• N&PD Moderators: Skorpio | someguyontheinternet

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

Is huperzine a an adequate NMDA antagonist? I had to get codeine this week instead of hydrocodone. It appears that DXM is an inhibitor of cyp2d6. I can barely get any effects of the codeine while DXM. I don't want my tolerance to skyrocket though.

I took 360 mg codeine today using DXM and it was about the same as what I would have gotten off of 20 mg hydrocdone.
 
Memantine is a great tolerance reducer.

3 days of low DXM? Why not just one day of high DXM (P3)? It worked right after in my experience. I dunno what your body weight is and what a low dose to you is either.

thanks for reply. well tbh i read lots of bad stuff about dxm and how damaging it is for body. also seems to deplate your seretonin if used recreationally. I am around 55kg so was thinking about doing 30mg for a couple of days prior to mephedrone/mdma/speed use. or would be better to do low dose (10-20mg) of Ket instead?
 
Would like to hear some opinions on this...

I have used DXM to lower my amphetamine tolerance in the past. I have noticed there seems to be a rise in blood pressure from combining the two, which results in more taxation on my heart.

Can anyone confirm this, or is this simply my imagination? DXM absolutely reduces my tolerance, but I'm wondering at what cost. Should I be worried about the safety of this? I usually only take 15mg's worth of the DXM Extended Formula in conjunction with 5-10 mg's of Dexedrine.

Tomer
 
Is DXM a dopamine reuptake inhibitor like ket is (and methoxetamine is thought to be)?

If so, surely that would explain any rise in blood pressure when combining with dopaminergic stimulants?
 
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Is DXM a dopamine reuptake inhibitor like ket is (and methoxetamine is thought to be)?

If so, surely that would explain any rise in blood pressure when combining with dopaminergic stimulants?

Im pretty sure dxm hits opiate receptors at high doses and is an ssri as well. Dont think its a DRI like ketamine.
 
I'm using 30mg memantine + 120mg DXM per day to slow tolerance to (primarily) Dexedrine and dihydrocodeine. Also cannabis, clonazepam and nicotine. As I take so many drugs (despite some being prn and not daily), it'd be a fair assumption that my anti-tolerance needs are gonna be substantially greater than someone just focusing on one drug, and a tiny 10mg memantine dose, for example, just ain't gonna cut it.

Before I was just using memantine for tolerance and, although it seemed to mildly help, it wasn't enough to allow more than 1 day on / 2 days off type dosing of Dex (I have a naturally very rapid tolerance to Dexedrine in particular). Similar for DHC (I rotate between Dex days, DHC days, and break days for anhedonia etc.). Since I added 2 x 60mg DXM into the mix a few days ago, I noticed I was able to sustain the amphetamine mood effect for 2 days instead of 1, before requiring a break to get back to where I was prior to dosing. It might be that now I can do 2 days on / 1 day off, the inverse of my previous usage pattern.

As my tolerances to Dex and DHC are both high due to laziness in taking breaks, I'll need a 3-5 day break to get tolerance down to near baseline. Then I'll be able to properly test the effect on tolerance.

Some observations on tolerance preventing:

  • Memantine above 40mg brought with it severe cognitive impairment that didn't fade away with the adaptation time. That's why I'm not just using a big dose of memantine rather than two NMDA modulators together, though I'll probably go back up to 40mg at some point. 50 and 60mg were the problematic doses.

  • As someone mentioned, the BP and heart rate increase from Dexedrine seems to have been mildly but noticeably increased since adding DXM on top of memantine. Whether this is just a general effect of NMDA blocking, or something more specific to the pharmacodynamics of DXM, I dunno. But I wouldn't want to take stimulants on a recreational DXM dose (not that I'd have any reason to anyway) based on experience with 120mg/day.

  • NMDA antagonists do indeed appear to speed up the reversal of tolerance, in addition to slowing the development of tolerance.

Oh yeah, I also use 100-150mg/day of amisulpride (presynaptic selective doses) in combination with Dexedrine, on the days I take it. This is on my theory that as stimulants increase synaptic DA, it in turn agonises D2/D3 autoreceptors and inhibits DA synthesis + release as part of the feedback loop, accounting for the biphasic progression of stimulant effects like such - mood lift (for a number of hours) -> possible crash -> lingering stimulation with no euphoria or mood lift, fading slowly as the drug clears your body. A study stated D2 autoreceptors inhibit DA synthesis via reduction of tyrosine hydroxylase, and D3 autoreceptors inhibit DA release. One would assume releasing agents like amphetamine aren't vulnerable to the D3 autoreceptors (as they force dopamine release from the presynaptic neuron) but are to D2-mediated DA synthesis reduction, while reuptake inhibitors like MPH would be affected by both.

