and glutamate/kainate receptors are important for sensitization to dopamine... Tell me again why we would want to antagonize NMDA? And I was under the impression that dopamine antagonism generally leads to dopamine efflux (especially D3 antagonism) and that anticholinergics lead to dopamine efflux.

I didn't say that ampakines agonize NMDA. The reason why anything excitable will increase the likelihood that NMDA will fire and LTP will be induced is that the NMDA takes a lot of stimulation to remove the magnesium blocking the channel, that's why they call NMDA "coincidence receptors", there has to be several inputs firing at once in order to remove the Mg block
 
BobbyDick said:
To this cannabinoids strongly inhibit ejection of glutamate and certainly everyone in this forum can confirm that cannabinoids significantly sharpen the senses
Click to expand...

The objective studies can confirm that cannabinoids are bad for short term memory specifically because of the issues with not receiving enough stimulation to remove the magnesium block - from wiki "[18]NMDA receptors are believed to be involved in cellular hippocampal LTP and LTD processes, in respect to memory consolidation and forgetting factors.[2][16] For these process to occur on the cellular level, a high enough excitatory postsynaptic potential must occur to depolarize the CA1 hippocampal postsynaptic membranes and remove the magnesium blockade on NMDA receptors.[19][20] Glutamate plays the role in activating NMDA receptors, allowing hippocampal calcium to flow through NMDA receptor channels—calcium NMDA receptor transmission is critical in inducing both LTP and LTD.[16][19] Optical imaging evidence that monitors synaptic activity on in vitro hippocampal neurons, demonstrates that CB1 agonists (including THC) reduce glutamate release.[21] Since glutamate release is required for NMDA receptor activation, and removing the magnesium blockade, a reduction of glutamate release causes a reduction of excitatory postsynaptic potential, suggesting an impairment of LTP and LTD is mediated via hippocampal NMDA receptors.[16][19][20] This finding not only suggests that memory impairment affects long-term synaptic plasticity, but is also supported via experimental data.[16] In fact, research shows that CB1 agonists in the hippocampus do not impair LTP and LTD, when the NMDA magnesium blockade is instrumentally removed on hippocampal CA1 neurons.[22] Ultimately, with the consistency of scientific inference and experimental data, cannabinoid effects on memory are compellingly supported via the modulation of glutamate release.[2][16][17]"
 
Dopamine agonists may don't work, because they need to well working cholinergic system. nAchRs agonists sintesize dopaminergic system.
Glutamate isn't responsible for tolerance development in high degree. nAchRs are mainly responsible for building tolerance.
Generally, the most important are the nicotinic receptors which control the level of sensitivity of receptors and the rate of formation of new neurotransmitters and their level of ejection. Unfortunately, persistent stimulation of theirs is only a temporary solution because outside the desensitization of the receptors also created "downstream tolerance", which is formed at the level of tolerance is not the same receptors but only at the level of the effects of further stimulation. Downstream tolerance seem to prevent nAChR antagonists like MXE, DXM or Ibogaine.

How blockade of nicotinic receptors affects other neurotransmitters?
Reduces or even completely block their ejection. For example, when nAchRs are blocked, it's extremely difficult to achieve euphoria, indicating that blocking dopamine ejection. For this blocking these receptors results in anhedonia, amotywation, depression and psychotic symptoms. Just remember the worst exit after any euphoric drug (eg. Mephedrone) and these are the symptoms of a strong blocking nicotinic receptors.
 
Do you have any evidence for acetylcholine's role for being so important in regulating neuro transmission? All the acetylcholine knockout studies only show basically some diminished learning capability except for the a3 subunit knockouts which all mice died at 3 days

I would expect Parkinson's symptoms from significant anticholinergic activity if acetylcholine was playing a big role in dopamine transmission, instead anticholinergics are actually used to increase dopamine in Parkinson's patient and patients on strong anti psychotics.
 
I just took phenibut and piracetam today , I don't know what it was , but I felt a slight mood boost for up to an hour. An hour and a half later , ate breakfast. Unfortunately, there wern't any eggs to provide as a choline source. So I suffered from extreme brain fog and only saw things get brighter lol . Took my concerta as usual , noticed the effects to be less pronounced somehow ? Maybe because I ate too much breakfast , which is why my concerta metabolized slowly I guess. The posts are causing confusion lol, if you upregulate nmda receptors , doesn't it agonize overtime? Apparently that's what it says on powder city. According to the posts , should I continue taking piracetam? And I am still waiting for an answer to my above post as well :) thanks again.
 
Interesting, it does seem that acetylcholine is important for dopamine in the striatum which makes the case for racetams (which typically increase acetylcholine). I mean, assuming the receptors are co localized in the prefrontal cortex where working memory is concerned.

Anyways sorry Jason lol, I would keep experimenting with racetams and see if you find anything that helps you but you could honestly start taking concerta and the racetams together at this point, you just didn't seem to get much out of the last break you took and I think concerning LTP there is momentum involved. There's not much else we can do
 
It's okay lol , can you create like a regimen or an outline for how to incorporate concerta , piracetam and cardio together? (Dosages , when to take breaks etc)then just post it here :)
 
Cardio everyday or as often as possible, best done early in the day. Piracetam/other racetam (2g twice a day or more for piracetam) with concerta, every 5 days a break from piracetam or just don't bother if the piracetam isn't working out well for whatever reason, and then use the concerta steadily.

That's pretty much the best we can do, there isn't any magic bullet for tolerance so try to be content with what you get out of this. If you start getting any problems with mood or anything the first thing I would do is stop the racetams and just do concerta and exercise. There are other supplements you might experiment with for help with memory and such and of course there are the hormone peptide things
 
Will do , thank you so much for your support. I am really grateful that you've came this far to help me with the issues that I am having. I hope this resolves the problem I have been struggling with. Not only me , but others who have seen this thread , hopefully also received your support. Btw I inboxed you , anyone else who comes across this thread, feel free to contribute anything you would find helpful. I hope this thread still remains active , and I'll come across this thread every once in a while to update on my progress or take any useful information by others into consideration as long as they are backed up by research. All I can say is , the information I'm receiving so far seems like it could really help.
 
No problem, best of luck to you. My last piece of advice is mindfulness meditation. I think you will be in a much better place a couple years from now if you practiced it everyday for just 10 minutes before bed than if you didn't. Similar meditation like things such as biofeedback have also proven successful for treating ADHD. Toodles!
 
If there was a way to reverse tolerance then I would be doing backflips, alas, I think there might only be ways to boost LTP which might sensitize one to drugs.

I did some more research and found NMDA antagonists actually induce DeltaFosB in the nucleus accumbens so maybe NMDA antagonists will help increase stimulant euphoria after all.

"The reinforcing properties of PCP and ketamine are mediated by the binding of these drugs to specific sites in the channel of the NMDA glutamate receptor, where they act as noncompetitive antagonists. PCP is self-administered directly into the NAc, where its reinforcing effects are believed to result from the blockade of excitatory glutamatergic input to the same medium spiny NAc neurons inhibited by opioids and dopamine".

These MSNs (medium spiny neurons) are GABA inhibitory interneurons, so when glutamate activates a GABA interneuron it inhibits the nucleus accumbens. Therefore blocking NMDA increases activity there.

So concerning rewarding effects NMDA antagonists might be the way to go, but I'll have to give a warning about addiction and such, as well as possible long term anhedonia with withdrawal.
 
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