D aspartic acid as a novel way for tolerance prevention?

[MeDieViL]

Take in mind this is only based on 2 anecdotal reports but it looks like DAA is capable of reversing stimulant and ketamine tolerance; its a nmda agonist and how it does this is currently unknown.

I would like to see more experiences on it for tolerance reversal; as its only based on 2 anecdotes it may turn out to be useless but optimistic as i am (eg nmda antagonists) i also look at this one optimistical and would like to encourage others to give it a try.

Its mostly used to raise testosterone levels.

 

[sekio]

I highly doubt any amino acid can lower drug tolerances. D-aspartate is the "artificial" isomer though.

its a nmda agonist and how it does this is currently unknown.

Glutamate site @ NMDAr, but thats only in vitro.. in humans I doubt it has central fx at all... most amino acids do not. for example gluta,ate

 

[MeDieViL]

Its definatly active; many including me have reported central effects.

It increases test because of the nmda agonism.

 

[SerotonergicHaze]

In what way would NMDA agonism be helpful in reversing or even reducing stimulant eg. amphetamine tolerance? My understanding is that activating the NMDA receptor causes an influx of Calcium of into the neuron, and this is one of the factors by which tolerance is effected, so if you're drug was active, it sounds like it would be counterproductive and even potentially neurotoxic

Perhaps, it could be helpful in treating Ketamine tolerance. Since it would downregulate the NMDA receptor, if it was indeed active.

Your compound does however sound rather exciting! XD

 

[Jabberwocky]

Amphetamine tolerance is caused by excess Ca++ influx through the NMDA receptor gated calcium channels on the outer membranes of the dopamine cells bodies in the ventral tegental area, one of two areas in the brain with concentrations of dopamine producing neurons.
As alluded to above, taking an appropriate NMDA (partial) antagonist will prevent the development of a tolerance for the effects of an amphetamine or amphetamine-like stimulant. Also, by preventing excess Ca++ influx into the neuron, an NMDA antagonist will prevent associated brain alterations and damage (excitotoxicity).

Studies have indicated that amphetamine tolerance is prevented by exogenous or endogenous agents that are able to inhibit excess Ca++ influx into the neuron through the gated calcium channels on the neuronal membrane that have NMDA subtype glutamate receptors.Glutamate , the body’s major excitatory neurotransmitter, opens the gated calcium ion channels upon attaching to the NMDA receptor. A number of other receptors are also expressed on these calcium channels, which, when stimulated, either facilitate or inhibit glutamate’s action.

It is also important that agents that inhibit calcium channel activity not also cause deficient Ca++ influx. For example, ketamine is a full NMDA receptor antagonist, that prevents excess Ca++ influx and amphetamine tolerance. But being a full NMDA antagonist, ketamine in excessive doses results in deficient Ca++ influx. This could be one of the reasons it leaves K-user in a state of disassociation.

taken from http://www.dr-bob.org/babble/20031015/msgs/270735.html

the same goes for opiates. you need an agonist in order to reduce tolerance as excess c++ molecules are stopped from entering the neurotransmitters, which is what causes the tolerance to begin with. it wouldn't exactly reverse a tolerance but it would prevent it from building up.

now back on topic, d-aspartic acid stimulants nmda receptors but only ever so slightly. you'd surely need an incredibly large dose in order to prevent the tolerance which would not be economical or healthy i presume. although all methods are not exactly healthy. i guess it could work, but you need a measure as to how much it effects the nmda receptor first.

 

[Epsilon Alpha]

Errr, this might work in the case of "I think I made myself schizophrenic bro" but as far as I can tell in healthy humans its not going to do anything beneficial.
http://www.ncbi.nlm.nih.gov/pubmed/18842900
Its probably going to worsen stimulant tolerance long term, though provide short term potentiation.

As a side note: if this turns into a unfounded "fix mah schizophrenia/depression" thread I'm closing it.

 

[MeDieViL]

Errr, this might work in the case of "I think I made myself schizophrenic bro" but as far as I can tell in healthy humans its not going to do anything beneficial.
http://www.ncbi.nlm.nih.gov/pubmed/18842900
Its probably going to worsen stimulant tolerance long term, though provide short term potentiation.

As a side note: if this turns into a unfounded "fix mah schizophrenia/depression" thread I'm closing it.

What are you on about?

Logic would indeed say it would worsen stimulant tolerance but im interested because of the anecdotes ive read.

 

[Epsilon Alpha]

What are you on about?

Logic would indeed say it would worsen stimulant tolerance but im interested because of the anecdotes ive read.

Well, if the animal studies apply to humans directly, D-aspartic acid might prevent the aspects of tolerance/sensitization which resemble the negative symptoms of schizophrenia. I'd look more closely on the backgrounds of the reports you read and see if you can find anything hinting towards schizophrenia or bipolar disease (mind posting links to them actually?). The more I read about amphetamine tolerance and sensitization the more links I see to bipolar and schizophrenia. So in individuals predisposed to developing the schizophrenic type tolerance I can imagine that this might actually reverse tolerance for them, while it would likely worsen it in other populations if that makes sense.

I'm just terrified that bluelight will have to deal with a influx of "help with my mental health problems" posters like M&M was in its last days, sorry if that came off as offensive.