When I took Dexedrine alone before, I got around 2-3 hours of balanced mood/stimulatory effects, followed by a crash (pretty mild still - memantine at work?) for 1 hour or so, followed by neutral mood with adrenergic stimulation tapering down over 3-6 hours (approx.). However, combined with low dose amisulpride, the initial "mood phase" didn't really shift into the crash/stimulation part nearly as much, and instead remained relatively balanced for the duration (naturally declining with time, but I got about double the time I had than before in the positive mood phase). I'm guessing amisulpride blocked the D2 autoreceptors in particular from sending their "halt TH now!" message upon amph's increasing of synaptic DA, and as a result L-dopa->DA levels weren't shot down by the time a few hours had passed (which before gave the crash / loss of hedonic effect) and the positives were free to continue for longer. Amisulpride had a similar effect on MPH if I recall correctly. I do know that receptor desensitisation also plays a role in the crash etc., but I think those autoreceptors do have a big part in it all. ...Very reductionist and pseudosciencey I know, but whatever, I did say it was only a theory & I'm no scientist.

Amisulpride has poor central vs. peripheral selectivity, which isn't usually good (man-boobs and stuff), but in combo with a stimulant this could be beneficial, as in the brain it'd be at presynaptic-selective concentrations, while peripherally it'd be also acting postsynaptically, and oppose the peripheral dopaminergic effects of stimulants including nausea/appetite suppression. It seems to help appetite a bit for me, although amp still has a major anorexic effect overall.
 
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2 days? try to double the DXM dose, you should be able to take amphetamine even in recreational doses for weeks on end without any sign of tolerance.
 
Ive tried memantine up to 80mg, i doubled the dose from 40mg, to prevent severe side effects i loaded up on 20 gram of piracetam wich inhibits the initial side effects quite well, i still felt pretty dizzy and had a doube vision, saw everytime the same car or person twice in front of me, wich went away after several days, worked like a charm with amphetamine but felt a bit impaired without it, felt quite confused when i took the train to work, so lowered to 60mg again wich in my case worked excellent without any noticable impairement. Tough many ppl would get quite a big of cognitive impairment above 40mg.
 
I frequently hear about people never getting effects off of small doses of hydrocodone after developing a considerable opioid habit. My habit peaked at 100 mg oxycodone. After tapering, I'm still able to get high off of 15 mg hydrocodone.
I take huperzine a (NMDA antagonist)400 mcg daily, dextromethorphan polistirex (NMDA antagonist) 120 mg daily, and melatonin(Nitric oxide synthase inhibitor) 3 mg daily. Probably each one of these plays some role in my high resistance to developing tolerance.

Re the tolerance, seems some people, once they hit a point of tolerance, they'll almost never reach a "low" level again that they can feel. Others do. Def be happy you're one of them, if you can get high off 10% your original dose (well, "peaked" could mean you did 100mg once, or did it daily for months - big difference here).

Re your melatonin, if you're using it as a "nitric oxide synthase inhibitor", no comments there, but if you're doing it for sleep of any sort, I'd lower it ;)

Re the club moss (hupzerzineA), remember also that it's a (quite potent if I'm correct, actually) acetylcholinasterase-inhibitor, and there is a significant concern for withdrawal/hangover/whatever effects to huperzineA, so yeah keep that in mind!

Upped Alprazolam dose on some days as i had to so cant give accurate answer but for the most part DXM in the form of Robitussin 60mg twice a day seemed to work. I will give this another go in about a week
interested in your future experiments, but the "had to go back on alprazolam" kinda negates your result of "seemed to work". I'm really interested in future experiments of any "lab monkeys" who want to try whatever, it only helps the rest of society, so don't think of that as a criticism, merely pointing out a "methodological flaw" so to speak :)

The only NMDA antagonist I have experience with is Memantine, which I began using to help curb my growing Adderall tolerance (RX'd 20mg XR x 2). For this purpose I've found it to be quite effective, and at only 10mg per day. My tolerance dropped drastically after a short break from the stimulant.
I'm confused - to paraphrase, you say "I found memantine 10mg/d to be effective. Tolerance dropped after short cessation of stimulants". Are you trying to attribute your "dropped tolerance" to the short break or the memantine, or a combo of both? Plz clarify the roles you think both took if you can :)

