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NMDA antagonists for tolerance, a collection of the evidence and anecdotal reports

Wow mk, glad you are alright! Thanks for posting that; I just assumed that when I worked up to 40mg of memantine and adapted to it, it would be ok to take my standard dose of MDMA. I guess, I'll take a week or more off first to be safe.

But for tolerance prevention, don't you have to take the drug with the memantine?
 
I tend to have any adverse reaction that is clinically possible - my body really dislikes pharmaceutical drugs so don't take my word as the final word, it was more a word of caution - but cardiac events do appear to be a problem with memantine.

I switched to DXM starting last night by taking 5mL of Delsym at midnight. I then SKIPPED my Valium dose and took another 5mL at 6AM then fell asleep about 11AM. I woke up about 3PM, which meant I missed my afternoon dose of Valium as well and then about 4:30 I finally took 5mg of Valium and that's all I've had today. I took another 5mL of Delsym when I woke up and another 5mL at 7:30 or so and will take another 5mL at midnight. Normally I'd have taken 20mg of Valium in this time period so there is definitely something to dextromethorphan versus memantine. I should also note that I have experienced no respiratory suppression or heart abnormalities since I stopped taking the memantine, even with the extreme decrease in Valium.

Even more amazing is the fact that when all this went on with the heart racing out of control on the MDMA/Mescaline combo and the drinking that ensued, I ended up taking a full extra 20mg of Valium that day but I'm still able to come down so quickly off of it the day after the fact.

As for the tolerance prevention, just go back on the memantine after you come down from the MDMA. Memantine has quite a long half-life though so there's still a chance that a good bit of it could be in your system even a week later. Even at the low side of 60 hours, that's 2.5 days before your blood level of memantine is halved and another 2.5 days before its quartered, meaning that it takes 5 days to get down to 10mg plasma levels after taking 40mg. On the high end, the half life is 100 hours so you'd be looking at just over 4 days before your plasma levels would hit 20mg after dosing 40mg.

Either way, it seems that all of the NMDA antagonists have the ability to cause severe CNS issues including respiratory failure, heart attack, and stroke, so just be careful with them. Ketamine has been known to cause significant increases in pulse and blood pressure and everyone knows that recreational levels of dextromethorphan cause tachycardia and hypertension.

All that being said, the 120mg of dextromethorphan polisterex I have taken is having less of an impact on my pulse and blood pressure than 40mg of memantine did.
 
My oxy tolerance is way out of hand lately and I want to try to lower it using DXM.

How much DXM should I be taking and how often/ when in relation to when i take my opiates should I be taking it? For those that have been successful with this, how long did it take to notice a lowering of tolerance?

I know nobody really knows this stuff for sure but could someone give me a regimen of sorts to try/ start with and Ill post my results with it weather it works or not, for the sake of science of course.

Also does it matter if im using DXM polystirex or DXM Hbr? can i use any preparation with dxm in it because the doses are relatively low or should i use something where DXM is the only active?
 
MeDieViL said:
NMDA antagonists work for tolerance by inducing receptor upregulation, the effects of ketamine last a few weeks for depression, while this has been associated with rapid synaptogenesis this doesnt explain everything as the antidepressants effects disappear rapidly again, perhaps receptor upregulation of differend neurotransmitter systems plays a major role too, in that case a singly high dose of ketamine should reverse tolerance quite a bit to several substancs, after wich you should be able to maintain this with memantine or DXM, however i'm just speculating on this, would be interesting to see how it would work.
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Is it known that NMDA antagonists act on/against tolerance mechanisms when they are taken on their own? Could one take memantine for a couple of weeks, then take a week off before consuming the desired substance, and still see a benefit, while perhaps reducing the chances for negative interaction?

What about DXM? I've read about people using DXM the day before taking mdma and finding that it restores some magic.

Does the benefit remain after the nmda antagonist has left the building? Or is it necessary to consume it in conjunction with the substance it's supposed to help with?
 
MeDieViL said:
NMDA antagonists work for tolerance by inducing receptor upregulation, the effects of ketamine last a few weeks for depression, while this has been associated with rapid synaptogenesis [...]
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I thought NMDA receptors were important for neuroplasticity, does the synaptogenesis happen once the effects have worn off as some sort of rebound effect?
 
crOOk said:
I thought NMDA receptors were important for neuroplasticity, does the synaptogenesis happen once the effects have worn off as some sort of rebound effect?
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It occurs rapidly as ketamine activates the mTOR pathway.
 
M Brace said:
Is it known that NMDA antagonists act on/against tolerance mechanisms when they are taken on their own? Could one take memantine for a couple of weeks, then take a week off before consuming the desired substance, and still see a benefit, while perhaps reducing the chances for negative interaction?

What about DXM? I've read about people using DXM the day before taking mdma and finding that it restores some magic.

Does the benefit remain after the nmda antagonist has left the building? Or is it necessary to consume it in conjunction with the substance it's supposed to help with?
Click to expand...

