• Neuroscience & Pharmacology Discussion Welcome Guest
    Posting Rules Bluelight Rules
    Recent Journal Articles Chemistry Mega-Thread
    FREE Chemistry Databases! Self-Education Guide

  • N&PD Moderators: Skorpio | someguyontheinternet

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

avcpl said:
ok! finished we 6 days of 120mg dxm daily on friday. we did the hbr at night and the delsym during the day. also took 200mg of chelated magnesium at night.

tried our usual oxycodone dose yesterday (sunday) and it actually did make a difference! it was significantly stronger than the last time we used it, two weeks ago. I don't think it was a placebo effect, since I am a born skeptic; I usually introduce an anti-placebo effect if anything.

The only bad thing is that the side effects were increased too--that is the itchiness. I know we're in the minority here that lots of people like the itchiness of opiates, but it drives me crazy and too much antihistamine ruins the high. Gonna try hydrocodone next weekend and see if that works any better.

we roll in four weeks so we'll see how it affects our mdma tolerance.

thanks to everyone for all the info!
Click to expand...

Cool thx for your update mate.
 
Would lower dosis then 120 mg have a similar effect? I'm considering using it daily alongside mirtazapine and methylphenidate, but don't really want to take more then 50 mg a day because of possible serotonergic side effects and other possible interactions. The serotonergic action of dxm at >90 mg's sucks as is for me, I cannot stand 200 mg's of 5-htp either. I get crazy insomnia from both at those dosages. The mirtazapine will probably make it even worse so it might be a bad idea after all.
 
MeDieViL said:
Comeon guys, anyone else that needs to get rhid of some tolerance? Give this shit a try!
Click to expand...

I'm at day 5 of a planned 7 day regimen of 120 mg per day of dxm, taken as 60mg in the morning and again in the early evening, with the hope that this will reverse some of my tolerance to mdma.

I'm also on a break from mdma. I had planned on going several months, and trying this a couple weeks before rolling, but I actually had a bad, bad cough and figured what-the-hell, might as well take the opportunity to drink the syrup.

I've never used dxm recreationally before. The first few days were not as easy as I hoped, but I think my body has gotten used to it now.

I'm still not clear on a couple of issues concerning this dxm tolerance reversal hypothesis:

1.) How long do I really need to wait between the end of my dxm regimen before rolling? Someone said earlier in this thread to wait two weeks, because of the info on the standard warning label, but I think that's a misinterpretation of the data on the label, which seems to me to say wait two weeks after stopping an MAOI before taking dxm.

2.) Is the tolerance reversal a semi-permanent neuro plasticity adaptation ? Can I wait two weeks after stopping dxm and still expect a lowered tolerance? Can I wait a month? A year?

I feel a bit like the dumb kid in algebra -- which I was !?!? -- who just doesn't quite get it yet. So thanks for bearing with me, that a-ha moment is hopefully near.

And OMG this stuff definitely potentiates caffeine....
 
Mbrace, it was I that said that about the two weeks. I realize it was about the MAOI on the label; I wasn't misinterpreting the label, I meant that would probably be a good rule of thumb, just thinking "hey, if a two week buffer is ok for maoi/dxm usage, then probably can't go too wrong with a two week buffer for dxm/mdma". Just my personal opinion, so take it for what it's worth!
]
I believe from reading the comments in this thread that the tolerance reversal should last until you blow it again. MeDieViL has said that the NMDA antagonist benefit should remain; I don't think you would lose it by just waiting..

Me and my wife have been very impressed with how it has worked with opiates and we roll in 11 days and are really looking forward to it!
 
As far as I know, these NMDA changes are permanent, they don't go away (remember, this is, in essence, a "helper" in trying to reverse a drug user's brain back to baseline/normal. You put your brain in a spot that it can benefit here, and it will benefit. If you stop using an NMDA antagonist, or you start using again, sure you can rewire things back to an addicted/tolerant/etc state, but when you cessate usage, or speed up cessation with NMDA antagonists (or use them during usage, to slow tolerance buildup, if that is demonstratable outside of theory/anecdote), you're using a chemical to 'fix' things, bring them closer to where your body wanted it to be, so no it doesn't stop once the NMDA antonist is stopped ;-P )
 
I just registered to the forum because I jumped on the memantine bandwagon to counteract amphetamine tolerance. I want to start Adderall again for my ADD. I take Lyrica (150mg 2x day) and started pristiq 20 days ago. Lyrica is amazing to counteract the side effects of Adderall and for anxiety. I eliminated clonazepam from my regimen thanks to Lyrica (still pop one once in while, mainly to sleep).

Pristiq is a pain since it make me feel tired but "nervous" at the same time (can't stop shaking my legs). I don't think I will keep it for long but I give it a try for a few more weeks.

Without Lyrica I could barely handle 10 mg of Adderall. I can go up to 30 mg with my current dose of Lyrica. (But 20 mg seems enough). Sadly, it doesn't help with tolerance.

I started memantine 2 days ago. I want to titrate fast. No brain fog noted so far at 10 mg. Others have reported that memantine greatly potentiate Lyrica. From my experience so far this seems to be true. When I took 75 mg of Lyrica Yesterday and this morning, I got a feeling of heaviness that I don't get at 150 mg.

