• N&PD Moderators: Skorpio | thegreenhand

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

True, well i have a high tolerance to xanax & have for around six years so hoping this works. Can't see it happening but see what happens

I hope it will for ya too, keep us updated on this one mate!
 
Just can't see how it would work while i'm still taking xanax
 
Check out those experiences, those are all that tried it meaning it so far consistently worked for everyone, no mixed reports wich make it look extremely interesting:
Well I am down 50% on my valium now but its not comfortable - I may have to go back up or increase the memantine or add Delsym or something.

I get the distinct impression that DXM is more effective for benzos than memantine is but at the same time, I was taking 60mg of Delsym twice a day versus taking 20mg of memantine twice a day so maybe I just need to go up in the mem dose.

Personally, I think Delsym was working quite well with the valium withdrawal though - my tolerance to it was going down when I was on the Delsym and it started on the second or third day... I switched to memantine due to concerns about drug interactions with DXM but I may switch back because memantine has suppressed my breathing when I take too much (up to 60mg a day) and doesn't appear to be working as well as DXM does. Plus I quit taking drugs altogether in order to do my taper as quickly as possible and get back to work.

Can anyone comment on how well DXM works versus memantine for benzo withdrawal? I would imagine that it is superior - I remember that my valium tolerance dropped on its own when I was doing the Delsym whereas the memantine seems to just reduce the withdrawal symptoms (ie., no brain fog, no memory problems, still functional, no panic attacks, but still psychological symptoms like feeling that your heart is going to give out, weird body feelings, but nothing physical to back it up other than random pains).

It seems to be somewhat commonly reported that for whatever reason, DXM users can keep using the drug they are tolerant to and still experience a tolerance reduction but this does not seem to be the case with memantine.

I guess I may have to just suck it up and switch to the syrup and just make sure to avoid serotonergic drugs, although I wonder how much damage a roll would do with therapeutic levels of Delsym - I won't be trying it though.
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.

I took Alprazolam for 3 years, then went through accidental cold-turkey withdrawal because the local pharmacies weren't carrying any (happens where I live occasionally, sucky country/city). I experienced severe withdrawal symptoms including paranoia and transient psychosis but soon I got again on Alprazolam and thankfully didn't have a seizure. During that period I was completely tolerant to 2 mg Alprazolam's both sedative and anxiolytic effects.

Since I started taking Memantine, the tolerance was reversed somewhat and 1 mg was anxiolytic and practical enough for social anxiety disorder. 2 mg was very effective sedative. Tolerance didn't develop any further from this point on.

When I began tapering off Alprazolam for good, I was on 2 mg/day and the withdrawal was pretty negligible, only symptoms were irritability and slight sense of panicking, despite the rapid taper process.
I'm totally getting similar results from Huperazine A. I've been taking 100 mcg twice daily for 4 days. I wonder if anyone else can relate to this w/r/t huperazine.

In case it's of interest to you, I've cut my alprazolam consumption in half. Not because I'm trying to give it up but because it's suddenly too potent. FWIW I have a 6-year daily alprazolam habit.

The experiences need to keep coming it, and the addition of DXM doesnt need much efford, so not much reason not to try it.
 
Have read those but how would it work while still taking a benzo?
 
I'm giving it a go, shit anything to lower tolerance but just can't see it happening while still taking xanax. Maybe if i stopped taking xanax for a day & just had dxm i could see it happening but otherwise no lol
 
I'm giving it a go, shit anything to lower tolerance but just can't see it happening while still taking xanax. Maybe if i stopped taking xanax for a day & just had dxm i could see it happening but otherwise no lol

Well, you may be the one convincing people that still think the same about this right now;)
 
I just came acros this post:
Originally Posted by caseface99
^^ Not to mention doesn't DXM help dampen tolerance from increasing?
That's the theory but several of us tried a lengthy experiment to test this and didn't get very impressive results... not that's its scientific but I haven't met anyone on here who has tried this over a substantial amount of time while using a lot and can definitely say "this greatly slowed tolerance acquisition" let alone reversed any.
http://www.bluelight.ru/vb/showthread.php?t=543949

I'm posting this to encourage those not getting as positive results to report their experience too.

He's experience did not an increase in tolerance tough, just that dxm didnt reverse he's tolerance:
I had been taking opioids for years for pain but I was taking very consistent doses that hadn't changed substantially after 2+ years of use at that time. I was taking 60mg DXM Hbr TID when I was doing it but I don't think my worthless results imply much if anything to people looking to use DXM to attenuate tolerance acquisition associated with recreational use.

My tolerance wasn't rising so I was hoping that I could reduce my tolerance some so when I say it was worthless THIS is what I mean. At the time main were theorizing that it could be used to REVERSE tolerance some and not just slow the development.
 
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Ok, thanks for those posts. I'll see how it goes in a few days
 
I'm giving it a go, shit anything to lower tolerance but just can't see it happening while still taking xanax. Maybe if i stopped taking xanax for a day & just had dxm i could see it happening but otherwise no lol

The brain is an incredibly complex system, and we still don't fully understand it, however, what we can do is use science to help predict what will happen when we make a particular change, based on past experience.

Past experience in this case shows that 100% of the time, DXM will reduce tolerance even when taken with the substance of abuse.