It would also account for some of the tryptophan metabolite/NMDA interactions in schizophrenia, in addition to a several other aspects.
http://journals.cambridge.org/downl...83a.pdf&code=9c2fa910e3e42f3291802b67ab63f032

 

[Jabberwocky]

Wouldn't any additional NMDA agonism - and this in a case, when these receptors are upregulated from antagonist usage (K, MXE ...) - cause a risk of overstimulation / anxiety etc. and also excitotoxicity?

But it makes sense in that downregulation due to agonists is comparable to antagonist blockade in tolerance reducing ... just switching between these two when one stops to work seems dangerous to me - or am I wrong?

yes of course, but we are talking extreme amounts of antagonist use here. this is a simple ammino acid, under which we are not sure of how much it affects the nmda receptors in the brain. it wouldn't cause overstimulation unless it were an extreme dose that a person were taking. as for tolerance reduction i agree with epsilon, it would not reduce tolerance long turn but potentiate short term as it is very weak in comparison to say DXM. switching wouldnt cause a problem i don't think if you were to use an agonist and then an antagonist. you are simply blocking out the receptor to be used, thus you'd need a higher doseage of whatever to make it hit harder.

as for the reduction of symptoms of scitzophrenia, doesn't excess dopamine in the synaptic clafts cause the problem? i stand to be corrected once more. it seems as if it has the same effects long term as haldol in that it prevents oxidaic bonds from forming in the nmda receptors of the brain, which is partly what causes stimulant tolerance. there still lies the issue of c++ molecules being built up in parts of the brain too.

 

[Amu]

Do note when D-AA/Sarcosine wear off you'll be left with down-regulated NMDA receptors, if dysfunctional dopamine neurotransmission is bad after a stimulant comedown, glutamate dysfunction won't be too fun either. D-AA does have in vivo effects, I've seen reports of it causing severe mania

 

[MeDieViL]

I'm just terrified that bluelight will have to deal with a influx of "help with my mental health problems" posters like M&M was in its last days, sorry if that came off as offensive.

no offense was taken; and i will gladly do my own contributions to keep this site running and agreed mental disorder threads maybe should be minimalised; the biggest problem was not that on mind and muscle tough but the disappearance of the most knowledgeable members having a rather big impact.

 

[MeDieViL]

yes of course, but we are talking extreme amounts of antagonist use here. this is a simple ammino acid, under which we are not sure of how much it affects the nmda receptors in the brain. it wouldn't cause overstimulation unless it were an extreme dose that a person were taking. as for tolerance reduction i agree with epsilon, it would not reduce tolerance long turn but potentiate short term as it is very weak in comparison to say DXM. switching wouldnt cause a problem i don't think if you were to use an agonist and then an antagonist. you are simply blocking out the receptor to be used, thus you'd need a higher doseage of whatever to make it hit harder.

as for the reduction of symptoms of scitzophrenia, doesn't excess dopamine in the synaptic clafts cause the problem? i stand to be corrected once more. it seems as if it has the same effects long term as haldol in that it prevents oxidaic bonds from forming in the nmda receptors of the brain, which is partly what causes stimulant tolerance. there still lies the issue of c++ molecules being built up in parts of the brain too.

Excessive tonic dopamine is a downstream effect of the true problem (glutaminergic dysfunctioning) with that there's also phasic da hypoactivity causing negative symptions and indeed amphetamine is a effective treatment for this:
http://www.shire.com/shireplc/en/investors/irshirenews?id=477

But as it also increases tonic da making positive symptions worse it should be combined with a ap or something else that helps positives.

 

[MeDieViL]

Well, if the animal studies apply to humans directly, D-aspartic acid might prevent the aspects of tolerance/sensitization which resemble the negative symptoms of schizophrenia. I'd look more closely on the backgrounds of the reports you read and see if you can find anything hinting towards schizophrenia or bipolar disease (mind posting links to them actually?). The more I read about amphetamine tolerance and sensitization the more links I see to bipolar and schizophrenia. So in individuals predisposed to developing the schizophrenic type tolerance I can imagine that this might actually reverse tolerance for them, while it would likely worsen it in other populations if that makes sense.

I'm just terrified that bluelight will have to deal with a influx of "help with my mental health problems" posters like M&M was in its last days, sorry if that came off as offensive.

It would also account for some of the tryptophan metabolite/NMDA interactions in schizophrenia, in addition to a several other aspects.
http://journals.cambridge.org/downl...83a.pdf&code=9c2fa910e3e42f3291802b67ab63f032

Alot of interesting food for tought wich is exactly why i made this thread with intrest and would like to see others replicate the same results; that way well know.

Shizo indeed is a strange disorder; i was completely immume to tolerance or physical dependency forming to GBL and a shizo friend noticed the same with opiates till we fixed ourselves more... And indeed we both had a hyperresponse to stimulants but with that immediate tolerance (rapid downregulation) def allways occured for me.

But enough of that we go a bit offtopic with the shizo stuff.

 

[MeDieViL]

Well, if the animal studies apply to humans directly, D-aspartic acid might prevent the aspects of tolerance/sensitization which resemble the negative symptoms of schizophrenia.

Can you be more clear on what you mean in this sentence? Are we talking about sensitization to for example amp in a shizorodent model wich was prevented by DAA? As the same can easily apply to the healthy rodents when snorting a bit...

Just a bit confused what your referring too; im interested.