Too soon to report on Adderall tolerance with memantine (just popped 20 mg of Adderall and I feel great!). Usually I get about two hours of motivation and mood lifting, followed by 6-8 hours of "awakening" effect on the first day after a few days break. It take only a few days for the tolerance to develop.

Should I expect memantine to have an effect on tolerance right away or do I need to take it many days in a row before getting any benefits?

By the way, do you guys note a difference between Adderall and Dexedrine Extended-Release?
 
Currently im taking 60mg DXM 3 times a day combined with 666mg acamprosate 3 times a day, well see how it goes.

Goal is to prevent tolerance to dexedrine, valium and GBL.
 
Last edited:
Given this isn't too busy a thread, lemme ask you something.

I know you've been reading up on NMDA/pathways, and am curious what you've found with regards to "time til normal" after cessation of a strong NMDA agonist (coke, heroin, whatever). How long til "rewired-to-normal"? High/low correlation with time/dosage/administration-route? Highly individual/variable? Just interested, I know there's no real "concrete" answers for a lot of that just yet.
 
Well, I was really hoping to just hear your thoughts. I've been learning about NMDA, glutamate, reward pathways, neuroplasticity, etc, but it's from a non-biological-sciences-background. I wanted to hear what you've found in the areas I'd mentioned.
If you want me to be more specific, I'd be interested to know if/what data/thoughts exist with regards to someone "returning to normal", as far as their 'circuitry' is concerned, after, say, 5yrs of crack, or 20 of xanax. Between friends I have/am trying to help, and family who have been on addictive, doctor-sanctioned meds for decades, I have a keen interest in "recovery" and the re-wiring of these pathways.
 
(and further - I'm correct in that the NMDA pathway is the primary source of addiction, right? Regardless of whether it's crack, xanax or heroin, it's dopamine/glutamate/NMDA-agonism that cause addiction (not dependence, *addiction*)
 
SangerRainsford said:
Well, I was really hoping to just hear your thoughts. I've been learning about NMDA, glutamate, reward pathways, neuroplasticity, etc, but it's from a non-biological-sciences-background. I wanted to hear what you've found in the areas I'd mentioned.
If you want me to be more specific, I'd be interested to know if/what data/thoughts exist with regards to someone "returning to normal", as far as their 'circuitry' is concerned, after, say, 5yrs of crack, or 20 of xanax. Between friends I have/am trying to help, and family who have been on addictive, doctor-sanctioned meds for decades, I have a keen interest in "recovery" and the re-wiring of these pathways.
Click to expand...

Can you specify what symptons those ppl are suffering from, and what should be normalised?
I assume were talking about things like anhedonia here?

I beleive NMDA antagonists should help, but i'm a bit insure about this subject.
 
SangerRainsford said:
(and further - I'm correct in that the NMDA pathway is the primary source of addiction, right? Regardless of whether it's crack, xanax or heroin, it's dopamine/glutamate/NMDA-agonism that cause addiction (not dependence, *addiction*)
Click to expand...

NMDA, CREB, KAPPA, Mu opioid, CB1, 5HT3, GABAB and tons more receptors involved, its not that NMDA is the premirary mediated, but the nmda complex does play a keyrole in many addictions, and disrubting it with NMDA antagonism can be highly beneficial.
 
Last edited:
Okay, definitely have to scale back on the smart-talk ;P
I'm unsure what role mu-opioid receptors play in cocaine *addiction*.
To be more to the point, I was under the impression that ALL drug addiction involved the effects of dopamine in the "NMDA system". Surely there are more systems involved in specific-drug cases, that's not what I'm referring to. I'm referring to the common pathways shared by *all* drugs of addiction that cause the reinforcing, rewarding feelings that make one continue to use despite it being to their detriment. Doesn't every drug-addiction involve the reward pathways, and isn't this the central role of NMDA in addiction?

I'm not talking about drug-specific withdrawals, drug-specific dependence, or drug-specific anything. I'm talking about the long-term changes one's brain undergoes during drug addictive behavior being rewarded over and over, whether crack, heroin, even compulsive gambling - are they not all dopamine/NMDA based? If they are, then the question is simply "how long after one stops gambling/doing crack will these changes reverse?"
 
Reading how you phrased your post, I just want to be clear that the distinctions between abuse, dependence, addiction, tolerance, etc in any post I made in this thread were meant in the most literal sense.
/you think I'm referring to "tolerance" reversal, don't you? I'm talking about addiction-reversal, reversing the changes that occured in one's brain due to years of reinforcing a "gambling feels good" sensation. Once one stops gambling, off the bat, gambling still feels right. At some point it doesn't feel as right. It's my understanding this is due to the aforementioned pathways, the reinforcements that "gambling's right" for many years - once the reinforcements from drugs/gambling stop, how long til said pathways are not thinking about drugs/gambling? I'm under the impression that the brain eventually abandons such pathways once reinforcements stop, and that it is mediated by dopamine/NMDA agonism.
 
You must log in or register to reply here.
Top