Funny thing is, we do understand this mechanism fairly well, and if you read the journals in this thread you'll hopefully be able to understand why.

Good luck to you.
 
How the hell can i get this thing more popular so more people try it? I first posted it in other drugs thinking a ton of ppl will try it as they have major tolerance issues there, i got 2 comments saying good work and none tried it to my suprise, after it got moved to ADD then people started trying it however considering the succes ppl have been having far more people should try it, if poeple keep having succes eventually i would like to get this thing to become the basic first thing poeple try when fighting drug tolerance or addiction.
 
Another thing NMDA antagonists have potential for is turning certain addictive meds into sustainable long term treatments for mental disorders such as opiates and amphetamine's, normally they cant be used for that since tolerance will occur rapidly, however it may just be easier to counteract those issues rather then coming up with new novel compounds.

I like the quote someone put here before, NMDA antagonists certainly arent the magic bullets, however they are the next best thing after the magic bullets.
 
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^^^ I took part in a study years ago measuring the NMDA antagonistic effects of the separate isomers of methadone. This is the primary reason methadone tolerance does not skyrocket like traditional agonists.....

Great work by the way, makes for fascinating reading.

Separate but similar study:


The d- and l- isomers of methadone bind to the non-competitive site on the N-methyl-D-aspartate (NMDA) receptor in rat forebrain and spinal cord

A. Laurel Gorman, Kathryn J. Elliott and Charles E. Inturrisi*
Department of Pharmacology, Cornell University Medical College, 1300 York Avenue, New York, NY 10021, USA
Received 3 December 1996; revised 7 January 1997; accepted 7 January 1997. Available online 28 January 1998.
Abstract
Racemic (dl)-methadone has antagonist activity at the N-methyl-D

-aspartate (NMDA) receptor. We evaluated dl-methadone, the opioid active (l-) and the opioid inactive (d-) isomers in competition binding assays. dl-Methadone and its d- and l- isomers exhibited low micromolar affinities for the [3H]MK-801-labeled non-competitive site of the NMDA receptor in both rat forebrain and spinal cord synaptic membranes, with Ki values and displacement curves similar to those of dextromethorphan, an established NMDA receptor antagonist. They lacked affinity at the [3H]CGS-19755-labeled competitive site of the NMDA receptor. Therefore, both methadone and its the d- and l- isomers differ from morphine, hydromorphone, and naltrexone in that they have non-competitive antagonist activity at the NMDA receptor. A non-opioid NMDA receptor antagonist, such as d-methadone, may improve the efficacy of morphine by attenuating the development of tolerance.
 
How the hell can i get this thing more popular so more people try it? I first posted it in other drugs thinking a ton of ppl will try it as they have major tolerance issues there, i got 2 comments saying good work and none tried it to my suprise, after it got moved to ADD then people started trying it however considering the succes ppl have been having far more people should try it, if poeple keep having succes eventually i would like to get this thing to become the basic first thing poeple try when fighting drug tolerance or addiction.

I've been sending people here from from EADD when I think they could use the advice, but I think the movement to ADD in some ways highlights the problem. This thread is full of excellent evidence, studies and journal pages, but non ADD'ers don't want/have time to read and understand all of the evidence, they want to read a single page with a brief summary, what they need to do, and an FAQ.
They're quite happy to trust us to have read the studies properly, they just need to know what to do. It's often a shame, but most people will trust scientists pretty blindly.

Write up the key points here into layman's terms, have it stickied in the dark side, and water liberally, pruning in spring.
 
I really want to try, but I just can't adapt. After just three days of memantine (5, 10, 15mg), I had to stop due to side effects. I'll give dxm a try after I stop my saint john's wort, but seriously doubt I'll be able to get to the levels required to reverse tolerance...
 
I too would like to try this for MDMA tolerance, but I'd like to learn more about the safety of taking dxm within even one day's proximity of MDMA. The memantine heart issues are also of concern. That said, I've been very interested in this thread. Keep it going!
 
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.

Mbrace, as MeDieViL stated above, that the NMDA antagonist benefit should remain, so would you really need to take the DXM so close to the MDMA?

Maybe first try the DXM 60mg 2x/day for a week for tolerance reversal/upregulation and then wait a week (or more) before you roll?

That's my plan (in between my trials of 6g/day of SJW, since it's not good to combine the two), but I worry it will make me too lightheaded since I often use powertools or am up on a roof or driving and that might be too risky.

I should also add that on memantine, when I was exercising my heartrate was easily 15bpm higher than it normally is and was getting into an uncomfortable range...



.
 
Rodent study's indicate that nmda antagonists prevents tolerance to the sedative effect, however another study showed that an NMDA antagonist did not prevent tolerance to the anxiolytic effects.

Hopefully it reverses the tolerance to the anxiolytic effects in humans otherwise there's no point. 4th Day so far, runnin low, time to buy a new bottle tomorrow lol
 
just want to share my story. was iv heroin user for 5 years, opiates for 8. tried suboxone and it didnt work and methadone i couldnt function.

now im off all opiates (including suboxone and dont have PAWS)

day1-day4 25%decrease per day on suboxone
day 4- 100mg rectal 4meoPCP
day 5- heroin (new years, cmon) and coke
day 6-8 quick taper off methadone
day 8 methoxetamine

done.
no w/d
feeling pretty good.
 
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