Now I'm hoping it will aid me in kicking my current Valium addiction. I recently crossed over from Klonopin (approx 1-2mg daily for a year) and I'm close to completely stablized on 15mg Diaz per day.
Good for you!! Very good!! Benzo's are a nasty long-term treatment, whether clinically- or self- medicated, so seeing someone swap to a (the!) long half -life benzo from a short-actor, well, it always makes me smile :) Remember too that you're already progressing significantly, you were on a high-potency, short half-life benzo for a year, and now you're stabilized at about HALF your daily dosage, so congrats on the decreased benzo dosage + swap to a realistic "stabilizer", at your rate I (personally) wouldn't recommend going into "new ideas", as you're doing fantastic with the age-old "taper appropriately" mechanism from what I can see - you swapped to the appropriate benzo, and have already begun a taper that's significantly lower than your clonazepam dosage, and is quite low in general (roughly 75% of a milligram of xanax or clonazepam).

I've bumped up my Memantine to 15mg (7.5 AM, 7.5 PM). I know that's a low dose but the brain fog can be pretty intense for me. Once that clears up I'll start the taper, see how things go, and update on my progress. Let the fun begin :).
??
You're doing well on a benzo-taper, a proper, well-documented approach, and instead of staying the course, you're going to try experimental approaches, despite having already experienced "intense brain fog"?? To each their own, but could you tell me why you're thinking this way instead of just continuing the taper as you had been? Seems it was doing fine on its own (and congrats btw, benzos are quite tough to get off of for most people)

simular to something we see in ADHD, if in your case the last thing is the case, i see nothing wrong with this treatment.
It's not his/her case - ADHD is almost the opposite actually, he/she has anxiety/depression, unless that was aimed at someone besides lovehatelove.

Some ppl may benefit best from NMDA agonists combined with therapy yes,
I'd say people benefit most from therapy, and if necessary, drug intervention (which would include maintenance drugs, taper-drugs <sometimes the same chemicals fwiw>, any "anti- tolerance/dependence/craving drugs", whether naloxone or memantine, and obviously, symptom management (sleep, bowels, etc) wherever/as needed.

but as with all mental disorders i beleive they can be caused both by passed events, or learned fear and also hypofunctioning,
I'm a bit unclear on your meaning here - surely you're not referring to that as a basis for "all mental disorders", or are you? Are you referring strictly to ADHD? Just curious because I've never seen a single model of addiction that did not account for the "nature" side of things, I mean clearly people suffer addiction as both a result of the stimuli (drugs) and how they respond (nature + nurture).

This may sound like a crazy idea.

But in case i would want to get some human study's started showing the effiacy of NMDA antagonists against tolerance, what would i need to do?
Isn't that what this thread is? :PP
Without the slightest bit of sarcasm, I'd say one of two routes:
SOLO:
- learn far more about pharmacokinetics and the brain,
- accumulate some cash to get it going (you said you were close to broke - a basic/cheap "study" would be easy, hell one has already been done here - but you need real cash to get a study anyone's going to care about)
WITH HELP:
- could start petitions on bl/internet/MAPS (applicable?)/erowid/online-anywhere,
- apply for a "normal" grant (w/o the 1st requirement under "solo", I'd imagine you'll get nowhere here - also, weigh your prior work in the area, knowledge of the area, education/resume, and ask yourself if you see sponsorship/grant dollars flowing your way)
<<If you don't mind me asking, are you a student, hobbyist, scientist, a combo of those? Have you ever been involved in human trials? How extensive is your knowledge/work in this area already?>>

Looking at the potential its damn worth investing in this! Just need to find the right people haha.
Something's only worth what the market will give - if someone pays, it was worth it, if not, it likely wasn't (market's aren't perfect, well except on paper ;) ). Sry, the economics dork comes out lol

Ive tried memantine up to 80mg, i doubled the dose from 40mg, to prevent severe side effects i loaded up on 20 gram of piracetam wich inhibits the initial side effects quite well, i still felt pretty dizzy and had a doube vision, saw everytime the same car or person twice in front of me, wich went away after several days, worked like a charm with amphetamine but felt a bit impaired without it, felt quite confused when i took the train to work, so lowered to 60mg again wich in my case worked excellent without any noticable impairement. Tough many ppl would get quite a big of cognitive impairment above 40mg.
I'm confused - you're saying that it "prevented severe side effects" but went on to mention some severe sides you had. You also say "worked like a charm". Kinda confused here.. also, if you're really onto the memantine (or ketamine I guess, but that/DXM were never really your approaches per se, just other nmda antagonists that others tried/you supported)
 
WHOA!!!!!!!!!! Apologies for the length of that, haven't slept in quite a bit, and tend to drag text to doc's then cut/paste it back, makes it tougher to realize how huge it comes out :P

Wish I was here when this thread began so I coulda tagged along from the get-go...