Great questions!!!!! I would love the answers to these as well; I would also be interested in knowing if a memantine/DXM combo would be more effective than either one alone...






.
 
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Would nmda antagonists lessen the euphoria if used during dosing with for example amphetamine. I assume it would as it would lower glutamate activity which is needed in the VTA and NAC for euphoria as much or more than dopamine. So i would worry about nmda antagonists dampening the euphoria of any drug that derives reward through the glutamatergic system... aka all stimulants and opiates.
 
uncompetitive nmda-antagonist do not block the binding site of glutamate, and it actually needs the binding of glutamate to it's nmda receptor.
 
Not to mention that NMDAr's are not the only receptors that are excitatory, which glutamate is an agonist for
 
While I found IV ketamine and nitrous oxide helpful for opioid withdrawal, DXM simply gave me some unwanted CNS-stimulation with inconvenient psychedelic effects.

If you are to use DXM to aid opioid withdrawal, do NOT use it for detoxing off of tramadol, pethidine, and other serotonergic opioids...
 
Smokey McPot said:
My oxy tolerance is way out of hand lately and I want to try to lower it using DXM.

How much DXM should I be taking and how often/ when in relation to when i take my opiates should I be taking it? For those that have been successful with this, how long did it take to notice a lowering of tolerance?

I know nobody really knows this stuff for sure but could someone give me a regimen of sorts to try/ start with and Ill post my results with it weather it works or not, for the sake of science of course.

Also does it matter if im using DXM polystirex or DXM Hbr? can i use any preparation with dxm in it because the doses are relatively low or should i use something where DXM is the only active?
Click to expand...

I'm not really sure about dosing as i dont really know the DXM formula's, there slow fast acting? powder and cough syrop etc, id take a look at the anecdotal reports scattered over the thread and then use simular doses, it seems delsym is most popular for this purpose.
 
M Brace said:
Is it known that NMDA antagonists act on/against tolerance mechanisms when they are taken on their own? Could one take memantine for a couple of weeks, then take a week off before consuming the desired substance, and still see a benefit, while perhaps reducing the chances for negative interaction?

What about DXM? I've read about people using DXM the day before taking mdma and finding that it restores some magic.

Does the benefit remain after the nmda antagonist has left the building? Or is it necessary to consume it in conjunction with the substance it's supposed to help with?
Click to expand...

I noticed the exact same thing with DXM, took a recreational dose and the next day is completely fucked of MDMA, rather then getting a shitty feeling wich i started doing everytime i took mdma because of massive abuse.

Yes the benefit should remain after the NMDA antagonist has been withdrawn as they upregulate a bunch of receptors implicated in drug reward, atleast thats how it looks in theory, ketamine after mdma also abolishes the crash for most, indicating it just upregulates receptors again that have been downregulated by MDMA.
 
bben said:
Would nmda antagonists lessen the euphoria if used during dosing with for example amphetamine. I assume it would as it would lower glutamate activity which is needed in the VTA and NAC for euphoria as much or more than dopamine. So i would worry about nmda antagonists dampening the euphoria of any drug that derives reward through the glutamatergic system... aka all stimulants and opiates.
Click to expand...

No, in fact they are known to potentiate it, while they do act as NMDA antagonists, they dont really affect glutamate (atleast some cause an increase in glutamate) and im not sure what role NMDA receptors temself play in drug induced reward, regardless excess blockage probably causes negative effects, but the NMDA antagonism doesnt come close to the nmda antagonist of certain drugs of abuse, wich are highly euphoric combined with other stuff (think ketamine with mdma etc).
 
MeDieViL said:
Check out nuke's post:
http://www.bluelight.ru/vb/showpost.php?p=9192577&postcount=18

Which is interesting is that regards to opiates NMDA antagonists dont upregulate the mu opioid receptors but act on a downstream mechanism.
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i think i remember hearing something about iNOS inhibitors preventing opiate tolerance as well. Curcumin is an iNOS inhibitor so this likely plays a role along with nmda antagonism, perhaps a more important role.
 
bben said:
i think i remember hearing something about iNOS inhibitors preventing opiate tolerance as well.
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Yes and proglumide and ultra low dose naltrexone, however the last 2 didnt really pan out in humans, causing rather incosistent results for those that tried it, i think nmda antagonists and possibly curcumin are the best options.
 
MeDieViL said:
Yes and proglumide and ultra low dose naltrexone, however the last 2 didnt really pan out in humans, causing rather incosistent results for those that tried it, i think nmda antagonists and possibly curcumin are the best options.
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yes since curcumin has 2 mechanisms to lower tolerance. possibly more, if only we could get it to hit the blood stream and stay bcm 95 is ok for it.
 
Are there any interactions between memantine and Saint John's Wort? (I've been searching but can't find any info; there does seem to be between SJW and DXM though...)
 
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