MeDieViL, don't take anything I said disparagingly - I will say some q's/points I've been making in posts today are kinda 'devil's advocate' types of replies, and I'm not really one to insult/talk down anyways, or so I like to think :)
 
Quote:
Originally Posted by Dunno View Post
Upped Alprazolam dose on some days as i had to so cant give accurate answer but for the most part DXM in the form of Robitussin 60mg twice a day seemed to work. I will give this another go in about a week -

interested in your future experiments, but the "had to go back on alprazolam" kinda negates your result of "seemed to work". I'm really interested in future experiments of any "lab monkeys" who want to try whatever, it only helps the rest of society, so don't think of that as a criticism, merely pointing out a "methodological flaw" so to speak

Ive always been on alprazolam never took a day off - trying 120mg daily as of today again
 
WHOA!!!!!!!!!! Apologies for the length of that, haven't slept in quite a bit, and tend to drag text to doc's then cut/paste it back, makes it tougher to realize how huge it comes out :P

Wish I was here when this thread began so I coulda tagged along from the get-go...

MeDieViL, don't take anything I said disparagingly - I will say some q's/points I've been making in posts today are kinda 'devil's advocate' types of replies, and I'm not really one to insult/talk down anyways, or so I like to think :)

No worry's, i'l reply to everything soon, i'm a bit unsure what you mean with severe memantine side effects i have? Cant remember any of that unless you mean the initial side effects of the adaptation phase from jumping 80 at once from 40.
 
I'm confused - to paraphrase, you say "I found memantine 10mg/d to be effective. Tolerance dropped after short cessation of stimulants". Are you trying to attribute your "dropped tolerance" to the short break or the memantine, or a combo of both? Plz clarify the roles you think both took if you can :)


Good for you!! Very good!! Benzo's are a nasty long-term treatment, whether clinically- or self- medicated, so seeing someone swap to a (the!) long half -life benzo from a short-actor, well, it always makes me smile :) Remember too that you're already progressing significantly, you were on a high-potency, short half-life benzo for a year, and now you're stabilized at about HALF your daily dosage, so congrats on the decreased benzo dosage + swap to a realistic "stabilizer", at your rate I (personally) wouldn't recommend going into "new ideas", as you're doing fantastic with the age-old "taper appropriately" mechanism from what I can see - you swapped to the appropriate benzo, and have already begun a taper that's significantly lower than your clonazepam dosage, and is quite low in general (roughly 75% of a milligram of xanax or clonazepam).


??
You're doing well on a benzo-taper, a proper, well-documented approach, and instead of staying the course, you're going to try experimental approaches, despite having already experienced "intense brain fog"?? To each their own, but could you tell me why you're thinking this way instead of just continuing the taper as you had been? Seems it was doing fine on its own (and congrats btw, benzos are quite tough to get off of for most people)


It's not his/her case - ADHD is almost the opposite actually, he/she has anxiety/depression, unless that was aimed at someone besides lovehatelove.
It's a combo of both, but it's better with memantine. Now (on 15mg mem) I only take sunday's off Adderall. In terms of tolerance reduction, that one day off is equal to probably 3-5 days sans memantine. So I go from being able use therapeutic stim doses 3-4 days a week to 6.

As far as my benzo taper goes, I was already stabilized at 10mg memantine, this wasn't a random experimental idea thrown into the mix. I experience brain fog above 15mg. Seeing as it's main purpose for me is amphetamine tolerance (but it could possibly help with coming off benzodiazepine's) I saw no reason to remove it.

Btw I feel the main contributor to my anxiety/depression is my inattentive ADD (which went untreated until less than a year ago).
 
I'm sorry I misspoke.
Your result here, "seemed to work", is invalidated by the fact you changed your xanax dosage.
Sorry if my meaining isn't clear, super tired now lol

Yeah nothing new i always use bout 14-16mg in certain situations even when i first started bout six years ago
 
Day 2 of DXM wwill try avoid situations where i need to increase my dose lol
 
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!
 
Re the tolerance, seems some people, once they hit a point of tolerance, they'll almost never reach a "low" level again that they can feel. Others do. Def be happy you're one of them, if you can get high off 10% your original dose (well, "peaked" could mean you did 100mg once, or did it daily for months - big difference here).

Re your melatonin, if you're using it as a "nitric oxide synthase inhibitor", no comments there, but if you're doing it for sleep of any sort, I'd lower it ;)

Re the club moss (hupzerzineA), remember also that it's a (quite potent if I'm correct, actually) acetylcholinasterase-inhibitor, and there is a significant concern for withdrawal/hangover/whatever effects to huperzineA, so yeah keep that in mind!


interested in your future experiments, but the "had to go back on alprazolam" kinda negates your result of "seemed to work". I'm really interested in future experiments of any "lab monkeys" who want to try whatever, it only helps the rest of society, so don't think of that as a criticism, merely pointing out a "methodological flaw" so to speak :)


I'm confused - to paraphrase, you say "I found memantine 10mg/d to be effective. Tolerance dropped after short cessation of stimulants". Are you trying to attribute your "dropped tolerance" to the short break or the memantine, or a combo of both? Plz clarify the roles you think both took if you can :)


Good for you!! Very good!! Benzo's are a nasty long-term treatment, whether clinically- or self- medicated, so seeing someone swap to a (the!) long half -life benzo from a short-actor, well, it always makes me smile :) Remember too that you're already progressing significantly, you were on a high-potency, short half-life benzo for a year, and now you're stabilized at about HALF your daily dosage, so congrats on the decreased benzo dosage + swap to a realistic "stabilizer", at your rate I (personally) wouldn't recommend going into "new ideas", as you're doing fantastic with the age-old "taper appropriately" mechanism from what I can see - you swapped to the appropriate benzo, and have already begun a taper that's significantly lower than your clonazepam dosage, and is quite low in general (roughly 75% of a milligram of xanax or clonazepam).


??
You're doing well on a benzo-taper, a proper, well-documented approach, and instead of staying the course, you're going to try experimental approaches, despite having already experienced "intense brain fog"?? To each their own, but could you tell me why you're thinking this way instead of just continuing the taper as you had been? Seems it was doing fine on its own (and congrats btw, benzos are quite tough to get off of for most people)


It's not his/her case - ADHD is almost the opposite actually, he/she has anxiety/depression, unless that was aimed at someone besides lovehatelove.
I ment that it is extremely unlikely that anxiety or other disorders cant be mediated by neurochemical issues, simular to how ADHD is caused by (mostly DAT, tyrosyne hydroxilase, D4, etc) dysfunctioning of other receptors or other issues can also manifest in things like anxiety, if thats the case then using medication is the preferred route abose therapy (assuming therapy wont work here like with adhd).

I'd say people benefit most from therapy, and if necessary, drug intervention (which would include maintenance drugs, taper-drugs <sometimes the same chemicals fwiw>, any "anti- tolerance/dependence/craving drugs", whether naloxone or memantine, and obviously, symptom management (sleep, bowels, etc) wherever/as needed.

What makes you say most ppl would benefit mostly from therapy? Id say it could vary dramatically, and that medication definatly shouldnt be disregarded as a long term solution.


I'm a bit unclear on your meaning here - surely you're not referring to that as a basis for "all mental disorders", or are you? Are you referring strictly to ADHD? Just curious because I've never seen a single model of addiction that did not account for the "nature" side of things, I mean clearly people suffer addiction as both a result of the stimuli (drugs) and how they respond (nature + nurture).
I ment that all mental disorders can be caused by either learned fears or passed events and also because of neurochemical issues.

Isn't that what this thread is? :PP
Without the slightest bit of sarcasm, I'd say one of two routes:
SOLO:
- learn far more about pharmacokinetics and the brain,
- accumulate some cash to get it going (you said you were close to broke - a basic/cheap "study" would be easy, hell one has already been done here - but you need real cash to get a study anyone's going to care about)
WITH HELP:
- could start petitions on bl/internet/MAPS (applicable?)/erowid/online-anywhere,
- apply for a "normal" grant (w/o the 1st requirement under "solo", I'd imagine you'll get nowhere here - also, weigh your prior work in the area, knowledge of the area, education/resume, and ask yourself if you see sponsorship/grant dollars flowing your way)
<<If you don't mind me asking, are you a student, hobbyist, scientist, a combo of those? Have you ever been involved in human trials? How extensive is your knowledge/work in this area already?>>
I'm not a student, heck i dont know wheter i can ever properly study, i never finished highschool and have a bad criminal record, not the best situation. I just have a big intrest in all of this.

Something's only worth what the market will give - if someone pays, it was worth it, if not, it likely wasn't (market's aren't perfect, well except on paper ;) ). Sry, the economics dork comes out lol


I'm confused - you're saying that it "prevented severe side effects" but went on to mention some severe sides you had. You also say "worked like a charm". Kinda confused here.. also, if you're really onto the memantine (or ketamine I guess, but that/DXM were never really your approaches per se, just other nmda antagonists that others tried/you supported)

Never had severe side effects with memantine, the closest to severe was the adaptation but that wasnt really bad either.
 
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